SUMMARY OF THE INVENTION The invention is based in part upon the discovery of novel nucleic acid sequences encoding novel polypeptides. The disclosed FCTR1, FCTR2, FCTR3, FCTR4, FCTR5, FCTR6 and FCTR7 nucleic acids and polypeptides encoded therefrom, as well as derivatives, homologs, analogs and fragments thereof, will hereinafter be collectively designated as "FCTRX"nucleic acid or polypeptide sequences.

In one aspect, the invention provides an isolated FCTRX nucleic acid molecule encoding a FCTRX polypeptide that includes a nucleic acid sequence that has identity to the nucleic acids disclosed in SEQ ID NOS : 1, 3, 5, 7, 9, 10, 11, 12, 14, 16, 18, 20, 22, and 24. In some embodiments, the FCTRX nucleic acid molecule will hybridize under stringent conditions to a nucleic acid sequence complementary to a nucleic acid molecule that includes a protein-coding sequence of a FCTRX nucleic acid sequence. The invention also includes an isolated nucleic acid that encodes a FCTRX polypeptide, or a fragment, homolog, analog or derivative thereof. For example, the nucleic acid can encode a polypeptide at least 80% identical to a polypeptide comprising the amino acid sequences of SEQ ID NOS : 2, 4, 6, 8, 13, 15, 17, 19, 21, 23, and 25. The nucleic acid can be, for example, a genomic DNA fragment or a cDNA molecule that includes the nucleic acid sequence of any of SEQ ID NOS : 1, 3, 5, 7, 9, 10, 11, 12, 14, 16, 18, 20, 22, and 24.

Also included in the invention is an oligonucleotide, e. g, an oligonucleotide which includes at least 6 contiguous nucleotides of a FCTRX nucleic acid (e. g., SEQ ID NOS : 1, 3, 5, 7, 9, 10, 11, 12, 14, 16, 18, 20, 22, and 24) or a complement of said oligonucleotide.

Also included in the invention are substantially purified FCTRX polypeptides (SEQ ID NO : 2, 4, 6, 8, 13, 15, 17, 19, 21, 23, and 25). In certain embodiments, the FCTRX polypeptides include an amino acid sequence that is substantially identical to the amino acid sequence of a human FCTRX polypeptide.

The invention also features antibodies that immunoselectively-binds to FCTRX polypeptides, or fragments, homologs, analogs or derivatives thereof.

In another aspect, the invention includes pharmaceutical compositions that include therapeutically-or prophylactically-effective amounts of a therapeutic and a pharmaceutically- acceptable carrier. The therapeutic can be, e. g., a FCTRX nucleic acid, a FCTRX polypeptide, or an antibody specific for a FCTRX polypeptide. In a further aspect, the invention includes, in one or more containers, a therapeutically-or prophylactically-effective amount of this pharmaceutical composition.

In a further aspect, the invention includes a method of producing a polypeptide by culturing a cell that includes a FCTRX nucleic acid, under conditions allowing for expression of the FCTRX polypeptide encoded by the DNA. If desired, the FCTRX polypeptide can then be recovered.

In another aspect, the invention includes a method of detecting the presence of a FCTRX polypeptide in a sample. In the method, a sample is contacted with a compound that selectively binds to the polypeptide under conditions allowing for formation of a complex between the polypeptide and the compound. The complex is detected, if present, thereby identifying the FCTRX polypeptide within the sample.

The invention also includes methods to identify specific cell or tissue types based on their expression of a FCTRX.

Also included in the invention is a method of detecting the presence of a FCTRX nucleic acid molecule in a sample by contacting the sample with a FCTRX nucleic acid probe or primer, and detecting whether the nucleic acid probe or primer bound to a FCTRX nucleic acid molecule in the sample.

In a further aspect, the invention provides a method for modulating the activity of a FCTRX polypeptide by contacting a cell sample that includes the FCTRX polypeptide with a compound that binds to the FCTRX polypeptide in an amount sufficient to modulate the activity of said polypeptide. The compound can be, e. g., a small molecule, such as a nucleic acid, peptide, polypeptide, peptidomimetic, carbohydrate, lipid or other organic (carbon containing) or inorganic molecule, as further described herein.

Also within the scope of the invention is the use of a Therapeutic in the manufacture of a medicament for treating or preventing disorders or syndromes including, e. g., Colorectal cancer, adenomatous polyposis coli, myelogenous leukemia, congenital ceonatal alloimmune thrombocytopenia, multiple human solid malignancies, malignant ovarian tumours particularly at the interface between epithelia and stroma, malignant brain tumors, mammary tumors,

human gliomas, astrocytomas, mixed glioma/astrocytomas, renal cells carcinoma, breast adenocarcinoma, ovarian cancer, melanomas, renal cell carcinoma, clear cell and granular cell carcinomas, autocrine/paracrine stimulation of tumor cell proliferation, autocrine/paracrine stimulation of tumor cell survival and tumor cell resistance to cytotoxic therapy, paranechmal and basement membrane invasion and motility of tumor cells thereby contributing to metastasis, tumor-mediated immunosuppression of T-cell mediated immune effector cells and pathways resulting in tumor escape from immune surveilance, neurological disorders, neurodegenerative disorders, nerve trauma, familial myelodysplastic syndrome, Charcot- Marie-Tooth neuropathy, demyelinating Gardner syndrome, familial myelodysplastic syndrome ; mental health conditions, immunological disorders, allergy and infection, asthma, bronchial asthma, Avellino type eosinophilia, lung diseases, reproductive disorders, male infertility, female reproductive system disorders, male and female reproductive diseases, hemangioma, deafness, glycoprotein la deficiency, desmoid disease, turcot syndrome, liver cirrhosis, hepatitis C, gastric disorders, pancreatic diseases like diabetes, Schistosoma mansoni infection, Spinocerebellar ataxia, Plasmodium falciparum parasitemia, Corneal dystrophy- Groenouw type I, Comeal dystrophy-lattice type I, and Reis-Bucklers corneal dystrophy.

The Therapeutic can be, e. g., a FCTRX nucleic acid, a FCTRX polypeptide, or a FCTRX- specific antibody, or biologically-active derivatives or fragments thereof.

The invention further includes a method for screening for a modulator of disorders or syndromes including, e. g., Also within the scope of the invention is the use of a Therapeutic in the manufacture of a medicament for treating or preventing disorders or syndromes including, e. g., Colorectal cancer, adenomatous polyposis coli, myelogenous leukemia, congenital ceonatal alloimmune thrombocytopenia, multiple human solid malignancies, malignant ovarian tumours particularly at the interface between epithelia and stroma, malignant brain tumors, mammary tumors, human gliomas, astrocytomas, mixed glioma/astrocytomas, renal cells carcinoma, breast adenocarcinoma, ovarian cancer, melanomas, renal cell carcinoma, clear cell and granular cell carcinomas, autocrine/paracrine stimulation of tumor cell proliferation, autocrine/paracrine stimulation of tumor cell survival and tumor cell resistance to cytotoxic therapy, paranechmal and basement membrane invasion and motility of tumor cells thereby contributing to metastasis, tumor-mediated immunosuppression of T-cell mediated immune effector cells and pathways resulting in tumor escape from immune surveilance, neurological disorders, neurodegenerative disorders, nerve trauma, familial myelodysplastic syndrome, Charcot-Marie-Tooth neuropathy, demyelinating Gardner syndrome, familial myelodysplastic syndrome ; mental health conditions, immunological

disorders, allergy and infection, asthma, bronchial asthma, Avellino type eosinophilia, lung diseases, reproductive disorders, male infertility, female reproductive system disorders, male and female reproductive diseases, hemangioma, deafness, glycoprotein Ia deficiency, desmoid disease, turcot syndrome, liver cirrhosis, hepatitis C, gastric disorders, pancreatic diseases like diabetes, Schistosoma mansoni infection, Spinocerebellar ataxia, Plasmodium falciparum parasitemia, Corneal dystrophy-Groenouw type I, Corneal dystrophy-lattice type I, and Reis-Bucklers corneal dystrophy. The method includes contacting a test compound with a FCTRX polypeptide and determining if the test compound binds to said FCTRX polypeptide.

Binding of the test compound to the FCTRX polypeptide indicates the test compound is a modulator of activity, or of latency or predisposition to the aforementioned disorders or syndromes.

Also within the scope of the invention is a method for screening for a modulator of activity, or of latency or predisposition to an disorders or syndromes including, e. Also within the scope of the invention is the use of a Therapeutic in the manufacture of a medicament for treating or preventing disorders or syndromes including, e. g., Colorectal cancer, adenomatous polyposis coli, myelogenous leukemia, congenital ceonatal alloimmune thrombocytopenia, multiple human solid malignancies, malignant ovarian tumours particularly at the interface between epithelia and stroma, malignant brain tumors, mammary tumors, human gliomas, astrocytomas, mixed glioma/astrocytomas, renal cells carcinoma, breast adenocarcinoma, ovarian cancer, melanomas, renal cell carcinoma, clear cell and granular cell carcinomas, autocrine/paracrine stimulation of tumor cell proliferation, autocrine/paracrine stimulation of tumor cell survival and tumor cell resistance to cytotoxic therapy, paranechmal and basement membrane invasion and motility of tumor cells thereby contributing to metastasis, tumor-mediated immunosuppression of T-cell mediated immune effector cells and pathways resulting in tumor escape from immune surveilance, neurological disorders, neurodegenerative disorders, nerve trauma, familial myelodysplastic syndrome, Charcot- Marie-Tooth neuropathy, demyelinating Gardner syndrome, familial myelodysplastic syndrome ; mental health conditions, immunological disorders, allergy and infection, asthma, bronchial asthma, Avellino type eosinophilia, lung diseases, reproductive disorders, male infertility, female reproductive system disorders, male and female reproductive diseases, hemangioma, deafness, glycoprotein la deficiency, desmoid disease, turcot syndrome, liver cirrhosis, hepatitis C, gastric disorders, pancreatic diseases like diabetes, Schistosoma mansoni infection, Spinocerebellar ataxia, Plasmodium falciparum parasitemia, Comeal dystrophy- Groenouw type I, Corneal dystrophy-lattice type I, and Reis-Bucklers corneal dystrophy by

administering a test compound to a test animal at increased risk for the aforementioned disorders or syndromes. The test animal expresses a recombinant polypeptide encoded by a FCTRX nucleic acid. Expression or activity of FCTRX polypeptide is then measured in the test animal, as is expression or activity of the protein in a control animal which recombinantly- expresses FCTRX polypeptide and is not at increased risk for the disorder or syndrome. Next, the expression of FCTRX polypeptide in both the test animal and the control animal is compared. A change in the activity of FCTRX polypeptide in the test animal relative to the control animal indicates the test compound is a modulator of latency of the disorder or syndrome.

In yet another aspect, the invention includes a method for determining the presence of or predisposition to a disease associated with altered levels of a FCTRX polypeptide, a FCTRX nucleic acid, or both, in a subject (e. g., a human subject). The method includes measuring the amount of the FCTRX polypeptide in a test sample from the subject and comparing the amount of the polypeptide in the test sample to the amount of the FCTRX polypeptide present in a control sample. An alteration in the level of the FCTRX polypeptide in the test sample as compared to the control sample indicates the presence of or predisposition to a disease in the subject. Preferably, the predisposition includes, e. g., Also within the scope of the invention is the use of a Therapeutic in the manufacture of a medicament for treating or preventing disorders or syndromes including, e. g., Colorectal cancer, adenomatous polyposis coli, myelogenous leukemia, congenital ceonatal alloimmune thrombocytopenia, multiple human solid malignancies, malignant ovarian tumours particularly at the interface between epithelia and stroma, malignant brain tumors, mammary tumors, human gliomas, astrocytomas, mixed glioma/astrocytomas, renal cells carcinoma, breast adenocarcinoma, ovarian cancer, melanomas, renal cell carcinoma, clear cell and granular cell carcinomas, autocrine/paracrine stimulation of tumor cell proliferation, autocrine/paracrine stimulation of tumor cell survival and tumor cell resistance to cytotoxic therapy, paranechmal and basement membrane invasion and motility of tumor cells thereby contributing to metastasis, tumor- mediated immunosuppression of T-cell mediated immune effector cells and pathways resulting in tumor escape from immune surveilance, neurological disorders, neurodegenerative disorders, nerve trauma, familial myelodysplastic syndrome, Charcot-Marie-Tooth neuropathy, demyelinating Gardner syndrome, familial myelodysplastic syndrome ; mental health conditions, immunological disorders, allergy and infection, asthma, bronchial asthma, Avellino type eosinophilia, lung diseases, reproductive disorders, male infertility, female reproductive system disorders, male and female reproductive diseases, hemangioma, deafness,

glycoprotein la deficiency, desmoid disease, turcot syndrome, liver cirrhosis, hepatitis C, gastric disorders, pancreatic diseases like diabetes, Schistosoma mansoni infection, Spinocerebellar ataxia, Plasmodium falciparum parasitemia, Corneal dystrophy-Groenouw type I, Corneal dystrophy-lattice type I, and Reis-Bucklers corneal dystrophy. Also, the expression levels of the new polypeptides of the invention can be used in a method to screen for various cancers as well as to determine the stage of cancers.

In a further aspect, the invention includes a method of treating or preventing a pathological condition associated with a disorder in a mammal by administering to the subject a FCTRX polypeptide, a FCTRX nucleic acid, or a FCTRX-specific antibody to a subject (e. g., a human subject), in an amount sufficient to alleviate or prevent the pathological condition. In preferred embodiments, the disorder, includes, e. g., Also within the scope of the invention is the use of a Therapeutic in the manufacture of a medicament for treating or preventing disorders or syndromes including, e. g., Colorectal cancer, adenomatous polyposis coli, myelogenous leukemia, congenital ceonatal alloimmune thrombocytopenia, multiple human solid malignancies, malignant ovarian tumours particularly at the interface between epithelia and stroma, malignant brain tumors, mammary tumors, human gliomas, astrocytomas, mixed glioma/astrocytomas, renal cells carcinoma, breast adenocarcinoma, ovarian cancer, melanomas, renal cell carcinoma, clear cell and granular cell carcinomas, autocrine/paracrine stimulation of tumor cell proliferation, autocrine/paracrine stimulation of tumor cell survival and tumor cell resistance to cytotoxic therapy, paranechmal and basement membrane invasion and motility of tumor cells thereby contributing to metastasis, tumor- mediated immunosuppression of T-cell mediated immune effector cells and pathways resulting in tumor escape from immune surveilance, neurological disorders, neurodegenerative disorders, nerve trauma, familial myelodysplastic syndrome, Charcot-Marie-Tooth neuropathy, demyelinating Gardner syndrome, familial myelodysplastic syndrome ; mental health conditions, immunological disorders, allergy and infection, asthma, bronchial asthma, Avellino type eosinophilia, lung diseases, reproductive disorders, male infertility, female reproductive system disorders, male and female reproductive diseases, hemangioma, deafness, glycoprotein la deficiency, desmoid disease, turcot syndrome, liver cirrhosis, hepatitis C, gastric disorders, pancreatic diseases like diabetes, Schistosoma mansoni infection, Spinocerebellar ataxia, Plasmodium falciparum parasitemia, Corneal dystrophy-Groenouw type I, Corneal dystrophy-lattice type I, and Reis-Bucklers corneal dystrophy.

In yet another aspect, the invention can be used in a method to identity the cellular receptors and downstream effectors of the invention by any one of a number of techniques

commonly employed in the art. These include but are not limited to the two-hybrid system, affinity purification, co-precipitation with antibodies or other specific-interacting molecules.

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In the case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.

Other features and advantages of the invention will be apparent from the following detailed description and claims.

DETAILED DESCRIPTION The invention is based, in part, upon the discovery of novel nucleic acid sequences that encode novel polypeptides. The novel nucleic acids and their encoded polypeptides are referred to individually as FCTR1, FCTR2, FCTR3, FCTR4, FCTR5, FCTR6, and FCTR7.

The nucleic acids, and their encoded polypeptides, are collectively designated herein as "FCTRX".

The novel FCTRX nucleic acids of the invention include the nucleic acids whose sequences are provided in Tables 1A, 2A, 3A, 3C, 3E, 3F, 3G, 3H, 4A, 5A, 5C, 5E, 6A, 6C, and 7A inclusive ("Tables 1A-7A"), or a fragment, derivative, analog or homolog thereof.

The novel FCTRX proteins of the invention include the protein fragments whose sequences are provided in Tables 1B, 2B, 3B, 3I, 4B, 5B, 5D, 6B, 6D, and 7B inclusive ("Tables 1B- 7B"). The individual FCTRX nucleic acids and proteins are described below. Within the scope of this invention is a method of using these nucleic acids and peptides in the treatment or prevention of a disorder related to cell signaling or metabolic pathway modulation.

FCTR1 Novel FCTR1 is a growth factor ("FCTR") protein related to follistatin-like gene, and mac25. FCTR1 (also referred to by proprietary accession number 58092213. 0. 36) is a full- length clone of 771 nucleotides, including the entire coding sequence of a 105 amino acid protein from nucleotides 438 to 753. The clone was originally obtained from thyroid gland, kidney, fetal kidney, and spleen tissues.

The nucleotide sequence of FCTR1 as presently determined is reported in Table 1A.

The start and stop codons are bolded and the 5'and 3'untranslated regions are underlined.

Table 1A. FCTR1 nucleotide sequence (SEQ ID NO : 1).

GGTCCTCACCCCCTTCCTCTCTCCCAGCCTCGGTGTCTGGTTACGGCTCCTCTGCTC GCATTGTGACTTTGGGCCAGGCTGGGG GAAATGACCCGGGAGGGTCCCATGCGGCTACATAAAATTGGCAGCCTTAGAACTAGTGGG AAGGCGGGTGCGCGAAGTCGAGGG GCGGAGAGAGGGGGCCGGAGGAGCTGCTTTCTGAATCCAAGTTCGTGGGCTCTCTCAGAA GTCCTCAGGACGGAGCAGAGGTGG CCGGCGGGCCCGGCTGACTGCGCCTCTGCTTTCTTTCCATAACCTTTTCTTTCGGACTCG AATCACGGCTGCTGCGAAGGGTCT AGTTCCGGACACTAGGGCCCCAGATCGTGTCACATCCATATGACACTTGGAATGTGACAG GGCAGGATGTGATCTTTGGCTGTG <BR> <BR> AAGTGTTTGCCTACCCCATGGCCTCCATCGAGTGGAGGAAGGATGGCTTGGACATCCAGC TGCCAGGGGATGACCCCCACATCT<BR> <BR> <BR> CTGTGCAGTTTAGGGGTGGACCCCAGAGGTTTGAGGTGACTGGCTGGCTGCAGATCCAGG CTGTGCGTCCCAGTGATGAGGGCA CTTACCGCTGCCTTGCCCGCAATGCCCTGGGTCAAGTGGAGGCCCCTGCTAGCTTGACAG TGCTCACACCTGACCAGCTGAACT <BR> <BR> CTACAGGCATCCCCCAGCTGCGATCACTAAACCTGGTTCCTGAGGAGGAGGCTGAGAGTG AAGAGAATGACGATTACTACTAGG TCCAGAGCTCTGGCC The predicted amino acid sequence of FCTR1 protein corresponding to the foregoing nucleotide sequence is reported in Table 1B. FCTR1 was searched against other databases using SignalPep and PSort search protocols. The protein is most likely located in the cytoplasm (certainty=0. 6500) and seems to have no N-terminal signal sequence. The predicted molecularweightofFCTRl proteinis 11711. 8 daltons.

Table 1B. Encoded FCTR1 protein sequence (SEQ ID NO : 2). <BR> <BR> <BR> <BR> <P>MASIEWRKDGLDIQLPGDDPHISVQFRGGPQRFEVTGWLQIQAVRPSDEGT YRCLARNALGQVEAPASLTVLTPDQLNSTGIPQ<BR> <BR> LRSLNLVPEEEAESEENDDYY FCTR1 was initially identified with a TblastN analysis of a proprietary sequence file for a follistatin-like probe or homolog which was run against the Genomic Daily Files made available by GenBank. A proprietary software program (GenScanTM) was used to further predict the nucleic acid sequence and the selection of exons. The resulting sequences were further modified by means of similarities using BLAST searches. The sequences were then manually corrected for apparent inconsistencies, thereby obtaining the sequences encoding the full-length protein.

In an analysis of sequence databases, it was found, for example, that the FCTR1 nucleic acid sequence has 31/71 bases (43%) identical and 46/71 bases positively alike to a Mus Musculus IGFBP-like protein (TREMBL Accession Number : BAA21725) shown in Table 1C. In all BLAST alignments herein, the"E-value"or"Expect"value is a numeric indication of the probability that the aligned sequences could have achieved their similarity to the BLAST query sequence by chance alone, within the database that was searched. For example, as shown in Table 1 C, the probability that the subject ("Sbjct") retrieved from the FCTR1 BLAST analysis, in this case the Mus Musculus IGFBP-like protein, matched the Query FCTRl sequence purely by chance is 1. 2x10-

Table 1C. BLASTP of FCTRl against Mus Musculus IGFBP-like protein (SEQ ID NO : 38) PTNR : REMTREMBL-ACC : BAA21725 IGFBP-LIKE PROTEIN-MUS MUSCULUS (MOUSE), 270 AA.

LENGTH = 270 SCORE = 161 (56. 7 BITS), EXPECT = 1. 2E-11, P = 1. 2E-11 IDENTITIES = 31/71 (43%), POSITIVES = 46/71 (64%) QUERY : 9 DGLDIQLPGDDPHISVQFRGGPQRFEVTGWLQIQAVRPSDEGTYRCLARNALGQVEAPAS 68 +11+ +1111 41+11 1111 1 l 1+ 1 +1 111 1 1 1 ll+l+ ++ + SBJCT : 191 EGLE-ELPGDHVNIAVQVRGGPSDHETTSWILINPLRKEDEGVYHCHAANAIGEAQSHGT 249 QUERY : 69 LTVLTPDQLNS 79 +111 ++ I SBJCT : 250 VTVLDLNRYKS 260 The amino acid sequence of FCTR1 also had 26/58 bases (44%) identical, and 38/58 bases (65%) positive for Mus Musculus Follistatin-like Protein shown in Table 1D.

Table 1D. BLASTP of FCTR1 against Mus Musculus Follistatin-like Protein (SEQ ID NO : 39) PTNR : SPTREMBL-ACC : Q61581 FOLLISTATIN-LIKE 2 (FOLLISTATIN-LIKE PROTEIN)-MUS MUSCULUS (MOUSE), 238 AA.

LENGTH = 238 SCORE = 149 (52. 5 BITS), EXPECT = 1. 5E-10, P = 1. 5E-10 IDENTITIES = 26/58 (44%), POSITIVES = 38/58 (65%) QUERY : 15 LPGDDPHISVQFRGGPQRFEVTGWLQIQAVRPSDEGTYRCLARNALGQVEAPASLTVL 72 1111... I llil++ lilil+ + + I I I I I f+ II I I +II+ SBJCT : 165 LPGDRENLAIQTRGGPEKHEVTGWVLVSPLSKEDAGEYECHASNSQGQASAAAKITW 222 The amino acid sequence of FCTR1 also had 26/58 bases (44%) identical, and 38/58 bases (65%) positive for Homo sapie7ls MAC25 protein shown in Table 1E.

Table 1E. BLASTP of FCTR1 against Homo sapiens MAC25 protein (SEQ ID NO : 40) PTNR : SPTREMBL-ACC : Q07822 MAC25 PROTEIN-HOMO SAPIENS (HUMAN), 277 AA.

LENGTH = 277 SCORE = 149 (52. 5 BITS), EXPECT = 3. 2E-10, P = 3. 2E-10 IDENTITIES = 26/58 (44%), POSITIVES = 38/58 (65%) QUERY : 15 LPGDDPHISVQFRGGPQRFEVTGWLQIQAVRPSDEGTYRCLARNALGQVEAPASLTVL 72 1111 ++++1 llll++ 11111+ + + I I I 1 1 I+ II I I +II+ SBJCT : 209 LPGDRDNLAIQTRGGPEKHEVTGWVLVSPLSKEDAGEYECHASNSQGQASASAKITW 266 The amino acid sequence of FCTR1 also had 26/58 bases (44%) identical, and 38/58 bases (65%) positive forMus musculus MAC25 protein shown in Table IF.

Table IF. BLASTP of FCTR1 against Mus musculus MAC25 protein (SEQ ID NO : 41) PTNR : SPTREMBL-ACC : 088812 MAC25-MUS MUSCULUS (MOUSE), 281 AA LENGTH = 281 SCORE = 149 (52. 5 BITS), EXPECT = 3. 4E-10, P = 3. 4E-10 IDENTITIES = 26/58 (44%), POSITIVES = 38/58 (65%) QUERY : 15 LPGDDPHISVQFRGGPQRFEVTGWLQIQAVRPSDEGTYRCLARNALGQVEAPASLTVL 72 Hi) ++++) UU++) m) ++ + + I I I I I I+ II I I +II+ SBJCT : 208 LPGDRENLAIQTRGGPEKHEVTGWVLVSPLSKEDAGEYECHASNSQGQASAAAKITW 265 The amino acid sequence of FCTR1 also had 26/58 bases (44%) identical, and 38/58 bases (65%) positive for Homo sapiens Prostacyclin-stimulating factor shown in Table 1G.

Table 1G. BLASTP of FCTR1 against Homo sapiens Prostacyclin-stimulating factor (SEQ ID NO : 42) PTNR : SPTREMBL-ACC : Q16270 PROSTACYCLIN-STIMULATING FACTOR-HOMO SAPIENS (HUMAN), 282 AA LENGTH = 282 SCORE = 149 (52. 5 BITS), EXPECT = 3. 4E-10, P = 3. 4E-10 IDENTITIES = 26/58 (44W), POSITIVES = 38/58 (65%) QUERY : 15 LPGDDPHISVQFRGGPQRFEVTGWLQIQAVRPSDEGTYRCLARNALGQVEAPASLTVL 72 1111 ++++1 1111++ 11111+ + + I I I I I t+ 11 1 1 +11+ SBJCT : 209 LPGDRDNLAIQTRGGPEKHEVTGNVLVSPLSKEDAGEYECHASNSQGQASASAKITW 266 The amino acid sequence of FCTR1 also had 18/44 bases (40%) identical, and 25/44 bases (56%) positive for rat Colorectal cancer suppressor shown in Table 1H.

Table 1H. BLASTP of FCTR1 against rat Colorectal cancer suppressor (SEQ ID NO : 43) PTNR : PIR-ID : B40098 COLORECTAL CANCER SUPPRESSOR DCC-RAT (FRAGMENTS) LENGTH = 144 SCORE = 78 (27. 5 BITS), EXPECT = l. lE-05, SUM P (2) = 1. 1E-05 IDENTITIES = 18/44 (40%), POSITIVES = 25/44 (56%) QUERY : 33 FEVTGW--LQIQAVRPSDEGTYRCLARNALGQVEAPASLTVLTP 74 1++ 1 1+1 1 1111 1+1+1 1 1 ++ I t ! t SBJCT : 101 FQIVGGSNLRILGVVKSDEGFYQCVAENEAGNAQSSAQLIVPKP 144 SCORE = 37 (13. 0 BITS), EXPECT = 1. 1E-05, SUM P (2) = 1. lE-05 IDENTITIES = 8/19 (42%), POSITIVES = 12/19 (63%) QUERY : 1 MASIEWRKDGLDIQL-PGD 18 I +1 1+1+ 1+ III SBJCT : 30 MPTIHWQKNQQDLTPNPGD 48 The amino acid sequence of FCTR1 also had 32/83 bases (38%) identical, and 45/83 bases (54%) positive to bases 55-137, and 24/68 bases (35%) identical, and 37/68 bases (54%) positive to bases 166-225 of Homo sapiens PTPsigma- (Brain) Precursor shown in Table 1I.

Table 11. BLASTP of FCTR1 against Homo sapiens PTPsigma-(Brain) Precursor (SEQ ID NO : 44) PTNR : TREMBLNEW-ACC : AAD09360 PTPSIGMA- (BRAIN) PRECURSOR - HOMO SAPIENS (HUMAN), 1502 AA.

LENGTH = 1502 SCORE = 109 (38. 4 BITS), EXPECT = 0. 00010, P = 0. 00010 IDENTITIES = 32/83 (380), POSITIVES = 45/83 (54%) QUERY : 14 QLPGDD-PHISVQFRG---GPQRFEVTGW-------LQIQAVR-PSDEGTYRCLARNALG 61 I II I ++ +) IIII + I+II +I I II I I+I+I++ SBJCT : 55 QATGDPKPRVTWNKKGKKVNSQRFETIEFDESAGAVLRIQPLRTPRDENVYECVAQNSVG 114 QUERY : 62 QVEAPASLTVLTPDQLNSTGIPQL 85 ++ I IIII III I I + SBJCT : 115 EITVHAKLTVLREDQLPS-GFPNI 137 SCORE = 77 (27, 1 BITS), EXPECT = 0. 25, P = 0. 22 IDENTITIES = 24/68 (35%), POSITIVES = 37/68 (54%) QUERY : 4 IEWRKDGLDIQLPGDDPHISVQFRGGPQRFEVTGWLQIQAVRPSDEGTYRCLARNALG-Q 62 I I II I + II I I ++ + 111++ ++ I 1+I I+ I + SBJCT : 166 ITWFKDFLPV-----DPSAS---NGRIKQLR-SGALQIESSEETDQGKYECVATNSAGVR 216 QUERY : 63 VEAPASLTV 71 +1 1+1 1 SBJCT : 217 YSSPANLYV 225 The amino acid sequence of FCTR1 also had 32/83 bases (38%) identical, and 45/83 bases (54%) positive for amino acids 55-137 and 26/69 bases (37%) identical, and 38/69 (54%) positive for amino acids 166-234 of Homo sapiens Protein-Tyrosine Phosphatase Sigma shown in Table 1J.

Table 1J. BLASTP of FCTR1 against Homo sapiens PTPsigma- (Brain) Precursor (SEQ ID NO : 45) PTNR : SPTREMBL-ACC : Q13332 PROTEIN-TYROSINE PHOSPHATASE, RECEPTOR-TYPE, S PRECURSOR (EC 3. 1. 3. 48) (PROTEIN-TYROSINE PHOSPHATASE SIGMA) (R-PTP-SIGMA) (PTPRS)-HOMO SAPIENS (HUMAN), 1948 AA.

LENGTH = 1948 SCORE = 109 (38. 4 BITS), EXPECT = 0. 00013, P = 0. 00013 IDENTITIES = 32/83 (38%), POSITIVES = 45/83 (54W) QUERY : 14 QLPGDD-PHISVQFRG---GPQRFEVTGW-------LQIQAVR-PSDEGTYRCLARNALG 61 II I ++ +1 1111 + 1+11 +1 1 11 l 1+1+1++1 SBJCT : 55 QATGDPKPRVTWNKKGKKVNSQRFETIEFDESAGAVLRIQPLRTPRDENVYECVAQNSVG 114 QUERY : 62 QVEAPASLTVLTPDQLNSTGIPQL 85 ++ I 1111 111 1 1 1 + SBJCT : 115 EITVHAKLTVLREDQLPS-GFPNI 137 SCORE = 88 (31. 0 BITS), EXPECT = 0. 023, P = 0. 022 IDENTITIES = 26/69 (37%), POSITIVES = 38/69 (55%) QUERY : 4 IEWRKDGLDIQLPGDDPHISVQFRGGPQRFEVT---GWLQIQAVRPSDEGTYRCLARNAL 60 I I 11 1 + + I I I + 11 1 1 lll++ +1+1 l 1+1 1+ SBJCT : 166 ITWFKDFLPVDPSASNGRIK-QLRS--ETFESTPIRGALQIESSEETDQGKYECVATNSA 222 QUERY : 61 G-QVEAPASLTV 71 ! + +11+1 1 SBJCT : 223 GVRYSSPANLYV 234

A ClustalW analysis comparing the protein of the invention with related protein sequences is given in Table 1K, with FCTR1 shown on line 2. In the ClustalW alignment of the FCTR1 protein, as well as all other ClustalW analyses herein, the black outlined amino acid residues indicate regions of conserved sequence (i. e., regions that may be required to preserve structural or functional properties), whereas non-highlighted amino acid residues are less conserved and can potentially be mutated to a much broader extent without altering protein structure or function.

Table 1K. ClustalW Analysis of FCTR1 1) Q07822 MAC25 PROTEIN. (SEQ ID NO : 40) 2) Q16270 PROSTACYCLIN-STIMULATING FACTOR. (SEQ ID NO : 42) 3) Q61581FOI, FOLLISTATIN-LIKE 2 : FOLLISTATIN-LIKE 2 (FOLLISTATIN-LIKE PROTEIN) (SEQ ID NO : 39) 4) BAA21725 IGFBP-LIKE PROTEIN (SEQ ID NO : 38) 5) FCTR1 (SEQ ID NO : 2) 6) B40098 COLORECTAL CANCER SUPPRESSOR DCC-RAT (FRAGMENTS) (SEQ ID NO : 43) Q07822 s ASi iFGP B tNSStYW T-EPAS E PLPSLGCLLGET S Q16270 PS'TEPASmPVPLGCLZGET' Q61581 E p p < BAA21725 MPMLPILLEIPSLARGIGZPDAG RRHPEESMQQDRMIAPSICPAPWISAMEM FCTR1 B40098 Q07822 PMBAIOJEEPHIGGIAGilY Q16270 PMARmEPmGGQAGmY''I"'VS'' Q61581 1 ! H BAA21725 ARHLG15 PVGSRGT : VDA m ASOTiPE T AQOGAm FCTR1 B40098 PFRFLSQTESXT Q07822 T 'Q'A '' Q16270. mQiZMiMZIA Q61581 NI .. L.. p BAA21725 SRjSgSlgAJjgLRARHEPRAHHGH j'HKARDeP'SFSVVItMRHEEE TBS FCTR1 B40098 EMgDgVLLKEEI'DPMPTIHWQKNQQDLTPNPGDSRVVVpgNFNHgSNAYESMD Q0782'Y v. y, . r A ' Q16270 Y GDY 'm D ' Q61581 t StS ts qtUD@S3EtX « 4M « St q BAR2 17 2 5 1rlKAv=T=H S PEgTE GLgE=HV » 5S DETiS » g FCTR1 MASlIERDGLDIO....... DPHS E"QRF ; QQA B40098 ISDYFIVSN....... R'LG KIR.... Q61581 = w4Xi BAElZ P KIGIG2Q Q16270 ESB ! ! SS9 ! n ! ! ! SEiBSS ! EH5 ! -""--"--"--. KE Q61581 BSBSSSa ! ! S ! ! ! ! SS ! SS ! SH ! jPS................ KEGGSQ BAA21725 eR v w BAA21725 FCTR1 tRPSIEIT§RiLBRIAL EjVEIPiSW X gTPDQLNSTGIPQLRSLNLVPEEEAESE P D s Q07822 Q07822 Q16270 g. Q61581 l- BAA21725 DL FCTR1 YY

IGFBP is expressed in neurostem cell and developing central nervous system. MAC- 25, a follistatin like protein is a growth suppressor of osteosarcoma cells, and meningiomas.

DCC is expressed in most normal tissues especially in colonic mucosa, but is deleted in colorectal cancers.

Since FCTR1 has similarity to these proteins (shown in BlastP, Tables 1C-1J, and in clustalW, Table 1K) it is likely that it has similar function. Therefore FCTR1 could function as on or more of the following : a tumor suppressor geneor regulator of neurological system development.

Based on the protein similarity and tissue expression, FCTR1 may be useful in the following diseases and uses : (i) Tissue regeneration in vitro and in vivo (ii) Neurological disorders, neurodegenerative disorders, nerve trauma (iii) Reproductive health (iv) Immunological disorders, allergy and infection (v) In cancer as a diagnostic and prognostic marker, as well as a protein therapeutic FCTR2 FCTR2 (alternatively referred to herein as AC012614_1. 0. 123), is a growth factor bearing sequence similarity to human KIAA1061 protein and to genes involved in neuronal development and reproductive physiology (e. g., cell adhesion molecules, follistatin, roundabout and frazzled). FCTR2 is a full-length clone of 5502 nucleotides, including the entire coding sequence of a 815 amino acid protein. This sequence is expressed in glioma, osteoblast, other cancer cells, lung carcinoma, small intestine (This sequence maps to Unigene Hs. 123420 which is expressed in brain, breast, kidney, pancreas, pooled tissue).

A FCTR2 ORF begins with an ATG initiation codon at nucleotides 420-422 and ends with a TGA codon at nucleotides 2865-2867. Putative untranslated regions upstream from the initiation codon and downstream from the termination codon are underlined in Table 2A, and the start and stop codons are in bold letters.

Table 2A. FCTR2 Nucleotide Sequence (SEQ ID NO : 3). <BR> <BR> <BR> <BR> <P>CAATTTCACACAGGAAACAGCTATGCCATGATTACGCAAGTTGGTACCGAG CTCGGATCCACTAGTAACGGCCGCCAGTG<BR> <BR> <BR> TGCTGGAATTCGGCTTACTCACTATAGGGCTCGAGCGGCTGCCCGGGCAGGTCATTAATT CCATTTCTTTTTAGAGTATC ACAGCTTTCTCCTTCACTGACCACCCTTTGCTTCCTGTCAGAAAGCCCTGGACAGAACTC TCTGTGGGATTCTGCCCATG TTTCTGAGATATCGCCTCAATTGTCCTGGCTGGGCTGTCGGGTCTGCCCGTTTTACAGAT GGGCAAACTGGAGTGGGAAG TATCCGGGTGGCTTCCTCAGGCCTGCAGCTGGTGGAGCAGCTACTGAAACAATCAGGAGC CCAGAAGCTTTGAAGTCACA<BR> <BR> <BR> AGAAGAGAAGACTCCCAGAATGCAGTGTGATGTTGGTGATGGACGCCTGTTTCGCCTTTC ACTTAAACGTGCCCTTTCCA<BR> <BR> <BR> GCTGCCCTGACCTCTTTGGGCTTTCCAGCCGCAACGAGCTGCTGGCCTCCTGCGGGAAGA AGTTCTGCAGCCGAGGGAGC CGGTGCGTGCTCAGCAGGAAGACAGGGGAGCCCGAATGCCAGTGCCTGGAGGCATGCAGG CCCAGCTACGTGCCTGTGTG CGGCTCTGATGGGAGGTTTTATGAAAACCACTGTAAGCTCCACCGTGCTGCTTGCCTCCT GGGAAAGAGGATCACCGTCA TCCACAGCAAGGACTGTTTCCTCAAAGGTGACACGTGCACCATGGCCGGCTACGCCCGCT TGAAGAATGTCCTTCTGGCA

CTCCAGACCCGTCTGCAGCCACTCCAAGAAGGAGACAGCAGACAAGACCCTGCCTCCCAG AAGCGCCTCCTGGTGGAATC<BR> <BR> <BR> <BR> TCTGTTCAGGGACTTAGATGCAGATGGCAATGGCCACCTCAGCAGCTCCGAACTGGCTCA GCATGTGCTGAAGAAGCAGG ACCTGGATGAAGACTTACTTGGTTGCTCACCAGGTGACCTCCTCCGATTTGACGATTACA ACAGTGACAGCTCCCTGACC <BR> <BR> <BR> CTCCGCGAGTTCTACATGGCCTTCCAAGTGGTTCAGCTCAGCCTCGCCCCCGAGGACAGG GTCAGTGTGACCACAGTGAC CGTGGGGCTGAGCACAGTGCTGACCTGCGCCGTCCATGGAGACCTGAGGCCACCAATCAT CTGGAAGCGCAACGGGCTCA <BR> <BR> <BR> CCCTGAACTTCCTGGACTTGGAAGACATCAATGACTTTGGAGAGGATGATTCCCTGTACA TCACCAAGGTGACCACCATC CACATGGGCAATTACACCTGCCATGCTTCCGGCCACGAGCAGCTGTTCCAGACCCACGTC CTGCAGGTGAATGTGCCGCC <BR> <BR> <BR> AGTCATCCGTGTCTATCCAGAGAGCCAGGCACAGGAGCCTGGAGTGGCAGCCAGCCTAAG ATGCCATGCTGAGGGCATTC<BR> <BR> <BR> <BR> CCATGCCCAGAATCACTTGGCTGAAAAACGGCGTGGATGTCTCAACTCAGATGTCCAAAC AGCTCTCCCTTTTAGCCAAT<BR> <BR> <BR> <BR> GGGAGCGAACTCCACATCAGCAGTGTTCGGTATGAAGACACAGGGGCATACACCTGCATT GCCAAAAATGAAGTGGGTGT GGATGAAGATATCTCCTCGCTCTTCATTGAAGACTCAGCTAGAAAGACCCTTGCAAACAT CCTGTGGCGAGAGGAAGGCC TCAGCGTGGGAAACATGTTCTATGTCTTCTCCGACGACGGTATCATCGTCATCCATCCTG TGGACTGTGAGATCCAGAGG <BR> <BR> <BR> CACCTCAAACCCACGGAAAAGATTTTCATGAGCTATGAAGAAATCTGTCCTCAAAGAGAA AAAAATGCAACCCAGCCCTG CCAGTGGGTATCTGCAGTCAATGTCCGGAACCGGTACATCTATGTGGCCCAGCCAGCACT GAGCAGAGTCCTTGTGGTCG <BR> <BR> <BR> ACATCCAAGCCCAGAAAGTCCTACAGTCCATAGGTGTGGACCCTCTGCCGGCTAAGCTGT CCTATGACAAGTCACATGAC CAAGTGTGGGTCCTGAGCTGGGGGGACGTGCACAAGTCCCGACCAAGTCTCCAGGTGATC ACAGAAGCCAGCACCGGCCA GAGCCAGCACCTCATCCGCACACCCTTTGCAGGAGTGGATGATTTCTTCATTCCCCCAAC AAACCTCATCATCAACCACA TCAGGTTTGGCTTCATCTTCAACAAGTCTGATCCTGCAGTCCACAAGGTGGACCTGGAAA CAATGATGCCCCTCAAGACC ATCGGCCTGCACCACCATGGCTGCGTGCCCCAGGCCATGGCACACACCCACCTGGGCGGC TACTTCTTCATCCAGTGCCG <BR> <BR> <BR> ACAGGACAGCCCCGCCTCTGCTGCCCGACAGCTGCTCGTTGACAGTGTCACAGACTCTGT GCTTGGCCCCAATGGTGATG TAACAGGCACCCCACACACATCCCCCGACGGGCGCTTCATAGTCAGTGCTGCAGCTGACA GCCCCTGGCTGCACGTGCAG <BR> <BR> <BR> GAGATCACAGTGCGGGGCGAGATCCAGACCCTGTATGACCTGCAAATAAACTCGGGCATC TCAGACTTGGCCTTCCAGCG<BR> <BR> <BR> <BR> CTCCTTCACTGAAAGCAATCAATACAACATCTACGCGGCTCTGCACACGGAGCCGGACCT GCTGTTCCTGGAGCTGTCCA<BR> <BR> <BR> <BR> CGGGGAAGGTGGGCATGCTGAAGAACTTAAAGGAGCCACCCGCAGGGCCAGCTCAGCCCT GGGGGGGTACCCACAGAATC ATGAGGGACAGTGGGCTGTTTGGACAGTACCTCCTCACACCAGCCCGAGAGTCACTGTTC CTCATCAATGGGAGACAAAA <BR> <BR> CACGCTGCGGTGTGAGGTGTCAGGTATAAAGGGGGGGACCACAGTGGTGTGGGTGGGTGA GGTATGAAGGGCCCAGAGCA<BR> <BR> <BR> <BR> GAGCCCTGGGCCAAGGAACACCCCCTAGTCCTGACACTGCAGCCTCAAGCAGGTACGCTG TACATTTTTACAGACAAAAG CAAAAACCTGTACTCGCTTTGTGGTTCAACACTGGTCTCCTTGCAAGTTTCCTAGTATAA GGTATGCGCTGCTACCAAGA TTGGGGTTTTTTCGTTAGGAAGTATGATTTATGCCTTGAGCTACGATGAGAACATATGCT GCTGTGTAAAGGGATCATTT CTGTGCCAAGCTGCACACCGAGTGACCTGGGGACATCATGGAACCAAGGGATCCTGCTCT CCAAGCAGACACCTCTGTCA <BR> <BR> GTTGCCTTCACATAGTCATTGTCCCTTACTGCCAGACCCAGCCAGACTTTGCCCTGACGG AGTGGCCCGGAAGCAGAGGC CGACCAGGAGCAGGGGCCTCCCTCCCGAACTGAAAGCCCATCCGTCCTCGCGTGGGACCG CATCTTCTCCCTCGCAGCTG CTTCTTGCTTTTCTTTCCATTTGACTTGCTGTAAGCCTGAGGGAGAGCCAACAAGACTTA CTGCATCTTGGGGGATGGGG <BR> <BR> AAATCACTCACTTTATTTTGGAAATTTTTGATTAAAAAAAAATTTTATAATCTCAAATGC TAGTAAGCAGAAAGATGCTC TCCGAGGTCCAACTATATCCTTCCCTGCCTTAGGCCGAGTCTCGGGGGTGGTCACAACCC CACATCCCACAGCCAGAAAG AACAATGGTCATCTGAGAATACTGGCCCTGTCGACTATTGCCACCCTGCTTCTCCAAGAG CAGACCAGGCCACCTCATCC <BR> <BR> GTAAGGACTCGGTTCTGTGTTGGGACCCCAAAAAACCAGAACAAGTTCTGTGTGCCTCCT TTCAGCACAGAAGGGAGACA TCTCATTAGTCAGGTCTGGTACCCCAGATTCAGGGCAGACTGGGCTTGCCTGGCAAGGTA TGGGTGGCCTCCAGGCTCAA <BR> <BR> TGCAGAAACCCCAAGGACACGAGTGGGGCCAGGTGAGTTCCTGAAGCTATACCTTTTCAA AACAGATTTTGTTTTCCTAC CTGTGGCCCATCCACTCCTCTCTGGTACCCCATCCCCGCATCAGCACTGCAGAGAGAACA CATTTCGGCGAGGGTTTTCT TACCCACATTCCCCAATCAATACACACACACTGCAGAACCCAGAACAGAAGGCCACAGGC TGGCACTACTGCATTCTCCT TATGTGTCTCAGGCTGTGGTGACTCTCACATGGGCATCGAAGAAGTACAACCCACATAGC CCTCTGGAGACCGCCTAGAT CAGAGACTCAGCAAAAACAGGCTCGCCTTCCCTCTCCCACATATGAGTGGAACTTACATG TGTCCTGGTTTGAATGATCA TTTTGCAAGCCACACGGGTTGGGAGAGGTGGTCTCACCACAGACGTCTTTGCTAATTTGG CCACCTTCACCTACTGACAT <BR> <BR> GACCAGGATTTTCCTTTGCCATTAAGGAATGAACTCTTTCAAGGAGAGGAAACCCTAGAC TCTGTGTCACTCTCAACACA<BR> <BR> <BR> <BR> <BR> CACAGCTCCTTTCACTCCTGCCTGACTGCCAAGCCACCTGCATCCCCCGCCCCAGATCTC ATGAGATCAATCACTTGTAT<BR> <BR> <BR> <BR> GTCTCACGCAACTTGGTCCACCAAACGCCTGTCCCCTGTAACTCCTAGGGGTGCGCCTAG ACAGGTACGTCTGTTTTTTA<BR> <BR> <BR> <BR> TTTTAAAAGATATGCTATGTAGATATAAGTTGAGGAAGCTCACCTCAAAAGCCTAGAATG CAGTTTCACAGTAGCTGGGA TGCATGGATGACCCATCTCACCCCTTTTTTTTTCCTGCCTCAATATCTTGATATGTTATG TTTACTCCCAATCTCCCATT TTTACCACTAAAATTCTCCAACTTTCATAAACTTTTTTTTGGAAAAATTTCCATTGTATC AGCCCCTGACAGAAAAAGGA <BR> <BR> TCTCTGAGCCTAAAGGAGGAAAAGTCCCACCAACTACCAGACCAGAACACGAGCCCCTCT GGGCAGCAGGATTCCTAAGT CAAAGACCAGTTTGACCCAAACTGGCCTTTTAAAATAATCAGGAGTGACAGAGTCAACTT CTGCAGCACCTGCTTCTCCC CCACTGTCCCTTCCATCTTGGAATGTGTCTAAAAAAGCATAGCTGCCCTTTGCTGTCCTC AGAGTGCATTTCCTGGAGAC <BR> <BR> GGCAGGCTTAGGTCTCACTGACASCATGCCAGACACAACTGAATCGAAGCAGGCCTGAAG CCTAGGTCAGGGTTTCAGGA<BR> <BR> <BR> <BR> GTCCAGCCCCAGGAGGCAAAGTCACCAATGCAGGGAGGTAAATGCCTTTTGGCAGGAAAA CCAATAGAGTTGGTTGGGTG GGGAGTCAGGGGTGGGAGGAGAAGGAGGAAGAGGAGGAAGGCCAGACTGGCCTGCCCTTT CTCCCATACTTCACCCCAGC AGAGGTTCATGGGACACAGTTGGAAAGCCACTGGGAGGAAATGCCTCACTACAGGGGGGC CTCCTGTAGCAAGCCCAGCC GGTAATCCTCCTAATGAACCCACAAGGTCAATTCACAACTGATATCTTAGCTATTAAAGA AGTACTGACTTTACCAAAAG AATCATCAAGAAAGCTATTTATATAAACCCCCTCAGTCATTTTGAAATAAAATTAATTTT AC The predicted amino acid sequence of FCTR2 protein corresponding to the foregoing nucleotide sequence is reported in Table 2B. FCTR2 was searched against other databases using SignalPep and PSort search protocols. The protein is most likely located in the

mitochondrial matrix space (certainty=0. 4718) and seems to have no N-terminal signal sequence. The predicted molecular weight is 90346. 9 Daltons.

Table 2B. FCTR2 Protein Sequence (SEQ ID NO : 4).

MQCDVGDGRLFRLSLKRALSSCPDLFGLSSRNELLASCGKKFCSRGSRCVLSRKTGE PECQCLEACRPSYVPVCGSDGRFYENH <BR> <BR> CKLHRAACLLGKRITVIHSKDCFLKGDTCTMAGYARLKNVLLALQTRLQPLQEGDSRQDP ASQKRLLVESLFRDLDADGNGHLS<BR> <BR> SSELAQHVLKKQDLDEDLLGCSPGDLLRFDDYNSDSSLTLREFYMAFQWQLSLAPEDRVS VTTVTVGLSTVLTCAVHGDLRPP<BR> <BR> <BR> IIWKRNGLTLNFLDLEDINDFGEDDSLYITKVTTIHMGNYTCHASGHEQLFQTHVLQVNV PPVIRVYPESQAQEPGVAASLRCH<BR> <BR> AEGIPMPRITWLKNGVDVSTQMSKQLSLLANGSELHISSVRYEDTGAYTCIAKNEVGVDE DISSLFIEDSARKTLANILWREEG<BR> <BR> LSVGNMFYVFSDDGIIVIHPVDCEIQRHLKPTEKIFMSYEEICPQREKNATQPCQWVSAV NVRNRYIYVAQPALSRVLVVDIQA QKVLQSIGVDPLPAKLSYDKSHDQVWVLSWGDVHKSRPSLQVITEASTGQSQHLIRTPFA GVDDFFIPPTNLIINHIRFGFIFN <BR> <BR> KSDPAVHKVDLETMMPLKTIGLRHHGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLLVD SVTDSVLGPNGDVTGTPHTSPDGR<BR> <BR> FIVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQRSFTESNQYNIYAALHTEP DLLFLELSTGKVGMLKNLKEPPAG<BR> <BR> PAQPWGGTHRIMRDSGLFGQYLLTPARESLFLINGRQNTLRCEVSGIKGGTTWWVGEV In a BLASTN search it was also found that nucleotides 784-5502 of FCTR2 nucleic acid had 4672 of 4719 bases (99%) identical to Homo sapiens MRNA for KIAA 1061 protein, partial cds (GenBank Acc : AB028984) (Table 2C).

Table 2C. BLASTN of FCTR2 against Homo sapiens MARNA for KIAA1061 protein (SEQ ID NO : 46) >Gll5689458ZDBJlAB028984. 1lAB028984 HOMO SAPIENS MRNA FOR KIAA1061 PROTEIN, PARTIAL CDS LENGTH = 4719 SCORE = 9075 BITS (4578), EXPECT = 0. 0 IDENTITIES = 4672/4719 (99%) STRAND = PLUS/PLUS QUERY : 784 AGAATGTCCTTCTGGCACTCCAGACCCGTCTGCAGCCACTCCAAGAAGGAGACAGCAGAC 843 111111111111111111111111111111111111111111111111111111111111 SBJCT : 1 AGAATGTCCTTCTGGCACTCCAGACCCGTCTGCAGCCACTCCAAGAAGGAGACAGCAGAC 60 QUERY : 844 AAGACCCTGCCTCCCAGAAGCGCCTCCTGGTGGAATCTCTGTTCAGGGACTTAGATGCAG 903 m m m m m m m m m mm m m m m mm m mm SBJCT : 61 AAGACCCTGCCTCCCAGAAGCGCCTCCTGGTGGAATCTCTGTTCAGGGACTTAGATGCAG 120 SBJCT : 61 AAGACCCTGCCTCCCAGAAGCGCCTCCTGGTGGAATCTCTGTTCAGGGACTTAGATGCAG 120 QUERY : 904 ATGGCAATGGCCACCTCAGCAGCTCCGAACTGGCTCAGCATGTGCTGAAGAAGCAGGACC 963 SBJCT : 121 ATGGCAATGGCCACCTCAGCAGCTCCGAACTGGCTCAGCATGTGCTGAAGAAGCAGGACC 180 m m m mm m m m m m m m m mm m m m mm QUERY : 964 TGGATGAAGACTTACTTGGTTGCTCACCAGGTGACCTCCTCCGATTTGACGATTACAACA 1023 11111111111111111111111111111111111111111111111111111111111 SBJCT : 181 TGGATGAAGACTTACTTGGTTGCTCACCAGGTGACCTCCTCCGATTTGACGATTACAACA 240 QUERY : 1024 GTGACAGCTCCCTGACCCTCCGCGAGTTCTACATGGCCTTCCAAGTGGTTCAGCTCAGCC 1083 Illllllllilllllllllllllllllllllllllllllllllllllllllllllllll} SBJCT : 241 GTGACAGCTCCCTGACCCTCCGCGAGTTCTACATGGCCTTCCAAGTGGTTCAGCTCAGCC 300 m)) mmmm mm mmm) m mm mm m m mm QUERY : 1084 TCGCCCCCGAGGACAGGGTCAGTGTGACCACAGTGACCGTGGGGCTGAGCACAGTGCTGA 1143 llilllllllllllllllllllllllllllllllllllllllllllllllllllllllll SBJCT : 30l TCGCCCCCGAGGACAGGGTCAGTGTGACCACAGTGACCGTGGGGCTGAGCACAGTGCTGA 360 QUERY : 1144 CCTGCGCCGTCCATGGAGACCTGAGGCCACCAATCATCTGGAAGCGCAACGGGCTCACCC 1203 IIIIIIIIIIIIIIIIIIIIIIIIIIIIillllllllllllllllllllllllllllill SBJCT : 361 CCTGCGCCGTCCATGGAGACCTGAGGCCACCAATCATCTGGAAGCGCAACGGGCTCACCC 420 QUERY : 1204 TGAACTTCCTGGACTTGGAAGACATCAATGACTTTGGAGAGGATGATTCCCTGTACATCA 1263 llllllllllllllllllllllllllllllllllllllllllllllllllllllllllll

SBJCT : 421 TGAACTTCCTGGACTTGGAAGACATCAATGACTTTGGAGAGGATGATTCCCTGTACATCA 480 QUERY : 1264 CCAAGGTGACCACCATCCACATGGGCAATTACACCTGCCATGCTTCCGGCCACGAGCAGC 1323 I SBJCT : 481 CCAAGGTGACCACCATCCACATGGGCAATTACACCTGCCATGCTTCCGGCCACGAGCAGC 540 QUERY : 1324 TGTTCCAGACCCACGTCCTGCAGGTGAATGTGCCGCCAGTCATCCGTGTCTATCCAGAGA 1383 111111111111111111111111111111111111111111111111111111111111 SBJCT : 541 TGTTCCAGACCCACGTCCTGCAGGTGAATGTGCCGCCAGTCATCCGTGTCTATCCAGAGA 600 QUERY : 1384 GCCAGGCACAGGAGCCTGGAGTGGCAGCCAGCCTAAGATGCCATGCTGAGGGCATTCCCA 1443 IllllllllllllllllllllllllllllllllllllllllllllllllllllllWllll SBJCT : 601 GCCAGGCACAGGAGCCTGGAGTGGCAGCCAGCCTAAGATGCCATGCTGAGGGCATTCCCA 660 QUERY : 1444 TGCCCAGAATCACTTGGCTGAAAAACGGCGTGGATGTCTCAACTCAGATGTCCAAACAGC 1503 111111111111111111111111111111111111111111111111111111111111 SBJCT : 661 TGCCCAGAATCACTTGGCTGAAAAACGGCGTGGATGTCTCAACTCAGATGTCCAAACAGC 720 QUERY : 1504 TCTCCCTTTTAGCCAATGGGAGCGAACTCCACATCAGCAGTGTTCGGTATGAAGACACAG 1563 111111111111111111111111111111111111111111111111111111111111 SBJCT : 721 TCTCCCTTTTAGCCAATGGGAGCGAACTCCACATCAGCAGTGTTCGGTATGAAGACACAG 780 QUERY : 1564 GGGCATACACCTGCATTGCCAAAAATGAAGTGGGTGTGGATGAAGATATCTCCTCGCTCT 1623 I SBJCT : 781 GGGCATACACCTGCATTGCCAAAAATGAAGTGGGTGTGGATGAAGATATCTCCTCGCTCT 840 QUERY : 1624 TCATTGAAGACTCAGCTAGAAAGACCCTTGCAAACATCCTGTGGCGAGAGGAAGGCCTCA 1683 111111111111111111111111111111111111111111111111111111111111 SBJCT : 841 TCATTGAAGACTCAGCTAGAAAGACCCTTGCAAACATCCTGTGGCGAGAGGAAGGCCTCA 900 QUERY : 1684 GCGTGGGAAACATGTTCTATGTCTTCTCCGACGACGGTATCATCGTCATCCATCCTGTGG 1743 Illllllllllllllllllillilllllilllllllilllllllllllllllllllllii ' SBJCT : 901 GCGTGGGAAACATGTTCTATGTCTTCTCCGACGACGGTATCATCGTCATCCATCCTGTGG 960 QUERY : 1744 ACTGTGAGATCCAGAGGCACCTCAAACCCACGGAAAAGATTTTCATGAGCTATGAAGAAA 1803 IllllllllllWltllllllllllllllllllllllllllllllllllllllllllllll SBJCT : 961 ACTGTGAGATCCAGAGGCACCTCAAACCCACGGAAAAGATTTTCATGAGCTATGAAGAAA 1020 SBJCT : 961 ACTGTGAGATCCAGAGGCACCTCAAACCCACGGAAAAGATTTTCATGAGCTATGAAGAAA 1020 QUERY : 1804 TCTGTCCTCAAAGAGNNNNNNNTGCAACCCAGCCCTGCCAGTGGGTATCTGCAGTCAATG 1863 IIIIIIIII (IIIII Illllllilllllllllllllllllllllllillllil SBJCT : 1021 TCTGTCCTCAAAGAGAAAAAAATGCAACCCAGCCCTGCCAGTGGGTATCTGCAGTCAATG 1080 m n m m m m m mm m mm mm mtmmm mm QUERY : 1864 TCCGGAACCGGTACATCTATGTGGCCCAGCCAGCACTGAGCAGAGTCCTTGTGGTCGACA 1923 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll SBJCT : 1081 TCCGGAACCGGTACATCTATGTGGCCCAGCCAGCACTGAGCAGAGTCCTTGTGGTCGACA 1140 m m m m m m m mm m m m m m m m m m mm QUERY : 1924 TCCAAGCCCAGAAAGTCCTACAGTCCATAGGTGTGGACCCTCTGCCGGCTAAGCTGTCCT 1983 SBJCT : 1141 TCCAAGCCCAGAAAGTCCTACAGTCCATAGGTGTGGACCCTCTGCCGGCTAAGCTGTCCT 1200 urn m mmmmmmmmmmm mmmmt mm QUERY : 1984 ATGACAAGTCACATGACCAAGTGTGGGTCCTGAGCTGGGGGGACGTGCACAAGTCCCGAC 2043 111111111111111111111111111111111111111111111111111111111111 SBJCT : 1201 ATGACAAGTCACATGACCAAGTGTGGGTCCTGAGCTGGGGGGACGTGCACAAGTCCCGAC 1260 m m m m m m m m m mm mm m m m m m mm QUERY : 2044 CAAGTCTCCAGGTGATCACAGAAGCCAGCACCGGCCAGAGCCAGCACCTCATCCGCACAC 2103 Illlllllllllllllllllllllllllllllllllllllllllllllll1111111111 SBJCT : 1261 CAAGTCTCCAGGTGATCACAGAAGCCAGCACCGGCCAGAGCCAGCACCTCATCCGCACAC 1320 ) m m) m) m) m m) m m m m m m m m m m) m m QUERY : 2104 CCTTTGCAGGAGTGGATGATTTCTTCATTCCCCCAACAAACCTCATCATCAACCACATCA 2163 111111111111111111111111111ß1111111111111111111111111111111 1 SBJCT : 1321 CCTTTGCAGGAGTGGATGATTTCTTCATTCCCCCAACAAACCTCATCATCAACCACATCA 1380 m mm mm mmm mmummmmmmmm m) QUERY : 2164 GGTTTGGCTTCATCTTCAACAAGTCTGATCCTGCAGTCCACAAGGTGGACCTGGAAACAA 2223 Ililllllillllllillilllllllllilllllllilllllilillillili ! llllll SBJCT : 1381 GGTTTGGCTTCATCTTCAACAAGTCTGATCCTGCAGTCCACAAGGTGGACCTGGAAACAA 1440 m m mm mm m) m m m m mmm m m m)) mm QUERY : 2224 TGATGCCCCTCAAGACCATCGGCCTGCACCACCATGGCTGCGTGCCCCAGGCCATGGCAC 2283 Illllllllllllllllllßlllillllllll} 111111111111111111111111111 SBJCT : 1441 TGATGCCCCTCAAGACCATCGGCCTGCACCACCATGGCTGCGTGCCCCAGGCCATGGCAC 1500

QUERY : 2284 ACACCCACCTGGGCGGCTACTTCTTCATCCAGTGCCGACAGGACAGCCCCGCCTCTGCTG 2343 111111111111111111111111111111111111111111111111111111111111 SBJCT : 1501 ACACCCACCTGGGCGGCTACTTCTTCATCCAGTGCCGACAGGACAGCCCCGCCTCTGCTG 1560 QUERY : 2344 CCCGACAGCTGCTCGTTGACAGTGTCACAGACTCTGTGCTTGGCCCCAATGGTGATGTAA 2403 111111111111111111111111111111111111111111111111111111111111 SBJCT : 1561 CCCGACAGCTGCTCGTTGACAGTGTCACAGACTCTGTGCTTGGCCCCAATGGTGATGTAA 1620 QUERY : 2404 CAGGCACCCCACACACATCCCCCGACGGGCGCTTCATAGTCAGTGCTGCAGCTGACAGCC 2463 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll SBJCT : 1621 CAGGCACCCCACACACATCCCCCGACGGGCGCTTCATAGTCAGTGCTGCAGCTGACAGCC 1680 QUERY : 2464 CCTGGCTGCACGTGCAGGAGATCACAGTGCGGGGCGAGATCCAGACCCTGTATGACCTGC 2523 111111111111111111111111111111111111111111111111111111111111 SBJCT : 1681 CCTGGCTGCACGTGCAGGAGATCACAGTGCGGGGCGAGATCCAGACCCTGTATGACCTGC 1740 QUERY : 2524 AAATAAACTCGGGCATCTCAGACTTGGCCTTCCAGCGCTCCTTCACTGAAAGCAATCAAT 2583 IIIIllllllllllllllllllllllllllllllllllllllllllllllllllllllll SBJCT : 1741 AAATAAACTCGGGCATCTCAGACTTGGCCTTCCAGCGCTCCTTCACTGAAAGCAATCAAT 1800 QUERY : 2584 ACAACATCTACGCGGCTCTGCACACGGAGCCGGACCTGCTGTTCCTGGAGCTGTCCACGG 2643 II) IIIIf SBJCT : 1801 ACAACATCTACGCGGCTCTGCACACGGAGCCGGACCTGCTGTTCCTGGAGCTGTCCACGG 1860 m m) m m m m m m m m m) m m m m m m m mi QUERY : 2644 GGAAGGTGGGCATGCTGAAGAACTTAAAGGAGCCACCCGCAGGGCCAGCTCAGCCCTNNN 2703 111111111111111111111111111111111111111111111111111111111 SBJCT : 1861 GGAAGGTGGGCATGCTGAAGAACTTAAAGGAGCCACCCGCAGGGCCAGCTCAGCCCTGGG 1920 m) m m) m m) m m m mm m m m m m m m m QUERY : 2704 NNNNTACCCACAGAATCATGAGGGACAGTGGGCTGTTTGGACAGTACCTCCTCACACCAG 2763 Illlllllllllllllllllllllllllllllllllllllllllllllllllilll SBJCT : 1921 GGGGTACCCACAGAATCATGAGGGACAGTGGGCTGTTTGGACAGTACCTCCTCACACCAG 1980 m m) m ! m m m m mmm m m m m ! m m m) ! QUERY : 2764 CCCGAGAGTCACTGTTCCTCATCAATGGGAGACAAAACACGCTGCGGTGTGAGGTGTCAG 2823 IIIIII m m m m m m m mm mmm m m m m m m mm SBJCT : 1981 CCCGAGAGTCACTGTTCCTCATCAATGGGAGACAAAACACGCTGCGGTGTGAGGTGTCAG 2040 QUERY : 2824 GTATAAANNNNNNNACCACAGTGGTGTGGGTGGGTGAGGTATGAAGGGCCCAGAGCAGAG 2883 1111111 1111111111111111111111111111111111111111111111 SBJCT : 2041 GTATAAAGGGGGGGACCACAGTGGTGTGGGTGGGTGAGGTATGAAGGGCCCAGAGCAGAG 2100 QUERY : 2884 CCCTGGGCCAAGGAACACCCCCTAGTCCTGACACTGCAGCCTCAAGCAGGTACGCTGTAC 2943 111111111111111111111111111111111111111111111111111111111111 SBJCT : 2101 CCCTGGGCCAAGGAACACCCCCTAGTCCTGACACTGCAGCCTCAAGCAGGTACGCTGTAC 2160 QUERY : 2944 ATTTTTACAGACAAAAGCAAAAACCTGTACTCGCTTTGTGGTTCAACACTGGTCTCCTTG 3003 111111111111111111111111111111111111111111111111111111111111 SBJCT : 2161 ATTTTTACAGACAAAAGCAAAAACCTGTACTCGCTTTGTGGTTCAACACTGGTCTCCTTG 2220 QUERY : 3004 CAAGTTTCCTAGTATAAGGTATGCGCTGCTACCAAGATTGGGGTTTTTTCGTTAGGAAGT 3063 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll SBJCT : 2221 CAAGTTTCCTAGTATAAGGTATGCGCTGCTACCAAGATTGGGGTTTTTTCGTTAGGAAGT 2280 QUERY : 3064 ATGATTTATGCCTTGAGCTACGATGAGAACATATGCTGCTGTGTAAAGGGATCATTTCTG 3123 11111111111111111111111|111111111111111111111111111111111111 SBJCT : 2281 ATGATTTATGCCTTGAGCTACGATGAGAACATATGCTGCTGTGTAAAGGGATCATTTCTG 2340 QUERY : 3124 TGCCAAGCTGCACACCGAGTGACCTGGGGACATCATGGAACCAAGGGATCCTGCTCTCCA 3183 IIIIIIIIIIIIIIIIIIIIIIIIIII SBJCT : 2341 TGCCAAGCTGCACACCGAGTGACCTGGGGACATCATGGAACCAAGGGATCCTGCTCTCCA 2400 QUERY : 3184 AGCAGACACCTCTGTCAGTTGCCTTCACATAGTCATTGTCCCTTACTGCCAGACCCAGCC 3243 111111111111111111111111111111111111111111111111111111111111 SBJCT : 2401 AGCAGACACCTCTGTCAGTTGCCTTCACATAGTCATTGTCCCTTACTGCCAGACCCAGCC 2460 QUERY : 3244 AGACTTTGCCCTGACGGAGTGGCCCGGAAGCAGAGGCCGACCAGGAGCAGGGGCCTCCCT 3303 111111111111111111111111111111111111111111111111111111111111 SBJCT : 2461 AGACTTTGCCCTGACGGAGTGGCCCGGAAGCAGAGGCCGACCAGGAGCAGGGGCCTCCCT 2520 QUERY : 3304 CCCGAACTGAAAGCCCATCCGTCCTCGCGTGGGACCGCATCTTCTCCCTCGCAGCTGCTT 3363 111111111111111111111111111111111111111111111111111111111111

SBJCT : 2521 CCCGAACTGAAAGCCCATCCGTCCTCGCGTGGGACCGCATCTTCTCCCTCGCAGCTGCTT 2580 QUERY : 3364 CTTGCTTTTCTTTCCATTTGACTTGCTGTAAGCCTGAGGGAGAGCCAACAAGACTTACTG 3423 III SBJCT : 2581 CTTGCTTTTCTTTCCATTTGACTTGCTGTAAGCCTGAGGGAGAGCCAACAAGACTTACTG 2640 QUERY : 3424 CATCTTGGGGGATGGGGAAATCACTCACTTTATTTTGGAAATTTTTGATTNNNNNNNNNT 3483 11111111111111111111111115111111111111111111111811 SBJCT : 2641 CATCTTGGGGGATGGGGAAATCACTCACTTTATTTTGGAAATTTTTGATTAAAAAAAAAT 2700 QUERY : 3484 TTTATAATCTCAAATGCTAGTAAGCAGAAAGATGCTCTCCGAGGTCCAACTATATCCTTC 3543 IllllllllllllllllllllllllllllllllllllllWlllllllllllllllllllf SBJCT : 2701 TTTATAATCTCAAATGCTAGTAAGCAGAAAGATGCTCTCCGAGGTCCAACTATATCCTTC 2760 SBJCT : 2701 TTTATAATCTCAAATGCTAGTAAGCAGAAAGATGCTCTCCGAGGTCCAACTATATCCTTC 2760 QUERY : 3544 CCTGCCTTAGGCCGAGTCTCGGGGGTGGTCACAACCCCACATCCCACAGCCAGAAAGAAC 3603 11111111111111111111111111111111111111111111111111111111|111 SBJCT : 2761 CCTGCCTTAGGCCGAGTCTCGGGGGTGGTCACAACCCCACATCCCACAGCCAGAAAGAAC 2820 QUERY : 3604 AATGGTCATCTGAGAATACTGGCCCTGTCGACTATTGCCACCCTGCTTCTCCAAGAGCAG 3663 111111111111111111111111111111111111111111111111111111111111 SBJCT : 2821 AATGGTCATCTGAGAATACTGGCCCTGTCGACTATTGCCACCCTGCTTCTCCAAGAGCAG 2880 QUERY : 3664 ACCAGGCCACCTCATCCGTAAGGACTCGGTTCTGTGTTGGGACCCCAAAAAACCAGAACA 3723 11111111111111111111111111111111111111111111111111111. 1111111 QUERY : 2881 ACCAGGCCACCTCATCCGTAAGGACTCGGTTCTGTGTTGGGACCCCAAAAAACCAGAACA 2940 m urn num ! mnHmnnmmH) mH nmn) m urn QUERY : 3724 AGTTCTGTGTGCCTCCTTTCAGCACAGAAGGGAGACATCTCATTAGTCAGGTCTGGTACC 3783 111111911111111111111111111111111111111111111111111111111111 SBJCT : 2941 AGTTCTGTGTGCCTCCTTTCAGCACAGAAGGGAGACATCTCATTAGTCAGGTCTGGTACC 3000 m) H m)) H) t ! N t m m) N) H n) m H m) H i m N H m)) n QUERY : 3784 CCAGATTCAGGGCAGACTGGGCTTGCCTGGCAAGGTATGGGTGGCCTCCAGGCTCAATGC 3843 IllllllllllllllllllllllllllllllllllllllllllllllllIIIIIIIIIII SBJCT : 3001 CCAGATTCAGGGCAGACTGGGCTTGCCTGGCAAGGTATGGGTGGCCTCCAGGCTCAATGC 3060 QUERY : 3844 AGAAACCCCAAGGACACGAGTGGGGCCAGGTGAGTTCCTGAAGCTATACCTTTTCAAAAC 3903 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII (IIIIIIII SBJCT : 3061 AGAAACCCCAAGGACACGAGTGGGGCCAGGTGAGTTCCTGAAGCTATACCTTTTCAAAAC 3120 QUERY : 3904 AGATTTTGTTTTCCTACCTGTGGCCCATCCACTCCTCTCTGGTACCCCATCCCCGCATCA 3963 111111111111111111111111111111111111111111111111111111111111 SBJCT : 3121 AGATTTTGTTTTCCTACCTGTGGCCCATCCACTCCTCTCTGGTACCCCATCCCCGCATCA 3180 QUERY : 3964 GCACTGCAGAGAGAACACATTTCGGCGAGGGTTTTCTTACCCACATTCCCCAATCAATAC 4023 1111111111111111111111111111|1111111111111111111111111111111 SBJCT : 3181 GCACTGCAGAGAGAACACATTTCGGCGAGGGTTTTCTTACCCACATTCCCCAATCAATAC 3240 QUERY : 4024 ACACACACTGCAGAACCCAGAACAGAAGGCCACAGGCTGGCACTACTGCATTCTCCTTAT 4083 111111111111111111111111111111111111111111111111111111811111 SBJCT : 3241 ACACACACTGCAGAACCCAGAACAGAAGGCCACAGGCTGGCACTACTGCATTCTCCTTAT 3300 QUERY : 4084 GTGTCTCAGGCTGTGGTGACTCTCACATGGGCATCGAAGAAGTACAACCCACATAGCCCT 4143 11111111111111111111111111111111} 111111l11111111111111} 11111 SBJCT : 3301 GTGTCTCAGGCTGTGGTGACTCTCACATGGGCATCGAAGAAGTACAACCCACATAGCCCT 3360 SBJCT : 3301 GTGTCTCAGGCTGTGGTGACTCTCACATGGGCATCGAAGAAGTACAACCCACATAGCCCT 3360 m m m mm mm m mmmm m m m m m m mm QUERY : 4144 CTGGAGACCGCCTAGATCAGAGACTCAGCAAAAACAGGCTCGCCTTCCCTCTCCCACATA 4203 Illlllllllllllllllilllllllilllllllllllllllllllllllllllllllll SBJCT : 3361 CTGGAGACCGCCTAGATCAGAGACTCAGCAAAAACAGGCTCGCCTTCCCTCTCCCACATA 3420 QUERY : 4204 TGAGTGGAACTTACATGTGTCCTGGTTTGAATGATCATTTTGCAAGCCACACGGGTTGGG 4263 111111111111111111111111111111111111111111111111111111111111 SBJCT : 3421 TGAGTGGAACTTACATGTGTCCTGGTTTGAATGATCATTTTGCAAGCCACACGGGTTGGG 3480 QUERY : 4264 AGAGGTGGTCTCACCACAGACGTCTTTGCTAATTTGGCCACCTTCACCTACTGACATGAC 4323 111111111111111111111111111111111111111111111111111111111111 SBJCT : 3481 AGAGGTGGTCTCACCACAGACGTCTTTGCTAATTTGGCCACCTTCACCTACTGACATGAC 3540 QUERY : 4324 CAGGATTTTCCTTTGCCATTAAGGAATGAACTCTTTCAAGGAGAGGAAACCCTAGACTCT 4383 111111111111111111111111111111111111111111111111111111111111 SBJCT : 3541 CAGGATTTTCCTTTGCCATTAAGGAATGAACTCTTTCAAGGAGAGGAAACCCTAGACTCT 3600

QUERY : 4384 GTGTCACTCTCAACACACACAGCTCCTTTCACTCCTGCCTGACTGCCAAGCCACCTGCAT 4443 mm m m m m m m mm m m m m m m m m m m SBJCT : 3601 GTGTCACTCTCAACACACACAGCTCCTTTCACTCCTGCCTGACTGCCAAGCCACCTGCAT 3660 SBJCT : 3601 GTGTCACTCTCAACACACACAGCTCCTTTCACTCCTGCCTGACTGCCAAGCCACCTGCAT 3660 QUERY : 4444 CCCCCGCCCCAGATCTCATGAGATCAATCACTTGTATGTCTCACGCAACTTGGTCCACCA 4503 111111111111111111111111111111111111111111111111111111111111 SBJCT : 3661 CCCCCGCCCCAGATCTCATGAGATCAATCACTTGTATGTCTCACGCAACTTGGTCCACCA 3720 QUERY : 4504 AACGCCTGTCCCCTGTAACTCCTAGGGGTGCGCCTAGACAGGTACGTCTGTTTTTTATTT 4563 111111111111111111111111111111111111111111111111111111111111 SBJCT : 3721 AACGCCTGTCCCCTGTAACTCCTAGGGGTGCGCCTAGACAGGTACGTCTGTTTTTTATTT 3780 mm m m m m mmm m m mm m m m m m m m QUERY : 4564 TAAAAGATATGCTATGTAGATATAAGTTGAGGAAGCTCACCTCAAAAGCCTAGAATGCAG 4623 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIilllllllllllllllillllllllllllll SBJCT : 3781 TAAAAGATATGCTATGTAGATATAAGTTGAGGAAGCTCACCTCAAAAGCCTAGAATGCAG 3840 QUERY : 4624 TTTCACAGTAGCTGGGATGCATGGATGACCCATCTCACCCCNNNNNNNNNCCTGCCTCAA 4683 IIIIIIIIIIIIII SBJCT : 3841 TTTCACAGTAGCTGGGATGCATGGATGACCCATCTCACCCCTTTTTTTTTCCTGCCTCAA 3900 QUERY : 4684 TATCTTGATATGTTATGTTTACTCCCAATCTCCCATTTTTACCACTAAAATTCTCCAACT 4743 llllllllllllllllllllllllllllllllllllllllllllllllllllllllllll SBJCT : 3901 TATCTTGATATGTTATGTTTACTCCCAATCTCCCATTTTTACCACTAAAATTCTCCAACT 3960 QUERY : 4744 TTCATAAACNNNNNNNNGGAAAAATTTCCATTGTATCAGCCCCTGACAGAAAAAGGATCT 4803 IIIIIIIII Illllllllllllllllllllllllllll SBJCT : 3961 TTCATAAACTTTTTTTTGGAAAAATTTCCATTGTATCAGCCCCTGACAGAAAAAGGATCT 4020 QUERY : 4804 CTGAGCCTAAAGGAGGAAAAGTCCCACCAACTACCAGACCAGAACACGAGCCCCTCTGGG 4863 111111111111111111111111111111111111111111111111111111111111 SBJCT : 4021 CTGAGCCTAAAGGAGGAAAAGTCCCACCAACTACCAGACCAGAACACGAGCCCCTCTGGG 4080 QUERY : 4864 CAGCAGGATTCCTAAGTCAAAGACCAGTTTGACCCAAACTGGCCTTTTAAAATAATCAGG 4923 m m m m m m m m m m m m m m m m m m m m SBJCT : 4081 CAGCAGGATTCCTAAGTCAAAGACCAGTTTGACCCAAACTGGCCTTTTAAAATAATCAGG 4140 SBJCT : 4081 CAGCAGGATTCCTAAGTCAAAGACCAGTTTGACCCAAACTGGCCTTTTAAAATAATCAGG 4140 QUERY : 4924 AGTGACAGAGTCAACTTCTGCAGCACCTGCTTCTCCCCCACTGTCCCTTCCATCTTGGAA 4983 Illlllllllllllllllllllllllllllllllllllilllllllllllllllllllll SBJCT : 4141 AGTGACAGAGTCAACTTCTGCAGCACCTGCTTCTCCCCCACTGTCCCTTCCATCTTGGAA 4200 QUERY : 4984 TGTGTCTAAAAAAGCATAGCTGCCCTTTGCTGTCCTCAGAGTGCATTTCCTGGAGACGGC 5043 111111111111111111111111111111111111111111111111111111111111 SBJCT : 4201 TGTGTCTAAAAAAGCATAGCTGCCCTTTGCTGTCCTCAGAGTGCATTTCCTGGAGACGGC 4260 m H m m m m m m m mm m m m) m m m m mm QUERY : 5044 AGGCTTAGGTCTCACTGACAGCATGCCAGACACAACTGAATCGAAGCAGGCCTGAAGCCT 5103 Illlllllllllllllllllllllllllllllllllllllllllllllll1111111111 SBJCT : 4261 AGGCTTAGGTCTCACTGACAGCATGCCAGACACAACTGAATCGAAGCAGGCCTGAAGCCT 4320 m m m mmm m m ! mm mm m m)) mmm mm QUERY : 5104 AGGTCAGGGTTTCAGGAGTCCAGCCCCAGGAGGCAAAGTCACCAATGCAGGGAGGTAAAT 5163 Illllllllll1llllllllllllllllllllllllllllllllllllllllllllllil SBJCT : 4321 AGGTCAGGGTTTCAGGAGTCCAGCCCCAGGAGGCAAAGTCACCAATGCAGGGAGGTAAAT 4380 QUERY : 5164 GCCTTTTGGCAGGAAAACCAATAGAGTTGGTTGGGTGGGGAGTCAGGGGTGGGAGGAGAA 5223 111111111111111111111111111111111111111111111111111111111111 SBJCT : 4381 GCCTTTTGGCAGGAAAACCAATAGAGTTGGTTGGGTGGGGAGTCAGGGGTGGGAGGAGAA 4440 QUERY : 5224 GGAGGAAGAGGAGGAAGGCCAGACTGGCCTGCCCTTTCTCCCATACTTCACCCCAGCAGA 5283 111111111111111111111111111111111111111111111111111111111111 SBJCT : 4441 GGAGGAAGAGGAGGAAGGCCAGACTGGCCTGCCCTTTCTCCCATACTTCACCCCAGCAGA 4500 QUERY : 5284 GGTTCATGGGACACAGTTGGAAAGCCACTGGGAGGAAATGCCTCACTACAGGGGGGCCTC 5343 111111111111111111111111111111111111111111111111111111111111 SBJCT : 4501 GGTTCATGGGACACAGTTGGAAAGCCACTGGGAGGAAATGCCTCACTACAGGGGGGCCTC 4560 QUERY : 5344 CTGTAGCAAGCCCAGCCGGTAATCCTCCTAATGAACCCACAAGGTCAATTCACAACTGAT 5403 m) mi mmmmtmmmmmm m mmmm mm SBJCT : 4561 CTGTAGCAAGCCCAGCCGGTAATCCTCCTAATGAACCCACAAGGTCAATTCACAACTGAT 4620 QUERY : 5404 ATCTTAGCTATTAAAGAAGTACTGACTTTACCAAAAGAATCATCAAGAAAGCTATTTATA 5463 |11111111111111111111111111111111111111111111111111111111111

SBJCT : 4621 ATCTTAGCTATTAAAGAAGTACTGACTTTACCAAAAGAATCATCAAGAAAGCTATTTATA 4680 QUERY : 5464 TAAACCCCCTCAGTCATTTTGAAATAAAATTAATTTTAC 5502 Illllilllliiililllllllilllllillillillil SBJCT : 4681 TAAACCCCCTCAGTCATTTTGAAATAAAATTAATTTTAC 4719 The FCTR2 amino acid sequence has 473 of 810 amino acid residues (58%) identical to, and 616 of 810 residues (76%) positive with, the 850 amino acid residue proteins from Homo sapiens KIAA1263 Protein fragment (ptnr : TREMBLNEW-ACC : BAA86577) (SEQ ID NO : 47) (Table 2D).

Table 2D. BLASTP of FCTR2 against Homo sapiens KIAA1263 Protein fragment (SEQ ID NO : 47) ptnr : TREMBLNEW-ACC : BAA86577 KIAA1263 PROTEIN-Homo sapiens (Human), 850 aa (fragment) Length = B50 Score = 2573 (905. 7 bits), Expect = 2. 0e-267, P = 2. 0e-267 Identities = 473/810 (58%), Positives = 616/810 (76%) QUERY : 10 LFRLSLKRALSSCPDLFGLSSRNELLASCGKKFCSRGSRCVLSRKTGEPECQCLEACRPS 69 I II 1 + I ++ 11 1+1 1 li 11+11+ 11 1++ 1+ SBJCT : 40 LMRLRHKEKNQESSRVKGFMIQDGPFGSCENKYCGLGRHCVTSRETGQAECACMDLCKRH 99 QUERY : 70 YVPVCGSDGRFYENHCKLHRAACLLGKRITVIHSKDCFLKGDTCTMAGYARLKNVLLALQ 129 I IIIIIII IIIIiI++Ililii ++II++I++III III I I+++p +I II SBJCT : 100 YKPVCGSDGEFYENHCEVHRAACLKKQKITIVHNEDCFFKGDKCKTTEYSKMKNMLLDLQ 159 QUERY : 130 TRLQPLQEGDSRQ-DPASQKRLLVESLFRDLDADGNGHLSSSELAQHVLKKQDLDEDLLG 188 + +il ++ 1 1+1+111+ +1+ ll 11 + +11 1 1+1+++l +11 SBJCT : 160 NQKYIMQENENPNGDDISRKKLLVDQMFKYFDADSNGLVDINELTQ-VIKQEELGKDLFD 218 QUERY : 189 CSPGDLLRFDDYNSDSSLTLREFYMAFQWQLSLAPEDRVSVTTVTVGLSTVLTCAVHGD 248 in II++III+I I I III IIII+ILII + + I I III I II Il+ I SBJCT : 219 CTLYVLLKYDDFNADKHLALEEFYRAFQVIQLSLPEDQKLSITAATVGQSAVLSCAIQGT 278 QUERY : 249 LRPPIIWKRNGLTLNFLDLEDINDFGEDDSLYITKVTTIHMGNYTCHASGHEQLFQTHVL 308 iiiiiiiiii QUERY : 279 LRPPIIWKRNNIILNNLDLEDINDFGDDGSLYITKVTTTHVGNYTCYADCYEQVYQTHIF 338 QUERY : 309 QVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVDVSTQMSKQLSLLANG 368 IIIIIIIIIIIIIIII+Illl IIIIIIIIIII 1++ IIIII+I+ ++Ill+I Ill SBJCT : 339 QVNVPPVIRVYPESQAREPGVTASLRCHAEGIPKPQLGWLKNGIDITPKLSKQLTLQANG 398 QUERY : 369 SELHISSVRYEDTGAYTCIAKNEVGVDEDISSLFIEDSARKTLANILWREEGLSVGNMFY 428 ll+lll+llllllllllllllll 1111111111+111111111111111111 +11111 SBJCT : 399 SEVHISNVRYEDTGAYTCIAKNEAGVDEDISSLFVEDSARKTLANILWREEGLGIGNMFY 458 QUERY : 429 VFSDDGIIVIHPVDCEIQRHLKPTEKIEMSYEEICPQREKNATQPCQWVSAVNVRNRYIY 488 II +III il I+II Ifl+II+II+ +I+II+ I + i I I lilll++++II SBJCT : 459 VFYEDGIKVIQPIECEFQRHIKPSEKLLGFQDEVCPKAEGDEVQRCVWASAVNVKDKFIY 518 QUERY : 489 VAQPALSRVLWDIQAQKVLQSIGVDPLPAKLSYDKSHDQVWVLSWGDVHKSRPSLQVIT 548 I I I I I I 1 1+1 1+1+1 l 1+1++ l 1+1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 + 1+ 1+l 1 1 1 1 IIII I III+II+I+III+I++ p + I IIIIIIIIIIIIII + I+ +illl SBJCT : 519 VAQPTLDRVLIVDVQSQKV\7QAVSTDPVPVKLHYDKSHDQVWVLSWGTLEKTSPTLQVI T 578 QUERY : 549 EASTGQSQHLIRT-----PFAGVDDFFIPPTNLIINHIRFGFIFNKSDPAVHKVDLETMM 603 II I I I 1 1111111 1 111 1+11111 +1 + 1+ 1+11111 SBJCT : 579 LASGNVPHHTIHTQPVGKQFDRVDDFFIPTTTLIITHMRFGFILHKDEAALQKIDLETMS 638 QUERY : 604 PLKTIGLHHHGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDSVLGPNGDVTG 663 +111 1 + m+-H+mm+))) + ii ++) ++u m)) +)) u ! i SBJCT : 639 YIKTINLKDYKCVPQSLAYTHLGGYYFIGCKPDSTGAVSPQVMVDGVTDSVIGFNSDVTG 698

QUERY : 664 TPHTSPDGRFIVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQRSFTESNQYN 723 ll+ i+ IN ! ++n +)) U+Hi)) + ! +) i ! H)) t i))) ++ !)) SBJCT : 699 TPYVSPDGHYLVSINDVKGLVRVQYITIRGEIQEAFDIYTNLHISDLAFQPSFTEAHQYN 758 QUERY : 724 IYAALHTEPDLLFLELSTGKVGMLKNLKEPPAGPAQPWGGTHRIMRDSGLFGQYLLTPAR 783 Il + 1+ 1+11+111+111 1+1+1111 11 +1 ++111111111+11++ SBJCT : 759 IYGSSSTQTDVLFVELSSGKVKMIKSLKEPLKAEEWPWNRKNRQIQDSGLFGQYLMTPSK 818 QUERY : 784 ESLFLINGRQNTLRCEVSGIKGGTTWNVGE 814 +III+++II I I II++ ++ II+III+ SBJCT : 819 DSLFILDGRLNKLNCEITEVEKGNTVIWVGD 849 Amino acids 123-815 of FCTR2 also have 693 of 693 amino acid residues (100%) identical to, the 693 amino acid residue protein fragment of KIAA 1061 Protein from Homo sapiens (ptnr : TREMBLNEW-ACC : BAA83013) (SEQ ID NO : 48) (Table 2E).

Table 2E. BLASTP of FCTR2 against KIAA1061 Protein [Fragment] (SEQ ID NO : 48) ptnr : TREMBLNEW-ACC : BAA83013 KIAA1061 PROTEIN-Homo sapiens (Human), 693 aa (fragment).

Length = 693 , Score = 3623 (1275. 4 bits), Expect = 0. 0, P = 0. 0 Identities = 693/693 (100%), Positives = 693/693 (100%) QUERY : 123 NVLLALQTRLQPLQEGDSRQDPASQKRLLVESLFRDLDADGNGHLSSSELAQHVLKKQDL 182 NmmmtmmmmmmNNmmmmmmmm)) SBJCT : 1 NVLLALQTRLQPLQEGDSRQDPASQKRLLVESLFRDLDADGNGHLSSSELAQHVLKKQDL 60 QUERY : 183 DEDLLGCSPGDLLRFDDYNSDSSLTLREFYMAFQWQLSLAPEDRVSVTTVTVGLSTVLT 242 Illlllillilllllllililllllllllillllllllilllllllllllllllllllll SBJCT : 61 DEDLLGCSPGDLLRFDDYNSDSSLTLREFYMAFQWQLSLAPEDRVSVTTVTVGLSTVLT 120 QUERY : 243 CAVHGDLRPPIIWKRNGLTLNFLDLEDINDFGEDDSLYITKVTTIHMGNYTCHASGHEQL 302 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII SBJCT : 121 CAVHGDLRPPIIWKRNGLTLNFLDLEDINDFGEDDSLYITKVTTIHMGNYTCHASGHEQL 180 QUERY : 303 FQTHVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVDVSTQMSKQL 362 111111111111111111111111111111111111111111111111111111111111 SBJCT : 181 FQTHVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVDVSTQMSKQL 240 QUERY : 363 SLLANGSELHISSVRYEDTGAYTCIAKNEVGVDEDISSLFIEDSARKTLANILWREEGLS 422 Illlllllllllllllllllllllllllllllllllllllllflllllllllllllllll SBJCT : 241 SLLANGSELHISSVRYEDTGAYTCIAKNEVGVDEDISSLFIEDSARKTLANILWREEGLS 300 QUERY : 423 VGNMFYVFSDDGIIVIHPVDCEIQRHLKPTEKIFMSYEEICPQREKNATQPCQWVSAVNV 482 Ililllilllllllllllllllllllllllllllllllllllllllllllllllllllll SBJCT : 301 VGNMFYVFSDDGIIVIHPVDCEIQRHLKPTEKIFMSYEEICPQREKNATQPCQWVSAVNV 360 QUERY : 483 RNRYIYVAQPALSRVLVVDIQAQKVLQSIGVDPLPAKLSYDKSHDQVWVLSWGDVHKSRP 542 III SBJCT : 361 RNRYIYVAQPALSRVLVVDIQAQKVLQSIGVDPLPAKLSYDKSHDQVWVLSWGDVHKSRP 420 QUERY : 543 SLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRFGFIFNKSDPAVHKVDLETM 602 111111111111111111111111111111111111111111111111111111111111 SBJCT : 421 SLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRFGFIFNKSDPAVHKVDLETM 480 QUERY : 603 MPLKTIGLHHHGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDSVLGPNGDVT 662 111111111111111111111111111111111111111111111111111111111111 SBJCT : 481 MPLKTIGLHHHGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDSVLGPNGDVT 540 QUERY : 663 GTPHTSPDGRFIVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQRSFTESNQY 722

111111111111111111111111111111111111f11111111111111111111111 SBJCT : 541 GTPHTSPDGRFIVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQRSFTESNQY 600 QUERY : 723 NIYAALHTEPDLLFLELSTGKVGMLKNLKEPPAGPAQPWGGTHRIMRDSGLFGQYLLTPA 782 mtmmmmmHmmNmnmmmHnHNmmm SBJCT : 601 NIYAALHTEPDLLFLELSTGKVGMLKNLKEPPAGPAQPWGGTHRIMRDSGLFGQYLLTPA 660 QUERY : 783 RESLFLINGRQNTLRCEVSGIKGGTTVVWVGEV 815 ììììlil111ìlìlììììlìllìllììlìlììì SBJCT : 661 RESLFLINGRQNTLRCEVSGIKGGTTVVWVGEV 693 The amino acid sequence of the FCTR2 protein has 451 of 772 amino acid residues (58%) identical to, and 586 of 772 residues (75%) positive with, the 773 amino acid residue proteins hypothetical protein DKFZp566D234. 1 from Hoino sapiens (fragments) (ptnr : SPTREMBL-ACC : CAB70877. 1) (SEQ ID NO : 49) (Table 2F).

Table 2F. BLASTP of FCTR2 against hypothetical protein DKFZp566D234. 1 (SEQ ID NO : 49) >GI|11360192|PIR||T46283 HYPOTHETICAL PROTEIN DKFZP566D234. 1-HUMAN (FRAGMENTS) GI#6808053#EMB#CAB70877.1# (AL137695) HYPOTHETICAL PROTEIN [HOMO SAPIENS] LENGTH = 773 SCORE = 911 BITS (2354), EXPECT = 0. 0 IDENTITIES = 451/772 (58%), POSITIVES = 586/772 (75%), GAPS = 7/772 (0%) QUERY : 49 CVLSRKTGEPECQCLEACRPSYVPVCGSDGRFYENHCKLHRAACLLGKRITVIHSKDCFL 108 II ll+ll+ 11 1++ 1+ 1 IIIIIII 111111++|11111 ++11++1++111 SBJCT : 2 CVTSRETGQAECACMDLCKRHYKPVCGSDGEFYENHCEVHRAACLKKQKITIVHNEDCFF 61 QUERY : 109 KGDTCTMAGYARLKNVLLALQTRLQPLQEGDSRQ-DPASQKRLLVESLFRDLDADGNGHL 167 111 1 +++11+11 11 + +11 ++ I I+I+III+ ++ III I + SBJCT : 62 KGDKCKTTECSKMKNMLLDLQNQRYIMQENENPNGDDISRKKLLVDQMFKYFDADSNDLV 121 QUERY : 168 SSSELAQHVLKKQDLDEDLLGCSPGDLLRFDDYNSDSSLTLREFYMAFQWQLSLAPEDR 227 +II I I++++ +p I+ II++y ++ I I III IIII+IIII + + SBJCT : 122 DINELTQ-VIKQEELGKDLFDCTLYVLLKYDDFNADKHLALEEFYRAFQVIQLSLPEDQK 180 QUERY : 228 XXXXXXXXXXXXXXXCAVHGDLRPPIIWKRNGLTLNFLDLEDINDFGEDDSLYITKVTTI 287 ll+ I 1111111111 + 11 1 11111111+1 111111111 SBJCT : 181 LSITAATVGQSAVLSCAIQGTLRPPIIWKRNNIILNNLGLEDINDFGDDGSLYITKVTTT 240 QUERY : 288 HMGNYTCHASGHEQLFQTHVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITW 347 1+11111+1 1+11++Ill-1++ 1 SBJCT : 241 HVGNYTCYADGYEQVYQTHIFQVNVPPVIRVYPESQAREPGVTASLRCHAEGIPKPQLGW 300 QUERY : 348 LKNGVDVSTQMSKQLSLLANGSELHISSVRYEDTGAYTCIAKNEVGVDEDISSLFIEDSA 407 1111+1++ ++1111+1 11111+111+1111111111111111 1111111111+1111 SBJCT : 301 LKNGIDITPKLSKQLTLQANGSEVHISNVRYEDTGAYTCIAKNEAGVDEDISSLFVEDSA 360 QUERY : 408 RKTLANILWREEGLSVGNMFYVFSDDGIIVIHPVDCEIQRHLKPTEKIFMSYEEICPQRE 467 11111111111111 +1111111 +111 11 1++11 111+11+11+ +1+11 1 SBJCT : 361 RKTLANILWREEGLGIGNMFYVFYEDGIKVIQPIECEFQRHIKPSEKLLGFQDEVCPIAE 420 QUERY : 468 KNATQPCQWVSAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQSIGVDPLPAKLSYDKSHD 527 + I I 1 iiiii.... iiiiii 1 111+11+1+111+1++ 11+1 11 liiiii SBJCT : 421 GDEVQRCVWASAVNVKDKFIYVAQPTLDRVLIVDVQSQKVVQAVSTDPVPVKLHYDKSHD 480 QUERY : 528 QVWVLSWGDVHKSRPSLQVITEASTGQSQHLIRT-----PFAGVDDFFIPPTNLIINHIR 582 IIIIIIII + 1+ 1+11111 11 1 I I I lllllll 1 III I+I SBJCT : 481 QVWVLSWGTLEKTSPTLQVITLASGNVPHHTIHTQPVGKQFDRVDDFFIPTTTLIITHMR 540 QUERY : 583 FGFIFNKSDPAVHKVDLETMMPLKTIGLHHHGCVPQAMAHTHLGGYFFIQCRQDSPASAA 642 1111 +1 + 1+ 1+11111 +111 1 + 1111++1+111111+11 1+ 11 + +

SBJCT : 541 FGFILHKDEAALQKIDLETMSYIKTINLKDYKCVPQSLAYTHLGGYYFIGCKPDSTGAVS 600 QUERY : 643 RQLLVDSVTDSVLGPNGDVTGTPHTSPDGRFIVSAAADSPWLHVQEITVRGEIQTLYDLQ 702 1++Il + ; + 1111 ++ll + 11 11+l +1+ SBJCT : 601 PQVMVDGVTDSVIGFNSDVTGTPYVSPDGHYLVSINDVKGLVRVQYITIRGEIQEAFDIY 660 QUERY : 703 INSGISDIAFQRSFTESNQYNIYAALHTEPDLLFLELSTGKVGMLKNLKEPPAGPAQPWG 762 I IIIIIII IIII++illll + 1+ 1+11+111+111 1+1+1111 11 SBJCT : 661 TNLHISDLAFQPSFTEAHQYNIYGSSSTQTDVLFVELSSGKVKMIKSLKEPLKAEEWPWN 720 QUERY : 763 GTHRIMRDSGLFGQYLLTPARESLFLINGRQNTLRCEVSGIKGGTTVVWVGE 814 +1 ++Illllllll+II+++III+++II I I II++ ++ I II+III+ SBJCT : 721 RKNRQIQDSGLFGQYLMTPSKDSLFILDGRLNKLNCEITEVEKGNTVIWVGD 772 The amino acid sequence of the FCTR2 protein has 61 of 194 amino acid residues (31%) identical to, and 90 of 194 residues (45%) positive with, the 306 amino acid residue protein Follastin-Related Protein 1 Precursor from Rattus Norvegicus (ptnr : GenBank Acc : Q62632) (SEQ ID NO : 50) (Table 2G).

Table 2G. BLASTP of FCTR2 against Follastatin-Related Protein 1 Precursor from Rattus Norvegicus (SEQ ID NO : 50) >GI#2498392#SP#Q62632#FRP RAT FOLLISTATIN-RELATED PROTEIN 1 PRECURSOR GI#1083669#PIR##S51361 FOLLISTATIN-RELATED PROTEIN PRECURSOR-RAT GI#536900#GB#AAA66063.1# (U06864) FOLLISTATIN-RELATED PROTEIN PRECURSOR [RATTUS NORVEGICUS] LENGTH = 306 SCORE = 86. 4 BITS (213), EXPECT = 1E-15 IDENTITIES = 61/194 (31%), POSITIVES = 90/194 (45%), GAPS = 26/194 (13%) QUERY : 38 CGKKFCSRGSRCVLSRKTGEPECQCLEACRPSYVPVCGSDGRFYENHCKLHRAACLLGKR 97 1 1 !) ! ++)) i)) t+i) + ! !)) ! ! +) + i) H+ ! H))) i + SBJCT : 29 CANVFCGAGRECAVTEK-GEPTCLCIEQCKPHKRPVCGSNGKTYLNHCELHRDACLTGSK 87 QUERY : 98 ITVIHSKDCFLKGD--------TCTMAGYARLKNVLLA-LQTRLQPLQEGDSRQDPASQK 148 1 | + ++ l + + l l l SBJCT : 88 IQVDYDGHCKEKKSVSPSASPWCYQANRDELRRRIIQWLEAEIIP----DGWFSKGSNY 193 QUERY : 149 RLLVESLFRDLDADGNGHLSSSELAQHVLK-----------KQDLDEDLLGCSPGDLLRF 197 +++ I+ ! +I+ 11 111 + I + I+ ++ I I l+ SBJCT : 144 SEILDKYFKSFD-NGDSHLDSSEFLKFVEQNETAVNITAYPNQENNKLLRGLCVDALIEL 202 QUERY : 198 DDYNSDSSLTLREF 211 I 1+1 1+ +11 SBJCT : 203 SDENADWKLSFQEF 216 The amino acid sequence of the FCTR2 protein has 61 of 194 amino acid residues (31%) identical to, and 89 of 194 residues (45%) positive with, the 306 amino acid residue protein Follastin-Related Protein 1 Precursor from Mus musculus (GenBank Acc : Q62356) (SEQ ID NO : 51) (Table 2H).

Table 2H. BLASTP of FCTR2 against Follastatin-Related Protein 1 Precursor from Mus musculus (SEQ ID NO : 51) >GIl6679871lREFlNP 032073. 11 FOLLISTATIN-LIKE [MUS MUSCULUS] GII24983911SPIQ623561FRP MOUSE FOLLISTATIN-RELATED PROTEIN 1 PRECURSOR (TGF-BETA- INDUCIBLE PROTEIN TSC-36)

GI#481186#PIR##S38251 FOLLISTATIN-RELATED PROTEIN-MOUSE GII349006IGBIC37633. 11 (M91380) TGF-BETA-INDUCIBLE PROTEIN [MUS MUSCULUS] LENGTH = 306 SCORE = 85. 2 BITS (210), EXPECT = 3E-15 IDENTITIES = 61/194 (31%), POSITIVES = 89/194 (45%), GAPS = 26/194 (13%) QUERY : 38 CGKKFCSRGSRCVLSRKTGEPECQCLEACRPSYVPVCGSDGRFYENHCKLHRAACLLGKR 97 1 N) ! ++ i !) t t t+i ! +))) !)) +) + ! iN+iH H)) + SBJCT : 29 CANVFCGAGRECAVTEK-GEPTCLCIEQCKPHKRPVCGSNGKTYLNHCELHRDACLTGSK 87 QUERY : 98 ITVIHSKDCFLKGDT--------CTMAGYARLKNVLLA-LQTRLQPLQEGDSRQDPASQK 148 + t + I + l + + l l l SBJCT : 88'IQVDYDGHCKEKKSASPSASPWCYQANRDELRRRLIQWLEAEIIP----DGWFSKGS NY 143 QUERY : 149 RLLVESLFRDLDADGNGHLSSSELAQHVLKK-----------QDLDEDLLGCSPGDLLRF 197 +++ I+ I +I+ 11 111 + I + I+ ++ I l+ SBJCT : 144 SEILDKYFKSFD-NGDSHLDSSEFLKFVEQNETAINITTYADQENNKLLRSLCVDALIEL 202 QUERY : 198 DDYNSDSSLTLREF 211 1 1+1 1+ +11 SBJCT : 203 SDENADWKLSFQEF 216 The amino acid sequence of the FCTR2 protein has 63 of 193 amino acid residues (32%) identical to, and 89 of 193 residues (45%) positive with, the 299 amino acid residue protein Follastatin-Related Protein from the African Clawed Frog (GenBank Acc : JG0187) (SEQ ID NO : 52) (Table 2I).

Table 21. BLASTP of FCTR2 against Follastatin-Related Protein from the African Clawed Frog (SEQ ID NO : 52) >GI17512162) PIRIIJG0187 FOLLISTATIN-RELATED PROTEIN-AFRICAN CLAWED FROG LENGTH = 299 SCORE = 81. 8 BITS (201), EXPECT = 3E-14 IDENTITIES = 63/193 (32%), POSITIVES = 89/193 (45%), GAPS = 25/193 (12%) QUERY : 38 CGKKFCSRGSRCVLSRKTGEPECQCLEACRPSYVPVCGSDGRFYENHCKLHRAACLLGKR 97 11 1 1 ++ I 1+1 l 1+1 1+ 11111+1+ 1 111+111 111 1 + SBJCT : 28 CANVFCGAGRECAVTEK-GDPTCDCIEKCKSHKRPVCGSNGKTYLNHCELHRDACLTGSK 86 QUERY : 98 ITVIHSKDCFLK-GDT-------CTMAGYARL-KNVLLALQTRLQPLQEGDSRQDPASQK 148 I I + I 1 11 1 + + + 1+ 111 + I SBJCT : 87 IQVDYDGHCKEKTSDTPAAVPVACYQSDRDEMRRRVIHWLQTEITP----DGWFSKGSDY 142 QUERY : 149 RLLVESLFRDLDADGNGHLSSSELAQHVLKKQDL------DED----LLGCSPGDLLRFD 198 +++ t I II+ II I+Il + + I ll+ I l+ SBJCT : 143 SEILDRYFKKFD-DGDSHLDSAELQSFLEQSQSTNITTYKDEETNRMLKSLCVEALIELS 201 QUERY : 199 DYNSDSSLTLREF 211 1 1+1 1 11 SBJCT : 202 DENADWKLNKNEF 214 The amino acid sequence of the FCTR2 protein has 59 of 194 amino acid residues (30%) identical to, and 90 of 194 residues (45%) positive with, the 308 amino acid residue protein Follistatin-Related Protein 1 Precursor from Homo sapiens (GenBank Acc : Q12841) (SEQ ID NO : 53) (Table 2J).

Table 2J. BLASTP of FCTR2 against Follistatin-Related Protein 1 Precursor from Homo sapiens (SEQ ID NO : 53) >GIl5901956lREFlNP 009016. I ! FOLLISTATIN-LIKE 1 [HOMO SAPIENS] GI124983901SPJQ128411FP, P HUMAN FOLLISTATIN-RELATED PROTEIN 1 PRECURSOR GI#1082372#PIR##S51362 FOLLISTATIN-RELATED PROTEIN-HUMAN GI#536898#GB#AAA66062.1# (U06863) FOLLISTATIN-RELATED PROTEIN PRECURSOR [HOMO SAPIENS] GI#3184393#DBJ#BAA28707.1# (D89937) FOLLISTATIN-RELATED PROTEIN (FRP) [HOMO SAPIENS]- GI#12652619#GB#AAH00055.1#AAH00055 (BC000055) FOLLISTATIN-LIKE 1 [HOMO SAPIENS] LENGTH = 308 SCORE-82. 9 BITS (204), EXPECT = 1E-14 IDENTITIES = 59/194 (30%), POSITIVES = 9C/194 (45%), GAPS = 26/194 (13%) QUERY : 38 CGKKFCSRGSRCVLSRKTGEPECQCLEACRPSYVPVCGSDGRFYENHCKLHRAACLLGKR 97 1 i))) ++))) ! t ! +)) +)))))) +) + !)) ! +))) t) i) + SBJCT : 31 CANVFCGAGRECAVTEK-GEPTCLCIEQCKPHKRPVCGSNGKTYLNHCELHRDACLTGSK 89 QUERY : 98 ITVIHSKDCFLKGD--------TCTMAGYARLKNVLLA-LQTRLQPLQEGDSRQDPASQK 148 t ! + ! I ! + (+++ ! ++))) SBJCT : 90 IQVDYDGHCKEKKSVSPSASPWCYQSNRDELRRRIIQWLEAEIIP----DGWFSKGSNY 145 QUERY : 149 RLLVESLFRDLDADGNGHLSSSELAQHVLKK-----------QDLDEDLLGCSPGDLLRF 197 +++ I++ I +I+ I III + + +++)) t+ SBJCT : 146 SEILDKYFKNFD-NGDSRLDSSEFLKFVEQNETAINITTYPDQENNKLLRGLCVDALIEL 204 QUERY : 198 DDYNSDSSLTLREF 211 1 1+1 1+ +11 SBJCT : 205 SDENADWKLSFQEF 218 The amino acid sequence of the FCTR2 protein has 35 of 69 amino acid residues (50%) identical to, and 45 of 69 residues (64%) positive with, the 315 amino acid residue Flik protein [Gallus gallus] (EMBL Acc : CAB42968. 1) (SEQ ID NO : 54) (Table 2K).

Table 2K. BLASTP of FCTR2 against Flik protein [Gallus gallus] (SEQ ID NO : 54) >GI#4837645#EMB#CAB42968.1# (AJ238977) FLIK PROTEIN [GALLUS GALLUS] LENGTH = 315 SCORE = 79. 8 BITS (196), EXPECT = 1E-13 IDENTITIES = 35/69 (50%), POSITIVES = 45/69 (64%), GAPS = 1/69 (1%) QUERY : 38 CGKKFCSRGSRCVLSRKTGEPECQCLEACRPSYVPVCGSDGRFYENHCKLHRAACLLGKR 97 11 ll+ I ++ I III I 1+1 1+1 11111+1+ 1 IlI+lll f + SBJCT : 31 CANVFCGRGAECAVTEK-GEPTCLCIEQCKPHGRPVCGSNGKTYLNHCELHRDACLTGSK 89 QUERY : 98 ITVIHSKDC 106 1 I SBJCT : 90 IQVDYDGHC 98 The amino acid sequence of the FCTR2 protein has 49 of 152 amino acid residues (32%) identical to, and 65 of 152 residues (42%) positive with a 272-420 amino acid fragment and, 31 of 83 residues (37%) identical to and 44 of 83 residues (52%) positive with a 248-329 amino acid fragment, both of the 1375 amino acid residue Frazzled gene protein [Drosophila melanogaster] (GenBankAcc : T13822) (SEQ ID NO : 55) (Table 2L).

Table 2L. BLASTP of FCTR2 against Frazzled gene protein [Drosophila melanogaster] (SEQ ID NO : 55) >GI#7511861#PIR##T13822 FRAZZLED GENE PROTEIN-FRUIT FLY (DROSOPHILA MELANOGASTER) GI1621115 GBIAAC47314. 11 (U71001) FRAZZLED [DROSOPHILA MELANOGASTER] LENGTH = 1375 SCORE = 69. 4 BITS (169), EXPECT = 2E-10 IDENTITIES = 49/152 (32%), POSITIVES = 65/152 (42%), GAPS = 4/152 (2%) QUERY : 243 CAVHGDLRPPIIWKRNGLTLNFLDLEDINDFGEDDSLYITKVTTIHMGNYTCHASGH-EQ 301 I + ! I ! 111+ 1+1 1|+ + 1+ 1 1 zu 11 + SBJCT : 272 CVANGVPKPQIKWLRNGMDLDFNDLDSRFSIVGTGSLQISSAEDIDSGNYQCRASNTVDS 331 QUERY : 302 LFQTHVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVDVSTQMSKQ 361 1 +11 11 1+ 1+1 1 1 1 1 11111 ++ I SBJCT : 332 LDAQATVQVQEPPKFIKAPKDTTAHEKDEPELKCDIWGKPKPVIRWLKNGDLITPNDYMQ 391 QUERY : 362 LSLLANGSELHISSVRYEDTGAYTCIAKNEVG 393 1 +1 1 1 + I I + 1+ 1 1 SBJCT : 392---LVDGHNLKILGLLNSDAGMFQCVGTNAAG 420 SCORE = 52. 9 BITS (126), EXPECT = 1E-05 IDENTITIES = 31/83 (37%), POSITIVES = 44/83 (52%), GAPS = 2/83 (2%) QUERY : 311 NVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVDVS-TQMSKQLSLLANGS 369 +1 1 1 1 + I +1 1 1 1+1 1+1 l1+11+1+ + + 1++ lui SBJCT : 248 SVAPSFLVGPSPKTVREGDTVTLDCVANGVPKPQIKWLRNGMDLDFNDLDSRFSIVGTGS 307 QUERY : 370 ELHISSVRYEDTGAYTCIAKNEV 392 1 111 1+1 1 1 1 1 1 SBJCT : 308-LQISSAEDIDSGNYQCRASNTV 329 The amino acid sequence of the FCTR2 protein has 53 of 177 amino acid residues (29%) identical to, and 78 of 177 residues (43%) positive with a 366-539 amino acid fragment, 51 of 170 residues (30%) identical to and 74 of 170 residues (43%) positive with a 276-438 amino acid fragment, 46 of 165 amino acid residues (27%) identical to, and 74 of 165 amino acid residues positive with a 185-341 amino acid fragment, 48 of 167 amino acid residues (28%) identical to and 70 of 167 amino acid residues (41%) positive with a 77-243 amino acid fragment, and 28 of 84 amino acid residues (33%) and 37 of 84 amino acid residues positive with a 56-139 amino acid fragment all of the protein 1395 residue Roundabout 1 protein [Drosophila melanogaster] (GenBankAcc : AAC38849. 1) (SEQ ID NO : 56) (Table 2M).

Table 2M. BLASTP of FCTR2 against Roundabout 1 protein [Drosophila melanogaster] (SEQ ID NO : 56) >GI|2804782lGBlAAC38849. 1l (AF040989) ROUNDABOUT 1 [DROSOPHILA MELANOGASTER] LENGTH = 1395 SCORE = 69. 8 BITS (170), EXPECT = 1E-10 IDENTITIES = 53/177 (29%), POSITIVES = 78/177 (43%), GAPS = 11/177 (6%) QUERY : 243 CAVHGDLRPPIIWKRNGL-TLNFLDLEDINDF-GEDDSLYITKVTTIHMGNYTCHA---- 296 dz l + l + l+ l l l + + l +l SBJCT : 366 CMASGNPPPSVFWTKEGVSTLMFPNSSHGRQYVAADGTLQITDVRQEDEGYYVCSAFSW 425 QUERY : 297--SGHEQLFQTHVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNG VDV 354 1 1 + 11+1++ 1 +1 1 1+1 1 1 1 1 111 1 +1 1

SBJCT : 426 DSSTVRVFLQVSSVDERPPPIIQIGPANQTLPKGSVATLPCRATGNPSPRIKWFHDGHAV 485 QUERY : 355 STQMSKQLSLLANGSELHISSVRYEDTGAYTCIAKNEVGVDEDISSLFIEDSARKTL 411 + 1++ 1 1 1 + ++ 1+1 1 1 1 1 1 1 ++1 +1 +1 SBJCT : 486--QAGNRYSII-QGSSLRVDDLQLSDSGTYTCTASGERGETSWAATLTVEKPGSTSL 539 SCORE = 56. 3 BITS (135), EXPECT = lE-06 IDENTITIES = 51/170 (30%), POSITIVES = 74/170 (43%), GAPS = 12/170 (7%) QUERY : 243 CAVHGDLRPPIIWKRNGLTLNFLDLEDINDFGEDDSLYITKVTTIHMGNYTCHASGH-EQ 301 1+1 11 1 ++Il+ + ++1 + II I+ +I I I I I + I SBJCT : 276 CSVGGDPPPKVLWKKEEGNIPVSRARILHD---EKSLEISNITPTDEGTYVCEAHNNVGQ 332 QUERY : 302 LFQTHVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVDVSTQM--- 358 + 1+ 11 1 ++ I I I I I I + I I 1 111 1 SBJCT : 333 ISARASLIVHAPPNFTKRPSNKKVGLNGVVQLPCMASGNPPPSVFWTKEG--VSTLMFPN 390 QUERY : 359-SKQLSLLANGSELHISSVRYEDTGAYTCIAKNEVGVDEDISSLFIEDSA 407 I +I I I+ II II I I + II +++ + SBJCT : 391 SSHGRQYVAADGTLQITDVRQEDEGYYVCSAFSV--VDSSTVRVFLQVSS 438 SCORE = 51. 7 BITS (123), EXPECT = 3E-05 IDENTITIES = 46/165 (27%), POSITIVES = 74/165 (43%), GAPS = 20/165 (12%) QUERY : 251 PPIIWKRNGLTLNFLDLEDINDFG--------EDDSLYITKVTTIHMGNYTCHASG---- 298 I +11 ++1+ 1+ ll+ ++ 11 + +l in 1 1 111 1 1 SBJCT : 185 PTLIWIKDGVPLD--DLKAMS-FGASSRVRIVDGGNLLISNVEPIDEGNYKCIAQNLVGT 241 QUERY : 299 HEQLFQTHVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVDVSTQM 358 + ++l I I l+ I I l+ I I I l++ I I ++ SBJCT : 242 RESSYAKLIVQVK--PYFMKEPKDQVMLYGQTATFHCSVGGDPPPKVLWKKEEGNIPVSR 299 QUERY : 359 SKQLSLLANGSELHISSVRYEDTGAYTCIAKNEVGVDEDISSLFI 403 ++ +1 + i) i ++ i i i)) i i) + i i + SBJCT : 300 AR---ILHDEKSLEISNITPTDEGTYVCEAHNNVGQISARASLIV 341 SCORE = 44. 0 BITS (103), EXPECT = 0. 007 IDENTITIES = 48/167 (28%), POSITIVES = 70/167 (41%), GAPS = 13/167 (7%) QUERY : 243 CAVHGDLRPPIIWKRNGLTLNFLDLEDINDFGEDDSLYITKVTTIHM----GNYTCHASG 298 I 1 1 1 1 1 ++1 ++ + + +1 +1+ + I I I I SBJCT : 77 CKVEGKPEPTIEWFKDGEPVSTNEKKSHRVQFKDGALFFYRTMQGKKEQDGGEYWCVAKN 136 QUERY : 299 H-EQLFQTHV-LQVNV-PPVIRVYPESQAQEPGVAASLRCH-AEGIPMPRITWLKNGVDV 354 I 1 ll+ 1 11 1+ 1 1 1 1 +111 1 + 1+1+11 + SBJCT : 137 RVGQAVSRHASLQIAVLRDDFRVEPKDTRVAKGETALLECGPPKGIPEPTLIWIKDGVPL 196 QUERY : 355 STQMSKQLSL-----LANGSELHISSVRYEDTGAYTCIAKNEVGVDE 396 + + +1 I ll+l I I I lll+l 11 SBJCT : 197 DDLKAMSFGASSRVRIVDGGNLLISNVEPIDEGNYKCIAQNLVGTRE 243 SCORE = 42. 9 BITS (100), EXPECT = 0. 014 IDENTITIES = 28/84 (33%), POSITIVES = 37/84 (43%), GAPS = 4/84 (4%) QUERY : 314 PVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVDVSTQMSKQLSLLANGSELH- 372 I I +1 + 1+1 1 11 1 1 1 l 1+1 111 1 + I SBJCT : 56 PRIIEHPTDLWKKNEPATLNCKVEGKPEPTIEWFKDGEPVSTNEKKSHRVQFKDGALFF 115 QUERY : 373---ISSVRYEDTGAYTCIAKNEVG 393 + + +1 1 1 t+it 11 SBJCT : 116 YRTMQGKKEQDGGEYWCVAKNRVG 139 The amino acid sequence of the FCTR2 protein has 55 of 157 amino acid residues (35%) identical to, and 75 of 157 residues (47%) positive with a 620-775 amino acid fragment, 49 of 163 residues (30%) identical to and 71 of 163 residues (43%) positive with a

335-492 amino acid fragment, 32 of 85 amino acid residues (37%) identical to, and 48 of 85 amino acid residues (55%) positive with a 1305-1388 amino acid fragment, 37 of 143 amino acid residues (25%) identical to and 60 of 143 amino acid residues (41%) positive with a 183- 319 amino acid fragment, 43 of 174 amino acid residues (24%) and 70 of 174 amino acid residues (39%) positive with a 711-884 amino acid fragment, and 46 of 165 residues (27%) identical to and 69 of 165 residues positive with a 831-884 amino acid fragment all of the protein 1395 residue Down Syndrome Cell Adhesion Molecule Precursor (CHD2) from Homo Sapiens (GenBankAcc : 060469) (SEQ ID NO : 57) (Table 2N).

Table 2N. BLASTP of FCTR2 against Down Syndrome Cell Adhesion Molecule Precursor (SEQ ID NO : 57) >gil12643619lspl060469lDSCA HUMAN DOWN SYNDROME CELL ADHESION MOLECULE PRECURSOR (CHD2) GI|6740013lGBlAAF27525. 1lAF217525 1 (AF217525) DOWN SYNDROME CELL ADHESION MOLECULE [HOMO SAPIENS] LENGTH = 2012 SCORE = 70. 6 BITS (172), EXPECT = 6E-11 IDENTITIES = 55/157 (35%), POSITIVES = 75/157 (47%), GAPS = 7/157 (4%) QUERY : 245 VHGDLRPPIIWKRNGLTLNFLDLEDINDFGEDDSLYITKVTTIHMGNYTCHASGHEQLFQ 304 I 111 I 1+++1 + 1++ 11 1+ ++ +1 11111 1 + SBJCT : 620 VSGDLPITITWQKDGRPIPGSLGVTIDNIDFTSSLRISNLSLMHNGNYTCIARNEAAAVE 679 QUERY : 305 THV-LQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITW-LKNGVDVST----QM 358 I I 111 1 1 1 1 1 1 f 111 1+1 1 1 1 l + SBJCT : 680 HQSQLIVRVPPKFVVQPRDQDGIYGKAVILNCSAEGYPVPTIVWKFSKGAGVPQFQPIAL 739 QUERY : 359 SKQLSLLANGSELHISSVRYEDTGAYTCIAKNEVGVD 395 + ++ +1+111 1 1 1 11+1 1 1 1+11 1 SBJCT : 740 NGRIQVLSNGS-LLIKHWEEDSGYYLCKVSNDVGAD 775 SCORE = 50. 6 BITS (120), EXPECT = 7E-05 IDENTITIES = 49/163 (30%), POSITIVES = 71/163 (43%), GAPS = 16/163 (9%) QUERY : 243 CAVHGDLRPPIIWKRNGLTLNFLDLEDINDFGEDDSLYITKVTTIHMGNYTCHASGHEQL 302 1+1 1 + I 111 11 1 ++ I + + I I I + SBJCT : 335 CSVTGTEDQELSWYRNGEILNPGKNVRITGINHEN-LIMDHMVKSDGGAYQCFVRKDKLS 393 QUERY : 303 FQTH---VLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITW-------LKNGV 352 1 + U+) +) +) + i ! i i+ +i t+) i)) t i i SBJCT : 394 AQDYVQWLEDGTPKIISAFSE-ICWSPAEPVSLMCNVKGTPLPTITWTLDDDPILKGG-4 51 QUERY : 353 DVSTQMSKQLSLLAN-GSELHISSVRYEDTGAYTCIAKNEVGV 394 1 ++1+ ++ I 1 1+111 + I 1 1 1 1 1 11 SBJCT : 452--SHRISQMITSEGNWSYLNISSSQVRDGGVYRCTANNSAGV 492 SCORE = 47. 9 BITS (113), EXPECT = 5E-04 IDENTITIES = 32/85 (37%), POSITIVES = 48/85 (55%), GAPS = 6/85 (7%) QUERY : 333 LRCHAEGIPMPRITWLK--NGVDVSTQMSKQLSLLANGSELHISSVRYEDTGAYTCIAKN 390 t 1 I I I I + 1+1 11 + + 1+ +111 + I +I+ ll+l 1+111 1 SBJCT : 1305 LPCKAVGDPSPAVKWMKDSNGTPSLVTIDGRRSIFSNGSFI-IRTVKAEDSGYYSCIANN 1363 QUERY : 391 EVGVDEDISSLFIE---DSARKTLA 412 I I I I +I ++ I I I++ SBJCT : 1364 NWGSDEIILNLQVQVPPDQPRLTVS 1388 SCORE = 42. 9 BITS (100), EXPECT = 0. 015 IDENTITIES = 37/143 (25%), POSITIVES = 60/143 (41%), GAPS = 6/143 (4%)

QUERY : 270 INDFGEDDSLYITKVTTIHMGNYTCHASGHEQLFQTHVLQVNVPPVIRVYPESQAQEPGV 329 I 1 +)) t +)) + t)) + I I I + + SBJCT : 183 IKDVQNEDGLYNYRCITRHRYTGETRQSNSARLFVSD--PANSAPSILDGFDHRKAMAGQ 240 QUERY : 330 AASLRCHAEGIPMPRITWLKNGVDVSTQMSKQLSLLANGSELHISSVRYEDTGAYTCIAK 389 t I I I I I III+ ++ ++ + ++ I+I+I I SBJCT : 241 RVELPCKALGHPEPDYRWLKD--NMPLELSGRFQKTVTG--LLIENIRPSDSGSYVCEVS 296 QUERY : 390 NEVGVDEDISSLFIEDSARKTLA 412 I I + 1 1+++ + 1++ SBJCT : 297 NRYGTAKVIGRLYVKQPLKATIS 319 SCORE = 41. 3 BITS (96), EXPECT = 0. 047 IDENTITIES = 43/174 (24%), POSITIVES = 70/174 (39%), GAPS = 11/174 (6%) QUERY : 243 CAVHGDLRPPIIWK--RNGLTLNF--LDLEDINDFGEDDSLYITKVTTIHMGNYTCHASG 298 i+ t ! t+H +) + ! + N !) i) t ! SBJCT : 711 CSAEGYPVPTIVWKFSKGAGVPQFQPIALNGRIQVLSNGSLLIKHWEEDSGYYLCKVSN 770 QUERY : 299 H--EQLFQTHVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVDVST 356 + ++ I 1 +1 +1 11 + I + I I I + I I ++ SBJCT : 771 DVGADVSKSMYLTVKIPAMITSYPNTTLATQGQKKEMSCTAHGEKPIIVRWEKEDRIINP 830 QUERY : 357 QMSKQLSLLANGSELHISSVRY-----EDTGAYTCIAKNEVGVDEDISSLFIED 405 +1++ 1 1 il++- 11+1 ++1 1 1 1 1 1 1.. SBJCT : 831 EMARYLVSTKEVGEEVISTLQILPTVREDSGFFSCHAINSYGEDRGIIQLTVQE 884 SCORE = 40. 6 BITS (94), EXPECT = D. 074 IDENTITIES = 46/165 (27%), POSITIVES = 69/165 (40%), GAPS = 7/165 (4%) QUERY : 243 CAVHGDLRPPIIWKRNGLTLNFLDLEDINDFGEDDSLYITKVTT-IHMGNYTCHASGHEQ 301 I ! 1 t ! +1 1 ++ ! ++) +) ! !) + ! SBJCT : 525 CRVIGYPYYSIKWYKNSNLLPFNHRQVA--FENNGTLKLSDVQKEVDEGEYTCNVLVQPQ 582 QUERY : 302 LFQTHVLQVN--VPPVIRVYPESQAQEPGVAASLRCHAEGIPMP-RITWLKNGVDVSTQM 358 I + + I 111 1+ + I I + I +} 111 1+1 + + SBJCT : 583 LSTSQSVHVTVKVPPFIQPF-EFPRFSIGQRVFIPCWVSGDLPITITWQKDGRPIPGSL 641 QUERY : 359 SKQLSLLANGSELHISSVRYEDTGAYTCIAKNEVGVDEDISSLFI 403 + +)) i) ++ t) ! N ! +))) t i + SBJCT : 642 GVTIDNIDFTSSLRISNLSLMHNGNYTCIARNEARAVEHQSQLIV 686 The amino acid sequence of the FCTR2 protein has 55 of 194 amino acid residues (28%) identical to, and 86 of 194 residues (44%) positive with Limbic System-Associated Membrane Protein Precursor (LSAMP) from Homo sapiens (SWISSPROT Acc : Q13449) (SEQ ID NO : 58) (Table 20).

Table 20. BLASTP of FCTR2 against Limbic System-Associated Membrane Protein Precursor (SEQ ID NO : 58) PTNR : SWISSPROT-ACC : Q13449 LIMBIC SYSTEM-ASSOCIATED MEMBRANE PROTEIN PRECURSOR (LSAMP)-HOMO SAPIENS (HUMAN), 338 AA.

LENGTH = 338 SCORE = 191 (67. 2 BITS), EXPECT = 6. 7E-12, P = 6. 7E-12 IDENTITIES = 55/194 (28%), POSITIVES-86/194 (44%) The amino acid sequence of the FCTR2 protein has 68 of 190 amino acid residues (35%) identical to, and 92 of 190 residues (48%) positive with Putative Neuronal Cell

Adhesion Molecule, Short Form from Mus musculus (SPTREMBL Acc : 070246) (SEQ ID NO : 59) (Table 2P).

Table 2P. BLASTP of FCTR2 against Putative Neuronal Cell Adhesion Molecule, Short Form from Mus musculus (SEQ ID NO : 59) PTNR : SPTREMBL-ACC : 070246 PUTATIVE NEURONAL CELL ADHESION MOLECULE (PUNC) (PUTATIVE NEURONAL CELL ADHESION MOLECULE, SHORT FORM)-MUS MUSCULUS (MOUSE), 793 AA LENGTH = 793 SCORE = 203 (71. 5 BITS), EXPECT = 7. 0E-12, SUM P (2) = 7. 0E-12 IDENTITIES = 68/190 f35%), POSITIVES = 92/190 (48%) The amino acid sequence of the FCTR2 protein has 58 of 199 amino acid residues (29%) identical to, and 91 of 199 residues (45%) positive with CHLAMP, Gl l-Isoform Precursor from Gallus gallus (SPTREMBL Acc : 002869) (SEQ ID NO : 60) (Table 2Q).

Table 2Q. BLASTP of FCTR2 against CHLAMP, G114soform Precursor from Gallus gallus (SEQ ID N0 : 60) PTNR : SPTREMBL-ACC : 002869 CHLAMP, Gll-ISOFORM PRECURSOR-GALLUS GALLUS (CHICKEN), 350 AA.

LENGTH = 350 SCORE = 191 (67. 2 BITS), EXPECT = 7. 7E-12, P = 7. 7E-12 IDENTITIES = 58/199 (29%), POSITIVES = 91/199 (45%) The amino acid sequence of the FCTR2 protein has 55 of 194 amino acid residues (28%) identical to, and 86 of 194 residues (44%) positive with Limbic System-Associated Membrane Protein Precursor (LSAMP) fromRattus norvegicus (SWISSPROT Acc : Q62813) (SEQ ID N0 : 61) (Table 2R).

Table 2R. BLASTP of FCTR2 against Limbic System-Associated Membrane Protein Precursor (LSAMP) fromRattus norvegicus (SEQ ID NO : 61) PTNR : SWISSPROT-ACC : Q62813 LIMBIC SYSTEM-ASSOCIATED MEMBRANE PROTEIN PRECURSOR (LSAMP)-RATTUS NORVEGICUS (RAT), 338 AA.

LENGTH = 338 SCORE = 188 (66. 2 BITS), EXPECT = 1. 5E-11, P = 1. 5E-11 IDENTITIES = 55/194 (28%), POSITIVES = 86/194 (44%) FCTR2 protein has similarity to cell adhesion molecules, follistatin, roundabout and frazzled (see BlastP results). These genes are involved in neuronal development and reproductive physiology. Frazzled encodes a Drosophila member of the DCC immunoglobulin subfamily and is required for CNS and motor axon guidance (Cell 87 : 197- 204 (1996)). Characterization of a rat C6 glioma-secreted follistatin-related protein (FRP) and

cloning and sequence of the human homologue is described in Eur. J. Biochem. 225 : 937- 946 (1994). This protein may modulate the action of some growth factors on cell proliferation and differentiation. FRP binds heparin. The follistatin-related protein is a secreted protein and has one follistatin-like domain. The cloning and early dorsal axial expression of Flik, a chick follistatin-related gene and evidence for involvement in dorsalization/neural induction is presented in Dev. Biol. 178 : 327-342 (1996). Roundabout controls axon crossing of the CNS midline and defines a novel subfamily of evolutionarily conserved guidance receptors, as shown in Cell 92 : 205-215 (1998). cDNA cloning and structural analysis of the human limbic- system-associated membrane protein (LAMP) is described in Gene 170 : 189-195 (1996).

LAMP, a protein of the OBCAM family that contains three immunoglobulin-like C2-type domains, mediates selective neuronal growth and axon targeting. LAMP contributes to the guidance of developing axons and remodeling of mature circuits in the limbic system. This protein is essential for normal growth of the hippocampal mossy fiber projection. LAMP is attached to the membrane by a GPI-Anchor. It is expressed on limbic neurons and fiber tracts as well as in single layers of the superior colliculus, spinal chord and cerbellum.

Characterization of the human full-length PTK7 cDNA encoding a receptor protein tyrosine kinase-like molecule closely related to chick KLG is disclosed in J. Biochem. 119 : 235- 239 (1996). Based upon homology, FCTR2 proteins and each homologous protein or peptide may share at least some activity.

Functions and therapeutic uses : The OMIM gene map has identified this region which the invention maps to (Sq21- 5q31) as associated with susceptibility to the following diseases (OMIM Ids are underlined) : * Allergy and asthma * Hemangioma, * capillary infantile Schistosoma mansoni infection, susceptibility/resistance to Spinocerebellar ataxia * Bronchial asthma * Plasmodium falciparum parasitemia, * intensity of Corneal dystrophy, Groenouw type I, 121900 ; Corneal dystrophy, lattice type I, 122200 ; * Reis-Bucklers corneal dystrophy ; Corneal dystrophy, Avellino type Eosinophilia, familial Myelodysplastic syndrome ;

e Myelogenous leukemia, Acute Cutis laxa, recessive, type I, Deafness, autosomal dominant nonsyndromic sensorineural, 1 Contractural arachnodactyly, Congenital Neonatal alloimmune thrombocytopenia ; Glycoprotein la deficiency Male infertility ; * Charcot-Marie-Tooth neuropathy, Demyelinating Gardner syndrome ; * Adenomatous polyposis coli ; * Colorectal cancer ; Desmoid disease, hereditary, 135290 ; Turcot syndrome, 276300 ; * Adenomatous polyposis coli, attenuated Colorectal cancer Therefore the invention is implicated in at least all of the above mentioned diseases and may have therapeutic uses for these diseases.

This sequence has similarity to cell adhesion molecules, follistatin, roundabout and frazzled (see BlastP results). These genes are involved in neuronal development and reproductive physiology. Therefore the invention is also implicated in disorders such as or therapeutic uses for : * Neurodegenerative disorders, nerve trauma, epilepsy, mental health conditions * Tissue regeneration in vivo and in vitro Female reproductive system disorders and pregnancy FCTR3 FCTR3, is an amino acid type II membrane, neurestin-like protein. The FCTR3a nucleic acid of 1430 nucleotides (also designated 10129612. 0. 118) is shown in Table 3A. An ORF was identified beginning with an ATG initiation codon at nucleotides 69-71 and ending with a TAG codon at nucleotides 1212-1214. A putative untranslated region upstream from the initiation codon and downstream from the termination codon is underlined in Table 3A, and the start and stop codons are in bold letters.

Table 3A. FCTR3a Nucleotide Sequence (SEQ ID NO : 5) <BR> <BR> <BR> <BR> AAAAAAGGCGGGGGGTGGACTTAGCAGTGTAATTTGAGACCGGTGGTAAGGATTGGAGCG AGCTAGAGATGCTGCACGCTGCTA ACAAGGGAAGGAAGCCTTCAGCTGAGGCAGGTCGTCCCATTCCACCTACATCCTCGCCTA GTCTCCTCCCATCTGCTCAGCTGC <BR> <BR> CTAGCTCCCATAATCCTCCACCAGTTAGCTGCCAGATGCCATTGCTAGACAGCAACACCT CCCATCAAATCATGGACACCAACC CTGATGAGGAATTCTCCCCCAATTCATACCTGCTCAGAGCATGCTCAGGGCCCCAGCAAG CCTCCAGCAGTGGCCCTCCGAACC ACCACAGCCAGTCGACTCTGAGGCCCCCTCTCCCACCCCCTCACAACCACACGCTGTCCC ATCACCACTCGTCCGCCAACTCCC TCAACAGGAACTCACTGACCAATCGGCGGAGTCAGATCCACGCCCCGGCCCCAGCGCCCA ATGACCTGGCCACCACACCAGAGT CCGTTCAGCTTCAGGACAGCTGGGTGCTAAACAGCAACGTGCCACTGGAGACCCGGCACT TCCTCTTCAAGACCTCCTCGGGGA

GCACACCCTTGTTCAGCAGCTCTTCCCCGGGATACCCTTTGACCTCAGGAACGGTTTACA CGCCCCCGCCCCGCCTGCTGCCCA <BR> <BR> GGAATACTTTCTCCAGGAAGGCTTTCAAGCTGAAGAAGCCCTCCAAATACTGCAGCTGGA AATGTGCTGCCCTCTCCGCCATTG CCGCGGCCCTCCTCTTGGCTATTTTGCTGGCGTATTTCATAGTGCCCTGGTCGTTGAAAA ACAGCAGCATAGACAGTGGTGAAG <BR> <BR> CAGAAGTTGGTCGGCGGGTAACACAAGAAGTCCCACCAGGGGTGTTTTGGAGGTCACAAA TTCACATCAGTCAGCCCCAGTTCT<BR> <BR> <BR> <BR> TAAAGTTCAACATCTCCCTCGGGAAGGACGCTCTCTTTGGTGTTTACATAAGAAGAGGAC TTCCACCATCTCATGCCCAGTATG<BR> <BR> <BR> ACTTCATGGAACGTCTGGACGGGAAGGAGAAGTGGAGTGTGGTTGAGTCTCCCAGGGAAC GCCGGAGCATACAGACCTTGGTTC<BR> <BR> <BR> <BR> AGAATGAAGCCGTGTTTGTGCAGTACCTGGATGTGGGCCTGTGGCATCTGGCCTTCTACA ATGATGGAAAAGACAAAGAGATGG<BR> <BR> <BR> <BR> TTTCCTTCAATACTGTTGTCCTAGATGGGACCATCTAGTTGCAGAAAAACAAGCTCAGGG CGCCCACTGATTTGACATTATGAT TCAGTGCAGGACTGTCCACGTAACTGCCATGGGAATGGTGAATGTGTGTCCGGGGTGTGT CACTGTTTCCCAGGATTTCTAGGA CA CA The FCTR3 polypeptide (SEQ ID NO : 5) encoded by SEQ ID NO : 5 is 381 amino acid residues and is presented using the one-letter code in Table 3B.

Table 3B. Encoded FCTR3a protein sequence (SEQ ID NO : 6). <BR> <BR> <BR> <BR> <BR> <P>MLHAANKGRKPSAEAGRPIPPTSSPSLLPSAQLPSSHNPPPVSCQMPLLDS NTSHQIMDTNPDEEFSPNSYLLRACSGPQQASS<BR> <BR> <BR> <BR> SGPPNHHSQSTLRPPLPPPHNHTLSHHHSSANSLNRNSLTNRRSQIHAPAPAPNDLATTP ESVQLQbSWVLNSNVPLETRHFLF<BR> <BR> <BR> KTSSGSTPLFSSSSPGYPLTSGTVYTPPPRLLPRNTFSRKAFKLKKPSKYCSWKCAALSA IAAALLLAILLAYFIVPWSLKNSS<BR> <BR> <BR> <BR> IDSGEAEVGRRVTQEVPPGVFWRSQIHISQPQFLKFNISLGKDALFGVYIRRGLPPSHAQ YDFMERLDGKEKWSVVESPRERRS<BR> <BR> <BR> <BR> IQT LVQNEAVFVQYLDVGLWHLAFYNDGKDKEMVSFNTVVLDGTI In an alternative embodiment, the 5'end of the FCTR3a nucleic acid could be extended as it is in the 9826bp FCTR3b (also referred to herein as 10129612. 0. 405) shown in Table 3C. An ORF was identified beginning with an ATG initiation codon at nucleotides 280- 282 and ending with a TAA codon at nucleotides 8479-8481. A putative untranslated region upstream from the initiation codon and downstream from the termination codon is underlined in Table 3C, and the start and stop codons are in bold letters. Italicized bases 1-201 refer to a variable 5'region that will be further discussed below.

Table 3C. FCTR3b Nucleotide Sequence (SEQ ID NO : 7) TTTAAATCCTCATACCTTAAAGGAGATGTGTATATAAGGGAGTTGGAACCAGCATTAGAT GAGTTGACAAAAATGCAGTT <BR> <BR> TCAGTTCTAGAGGTCTGGGAAGTCCAAGAACAAGGTGCTGGCAGATTGGATTCCCCGTGA GGGCTTTCTTCCTGGCTTGA<BR> <BR> <BR> <BR> AGTTGGCTGCTTTCCTGCTGAGACTTCTCATGGCAGAGACFGAGGGTGGCAAAGTGACAA GTGCCAAAACTCAGGCCTGA<BR> <BR> <BR> <BR> CTTTTCTGAAAACATCAGCATTCTGCCATATCTGGAATAATGGATGTAAAGGACCGGCGA CACCGCTCTTTGACCAGAGG<BR> <BR> <BR> ACGCTGTGGCAAAGAGTGTCGCTACACAAGCTCCTCTCTGGACAGTGAGGACTGCCGGGT GCCCACACAGAAATCCTACA GCTCCAGTGAGACTCTGAAGGCCTATGACCATGACAGCAGGATGCACTATGGAAACCGAG TCACAGACCTCATCCACCGG GAGTCAGATGAGTTTCCTAGACAAGGAACCAACTTCACCCTTGCCGAACTGGGCATCTGT GAGCCCTCCCCACACCGAAG CGGCTACTGCTCCGACATGGGGATCCTTCACCAGGGCTACTCCCTTAGCACAGGGTCTGA CGCCGACTCCGACACCGAGG <BR> <BR> GAGGGATGTCTCCAGAACACGCCATCAGACTGTGGGGCAGAGGGATAAAATCCAGGCGCA GTTCCGGCCTGTCCAGTCGT<BR> <BR> <BR> GAAAACTCGGCCCTTACCCTGACTGACTCTGACAACGAAAACAAATCAGATGATGAGAAC GGTCGTCCCATTCCACCTAC ATCCTCGCCTAGTCTCCTCCCATCTGCTCAGCTGCCTAGCTCCCATAATCCTCCACCAGT TAGCTGCCAGATGCCATTGC TAGACAGCAACACCTCCCATCAAATCATGGACACCAACCCTGATGAGGAATTCTCCCCCA ATTCATACCTGCTCAGAGCA TGCTCAGGGCCCCAGCAAGCCTCCAGCAGTGGCCCTCCGAACCACCACAGCCAGTCGACT CTGAGGCCCCCTCTCCCACC CCCTCACAACCACACGCTGTCCCATCACCACTCGTCCGCCAACTCCCTCAACAGGAACTC ACTGACCAATCGGCGGAGTC AGATCCACGCCCCGGCCCCAGCGCCCAATGACCTGGCCACCACACCAGAGTCCGTTCAGC TTCAGGACAGCTGGGTGCTA AACAGCAACGTGCCACTGGAGACCCGGCACTTCCTCTTCAAGACCTCCTCGGGGAGCACA CCCTTGTTCAGCAGCTCTTC CCCGGGATACCCTTTGACCTCAGGAACGGTTTACACGCCCCCGCCCCGCCTGCTGCCCAG GAATACTTTCTCCAGGAAGG <BR> <BR> CTTTCAAGCTGAAGAAGCCCTCCAAATACTGCAGCTGGAAATGTGCTGCCCTCTCCGCCA TTGCCGCGGCCCTCCTCTTG<BR> <BR> <BR> <BR> GCTATTTTGCTGGCGTATTTCATAGTGCCCTGGTCGTTGAAAAACAGCAGCATAGACAGT GGTGAAGCAGAAGTTGGTCG<BR> <BR> <BR> GCGGGTAACACAAGAAGTCCCACCAGGGGTGTTTTGGAGGTCACAAATTCACATCAGTCA GCCCCAGTTCTTAAAGTTCA ACATCTCCCTCGGGAAGGACGCTCTCTTTGGTGTTTACATAAGAAGAGGACTTCCACCAT CTCATGCCCAGTATGACTTC ATGGAACGTCTGGACGGGAAGGAGAAGTGGAGTGTGGTTGAGTCTCCCAGGGAACGCCGG AGCATACAGACCTTGGTTCA <BR> <BR> GAATGAAGCCGTGTTTGTGCAGTACCTGGATGTGGGCCTGTGGCATCTGGCCTTCTACAA TGATGGAAAAGACAAAGAGA<BR> <BR> <BR> <BR> TGGTTTCCTTCAATACTGTTGTCCTAGATTCAGTGCAGGACTGTCCACGTAACTGCCATG GGAATGGTGAATGTGTGTCC<BR> <BR> <BR> <BR> GGGGTGTGTCACTGTTTCCCAGGATTTCTAGGAGCAGACTGTGCTAAAGCTGCCTGCCCT GTCCTGTGCAGTGGGAATGG<BR> <BR> <BR> <BR> ACAATATTCTAAAGGGACGTGCCAGTGCTACAGCGGCTGGAAAGGTGCAGAGTGCGACGT GCCCATGAATCAGTGCATCG

ATCCTTCCTGCGGGGGCCACGGCTCCTGCATTGATGGGAACTGTGTCTGCTCTGCTGGCT ACAAAGGCGAGCACTGTGAG GAAGTTGATTGCTTGGATCCCACCTGCTCCAGCCACGGAGTCTGTGTGAATGGAGAATGC CTGTGCAGCCCTGGCTGGGG TGGTCTGAACTGTGAGCTGGCGAGGGTCCAGTGCCCAGACCAGTGCAGTGGGCATGGCAC GTACCTGCCTGACACGGGCC TCTGCAGCTGCGATCCCAACTGGATGGGTCCCGACTGCTCTGTTGAAGTGTGCTCAGTAG ACTGTGGCACTCACGGCGTC TGCATCGGGGGAGCCTGCCGCTGTGAAGAGGGCTGGACAGGCGCAGCGTGTGACCAGCGC GTGTGCCACCCCCGCTGCAT TGAGCACGGGACCTGTAAAGATGGCAAATGTGAATGCCGAGAGGGCTGGAATGGTGAACA CTGCACCATTGGTAGGCAAA CGGCAGGCACCGAAACAGATGGCTGCCCTGACTTGTGCAACGGTAACGGGAGATGCACAC TGGGTCAGAACAGCTGGCAG TGTGTCTGCCAGACCGGCTGGAGAGGGCCCGGATGCAACGTTGCCATGGAAACTTCCTGT GCTGATAACAAGGATAATGA GGGAGATGGCCTGGTGGATTGTTTGGACCCTGACTGCTGCCTGCAGTCAGCCTGTCAGAA CAGCCTGCTCTGCCGGGGGT CCCGGGACCCACTGGACATCATTCAGCAGGGCCAGACGGATTGGCCCGCAGTGAAGTCCT TCTATGACCGTATCAAGCTC TTGGCAGGCAAGGATAGCACCCACATCATTCCTGGAGAGAACCCTTTCAACAGCAGCTTG GTTTCTCTCATCCGAGGCCA AGTAGTAACTACAGATGGAACTCCCCTGGTCGGTGTGAACGTGTCTTTTGTCAAGTACCC AAAATACGGCTACACCATCA CCCGCCAGGATGGCACGTTCGACCTGATCGCAAATGGAGGTGCTTCCTTGACTCTACACT TTGAGCGAGCCCCGTTCATG AGCCAGGAGCGCACTGTGTGGCTGCCGTGGAACAGCTTTTACGCCATGGACACCCTGGTG ATGAAGACCGAGGAGAACTC CATCCCCAGCTGTGACCTCAGTGGCTTTGTCCGGCCTGATCCAATCATCATCTCCTCCCC ACTGTCCACCTTCTTTAGTG <BR> <BR> <BR> CTGCCCCTGGGCAGAATCCCATCGTGCCTGAGACCCAGGTTCTTCATGAAGAAATCGAGC TCCCTGGTTCCAATGTGAAA CTTCGCTATCTGAGCTCTAGAACTGCAGGGTACAAGTCACTGCTGAAGATCACCATGACC CAGTCCACAGTGCCCCTGAA CCTCATTAGGGTTCACCTGATGGTGGCTGTCGAGGGGCATCTCTTCCAGAAGTCATTCCA GGCTTCTCCCAACCTGGCCT CCACCTTCATCTGGGACAAGACAGATGCGTATGGCCAAAGGGTGTATGGACTCTCAGATG CTGTTGTGTCTGTCGGGTTT <BR> <BR> <BR> GAATATGAGACCTGTCCCAGTCTAATTCTCTGGGAGAAAAGGACAGCCCTCCTTCAGGGA TTCGAGCTGGACCCCTCCAA<BR> <BR> <BR> <BR> <BR> CCTCGGTGGCTGGTCCCTAGACAAACACCACATCCTCAATGTTAAAAGTGGAATCCTACA CAAAGGCACTGGGGAAAACC AGTTCCTGACCCAGCAGCCTGCCATCATCACCAGCATCATGGGCAATGGTCGCCGCCGGA GCATTTCCTGTCCCAGCTGC AACGGCCTTGCTGAAGGCAACAAGCTGCTGGCCCCAGTGGCTCTGGCTGTTGGAATCGAT GGGAGCCTCTATGTGGGTGA <BR> <BR> <BR> CTTCAATTACATCCGACGCATCTTTCCCTCTCGAAATGTGACCAGCATCTTGGAGTTACG AAATAAAGAGTTTAAACATA GCAACAACCCAGCACACAAGTACTACTTGGCAGTGGACCCCGTGTCCGGCTCGCTCTACG TGTCCGACACCAACAGCAGG AGAATCTACCGCGTCAAGTCTCTGAGTGGAACCAAAGACCTGGCTGGGAATTCGGAAGTT GTGGCAGGGACGGGAGAGCA GTGTCTACCCTTTGATGAAGCCCGCTGCGGGGATGGAGGGAAGGCCATAGATGCAACCCT GATGAGCCCGAGAGGTATTG CAGTAGACAAGAATGGGCTCATGTACTTTGTCGATGCCACCATGATCCGGAAGGTTGACC AGAATGGAATCATCTCCACC <BR> <BR> CTGCTGGGCTCCAATGACCTCACTGCCGTCCGGCCGCTGAGCTGTGATTCCAGCATGGAT GTAGCCCAGGTTCGTCTGGA GTGGCCAACAGACCTTGCTGTCAATCCCATGGATAACTCCTTGTATGTTCTAGAGAACAA TGTCATCCTTCGAATCACCG AGAACCACCAAGTCAGCATCATTGCGGGACGCCCCATGCACTGCCAAGTTCCTGGCATTG ACTACTCACTCAGCAAACTA GCCATTCACTCTGCCCTGGAGTCAGCCAGTGCCATTGCCATTTCTCACACTGGGGTCCTC TACATCACTGAGACAGATGA GAAGAAGATTAACCGTCTACGCCAGGTAACAACCAACGGGGAGATCTGCCTTTTAGCTGG GGCAGCCTCGGACTGCGACT GCAAAAACGATGTCAATTGCAACTGCTATTCAGGAGATGATGCCTACGCGACTGATGCCA TCTTGAATTCCCCATCATCC TTAGCTGTAGCTCCAGATGGTACCATTTACATTGCAGACCTTGGAAATATTCGGATCAGG GCGGTCAGCAAGAACAAGCC TGTTCTTAATGCCTTCAACCAGTATGAGGCTGCATCCCCCGGAGAGCAGGAGTTATATGT TTTCAACGCTGATGGCATCC ACCAATACACTGTGAGCCTGGTGACAGGGGAGTACTTGTACAATTTCACATATAGTACTG ACAATGATGTCACTGAATTG ATTGACAATAATGGGAATTCCCTGAAGATCCGTCGGGACAGCAGTGGCATGCCCCGTCAC CTGCTCATGCCTGACAACCA <BR> <BR> GATCATCACCCTCACCGTGGGCACCAATGGAGGCCTCAAAGTCGTGTCCACACAGAACCT GGAGCTTGGTCTCATGACCT ATGATGGCAACACTGGGCTCCTGGCCACCAAGAGCGATGAAACAGGATGGACGACTTTCT ATGACTATGACCACGAAGGC <BR> <BR> CGCCTGACCAACGTGACGCGCCCCACGGGGGTGGTAACCAGTCTGCACCGGGAAATGGAG AAATCTATTACCATTGACAT<BR> <BR> <BR> <BR> <BR> TGAGAACTCCAACCGTGATGATGACGTCACTGTCATCACCAACCTCTCTTCAGTAGAGGC CTCCTACACAGTGGTACAAG<BR> <BR> <BR> <BR> ATCAAGTTCGGAACAGCTACCAGCTCTGTAATAATGGTACCCTGAGGGTGATGTATGCTA ATGGGATGGGTATCAGCTTC CACAGCGAGCCCCATGTCCTAGCGGGCACCATCACCCCCACCATTGGACGCTGCAACATC TCCCTGCCTATGGAGAATGG CTTAAACTCCATTGAGTGGCGCCTAAGAAAGGAACAGATTAAAGGCAAAGTCACCATCTT TGGCAGGAAGCTCCGGGTCC ATGGAAGAAATCTCTTGTCCATTGACTATGATCGAAATATTCGGACTGAAAAGATCTATG ATGACCACCGGAAGTTCACC CTGAGGATCATTTATGACCAGGTGGGCCGCCCCTTCCTCTGGCTGCCCAGCAGCGGGCTG GCAGCTGTCAACGTGTCATA <BR> <BR> <BR> CTTCTTCAATGGGCGCCTGGCTGGGCTTCAGCGTGGGGCCATGAGCGAGAGGACAGACAT CGACAAGCAAGGCCGCATCG TGTCCCGCATGTTCGCTGACGGGAAAGTGTGGAGCTACTCCTACCTTGACAAGTCCATGG TCCTCCTGCTTCAGAGCCAA <BR> <BR> CGTCAGTATATATTTGAGTATGACTCCTCTGACCGCCTCCTTGCCGTCACCATGCCCAGC GTGGCCCGGCACAGCATGTC<BR> <BR> <BR> <BR> CACACACACCTCCATCGGCTACATCCGTAATATTTACAACCCGCCTGAAAGCAATGCTTC GGTCATCTTTGACTACAGTG ATGACGGCCGCATCCTGAAGACCTCCTTTTTGGGCACCGGACGCCAGGTGTTCTACAAGT ATGGGAAACTCTCCAAGTTA <BR> <BR> TCAGAGATTGTCTACGACAGTACCGCCGTCACCTTCGGGTATGACGAGACCACTGGTGTC TTGAAGATGGTCAACCTCCA AAGTGGGGGCTTCTCCTGCACCATCAGGTACCGGAAGATTGGCCCCCTGGTGGACAAGCA GATCTACAGGTTCTCCGAGG AAGGCATGGTCAATGCCAGGTTTGACTACACCTATCATGACAACAGCTTCCGCATCGCAA GCATCAAGCCCGTCATAAGT GAGACTCCCCTCCCCGTTGACCTCTACCGCTATGATGAGATTTCTGGCAAGGTGGAACAC TTTGGTAAGTTTGGAGTCAT CTATTATGACATCAACCAGATCATCACCACTGCCGTGATGACCCTCAGCAAACACTTCGA CACCCATGGGCGGATCAAGG AGGTCCAGTATGAGATGTTCCGGTCCCTCATGTACTGGATGACGGTGCAATATGACAGCA TGGGCAGGGTGATCAAGAGG GAGCTAAAACTGGGGCCCTATGCCAATACCACGAAGTACACCTATGACTACGATGGGGAC GGGCAGCTCCAGAGCGTGGC CGTCAATGACCGCCCGACCTGGCGCTACAGCTATGACCTTAATGGGAATCTCCACTTACT GAACCCAGGCAACAGTGTGC <BR> <BR> <BR> GCCTCATGCCCTTGCGCTATGACCTCCGGGATCGGATAACCAGACTCGGGGATGTGCAGT ACAAAATTGACGACGATGGC TATCTGTGCCAGAGAGGGTCTGACATCTTCGAATACAATTCCAAGGGCCTCCTAACAAGA GCCTACAACAAGGCCAGCGG GTGGAGTGTCCAGTACCGCTATGATGGCGTAGGACGGCGGGCTTCCTACAAGACCAACCT GGGCCACCACCTGCAGTACT TCTACTCTGACCTCCACAACCCGACGCGCATCACCCATGTCTACAATCACTCCAACTCGG AGATTACCTCACTGTACTAC <BR> <BR> GACCTCCAGGGCCACCTCTTTGCCATGGAGAGCAGCAGTGGGGAGGAGTACTATGTTGCC TCTGATAACACAGGGACTCC TCTGGCTGTGTTCAGCATCAACGGCCTCATGATCAAACAGCTGCAGTACACGGCCTATGG GGAGATTTATTATGACTCCA ACCCCGACTTCCAGATGGTCATTGGCTTCCATGGGGGACTCTATGACCCCCTGACCAAGC TGGTCCACTTCACTCAGCGT GATTATGATGTGCTGGCAGGACGATGGACCTCCCCAGACTATACCATGTGGAAAAACGTG GGCAAGGAGCCGGCCCCCTT TAACCTGTATATGTTCAAGAGCAACAATCCTCTCAGCAGTGAGCTAGATTTGAAGAACTA CGTGACAGATGTGAAAAGCT GGCTTGTGATGTTTGGATTTCAGCTTAGCAACATCATTCCTGGCTTCCCGAGAGCCAAAA TGTATTTCGTGCCTCCTCCC

TATGAATTGTCAGAGAGTCAAGCAAGTGAGAATGGACAGCTCATTACAGGTGTCCAACAG ACAACAGAGAGACATAACCA GGCCTTCATGGCTCTGGAAGGACAGGTCATTACTAAAAAGCTCCACGCCAGCATCCGAGA GAAAGCAGGTCACTGGTTTG CCACCACCACGCCCATCATTGGCAAAGGCATCATGTTTGCCATCAAAGAAGGGCGGGTGA CCACGGGCGTGTCCAGCATC GCCAGCGAAGATAGCCGCAAGGTGGCATCTGTGCTGAACAACGCCTACTACCTGGACAAG ATGCACTACAGCATCGAGGG CAAGGACACCCACTACTTTGTGAAGATTGGCTCAGCCGATGGCGACCTGGTCACACTAGG CACCACCATCGGCCGCAAGG TGCTAGAGAGCGGGGTGAACGTGACCGTGTCCCAGCCCACGCTGCTGGTCAACGGCAGGA CTCGAAGGTTCACGAACATT GAGTTCCAGTACTCCACGCTGCTGCTCAGCATCCGCTATGGCCTCACCCCCGACACCCTG GACGAAGAGAAGGCCCGCGT CCTGGACCAGGCGAGACAGAGGGCCCTGGGCACGGCCTGGGCCAAGGAGCAGCAGAAAGC CAGGGACGGGAGAGAGGGGA GCCGCCTGTGGACTGAGGGCGAGAAGCAGCAGCTTCTGAGCACCGGGCGCGTGCAAGGGT ACGAGGGATATTACGTGCTT <BR> <BR> CCCGTGGAGCAATACCCAGAGCTTGCAGACAGTAGCAGCAACATCCAGTTTTTAAGACAG AATGAGATGGGAAAGAGGTA<BR> <BR> <BR> <BR> <BR> ACAAAATAATCTGCTGCCATTCCTTGTCTGAATGGCTCAGCAGGAGTAACTGTTATCTCC TCTCCTAAGGAGATGAAGAC CTAACAGGGGCACTGCGGCTGGGCTGCTTTAGGAGACCAAGTGGCAAGAAAGCTCACATT TTTTGAGTTCAAATGCTACT <BR> <BR> GTCCAAGCGAGAAGTCCCTCATCCTGAAGTAGACTAAAGCCCGGCTGAAAATTCCGAGGA AAACAAAACAAACGAATGAA<BR> <BR> <BR> <BR> <BR> TGAACAGACACACACAATGTTCCAAGTTCCCCTAAAATATGACCCACTTGTTCTGGGTCT ACGCAGAAAAGAGACGCAAA<BR> <BR> <BR> <BR> GTGTCCAAAAGGAACAAAAGAACAAAAACGAATAAGCAAAGAAGAAAACAAACAAAAACA AAACAAAACAAACACACGGA CCGATAAACAAAGAAGCGAAGATAAGAAAGAAGGCCTCATATCCAATTACCTCACTCATT CACATGTGAGCGACACGCAG <BR> <BR> ACATCCGCGAGGGCCAGCGTCACCAGACCAGCTGCGGGACAAACCACTCAGACTGCTTGT AGGACAAATACTTCTGACAT<BR> <BR> <BR> <BR> <BR> TTTCGTTTAAGCAAATACAGGTGCATTTAAAACACGACTTTGGGGGTGATTTGTGTGTAG CGCCTGGGGAGGGGGGATAA<BR> <BR> <BR> <BR> AAGAGGAGGAGTGAGCACTGGAAATACTTTTTAAAGAAAAAAAAACATGAGGGAATAAAA GAAATTCCTATCAAAAATCA<BR> <BR> <BR> <BR> <BR> AAGTGAAATAATACCATCCAGCACTTAACTCTCAGGTCCCAACTAAGTCTGGCCTGAGCT AATTTATTTGAGCGCAGAGT GTAAAATTTAATTCAAAATGGTGGCTATAATCACTACAGATAAATTTCATACTCTTTTGT CTTTGGAGATTCCATTGTGG ACAGTAATACGCAGTTACAGGGTGTAGTCTGTTTAGATTCCGTAGTTCGTGGGTATCAGT TTCGGTAGAGGTGCAGCATC GTGACACTTTTGCTAACAGGTACCACTTCTGATCACCCTGTACATACATGAGCCGAAAGG CACAATCACTGTTTCAGATT TAAAATTATTAGTGTGTTTGTTTGGTCCAGAAACTGAGACAATCACATGACAGTCACCAC GAGGAGAGAAAATTTAAAAA <BR> <BR> ATAAAAATAAAAACAAAAAAAATTTTAAAAATTAAAA1AACAAAAATAAAGTCTAATAAG AACTTTGGTACAGGAACTTT<BR> <BR> <BR> <BR> <BR> TTTGTAATATACATGTATGAATTGTTCATCGAGTTTTTATATTAATTTTAATTTGCTGCT AAGCAAAGACTAGGGACAGG<BR> <BR> <BR> <BR> CAAAGATAATTTATGGCAAAGTGTTTAAATTGTTTATACATAAATAAAGTCTCTAAAACT CCTGTG The FCTR3b polypeptide (SEQ It) NO : 8) encoded by SEQ ID NO : 7 is 2733 amino acid residues and is presented using the one-letter code in Table 3D. The protein has a predicted molecular weight of 303424. 3 daltons.

Table 3D. Encoded FCTR3b protein sequence (SEQ ID NO : 8). <BR> <BR> <BR> <BR> <BR> <P>MDVKDRRHRSLTRGRCGKECRYTSSSLDSEDCRVPTQKSYSSSETLKAYDH DSRMHYGNRVTDLIHRESDEFPRQGTNFTLAEL GICEPSPHRSGYCSDMGILHQGYSLSTGSDADSDTEGGMSPEHAAIRLWGRGIKSRRSSG LSSRENSALTLTDSDNENKSDDENG RPIPPTSSPSLLPSAQLPSSHNPPPVSCQMPLLDSNTSHQIMDTNPDEEFSPNSYLLRAC SGPQQASSSGPPNHHSQSTLRPPL <BR> <BR> PPPHNHTLSHHHSSANSLNRNSLTNRRSQIHAPAPAPNDLATTPESVQLQDSWVLNSNVP LETRHFLFKTSSGSTPLFSSSSPG<BR> <BR> <BR> <BR> YPLTSGTVYTPPPRLLPRNTFSRKAFKLKKPSKYCSWKCAALSAIAAALLLAILLAYFIV PWSLKNSSIDSGEAEVGRRVTQEV<BR> <BR> <BR> <BR> <BR> PPGVFWRSQIHISQPQFLKFNISLGKDALFGVYIRRGLPPSHAQYDFMERLDGKEKWSVV ESPRERRSIQTLVQNEAVFVQYLD<BR> <BR> <BR> <BR> VGLWHLAFYNDGKDKEMVSFNTWLDSVQDCPRNCHGNGECVSGVCHCFPGFLGADCAKAA CPVLCSGNGQYSKGTCQCYSGWK<BR> <BR> <BR> <BR> <BR> GAECDVPMNQCIDPSCGGHGSCIDGNCVCSAGYKGEHCEEVDCLDPTCSSHGVCVNGECL CSPGWGGLNCELARVQCPDQCSGH<BR> <BR> <BR> <BR> GTYLPDTGLCSCDPNWMGPDCSVEVCSVDCGTHGVCIGGACRCEEGWTGAACDQRVCHPR CIEHGTCKDGKCECREGWNGEHCT<BR> <BR> <BR> <BR> <BR> IGRQTAGTETDGCPDLCNGNGRCTLGQNSWQCVCQTGWRGPGCNVAMETSCADNKDNEGD GLVDCLDPDCCLQSACQNSLLCRG<BR> <BR> <BR> <BR> SRDPLDIIQQGQTDWPAVKSFYDRIKLLAGKDSTHIIPGENPFNSSLVSLIRGQWTTDGT PLVGVNVSFVKYPKYGYTITRQD<BR> <BR> <BR> <BR> <BR> GTFDLIANGGASLTLHFERAPFMSQERTVWLPWNSFYAMDTLVMKTEENSIPSCDLSGFV RPDPIIISSPLSTFFSAAPGQNPI<BR> <BR> <BR> <BR> VPETQVLHEEIELPGSNVKLRYLSSRTAGYKSLLKITMTQSTVPLNLIRVHLMVAVEGHL FQKSFQASPNLASTFIWDKTDAYG<BR> <BR> <BR> <BR> <BR> QRVYGLSDAVVSVGFEYETCPSLILWEKRTALLQGFELDPSNLGGWSLDKHHILNVKSGI LHKGTGENQFLTQQPAIITSIMGN<BR> <BR> <BR> <BR> GRRRSISCPSCNGLAEGNKLLAPVALAVGIDGSLYVGDFNYIRRIFPSRNVTSILELRNK EFKHSNNPAHKYYLAVDPVSGSLY<BR> <BR> <BR> <BR> <BR> VSDTNSRRIYRVKSLSGTKDLAGNSEVVAGTGEQCLPFDEARCGDGGKAIDATLMSPRGI AVDKNGLMYFVDATMIRKVDQNGI<BR> <BR> <BR> <BR> ISTLLGSNDLTAVRPLSCDSSMDVAQVRLEWPTDLAVNPMDNSLYVLENNVILRITENHQ VSIIAGRPMHCQVPGIDYSLSKLA<BR> <BR> <BR> <BR> <BR> IHSALESASAIAISHTGVLYITETDEKKINRLRQVTTNGEICLLAGAASDCDCKNDVNCN CYSGDDAYATDAILNSPSSLAVAP<BR> <BR> <BR> <BR> DGTIYIADLGNIRIRAVSKNKPVLNAFNQYEAASPGEQELYVFNADGIHQYTVSLVTGEY LYNFTYSTDNDVTELIDNNGNSLK<BR> <BR> <BR> <BR> <BR> IRRDSSGMPRHLLMPDNQIITLTVGTNGGLKVVSTQNLELGLMTYDGNTGLLATKSDETG WTTFYDYDHEGRLTNVTRPTGVVT<BR> <BR> <BR> <BR> SLHREMEKSITIDIENSNRDDDVTVITNLSSVEASYTVVQDQVRNSYQLCNNGTLRVMYA NGMGISFHSEPHVLAGTITPTIGR<BR> <BR> <BR> <BR> <BR> CNISLPMENGLNSIEWRLRKEQIKGKVTIFGRKLRVHGRNLLSIDYDRNIRTEKIYDDHR KFTLRIIYDQVGRPFLWLPSSGLA<BR> <BR> <BR> <BR> <BR> AVNVSYFFNGRLAGLQRGAMSERTDIDKQGRIVSRMFADGKVWSYSYLDKSMVLLLQSQR QYIFEYDSSDRLLAVTMPSVARHS<BR> <BR> <BR> <BR> MSTHTSIGYIRNIYNPPESNASVIFDYSDDGRILKTSFLGTGRQVFYKYGKLSKLSEIVY DSTAVTFGYDETTGVLKMVNLQSG<BR> <BR> <BR> <BR> <BR> GFSCTIRYRKIGPLVDKQIYRFSEEGMVNARFDYTYHDNSFRIASIKPVISETPLPVDLY RYDEISGKVEHFGKFGVIYYDINQ<BR> <BR> <BR> <BR> IITTAVMTLSKHFDTHGRIKEVQYEMFRSLMYWMTVQYDSMGRVIKRELKLGPYANTTKY TYDYDGDGQLQSVAVNDRPTWRYS<BR> <BR> <BR> <BR> <BR> YDLNGNLHLLNPGNSVRLMPLRYDLRDRITRLGDVQYKIDDDGYLCQRGSDIFEYNSKGL LTRAYNKASGWSVQYRYDGVGRRA<BR> <BR> <BR> <BR> SYKTNLGHHLQYFYSDLHNPTRITHVYNHSNSEITSLYYDLQGHLFAMESSSGEEYYVAS DNTGTPLAVFSINGLMIKQLQYTA YGEIYYDSNPDFQMVIGFHGGLYDPLTKLVHFTQRDYDVLAGRWTSPDYTMWKNVGKEPA PFNLYMFKSNNPLSSELDLKNYVT DVKSWLVMFGFQLSNIIPGFPRAKMYFVPPPYELSESQASENGQLITGVQQTTERHNQAF MALEGQVITKKLHASIREKAGHWF ATTTPIIGAGIMFAIKEGRVTTGVSSIASEDSRKVASVLNNAYYLDKMHYSIEGKDTHYF VKIGSADGDLVTLGTTIGRKVLES

GVNVTVSQPTLLVNGRTRRFTNIEFQYSTLLLSIRYGLTPDTLDEEKARVLDQARQRALG TAWAKEQQKARDGREGSRLWTEGE<BR> <BR> <BR> KQQLLSTGRVQGYEGYYVLPVEQYPELADSSSNIQFLRQNEMGKR In further alternative embodiments the italicized bases in the 5'end of the FCTR3b sequence in table 3C is a variable region. This region can be substituted for in other embodiments of FCTR3. The nucleotide sequence for 9823bp FCTR3c (also referred to herein as 10129612. 0. 154) has the same nucleotide sequence as FCTR3b except that the italicized region is replaced with the 201 base sequence shown in Table 3E. An ORF for the total FCTR3c nucleotide sequence was identified beginning with an ATG initiation codon at nucleotides 277-280 and ending with a TAG codon at nucleotides 8473-8475. This is the same open reading frame that is shown in Table 3C, with the corresponding base numbers for FCTR3c. This open reading frame will translate the same amino acid sequence as shown in Table 3C for FCTR3b.

Table 3E. Encoded FCTR3c 5'end nucleotide sequence (SEQ ID NO : 9).

GCTCCAAAGCGAGCTGGGACCGAAGACTCTAGGCTAAGTTATCTATGTAGATGGTGTCAG GGAGCGAAGCTACTGACCGA <BR> <BR> GCTGCTGTTACATCCAGCTTTTTAATTGCCTAAGCGGTCTGGGGCTTGCTTCGTCATTTG GCTTTGCTGTGGAGCACTCC<BR> <BR> TGTAAAGCCAGCTGAATTGTACATCGAAGATCCACCCTTTT In yet another embodiment, the italicized region shown in the 5'end of the sequence in Table 3C can be replaced with the sequence shown in Table 3F to form 9823bp FCTR3d (also referred to herein as 10129612. 0. 67). An ORF was identified beginning with an ATG initiation codon at nucleotides 277-280 and ending with a TAG codon at nucleotides 8473- 8475. This is the same open reading frame that is shown in Table 3C, with the corresponding base numbers for FCTR3d. This open reading frame will translate the same amino acid sequence as shown in Table 3D for FCTR3b.

Table 3F. Encoded FCTR3d 5'end nucleotide sequence (SEQ ID NO : 10).

GCTCCAAAGCGAGCTGGGACCGAAGACTCTAGGCTAAGTTATCTATGTAGATGGTGTCAG GGAGCGAAGCTACTGACCGA GCTGCTGTTACATCCAGCTTTTTAATTGCCTAAGCGGTCTGGGGCTTGCTTCGTCATTTG GCTTTGCTGTGGAGCACTCC TGTAAAGCCAGCTGAATTGTACATCGAAGATCCACCCTTTT In yet another embodiment, the italicized region shown in the 5'end of the sequence in Table 3C can be replaced with the sequence shown in Table 3G to form 9765 bp FCTR3e (also referred to as 10129612. 0. 258). An ORF was identified beginning with an ATG initiation codon at nucleotides 210-212 and ending with a TAG codon at nucleotides 8408-8410. This is the same open reading frame that is shown in Table 3C, with the corresponding base numbers for FCTR3e. This open reading frame will translate the same amino acid sequence as shown in Table 3D for FCTR3b.

Table 3G. Encoded FCTR3e 5'end nucleotide sequence (SEQ ID NO : 11). <BR> <BR> <BR> <BR> <BR> <P>CCAGCATTAGATGAGTTGACAAAAATGCAGTTTCAGCTCTGAAGGTCTGAA AGATTCTGCTGCAACTAAAGCTCTGAAGA<BR> <BR> <BR> TTCTGCTACAACTATGACATCCATTTTCTCCCACTTCAGACAGGATGAATACAA In yet another embodiment another FCTR3a homolog, FCTR3f (also referred to as 10129612. 0. 352) was found having the 9729bp sequence shown in Table 3H. An ORF was identified beginning with an ATG initiation codon at nucleotides 210-212 and ending with a TAG codon at nucleotides 8382-8384. A putative untranslated region upstream from the initiation codon and downstream from the termination codon is underlined in Table 3G, and the start and stop codons are in bold letters.

Table 3H. Encoded FCTR3f nucleotide sequence (SEQ ID NO : 12). <BR> <BR> <BR> <BR> <BR> <P>CCAGCATTAGATGAGTTGACAAAAATGCAGTTTCAGCTCTGAAGGTCTGAA AGATTCTGCTGCAACTAAAGCTCTGAAGA<BR> <BR> <BR> TTCTGCTACAACTATGACATCCATTTTCTCCCACTTCAGACAGGATGAATACAAGGTGGC AAAGTGACAAGTGCCAAAAC TCAGGCCTGACTTTCCTGAAAACATCAGCATTCTGCCATATCTGGAATAATGGATGTAAA GGACCGGCGACACCGCTCTT <BR> <BR> TGACCAGAGGACGCTGTGGCAAAGAGTGTCGCTACACAAGCTCCTCTCTGGACAGTGAGG ACTGCCGGGTGCCCACACAG<BR> <BR> <BR> <BR> AAATCCTACAGCTCCAGTGAGACTCTGAAGGCCTATGACCATGACAGCAGGATGCACTAT GGAAACCGAGTCACAGACCT<BR> <BR> <BR> <BR> CATCCACCGGGAGTCAGATGAGTTTCCTAGACAAGGAACCAACTTCACCCTTGCCGAACT GGGCATCTGTGAGCCCTCCC CACACCGAAGCGGCTACTGCTCCGACATGGGGATCCTTCACCAGGGCTACTCCCTTAGCA CAGGGTCTGACGCCGACTCC <BR> <BR> GACACCGAGGGAGGGATGTCTCCAGAACACGCCATCAGACTGTGGGGCAGAGGGATAAAA TCCAGGCGCAGTTCCGGCCT GTCCAGTCGTGAAAACTCGGCCCTTACCCTGACTGACTCTGACAACGAAAACAAATCAGA TGATGAGAACGGTCGTCCCA <BR> <BR> TTCCACCTACATCCTCGCCTAGTCTCCTCCCATCTGCTCAGCTGCCTAGCTCCCATAATC CTCCACCAGTTAGCTGCCAG ATGCCATTGCTAGACAGCAACACCTCCCATCAAATCATGGACACCAACCCTGATGAGGAA TTCTCCCCCAATTCATACCT GCTCAGAGCATGCTCAGGGCCCCAGCAAGCCTCCAGCAGTGGCCCTCCGAACCACCACAG CCAGTCGACTCTGAGGCCCC <BR> <BR> CTCTCCCACCCCCTCACAACCACACGCTGTCCCATCACCACTCGTCCGCCAACTCCCTCA ACAGGAACTCACTGACCAAT CGGCGGAGTCAGATCCACGCCCCGGCCCCAGCGCCCAATGACCTGGCCACCACACCAGAG TCCGTTCAGCTTCAGGACAG CTGGGTGCTAAACAGCAACGTGCCACTGGAGACCCGGCACTTCCTCTTCAAGACCTCCTC GGGGAGCACACCCTTGTTCA <BR> <BR> GCAGCTCTTCCCCGGGATACCCTTTGACCTCAGGAACGGTTTACACGCCCCCGCCCCGCC TGCTGCCCAGGAATACTTTC<BR> <BR> <BR> TCCAGGAAGGCTTTCAAGCTGAAGAAGCCCTCCAAATACTGCAGCTGGAAATGTGCTGCC CTCTCCGCCATTGCCGCGGC CCTCCTCTTGGCTATTTTGCTGGCGTATTTCATAGTGCCCTGGTCGTTGAAAAACAGCAG CATAGACAGTGGTGAAGCAG AAGTTGGTCGGCGGGTAACACAAGAAGTCCCACCAGGGGTGTTTTGGAGGTCACAAATTC ACATCAGTCAGCCCCAGTTC TTAAAGTTCAACATCTCCCTCGGGAAGGACGCTCTCTTTGGTGTTTACATAAGAAGAGGA CTTCCACCATCTCATGCCCA GTATGACTTCATGGAACGTCTGGACGGGAAGGAGAAGTGGAGTGTGGTTGAGTCTCCCAG GGAACGCCGGAGCATACAGA CCTTGGTTCAGAATGAAGCCGTGTTTGTGCAGTACCTGGATGTGGGCCTGTGGCATCTGG CCTTCTACAATGATGGAAAA <BR> <BR> GACAAAGAGATGGTTTCCTTCAATACTGTTGTCCTAGATTCAGTGCAGGACTGTCCACGT AACTGCCATGGGAATGGTGA ATGTGTGTCCGGGGTGTGTCACTGTTTCCCAGGATTTCTAGGAGCAGACTGTGCTAAAGC TGCCTGCCCTGTCCTGTGCA GTGGGAATGGACAATATTCTAAAGGGACGTGCCAGTGCTACAGCGGCTGGAAAGGTGCAG AGTGCGACGTGCCCATGAAT <BR> <BR> CAGTGCATCGATCCTTCCTGCGGGGGCCACGGCTCCTGCATTGATGGGAACTGTGTCTGC TCTGCTGGCTACAAAGGCGA<BR> <BR> <BR> <BR> GCACTGTGAGGAAGTTGATTGCTTGGATCCCACCTGCTCCAGCCACGGAGTCTGTGTGAA TGGAGAATGCCTGTGCAGCC<BR> <BR> <BR> <BR> CTGGCTGGGGTGGTCTGAACTGTGAGCTGGCGAGGGTCCAGTGCCCAGACCAGTGCAGTG GGCATGGCACGTACCTGCCT GACACGGGCCTCTGCAGCTGCGATCCCAACTGGATGGGTCCCGACTGCTCTGTTGAAGTG TGCTCAGTAGACTGTGGCAC TCACGGCGTCTGCATCGGGGGAGCCTGCCGCTGTGAAGAGGGCTGGACAGGCGCAGCGTG TGACCAGCGCGTGTGCCACC CCCGCTGCATTGAGCATGGGACCTGTAAAGATGGCAAATGTGAATGCCGAGAGGGCTGGA ATGGTGAACACTGCACCATT GATGGCTGCCCTGACTTGTGCAACGGTAACGGGAGATGCACACTGGGTCAGAACAGCTGG CAGTGTGTCTGCCAGACCGG <BR> <BR> CTGGAGAGGGCCCGGATGCAACGTTGCCATGGAAACTTCCTGTGCTGATAACAAGGATAA TGAGGGAGATGGCCTGGTGG ATTGTTTGGACCCTGACTGCTGCCTGCAGTCAGCCTGTCAGAACAGCCTGCTCTGCCGGG GGTCCCGGGACCCACTGGAC <BR> <BR> ATCATTCAGCAGGGCCAGACGGATTGGCCCGCAGTGAAGTCCTTCTATGACCGTATCAAG CTCTTGGCAGGCAAGGATAG CACCCACATCATTCCTGGAGAGAACCCTTTCAACAGCAGCTTGGTTTCTCTCATCCGAGG CCAAGTAGTAACTACAGATG GAACTCCCCTGGTCGGTGTGAACGTGTCTTTTGTCAAGTACCCAAAATACGGCTACACCA TCACCCGCCAGGATGGCACG TTCGACCTGATCGCAAATGGAGGTGCTTCCTTGACTCTACACTTTGAGCGAGCCCCGTTC ATGAGCCAGGAGCGCACTGT GTGGCTGCCGTGGAACAGCTTTTACGCCATGGACACCCTGGTGATGAAGACCGAGGAGAA CTCCATCCCCAGCTGTGACC TCAGTGGCTTTGTCCGGCCTGATCCAATCATCATCTCCTCCCCACTGTCCACCTTCTTTA GTGCTGCCCCTGGGCAGAAT CCCATCGTGCCTGAGACCCAGGTTCTTCATGAAGAAATCGAGCTCCCTGGTTCCAATGTG AAACTTCGCTATCTGAGCTC TAGAACTGCAGGGTACAAGTCACTGCTGAAGATCACCATGACCCAGTCCACAGTGCCCCT GAACCTCATTAGGGTTCACC TGATGGTGGCTGTCGAGGGGCATCTCTTCCAGAAGTCATTCCAGGCTTCTCCCAACCTGG CCTCCACCTTCATCTGGGAC <BR> <BR> AAGACAGATGCGTATGGCCAAAGGGTGTATGGACTCTCAGATGCTGTTGTGTCTGTCGGG TTTGAATATGAGACCTGTCC CAGTCTAATTCTCTGGGAGAAAAGGACAGCCCTCCTTCAGGGATTCGAGCTGGACCCCTC CAACCTCGGTGGCTGGTCCC <BR> <BR> <BR> TAGACAAACACCACATCCTCAATGTTARAAGTGGAATCCTACACAAAGGCACTGGGGAAA ACCAGTTCCTGACCCAGCAG CCTGCCATCATCACCAGCATCATGGGCAATGGTCGCCGCCGGAGCATTTCCTGTCCCAGC TGCAACGGCCTTGCTGAAGG CAACAAGCTGCTGGCCCCAGTGGCTCTGGCTGTTGGAATCGATGGGAGCCTCTATGTGGG TGACTTCAATTACATCCGAC <BR> <BR> <BR> GCATCTTTCCCTCTCGAAATGTGACCAGCATCTTGGAGTTACGAAATAAAGAGTTTAAAC ATAGCAACAACCCAGCACAC

AAGTACTACTTGGCAGTGGACCCCGTGTCCGGCTCGCTCTACGTGTCCGACACCAACAGC AGGAGAATCTACCGCGTCAA <BR> <BR> <BR> GTCTCTGAGTGGAACCAAAGACCTGGCTGGGAATTCGGAAGTTGTGGCAGGGACGGGAGA GCAGTGTCTACCCTTTGATG AAGCCCGCTGCGGGGATGGAGGGAAGGCCATAGATGCAACCCTGATGAGCCCGAGAGGTA TTGCAGTAGACAAGAATGGG <BR> <BR> <BR> CTCATGTACTTTGTCGATGCCACCATGATCCGGAAGGTTGACCAGAATGGAATCATCTCC ACCCTGCTGGGCTCCAATGA CCTCACTGCCGTCCGGCCGCTGAGCTGTGATTCCAGCATGGATGTAGCCCAGGTTCGTCT GGAGTGGCCAACAGACCTTG CTGTCAATCCCATGGATAACTCCTTGTATGTTCTAGAGAACAATGTCATCCTTCGAATCA CCGAGAACCACCAAGTCAGC ATCATTGCGGGACGCCCCATGCACTGCCAAGTTCCTGGCATTGACTACTCACTCAGCAAA CTAGCCATTCACTCTGCCCT GGAGTCAGCCAGTGCCATTGCCATTTCTCACACTGGGGTCCTCTACATCACTGAGACAGA TGAGAAGAAGATTAACCGTC TACGCCAGGTAACAACCAACGGGGAGATCTGCCTTTTAGCTGGGGCAGCCTCGGACTGCG ACTGCAAAAACGATGTCAAT <BR> <BR> <BR> TGCAACTGCTATTCAGGAGATGATGCCTACGCGACTGATGCCATCTTGAATTCCCCATCA TCCTTAGCTGTAGCTCCAGA TGGTACCATTTACATTGCAGACCTTGGAAATATTCGGATCAGGGCGGTCAGCAAGAACAA GCCTGTTCTTAATGCCTTCA ACCAGTATGAGGCTGCATCCCCCGGAGAGCAGGAGTTATATGTTTTCAACGCTGATGGCA TCCACCAATACACTGTGAGC CTGGTGACAGGGGAGTACTTGTACAATTTCACATATAGTACTGACAATGATGTCACTGAA TTGATTGACAATAATGGGAA TTCCCTGAAGATCCGTCGGGACAGCAGTGGCATGCCCCGTCACCTGCTCATGCCTGACAA CCAGATCATCACCCTCACCG TGGGCACCAATGGAGGCCTCAAAGTCGTGTCCACACAGAACCTGGAGCTTGGTCTCATGA CCTATGATGGCAACACTGGG CTCCTGGCCACCAAGAGCGATGAAACAGGATGGACGACTTTCTATGACTATGACCACGAA GGCCGCCTGACCAACGTGAC <BR> <BR> <BR> GCGCCCCACGGGGGTGGTAACCAGTCTGCACCGGGAAATGGAGAAATCTATTACCATTGA CATTGAGAACTCCAACCGTG ATGATGACGTCACTGTCATCACCAACCTCTCTTCAGTAGAGGCCTCCTACACAGTGGTAC AAGATCAAGTTCGGAACAGC <BR> <BR> <BR> TACCAGCTCTGTAATAATGGTACCCTGAGGGTGATGTATGCTAATGGGATGGGTATCAGC TTCCACAGCGAGCCCCATGT<BR> <BR> <BR> <BR> <BR> CCTAGCGGGCACCATCACCCCCACCATTGGACGCTGCAACATCTCCCTGCCTATGGAGAA TGGCTTAAACTCCATTGAGT GGCGCCTAAGAAAGGAACAGATTAAAGGCAAAGTCACCATCTTTGGCAGGAAGCTCCGGG TCCATGGAAGAAATCTCTTG <BR> <BR> <BR> TCCATTGACTATGATCGAAATATTCGGACTGAAAAGATCTATGATGACCACCGGAAGTTC ACCCTGAGGATCATTTATGA CCAGGTGGGCCGCCCCTTCCTCTGGCTGCCCAGCAGCGGGCTGGCAGCTGTCAACGTGTC ATACTTCTTCAATGGGCGCC <BR> <BR> <BR> TGGCTGGGCTTCAGCGTGGGGCCATGAGCGAGAGGACAGACATCGACAAGCAAGGCCGCA TCGTGTCCCGCATGTTCGCT<BR> <BR> <BR> <BR> <BR> GACGGGAAAGTGTGGAGCTACTCCTACCTTGACAAGTCCATGGTCCTCCTGCTTCAGAGC CAACGTCAGTATATATTTGA GTATGACTCCTCTGACCGCCTCCTTGCCGTCACCATGCCCAGCGTGGCCCGGCACAGCAT GTCCACACACACCTCCATCG GCTACATCCGTAATATTTACAACCCGCCTGAAAGCAATGCTTCGGTCATCTTTGACTACA GTGATGACGGCCGCATCCTG AAGACCTCCTTTTTGGGCACCGGACGCCAGGTGTTCTACAAGTATGGGAAACTCTCCAAG TTATCAGAGATTGTCTACGA <BR> <BR> <BR> CAGTACCGCCGTCACCTTCGGGTATGACGAGACCACTGGTGTCTTGAAGATGGTCAACCT CCAAAGTGGGGGCTTCTCCT GCACCATCAGGTACCGGAAGATTGGCCCCCTGGTGGACAAGCAGATCTACAGGTTCTCCG AGGAAGGCATGGTCAATGCC AGGTTTGACTACACCTATCATGACAACAGCTTCCGCATCGCAAGCATCAAGCCCGTCATA AGTGAGACTCCCCTCCCCGT <BR> <BR> <BR> TGACCTCTACCGCTATGATGAGATTTCTGGCAAGGTGGAACACTTTGGTAAGTTTGGAGT CATCTATTATGACATCAACC AGATCATCACCACTGCCGTGATGACCCTCAGCAAACACTTCGACACCCATGGGCGGATCA AGGAGGTCCAGTATGAGATG TTCCGGTCCCTCATGTACTGGATGACGGTGCAATATGACAGCATGGGCAGGGTGATCAAG AGGGAGCTAAAACTGGGGCC <BR> <BR> <BR> CTATGCCAATACCACGAAGTACACCTATGACTACGATGGGGACGGGCAGCTCCAGAGCGT GGCCGTCAATGACCGCCCGA CCTGGCGCTACAGCTATGACCTTAATGGGAATCTCCACTTACTGAACCCAGGCAACAGTG TGCGCCTCATGCCCTTGCGC TATGACCTCCGGGATCGGATAACCAGACTCGGGGATGTGCAGTACAAAATTGACGACGAT GGCTATCTGTGCCAGAGAGG <BR> <BR> <BR> GTCTGACATCTTCGAATACAATTCCAAGGGCCTCCTAACAAGAGCCTACAACAAGGCCAG CGGGTGGAGTGTCCAGTACC<BR> <BR> <BR> <BR> <BR> GCTATGATGGCGTAGGACGGCGGGCTTCCTACAAGACCAACCTGGGCCACCACCTGCAGT ACTTCTACTCTGACCTCCAC AACCCGACGCGCATCACCCATGTCTACAATCACTCCAACTCGGAGATTACCTCACTGTAC TACGACCTCCAGGGCCACCT CTTTGCCATGGAGAGCAGCAGTGGGGAGGAGTACTATGTTGCCTCTGATAACACAGGGAC TCCTCTGGCTGTGTTCAGCA TCAACGGCCTCATGATCAAACAGCTGCAGTACACGGCCTATGGGGAGATTTATTATGACT CCAACCCCGACTTCCAGATG GTCATTGGCTTCCATGGGGGACTCTATGACCCCCTGACCAAGCTGGTCCACTTCACTCAG CGTGATTATGATGTGCTGGC AGGACGATGGACCTCCCCAGACTATACCATGTGGAAAAACGTGGGCAAGGAGCCGGCCCC CTTTAACCTGTATATGTTCA AGAGCAACAATCCTCTCAGCAGTGAGCTAGATTTGAAGAACTACGTGACAGATGTGAAAA GCTGGCTTGTGATGTTTGGA TTTCAGCTTAGCAACATCATTCCTGGCTTCCCGAGAGCCAAAATGTATTTCGTGCCTCCT CCCTATGAATTGTCAGAGAG TCAAGCAAGTGAGAATGGACAGCTCATTACAGGTGTCCAACAGACAACAGAGAGACATAA CCAGGCCTTCATGGCTCTGG AAGGACAGGTCATTACTAAAAAGCTCCACGCCAGCATCCGAGAGAAAGCAGGTCACTGGT TTGCCACCACCACGCCCATC ATTGGCAAAGGCATCATGTTTGCCATCAAAGAAGGGCGGGTGACCACGGGCGTGTCCAGC ATCGCCAGCGAAGATAGCCG CAAGGTGGCATCTGTGCTGAACAACGCCTACTACCTGGACAAGATGCACTACAGCATCGA GGGCAAGGACACCCACTACT TTGTGAAGATTGGCTCAGCCGATGGCGACCTGGTCACACTAGGCACCACCATCGGCCGCA AGGTGCTAGAGAGCGGGGTG AACGTGACCGTGTCCCAGCCCACGCTGCTGGTCAACGGCAGGACTCGAAGGTTCACGAAC ATTGAGTTCCAGTACTCCAC GCTGCTGCTCAGCATCCGCTATGGCCTCACCCCCGACACCCTGGACGAAGAGAAGGCCCG CGTCCTGGACCAGGCGAGAC AGAGGGCCCTGGGCACGGCCTGGGCCAAGGAGCAGCAGAAAGCCAGGGACGGGAGAGAGG GGAGCCGCCTGTGGACTGAG GGCGAGAAGCAGCAGCTTCTGAGCACCGGGCGCGTGCAAGGGTACGAGGGATATTACGTG CTTCCCGTGGAGCAATACCC AGAGCTTGCAGACAGTAGCAGCAACATCCAGTTTTTAAGACAGAATGAGATGGGAAAGAG GTAACAAAATAATCTGCTGC CATTCCTTGTCTGAATGGCTCAGCAGGAGTAACTGTTATCTCCTCTCCTAAGGAGATGAA GACCTAACAGGGGCACTGCG <BR> <BR> GCTGGGCTGCTTTAGGAGACCAAGTGGCAAGAAAGCTCACATTTTTTGAGTTCAAATGCT ACTGTCCAAGCGAGAAGTCC<BR> <BR> <BR> <BR> <BR> CTCATCCTGAAGTAGACTAAAGCCCGGCTGAAAATTCCGAGGAAAACAAAACAhACGAAT GAATGAACAGACACACACAA TGTTCCAAGTTCCCCTAAAATATGACCCACTTGTTCTGGGTCTACGCAGAAAAGAGACGC AAAGTGTCCAAAAGGAACAA AAGAACAAAAACGAATAAGCAAAGAAGAAAACAAACAAAAACAAAACAAAACAAACACAC GGACCGATAAACAAAGAAGC <BR> <BR> GAAGATAAGAAAGAAGGCCTCATATCCAATTACCTCACTCATTCACATGTGAGCGACACG CAGACATCCGCGAGGGCCAG<BR> <BR> <BR> <BR> <BR> CGTCACCAGACCAGCTGCGGGACAALACCACTCAGACTGCTTGTAGGACAAATACTTCTG ACATTTTCGTTTAAGCAAATA<BR> <BR> <BR> <BR> <BR> CAGGTGCATTTAAAACACGACTTTGGGGGTGATTTGTGTGTAGCGCCTGGGGAGGGGGGA TAAAAGAGGAGGAGTGAGCA<BR> <BR> <BR> <BR> <BR> CTGGAAATACTTTTTAAAGAAAUU CATGAGGGAATAAAAGAAATTCCTATCAAAAATCAAAGTGAAATAATACCAT<BR&g t; <BR> <BR> <BR> <BR> CCAGCACTTAACTCTCAGGTCCCAACTAAGTCTGGCCTGAGCTAATTTATTTGAGCGCAG AGTGTAAAATTTAATTCAAA ATGGTGGCTATAATCACTACAGATAAATTTCATACTCTTTTGTCTTTGGAGATTCCATTG TGGACAGTAATACGCAGTTA CAGGGTGTAGTCTGTTTAGATTCCGTAGTTCGTGGGTATCAGTTTCGGTAGAGGTGCAGC ATCGTGACACTTTTGCTAAC <BR> <BR> AGGTACCACTTCTGATCACCCTGTACATACATGAGCCGAAAGGCACAATCACTGTTTCAG ATTTAAAATTATTAGTGTGT<BR> <BR> <BR> <BR> TTGTTTGGTCCAGAAACTGAGACAATCACATGACAGTCACCACGAGGAGAGAAAATTTAA AAAATAAAAATAAAAACAAA

AAAAATTTTAAAAATTAAAAAAACAAAAATAnAGTCTAATAAGAACTTTGGTACAGGAAC TTTTTTGTAATATACATGTA<BR> <BR> <BR> <BR> TGAATTGTTCATCGAGTTTTTATATTAATTTTAATTTGCTGCTAAGCAAAGACTAGGGAC AGGCAAAGATAATTTATGGC<BR> <BR> <BR> AAAGTGTTTAAATTGTTTATACATASATAAKGTCTCTAAAACTCCTGTG The FCTR3f polypeptide (SEQ ID NO : 13) encoded by SEQ ID NO : 12 is 2724 amino acid residues long and is presented using the one-letter code in Table 3I. This sequence differs from FCTR3b in that it is missing amino acids 758-766 from that polypeptide.

Table 3I. Encoded FCTR3f protein sequence (SEQ ID NO : 13) <BR> <BR> <BR> <BR> MDVKDRRHRSLTRGRCGKECRYTSSSLDSEDCRVPTQKSYSSSETLKAYDHDSRMHYGNR VTDLIHRESDEFPRQGTNFTLAEL GICEPSPHRSGYCSDMGILHQGYSLSTGSDADSDTEGGMSPEHAIRLWGRGIKSRRSSGL SSRENSALTLTDSDNENKSDDENG <BR> <BR> RPIPPTSSPSLLPSAQLPSSHNPPPVSCQMPLLDSNTSHQIMDTNPDEEFSPNSYLLRAC SGPQQASSSGPPNHHSQSTLRPPL<BR> <BR> <BR> <BR> PPPHNHTLSHHHSSANSLNRNSLTNRRSQIHAPAPAPNDLATTPESVQLQDSWVLNSNVP LETRHFLFKTSSGSTPLFSSSSPG<BR> <BR> <BR> YPLTSGTVYTPPPRLLPRNTFSRKAFKLKKPSKYCSWKCAALSAIAAALLLAILLAYFIV PWSLKNSSIDSGEAEVGRRVTQEV<BR> <BR> <BR> <BR> PPGVFWRSQIHISQPQFLKFNISLGKDALFGVYIRRGLPPSHAQYDFMERLDGKEKWSWE SPRERRSIQTLVQNEAVFVQYLD<BR> <BR> <BR> VGLWHLAFYNDGKDKEMVSFNTWLDSVQDCPRNCHGNGECVSGVCHCFPGFLGADCAKAA CPVLCSGNGQYSKGTCQCYSGWK<BR> <BR> <BR> GAECDVPMNQCIDPSCGGHGSCIDGNCVCSAGYKGEHCEEVDCLDPTCSSHGVCVNGECL CSPGWGGLNCELARVQCPDQCSGH<BR> <BR> <BR> <BR> GTYLPDTGLCSCDPNWMGPDCSVEVCSVDCGTHGVCIGGACRCEEGWTGAACDQRVCHPR CIEHGTCKDGKCECREGWNGEHCT<BR> <BR> <BR> IDGCPDLCNGNGRCTLGQNSWQCVCQTGWRGPGCNVAMETSCADNKDNEGDGLVDCLDPD CCLQSACQNSLLCRGSRDPLDIIQ<BR> <BR> <BR> <BR> QGQTDWPAVKSFYDRIKLLAGKDSTHIIPGENPFNSSLVSLIRGQVVTTDGTPLVGVNVS FVKYPKYGYTITRQDGTFDLIANG<BR> <BR> <BR> GASLTLEFERAPFMSQERTVWLPWNSFYAMDTLVMKTEENSIPSCDLSGFVRPDPIIISS PLSTFFSAAPGQNPIVPETQVLHE<BR> <BR> <BR> EIELPGSNVKLRYLSSRTAGYKSLLKITMTQSTVPLNLIRVHLMVAVEGHLFQICSFQAS PNLASTFIWDKTDAYGQRVYGLSDA<BR> <BR> <BR> <BR> VVSVGFEYETCPSLILWEKRTALLQGFELDPSNLGGWSLDKHHILNVKSGILHKGTGENQ FLTQQPAIITSIMGNGRRRSISCP<BR> <BR> <BR> SCNGLAEGNKLLAPVALAVGIDGSLYVGDFNYIRRIFPSRNVTSILELRNKEFKHSNNPA RKYYLAVDPVSGSLYVSDTNSRRI<BR> <BR> <BR> <BR> YRVKSLSGTKDLAGNSEVVAGTGEQCLPFDEARCGDGGKAIDATLMSPRGIAVDKNGLMY FVDATMIRKVDQNGIISTLLGSND<BR> <BR> <BR> LTAVRPLSCDSSMDVAQVRLEWPTDLAVNPMDNSLYVLENNVILRITENHQVSIIAGRPM HCQVPGIDYSLSKLAIHSALESAS<BR> <BR> <BR> AIAISHTGVLYITETDEKKINRLRQVTTNGEICLLAGAASDCDCKNDVNCNCYSGDDAYA TDAILNSPSSLAVAPDGTIYIADL<BR> <BR> <BR> <BR> GNIRIRAVSKNKPVLNAFNQYEAASPGEQELYVFNADGIHQYTVSLVTGEYLYNFTYSTD NDVTELIDNNGNSLKIRRDSSGMP<BR> <BR> <BR> RHLLMPDNQIITLTVGTNGGLKVVSTQNLELGLMTYDGNTGLLATKSDETGWTTFYDYDH EGRLTNVTRPTGVVTSLHREMEKS<BR> <BR> <BR> ITIDIENSNRDDDVTVITNLSSVEASYTWQDQVRNSYQLCNNGTLRVMYANGMGISFHSE PHVLAGTITPTIGRCHISLPMEN<BR> <BR> <BR> <BR> GLNSIEWRLRKEQIKGKVTIFGRKLRVHGRNLLSIDYDRNIRTEKIYDDHRKFTLRIIYD QVGRPFLWLPSSGLAAVNVSYFFN<BR> <BR> <BR> GRLAGLQRGAMSERTDIDKQGRIVSRMFADGKVWSYSYLDKSMVLLLQSQRQYIFEYDSS DRLLAVTMPSVARHSMSTHTSIGY<BR> <BR> <BR> <BR> IRNIYNPPESNASVIFDYSDDGRILKTSFLGTGRQVFYKYGKLSKLSEIVYDSTAVTFGY DETTGVLKMVNLQSGGFSCTIRYR<BR> <BR> <BR> KIGPLVDKQIYRFSEEGMVNARFDYTYHDNSFRIASIKPVISETPLPVDLYRYDEISGKV EHFGKFGVIYYDINQIITTAVMTL SKHFDTHGRIKEVQYEMFRSLMYWMTVQYDSMGRVIKRELKLGPYANTTKYTYDYDGDGQ LQSVAVNDRPTWRYSYDLNGNLHL LNPGNSVRLMPLRYDLRDRITRLGDVQYKIDDDGYLCQRGSDIFEYNSKGLLTRAYNKAS GWSVQYRYDGVGRRASYKTNLGHH <BR> <BR> LQYFYSDLHNPTRITHVYNHSNSEITSLYYDLQGHLFAMESSSGEEYYVASDNTGTPLAV FSINGLMIKQLQYTAYGEIYYDSN<BR> <BR> <BR> <BR> PDFQMVIGFHGGLYDPLTKLVHFTQRDYDVLAGRWTSPDYTMWKNVGKEPAPFNLYMFKS NNPLSSELDLKNYVTDVKSWLVMF<BR> <BR> <BR> GFQLSNIIPGFPRAKMYFVPPPYELSESQASENGQLITGVQQTTERHNQAFMALEGQVIT KKLHASIREKAGHWFATTTPIIGK<BR> <BR> <BR> GIMFAIKEGRVTTGVSSIASEDSRKVASVLNNAYYLDKMHYSIEGKDTHYFVKIGSADGD LVTLGTTIGRKVLESGVNVTVSQP TLLVNGRTRRFTNIEFQYSTLLLSIRYGLTPDTLDEEKARVLDQARQRALGTAWAKEQQK ARDGREGSRLWTEGEKQQLLSTGR VQGYEGYYVLPVEQYPELADSSSNIQFLRQNEMGKR In a BLASTN search it was found that the FCTR3a nucleic acid has homology to three fragments of Mus musculus odd Oz/ten-m homolog 2. It has 634 of 685 bases (92%) identical to bases 614-1298, 365 of 406 bases (89%) identical to bases 1420-1825, and 93 of 103 bases (90%) identical to bases 1823-1925 of Mus musculus odd Oz/ten-m homolog 2 (GenBank Acc : NM011856. 2) (Table 3J).

Table 3J. BLASTN of FCTR3a againstMus znusculus odd Oz/ten-m homolog 2 (SEQ ID NO : 62) >GII7657414IREFINM 011856. 2| MUS MUSCULUS ODD OZ/TEN-M HOMOLOG 2 (DROSOPHILA) (ODZ2), MRNA LENGTH = 8797 SCORE = 954 BITS (481), EXPECT = 0. 0 IDENTITIES = 634/685 (92%)

STRAND = PLUS/PLUS QUERY : 114 GGTCGTCCCATTCCACCTACATCCTCGCCTAGTCTCCTCCCATCTGCTCAGCTGCCTAGC 173 IIIIIIII (IIIIIIIIIIIIIIII III IIIIIIIIIIIIIIIIIIfIIIlllll SBJCT : 614 GGTCGTCCCATTCCACCTACATCCTCGTCTAGCCTCCTCCCATCTGCTCAGCTGCCTAGC 673 mm m m mm mm m mm m m m m m m m mm QUERY : 174 TCCCATAATCCTCCACCAGTTAGCTGCCAGATGCCATTGCTAGACAGCAACACCTCCCAT 233 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII SBJCT : 674 TCCCATAATCCTCCACCAGTTAGCTGCCAGATGCCATTGCTAGACAGCAACACCTCCCAT 733 QUERY : 234 CAAATCATGGACACCAACCCTGATGAGGAATTCTCCCCCAATTCATACCTGCTCAGAGCA 293 II 111111111111111111111111111111111111111111111111111111111 SBJCT : 734 CAGATCATGGACACCAACCCTGATGAGGAATTCTCCCCCAATTCATACCTGCTCAGAGCA 793 QUERY : 294 TGCTCAGGGCCCCAGCAAGCCTCCAGCAGTGGCCCTCCGAACCACCACAGCCAGTCGACT 353 11111111111111111111111111111111111111 11111111111111111 11 SBJCT : 794 TGCTCAGGGCCCCAGCAAGCCTCCAGCAGTGGCCCTCCAAACCACCACAGCCAGTCAACA 853 QUERY : 354 CTGAGGCCCCCTCTCCCACCCCCTCACAACCACACGCTGTCCCATCACCACTCGTCCGCC 413 I SBJCT : 854 CTGAGGCCCCCTCTGCCACCCCCTCATAACCACACCCTGTCCCACCACCACTCCTCGGCC 913 QUERY : 414 AACTCCCTCAACAGGAACTCACTGACCAATCGGCGGAGTCAGATCCACGCCCCGGCCCCA 473 11111111111111111111111111111111111111111 11111111111 11 11 SBJCT : 914 AACTCCCTCAACAGGAACTCACTGACCAATCGGCGGAGTCAAATCCACGCCCCAGCTCCT 973 QUERY : 474 GCGCCCAATGACCTGGCCACCACACCAGAGTCCGTTCAGCTTCAGGACAGCTGGGTGCTA 533 11111111 11111111111111 11111111 11111111 11111 11111111111 SBJCT : 974 GCGCCCAACGACCTGGCCACCACCCCAGAGTCTGTTCAGCTCCAGGATAGCTGGGTGCTG 1033 SBJCT : 974 GCGCCCAACGACCTGGCCACCACCCCAGAGTCTGTTCAGCTCCAGGATAGCTGGGTGCTG 1033 QUERY : 534 AACAGCAACGTGCCACTGGAGACCCGGCACTTCCTCTTCAAGACCTCCTCGGGGAGCACA 593 l SBJCT : 1034 AACAGTAACGTCCCACTGGAGACTCGGCACTTCCTTTTCAAAACGTCGTCTGGAAGCACA 1093 QUERY : 594 CCCTTGTTCAGCAGCTCTTCCCCGGGATACCCTTTGACCTCAGGAACGGTTTACACGCCC 653 III IIIIIlllllll IIIIIIIIIIIIIIIIIIIIIII II IIIII II II SBJCT : 1094 CCCCTGTTCAGCAGCTCTTCTCCGGGATACCCTTTGACCTCAGGGACCGTTTATACACCA 1153 QUERY : 654 CCGCCCCGCCTGCTGCCCAGGAATACTTTCTCCAGGAAGGCTTTCAAGCTGAAGAAGCCC 713 IIIIII SBJCT : 1154 CCACCCCGCCTGCTGCCACGGAATACATTCTCCAGGAAGGCCTTCAAGCTGAAGAAACCC 1213 QUERY : 714 TCCAAATACTGCAGCTGGAAATGTGCTGCCCTCTCCGCCATTGCCGCGGCCCTCCTCTTG 773 Illlllllllllll IIIIIIIIIIIIIIIII II Illll IIIII Illlllllllll SBJCT : 1214 TCCAAATACTGCAGTTGGAAATGTGCTGCCCTGTCTGCCATCGCCGCCGCCCTCCTCTTG 1273 QUERY : 774 GCTATTTTGCTGGCGTATTTCATAG 798 n) m m m) m ! mm SBJCT : 1274 GCCATTTTGCTGGCATATTTCATAG 1298 SCORE = 480 BITS (242), EXPECT = E-132 IDENTITIES = 365/406 (89%) STRAND = PLUS/PLUS QUERY : 797 AGTGCCCTGGTCGTTGAAAAACAGCAGCATAGACAGTGGTGAAGCAGAAGTTGGTCGGCG 856 1111k1111111 111|1111111111111111111111 11111111111111111111 SBJCT : 1420 AGTGCCCTGGTCATTGAAAAACAGCAGCATAGACAGTGGCGAAGCAGAAGTTGGTCGGCG 1479 QUERY : 857 GGTAACACAAGAAGTCCCACCAGGGGTGTTTTGGAGGTCACAAATTCACATCAGTCAGCC 916 111 11111 11111111111111111111111111111 11 11111111111111111 SBJCT : 1480 GGTGACACAGGAAGTCCCACCAGGGGTGTTTTGGAGGTCCCAGATTCACATCAGTCAGCC 1539 QUERY : 917 CCAGTTCTTAAAGTTCAACATCTCCCTCGGGAAGGACGCTCTCTTTGGTGTTTACATAAG 976 II 11111111111111111111111 11 11111 11 11111 11111 11 11111 SBJCT : 1540 TCAATTCTTAAAGTTCAACATCTCCCTGGGCAAGGATGCCCTCTTCGGTGTCTATATAAG 1599 QUERY : 977 AAGAGGACTTCCACCATCTCATGCCCAGTATGACTTCATGGAACGTCTGGACGGGAAGGA 1036 Illlllli IIIII lllllllllllllllllllllllllllll IIIII ll IIIII SBJCT : 1600 GAGAGGACTACCACCGTCTCATGCCCAGTATGACTTCATGGAACGCCTGGATGGAAAGGA 1659

QUERY : 1037 GAAGTGGAGTGTGGTTGAGTCTCCCAGGGAACGCCGGAGCATACAGACCTTGGTTCAGAA 1096 IIIII SBJCT : 1660 GAAATGGAGCGTGGTCGAGTCGCCCAGGGAACGCCGGAGCATCCAGACTCTGGTGCAGAA 1719 QUERY : 1097 TGAAGCCGTGTTTGTGCAGTACCTGGATGTGGGCCTGTGGCATCTGGCCTTCTACAATGA 1156 II 11 111111111111111 1111111111111111111 Illllllllllllllll SBJCT : 1720 CGAGGCTGTGTTTGTGCAGTACTTGGATGTGGGCCTGTGGCACCTGGCCTTCTACAATGA 1779 QUERY : 1157 TGGAAAAGACAAAGAGATGGTTTCCTTCAATACTGTTGTCCTAGAT 1202 II 11 111|1 11111111 11111111 111111111 11111 SBJCT : 1780 CGGCAAGGACAAGGAGATGGTCTCCTTCAACACTGTTGTCTTAGAT 1825 SCORE = 125 BITS (63), EXPECT = 7E-26 IDENTITIES = 93/103 (90%) STRAND = PLUS/PLUS QUERY : 1258 GATTCAGTGCAGGACTGTCCACGTAACTGCCATGGGAATGGTGAATGTGTGTCCGGGGTG 1317 III I IIIII I SBJCT : 1823 GATTCAGTGCAGGACTGTCCACGGAACTGTCACGGGAACGGTGAATGCGTGTCTGGACTG 1882 QUERY : 1318 TGTCACTGTTTCCCAGGATTTCTAGGAGCAGACTGTGCTAAAG 1360 IIIIIIIIIIII SBJCT : 1883 TGTCACTGTTTCCCAGGATTCCTAGGTGCAGACTGTGCTAAAG 1925 In another BLASTN search it was found that the FCTR3a nucleic acid has homology to three fragments of Gallus gallus mRNA for teneurin-2. It has 541 of 629 bases (86%) identical to bases 502-1130, 302 of 367 bases (82%) identical to bases 1330-1696, and 87 of 103 bases (84%) identical to bases 1711-1813 of Gallus gallus mRNA for teneurin-2 (EMBL Acc : AJ245711. 1) (Table 3K).

Table 3K. BLASTN of FCTR3a against Gallus gallus mRNA for teneurin-2 (SEQ ID NO : 63) >GI160100481EMBIAJ245711. IIGGA245711 GALLUS GALLUS MRNA FOR TENEURIN-2, SHORT SPLICE VARIANT (TEN2 GENE) LENGTH = 2496 SCORE = 549 BITS (277), EXPECT = E-153 IDENTITIES = 541/629 (86%) STRAND = PLUS/PLUS QUERY : 114 GGTCGTCCCATTCCACCTACATCCTCGCCTAGTCTCCTCCCATCTGCTCAGCTGCCTAGC 173 111111111111111111111111111 1111 11 11111111111111111111 11 SBJCT : 502 GGTCGTCCCATTCCACCTACATCCTCGTCTAGCCTTCTCCCATCTGCTCAGCTGCCCAGT 561 QUERY : 174 TCCCATAATCCTCCACCAGTTAGCTGCCAGATGCCATTGCTAGACAGCAACACCTCCCAT 233 II 11111111111111111111111111111111111111111111111 11 111111 SBJCT : 562 TCTCATAATCCTCCACCAGTTAGCTGCCAGATGCCATTGCTAGACAGCAATACGTCCCAT 621 QUERY : 234 CAAATCATGGACACCAACCCTGATGAGGAATTCTCCCCCAATTCATACCTGCTCAGAGCA 293 Illllllllllllllll Illll IIIII lllll II Illllllllll II llllll SBJCT : 622 CAAATCATGGACACCAATCCTGACGAGGAGTTCTCTCCTAATTCATACCTACTAAGAGCA 681 QUERY : 294 TGCTCAGGGCCCCAGCAAGCCTCCAGCAGTGGCCCTCCGAACCACCACAGCCAGTCGACT 353 II 11111111 11111 11 11111111111111 1 11111 11111111111 11 SBJCT : 682 TGTTCAGGGCCACAGCAGGCATCCAGCAGTGGCCCTTCARACCATCACAGCCAGTCAACG 741 QUERY : 354 CTGAGGCCCCCTCTCCCACCCCCTCACAACCACACGCTGTCCCATCACCACTCGTCCGCC 413 11111111 11111111 11 111111111111 1111111111111 11111111 111 SBJCT : 742 CTGAGGCCACCTCTCCCCCCTCCTCACAACCACTCGCTGTCCCATCATCACTCGTCTGCC 801 QUERY : 414 AACTCCCTCAACAGGAACTCACTGACCAATCGGCGGAGTCAGATCCACGCCCCGGCCCCA 473

11111111111111111111 11 11111 11 11 1 111111111l1 11 11 11 SBJCT : 802 AACTCCCTCAACAGGAACTCGCTCACCAACCGCCGCAACCAGATCCACGCGCCTGCTCCC 861 QUERY : 474 GCGCCCAATGACCTGGCCACCACACCAGAGTCCGTTCAGCTTCAGGACAGCTGGGTGCTA 533 II lillllllilllil IIIII II Iilll il illll Illllllllilllllll SBJCT : 862 GCTCCCAATGACCTGGCGACCACGCCTGAGTCTGTGCAGCTGCAGGACAGCTGGGTGCTC 921 QUERY : 534 AACAGCAACGTGCCACTGGAGACCCGGCACTTCCTCTTCAAGACCTCCTCGGGGAGCACA 593 11111111111111 111111111 1111 111 1 ll 11111 11 11 11 1 11 SBJCT : 922 AACAGCAACGTGCCGCTGGAGACCAGGCATTTCTTGTTTAAGACATCTTCTGGAACGACT 981 QUERY : 594 CCCTTGTTCAGCAGCTCTTCCCCGGGATACCCTTTGACCTCAGGAACGGTTTACACGCCC 653 III II II I SBJCT : 982 CCGCTGTTCAGTAGCTCTTCCCCTGGCTACCCACTGACCTCAGGAACAGTTTATACTCCA 1041 QUERY : 654 CCGCCCCGCCTGCTGCCCAGGAATACTTTCTCCAGGAAGGCTTTCAAGCTGAAGAAGCCC 713 II 111 1 111 1 11 11 11111 11 11111111 11 111111|1111 111111 SBJCT : 1042 CCTCCCAGGCTGTTACCTAGAAATACATTTTCCAGGAATGCATTCAAGCTGAAAAAGCCC 1101 QUERY : 714 TCCAAATACTGCAGCTGGAAATGTGCTGC 742 IIIII II li IIIIIIIIIIIIIIIII SBJCT : 1102 TCCAAGTATTGTAGCTGGAAATGTGCTGC 1130 SCORE = 212 BITS (107), EXPECT = 4E-52 IDENTITIES = 302/367 (82%) STRAND = PLUS/PLUS QUERY : 819 AGCAGCATAGACAGTGGTGAAGCAGAAGTTGGTCGGCGGGTAACACAAGAAGTCCCACCA 878 11111111111 11111 111 1111111111 11 111 11 11111 11 1 ! il SBJCT : 1330 AGCAGCATAGATAGTGGAGAAACAGAAGTTGGCCGCAAGGTCACCCAAGAGGTGCCCCCT 1389 QUERY : 879 GGGGTGTTTTGGAGGTCACAAATTCACATCAGTCAGCCCCAGTTCTTAAAGTTCAACATC 938 II IIIII III IIII Il II II Illll IIIII Illlll I IIIIIIIIIII SBJCT : 1390 GGAGTGTTCTGGCGGTCTCAGATCCATATCAGCCAGCCACAGTTCCTGAAGTTCAACATA 1449 QUERY : 939 TCCCTCGGGAAGGACGCTCTCTTTGGTGTTTACATAAGAAGAGGACTTCCACCATCTCAT 998 11111 11111111 111 ; 1 11 111111} 1 11111} 11111111 11111111 111 SBJCT : 1450 TCCCTAGGGAAGGATGCTCTTTTCGGTGTTTATATAAGAAGAGGACTCCCACCATCACAT 1509 QUERY : 999 GCCCAGTATGACTTCATGGAACGTCTGGACGGGAAGGAGAAGTGGAGTGTGGTTGAGTCT 1058 I SBJCT : 1510 GCACAGTATGATTTCATGGAACGCTTGGATGGGAAAGAGAAATGGAGTGTGGTGGAATCC 1569 QUERY : 1059 CCCAGGGAACGCCGGAGCATACAGACCTTGGTTCAGAATGAAGCCGTGTTTGTGCAGTAC 1118 IIII II II IIII I l SBJCT : 1570 CCACGGGAACGGCGAAGTATTCAGACTCTTGTTCAGAATGAGGCTGTGTTTGTTCAGTAC 1629 QUERY : 1119 CTGGATGTGGGCCTGTGGCATCTGGCCTTCTACAATGATGGAAAAGACAAAGAGATGGTT 1178 llllllllll IIIIIII IIIII II Illllllllll Il Illlllll IIII SBJCT : 1630 TTGGATGTGGGTTTGTGGCACCTGGCGTTTTACAATGATGGCAAGGACAAAGAAGTGGTC 1689 QUERY : 1179 TCCTTCA 1185 1111111 SBJCT : 1690 TCCTTCA 1696 SCORE = 77. 8 BITS (39), EXPECT = 1E-11 IDENTITIES = 87/103 (84%) STRAND = PLUS/PLUS QUERY : 1258 GATTCAGTGCAGGACTGTCCACGTAACTGCCATGGGAATGGTGAATGTGTGTCCGGGGTG 1317 Illllllll I SBJCT : 1711 GATTCAGTGCAAGACTGTCCACGTAATTGTCATGGCAATGGCGAGTGTGTTTCTGGTGTC 1770 QUERY : 1318 TGTCACTGTTTCCCAGGATTTCTAGGAGCAGACTGTGCTAAAG 1360 Il IIIIIIII ll IIIIIII llllllll IIIIIIIIII SBJCT : 1771 TGCCACTGTTTTCCCGGATTTCATGGAGCAGATTGTGCTAAAG 1813

In this search it was also found that the fragments of FCTR3bcd and e nucleic acids had homology to three fragments of Homo sapiens MRNA for KIAA1127 protein. It has 5537 of 5538 bases (99%) identical to bases 1-5538, 705 of 714 bases (98%) identical to bases 5609-6322, and 176 of 176 bases (100%) identical to bases 6385-6560 of Homo sapiens mRNA for KIAA1127 protein (GenBank Acc : AB032953) (Table 3L).

Table 3L. BLASTN of FCTR3b, c, d, and e againstHomo sapiens KIAA1127 mRNA (SEQ ID NO : 64) >GI#6329762#DBJ#AB032953.1#AB032953 HOMO SAPIENS MRNA FOR KIAA1127 PROTEIN, PARTIAL CDS LENGTH = 6560 SCORE = 1. 097E+04 BITS (5534), EXPECT = 0. 0 IDENTITIES = 5537/5538 (99%) STRAND = PLUS/PLUS QUERY : 3267 CACCTTCTTTAGTGCTGCCCCTGGGCAGAATCCCATCGTGCCTGAGACCCAGGTTCTTCA 3326 111111111111111111111111111111111111111111111111111111111111 SBJCT : 1 CACCTTCTTTAGTGCTGCCCCTGGGCAGAATCCCATCGTGCCTGAGACCCAGGTTCTTCA 60 QUERY : 3327 TGAAGAAATCGAGCTCCCTGGTTCCAATGTGAAACTTCGCTATCTGAGCTCTAGAACTGC 3386 Illlllllllllllllllllllllllllllllllll SBJCT : 61 TGAAGAAATCGAGCTCCCTGGTTCCAATGTGAAACTTCGCTATCTGAGCTCTAGAACTGC 120 QUERY : 3387 AGGGTACAAGTCACTGCTGAAGATCACCATGACCCAGTCCACAGTGCCCCTGAACCTCAT 3446 m m m m m m m m m m m m m m mm m m mm SBJCT : 121 AGGGTACAAGTCACTGCTGAAGATCACCATGACCCAGTCCACAGTGCCCCTGAACCTCAT 180 SBJCT : 121 AGGGTACAAGTCACTGCTGAAGATCACCATGACCCAGTCCACAGTGCCCCTGAACCTCAT 180 QUERY : 3447 TAGGGTTCACCTGATGGTGGCTGTCGAGGGGCATCTCTTCCAGAAGTCATTCCAGGCTTC 3506 111111111111111111111111111111111111111111111111111111111111 SBJCT : 181 TAGGGTTCACCTGATGGTGGCTGTCGAGGGGCATCTCTTCCAGAAGTCATTCCAGGCTTC 240 QUERY : 3507 TCCCAACCTGGCCTCCACCTTCATCTGGGACAAGACAGATGCGTATGGCCAAAGGGTGTA 3566 I SBJCT : 241 TCCCAACCTGGCCTACACCTTCATCTGGGACAAGACAGATGCGTATGGCCAAAGGGTGTA 300 )) n m H m n n) m n m H) n) m H H)) ! H H) m) ! H H N) H QUERY : 3567 TGGACTCTCAGATGCTGTTGTGTCTGTCGGGTTTGAATATGAGACCTGTCCCAGTCTAAT 3626 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIlIlllllllllllll SBJCT : 301 TGGACTCTCAGATGCTGTTGTGTCTGTCGGGTTTGAATATGAGACCTGTCCCAGTCTAAT 360 QUERY : 3627 TCTCTGGGAGAAAAGGACAGCCCTCCTTCAGGGATTCGAGCTGGACCCCTCCAACCTCGG 3686 1111111111111111111111111111111111111|1111111111111111111111 SBJCT : 361 TCTCTGGGAGAAAAGGACAGCCCTCCTTCAGGGATTCGAGCTGGACCCCTCCAACCTCGG 420 QUERY : 3687 TGGCTGGTCCCTAGACAAACACCACATCCTCAATGTTAAAAGTGGAATCCTACACAAAGG 3746 111111111111111111111111111111111111111111111111111111111111 SBJCT : 421 TGGCTGGTCCCTAGACAAACACCACATCCTCAATGTTAAAAGTGGAATCCTACACAAAGG 480 QUERY : 3747 CACTGGGGAAAACCAGTTCCTGACCCAGCAGCCTGCCATCATCACCAGCATCATGGGCAA 3806 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII SBJCT : 481 CACTGGGGAAAACCAGTTCCTGACCCAGCAGCCTGCCATCATCACCAGCATCATGGGCAA 540 QUERY : 38D7 TGGTCGCCGCCGGAGCATTTCCTGTCCCAGCTGCAACGGCCTTGCTGAAGGCAACAAGCT 3866 SBJCT : 541 TGGTCGCCGCCGGAGCATTTCCTGTCCCAGCTGCAACGGCCTTGCTGAAGGCAACAAGCT 600 QUERY : 3867 GCTGGCCCCAGTGGCTCTGGCTGTTGGAATCGATGGGAGCCTCTATGTGGGTGACTTCAA 3926 111111111111111111111111111111111111111111111111111111111111 SBJCT : 601 GCTGGCCCCAGTGGCTCTGGCTGTTGGAATCGATGGGAGCCTCTATGTGGGTGACTTCAA 660 QUERY : 3927 TTACATCCGACGCATCTTTCCCTCTCGAAATGTGACCAGCATCTTGGAGTTACGAAATAA 3986 11111111111111111111111111111111111111111111111111111111111 SBJCT : 661 TTACATCCGACGCATCTTTCCCTCTCGAAATGTGACCAGCATCTTGGAGTTACGAAATAA 720

QUERY : 3987 AGAGTTTAAACATAGCAACAACCCAGCACACAAGTACTACTTGGCAGTGGACCCCGTGTC 4046 m h ! N ! m m) N m m m m N ! m m m) H m m m N m ! SBJCT : 721 AGAGTTTAAACATAGCAACAACCCAGCACACAAGTACTACTTGGCAGTGGACCCCGTGTC 780 SBJCT : 721 AGAGTTTAAACATAGCAACAACCCAGCACACAAGTACTACTTGGCAGTGGACCCCGTGTC 780 ! H m m N ! ! m H) m ! mn ! mm m N ! N N N mm t) N ! H QUERY : 4047 CGGCTCGCTCTACGTGTCCGACACCAACAGCAGGAGAATCTACCGCGTCAAGTCTCTGAG 4106 IIIIfIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIilllllllllllllllll SBJCT : 781 CGGCTCGCTCTACGTGTCCGACACCAACAGCAGGAGAATCTACCGCGTCAAGTCTCTGAG 840 QUERY : 4107 TGGAACCAAAGACCTGGCTGGGAATTCGGAAGTTGTGGCAGGGACGGGAGAGCAGTGTCT 4166 t11111111111111111111111111111111111111111111111111111111111 SBJCT : 841 TGGAACCAAAGACCTGGCTGGGAATTCGGAAGTTGTGGCAGGGACGGGAGAGCAGTGTCT 900 QUERY : 4167 ACCCTTTGATGAAGCCCGCTGCGGGGATGGAGGGAAGGCCATAGATGCAACCCTGATGAG 4226 1111111111111|1111111111111111111111111111111111111111111111 SBJCT : 901 ACCCTTTGATGAAGCCCGCTGCGGGGATGGAGGGAAGGCCATAGATGCAACCCTGATGAG 960 QUERY : 4227 CCCGAGAGGTATTGCAGTAGACAAGAATGGGCTCATGTACTTTGTCGATGCCACCATGAT 4286 111111111111111111111111111111111111111111111111111111111111 SBJCT : 961 CCCGAGAGGTATTGCAGTAGACAAGAATGGGCTCATGTACTTTGTCGATGCCACCATGAT 1020 QUERY : 4287 CCGGAAGGTTGACCAGAATGGAATCATCTCCACCCTGCTGGGCTCCAATGACCTCACTGC 4346 111111111111111111111111111111111111111111111111111111111111 SBJCT : 1021 CCGGAAGGTTGACCAGAATGGAATCATCTCCACCCTGCTGGGCTCCAATGACCTCACTGC 1080 QUERY : 4347 CGTCCGGCCGCTGAGCTGTGATTCCAGCATGGATGTAGCCCAGGTTCGTCTGGAGTGGCC 4406 111111111111111111111111111111111111111111111111111111111111 SBJCT : 1081 CGTCCGGCCGCTGAGCTGTGATTCCAGCATGGATGTAGCCCAGGTTCGTCTGGAGTGGCC 1140 QUERY : 4407 AACAGACCTTGCTGTCAATCCCATGGATAACTCCTTGTATGTTCTAGAGAACAATGTCAT 4466 111111111111111111111111111111111111111111111111111111111111 SBJCT : 1141 AACAGACCTTGCTGTCAATCCCATGGATAACTCCTTGTATGTTCTAGAGAACAATGTCAT 1200 QUERY : 4467 CCTTCGAATCACCGAGAACCACCAAGTCAGCATCATTGCGGGACGCCCCATGCACTGCCA 4526 111111111111111111111111111111111111111111111111111111111111 SBJCT : 1201 CCTTCGAATCACCGAGAACCACCAAGTCAGCATCATTGCGGGACGCCCCATGCACTGCCA 1260 SBJCT : 1201 CCTTCGAATCACCGAGAACCACCAAGTCAGCATCATTGCGGGACGCCCCATGCACTGCCA 1260 m m H mm m m m) m m m m m) m !) !)) m)) m m) QUERY : 4527 AGTTCCTGGCATTGACTACTCACTCAGCAAACTAGCCATTCACTCTGCCCTGGAGTCAGC 4586 1111111111111111111111111sZ111111111111111111111111111111111 SBJCT : 1261 AGTTCCTGGCATTGACTACTCACTCAGCAAACTAGCCATTCACTCTGCCCTGGAGTCAGC 1320 QUERY : 4587 CAGTGCCATTGCCATTTCTCACACTGGGGTCCTCTACATCACTGAGACAGATGAGAAGAA 4646 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll SBJCT : 1321 CAGTGCCATTGCCATTTCTCACACTGGGGTCCTCTACATCACTGAGACAGATGAGAAGAA 1380 QUERY : 4647 GATTAACCGTCTACGCCAGGTAACAACCAACGGGGAGATCTGCCTTTTAGCTGGGGCAGC 4706 111111111111111111111111111111111111111111111111111111111111 SBJCT : 1381 GATTAACCGTCTACGCCAGGTAACAACCAACGGGGAGATCTGCCTTTTAGCTGGGGCAGC 1440 QUERY : 4707 CTCGGACTGCGACTGCAAAAACGATGTCAATTGCAACTGCTATTCAGGAGATGATGCCTA 4766 I SBJCT : 1441 CTCGGACTGCGACTGCAAAAACGATGTCAATTGCAACTGCTATTCAGGAGATGATGCCTA 1500 QUERY : 4767 CGCGACTGATGCCATCTTGAATTCCCCATCATCCTTAGCTGTAGCTCCAGATGGTACCAT 4826 111111111111111111111111111111111111111111111111111111111111 SBJCT : 1501 CGCGACTGATGCCATCTTGAATTCCCCATCATCCTTAGCTGTAGCTCCAGATGGTACCAT 1560 QUERY : 4827 TTACATTGCAGACCTTGGAAATATTCGGATCAGGGCGGTCAGCAAGAACAAGCCTGTTCT 4886 111111111111111111111111111111111111|11111111111111111111111 SBJCT : 1561 TTACATTGCAGACCTTGGAAATATTCGGATCAGGGCGGTCAGCAAGAACAAGCCTGTTCT 1620 QUERY : 4887 TAATGCCTTCAACCAGTATGAGGCTGCATCCCCCGGAGAGCAGGAGTTATATGTTTTCAA 4946 111111111111111111111111111111111111111111111111111111111111 SBJCT : 1621 TAATGCCTTCAACCAGTATGAGGCTGCATCCCCCGGAGAGCAGGAGTTATATGTTTTCAA 1680 QUERY : 4947 CGCTGATGGCATCCACCAATACACTGTGAGCCTGGTGACAGGGGAGTACTTGTACAATTT 5006 111111111111111111111111111111111111111111111111111111111111 SBJCT : 1681 CGCTGATGGCATCCACCAATACACTG. TGAGCCTGGTGACAGGGGAGTACTTGTACAATTT 1740 QUERY : 5007 CACATATAGTACTGACAATGATGTCACTGAATTGATTGACAATAATGGGAATTCCCTGAA 5066

mmmmmmmmmmmmmmmmmmmm SBJCT : 1741 CACATATAGTACTGACAATGATGTCACTGAATTGATTGACAATAATGGGAATTCCCTGAA 1800 SBJCT : 1741 CACATATAGTACTGACAATGATGTCACTGAATTGATTGACAATAATGGGAATTCCCTGAA 1800 QUERY : 5067 GATCCGTCGGGACAGCAGTGGCATGCCCCGTCACCTGCTCATGCCTGACAACCAGATCAT 5126 SBJCT : 1801 GATCCGTCGGGACAGCAGTGGCATGCCCCGTCACCTGCTCATGCCTGACAACCAGATCAT 1860 QUERY : 5127 CACCCTCACCGTGGGCACCAATGGAGGCCTCAAAGTCGTGTCCACACAGAACCTGGAGCT 5186 (m H m ! m N) (ft ! h N tN HN Nfmm m m N ( ! H ! m N H SBJCT : 1861 CACCCTCACCGTGGGCACCAATGGAGGCCTCAAAGTCGTGTCCACACAGAACCTGGAGCT 1920 QUERY : 5187 TGGTCTCATGACCTATGATGGCAACACTGGGCTCCTGGCCACCAAGAGCGATGAAACAGG 5246 I SBJCT : 1921 TGGTCTCATGACCTATGATGGCAACACTGGGCTCCTGGCCACCAAGAGCGATGAAACAGG 1980 QUERY : 5247 ATGGACGACTTTCTATGACTATGACCACGAAGGCCGCCTGACCAACGTGACGCGCCCCAC 5306 mmmmmmmmmmmmmmmmmmmm SBJCT : 1981 ATGGACGACTTTCTATGACTATGACCACGAAGGCCGCCTGACCAACGTGACGCGCCCCAC 2040 QUERY : 5307 GGGGGTGGTAACCAGTCTGCACCGGGAAATGGAGAAATCTATTACCATTGACATTGAGAA 5366 1111111111111111111llllllllllllt11111111lllllll11lllllll1111 SBJCT : 2041 GGGGGTGGTAACCAGTCTGCACCGGGAAATGGAGAAATCTATTACCATTGACATTGAGAA 2100 QUERY : 5367 CTCCAACCGTGATGATGACGTCACTGTCATCACCAACCTCTCTTCAGTAGAGGCCTCCTA 5426 IIIII SBJCT : 2101 CTCCAACCGTGATGATGACGTCACTGTCATCACCAACCTCTCTTCAGTAGAGGCCTCCTA 2160 QUERY : 5427 CACAGTGGTACAAGATCAAGTTCGGAACAGCTACCAGCTCTGTAATAATGGTACCCTGAG 5486 m m) m m m m m mm m m m ! mm m) m m m m SBJCT : 2161 CACAGTGETACAAGATCAAGTTCGGAACAGCTACCAGCTCTGTAATAATGGTACCCTGAG 2220 SBJCT : 2161 CACAGTGGTACAAGATCAAGTTCGGAACAGCTACCAGCTCTGTAATAATGGTACCCTGAG 2220 QUERY : 5487 GGTGATGTATGCTAATGGGATGGGTATCAGCTTCCACAGCGAGCCCCATGTCCTAGCGGG 5546 Illllllllllllllllllllllllllllllllllllllllllllllllllillllllll SBJCT : 2221 GGTGATGTATGCTAATGGGATGGGTATCAGCTTCCACAGCGAGCCCCATGTCCTAGCGGG 2280 m) m m m m m m m mm)) m mm mm m m m m QUERY : 5547 CACCATCACCCCCACCATTGGACGCTGCAACATCTCCCTGCCTATGGAGAATGGCTTAAA 5606 llllllllllllllllllllllllllllIIIIlllllllllllllIIIllllllllllll SBJCT : 2281 CACCATCACCCCCACCATTGGACGCTGCAACATCTCCCTGCCTATGGAGAATGGCTTAAA 2340 QUERY : 5607 CTCCATTGAGTGGCGCCTAAGAAAGGAACAGATTAAAGGCAAAGTCACCATCTTTGGCAG 5666 1111111111111111111|1111111111111111111111111111111111111111 SBJCT : 2341 CTCCATTGAGTGGCGCCTAAGAAAGGAACAGATTAAAGGCAAAGTCACCATCTTTGGCAG 2400 QUERY : 5667 GAAGCTCCGGGTCCATGGAAGAAATCTCTTGTCCATTGACTATGATCGAAATATTCGGAC 5726 111111111111111111111111111111111111111111111111111111111111 SBJCT : 2401 GAAGCTCCGGGTCCATGGAAGAAATCTCTTGTCCATTGACTATGATCGAAATATTCGGAC 2460 QUERY : 5727 TGAAAAGATCTATGATGACCACCGGAAGTTCACCCTGAGGATCATTTATGACCAGGTGGG 5786 111111111111111111111111111111111111111111111111111111111111 SBJCT : 2461 TGAAAAGATCTATGATGACCACCGGAAGTTCACCCTGAGGATCATTTATGACCAGGTGGG 2520 QUERY : 5787 CCGCCCCTTCCTCTGGCTGCCCAGCAGCGGGCTGGCAGCTGTCAACGTGTCATACTTCTT 5846 111111111111111111111111111111111111111111111111111111111111 SBJCT : 2521 CCGCCCCTTCCTCTGGCTGCCCAGCAGCGGGCTGGCAGCTGTCAACGTGTCATACTTCTT 2580 QUERY : 5847 CAATGGGCGCCTGGCTGGGCTTCAGCGTGGGGCCATGAGCGAGAGGACAGACATCGACAA 5906 111111111111111111111111111111111111111111111111111111111111 SBJCT : 2581 CAATGGGCGCCTGGCTGGGCTTCAGCGTGGGGCCATGAGCGAGAGGACAGACATCGACAA 2640 QUERY : 5907 GCAAGGCCGCATCGTGTCCCGCATGTTCGCTGACGGGAAAGTGTGGAGCTACTCCTACCT 5966 111111111111111111111111111111111111111111111111111111111111 SBJCT : 2641 GCAAGGCCGCATCGTGTCCCGCATGTTCGCTGACGGGAAAGTGTGGAGCTACTCCTACCT 2700 QUERY : 5967 TGACAAGTCCATGGTCCTCCTGCTTCAGAGCCAACGTCAGTATATATTTGAGTATGACTC 6026 111111111111111111111111111111111111111111111111111111111111 SBJCT : 2701 TGACAAGTCCATGGTCCTCCTGCTTCAGAGCCAACGTCAGTATATATTTGAGTATGACTC 2760 QUERY : 6027 CTCTGACCGCCTCCTTGCCGTCACCATGCCCAGCGTGGCCCGGCACAGCATGTCCACACA 6086 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII SBJCT : 2761 CTCTGACCGCCTCCTTGCCGTCACCATGCCCAGCGTGGCCCGGCACAGCATGTCCACACA 2820

QUERY : 6087 CACCTCCATCGGCTACATCCGTAATATTTACAACCCGCCTGAAAGCAATGCTTCGGTCAT 6146 Ilillllllllllllilllllllllllillllllllllllllllllllllllllll SBJCT : 2821 CACCTCCATCGGCTACATCCGTAATATTTACAACCCGCCTGAAAGCAATGCTTCGGTCAT 2880 QUERY : 6147 CTTTGACTACAGTGATGACGGCCGCATCCTGAAGACCTCCTTTTTGGGCACCGGACGCCA 6206 Illllllllllllllll1111111111111111R11111111111111llllllllllll SBJCT : 2881 CTTTGACTACAGTGATGACGGCCGCATCCTGAAGACCTCCTTTTTGGGCACCGGACGCCA 2940 QUERY : 6207 GGTGTTCTACAAGTATGGGAAACTCTCCAAGTTATCAGAGATTGTCTACGACAGTACCGC 6266 IIIIII (Illlllllllllllllllllllllilllllillllllflllllllllllllll SBJCT : 2941 GGTGTTCTACAAGTATGGGAAACTCTCCAAGTTATCAGAGATTGTCTACGACAGTACCGC 3000 QUERY : 6267 CGTCACCTTCGGGTATGACGAGACCACTGGTGTCTTGAAGATGGTCAACCTCCAAAGTGG 6326 Illlllllllllllllllllllllllllllllllllillllllllllillllllllllll SBJCT : 3001 CGTCACCTTCGGGTATGACGAGACCACTGGTGTCTTGAAGATGGTCAACCTCCAAAGTGG 3060 QUERY : 6327 GGGCTTCTCCTGCACCATCAGGTACCGGAAGATTGGCCCCCTGGTGGACAAGCAGATCTA 6386 1111111|1111111111111111111111111111111111111111111111111111 SBJCT : 3061 GGGCTTCTCCTGCACCATCAGGTACCGGAAGATTGGCCCCCTGGTGGACAAGCAGATCTA 3120 QUERY : 6387 CAGGTTCTCCGAGGAAGGCATGGTCAATGCCAGGTTTGACTACACCTATCATGACAACAG 6446 IIIIIIIIlllllllll SBJCT : 3121 CAGGTTCTCCGAGGAAGGCATGGTCAATGCCAGGTTTGACTACACCTATCATGACAACAG 3180 QUERY : 6447 CTTCCGCATCGCAAGCATCAAGCCCGTCATAAGTGAGACTCCCCTCCCCGTTGACCTCTA 6506 111111111111111111111111111111111111111111111111111111111111 SBJCT : 3181 CTTCCGCATCGCAAGCATCAAGCCCGTCATAAGTGAGACTCCCCTCCCCGTTGACCTCTA 3240 QUERY : 6507 CCGCTATGATGAGATTTCTGGCAAGGTGGAACACTTTGGTAAGTTTGGAGTCATCTATTA 6566 11111111111111111111111111111111111111111111111i111111111111 SBJCT : 3241 CCGCTATGATGAGATTTCTGGCAAGGTGGAACACTTTGGTAAGTTTGGAGTCATCTATTA 3300 QUERY : 6567 TGACATCAACCAGATCATCACCACTGCCGTGATGACCCTCAGCAAACACTTCGACACCCA 6626 Illlllllllllllllllllllllllllllllll. llllllllllllllllllllllllll SBJCT : 3301 TGACATCAACCAGATCATCACCACTGCCGTGATGACCCTCAGCAAACACTTCGACACCCA 3360 QUERY : 6627 TGGGCGGATCAAGGAGGTCCAGTATGAGATGTTCCGGTCCCTCATGTACTGGATGACGGT 6686 IIIII SBJCT : 3361 TGGGCGGATCAAGGAGGTCCAGTATGAGATGTTCCGGTCCCTCATGTACTGGATGACGGT 3420 QUERY : 6687 GCAATATGACAGCATGGGCAGGGTGATCAAGAGGGAGCTAAAACTGGGGCCCTATGCCAA 6746 111111111111111111111111111111111111111111111111111111111111 SBJCT : 3421 GCAATATGACAGCATGGGCAGGGTGATCAAGAGGGAGCTAAAACTGGGGCCCTATGCCAA 3480 QUERY : 6747 TACCACGAAGTACACCTATGACTACGATGGGGACGGGCAGCTCCAGAGCGTGGCCGTCAA 6806 SBJCT : 3481 TACCACGAAGTACACCTATGACTACGATGGGGACGGGCAGCTCCAGAGCGTGGCCGTCAA 3540 QUERY : 6807 TGACCGCCCGACCTGGCGCTACAGCTATGACCTTAATGGGAATCTCCACTTACTGAACCC 6866 1111111111111111111111111111111111111111111111111111111111f1 SBJCT : 3541 TGACCGCCCGACCTGGCGCTACAGCTATGACCTTAATGGGAATCTCCACTTACTGAACCC 3600 QUERY : 6867 AGGCAACAGTGTGCGCCTCATGCCCTTGCGCTATGACCTCCGGGATCGGATAACCAGACT 6926 11111111111111|111111111111111111111111111111111111111111111 SBJCT : 3601 AGGCAACAGTGTGCGCCTCATGCCCTTGCGCTATGACCTCCGGGATCGGATAACCAGACT 3660 QUERY : 6927 CGGGGATGTGCAGTACAAAATTGACGACGATGGCTATCTGTGCCAGAGAGGGTCTGACAT 6986 111111111111111111111111111111111111111111111111111111111111 SBJCT : 3661 CGGGGATGTGCAGTACAAAATTGACGACGATGGCTATCTGTGCCAGAGAGGGTCTGACAT 3720 QUERY : 6987 CTTCGAATACAATTCCAAGGGCCTCCTAACAAGAGCCTACAACAAGGCCAGCGGGTGGAG 7046 111111111111111111111111111111111111111111111111111111111111 SBJCT : 3721 CTTCGAATACAATTCCAAGGGCCTCCTAACAAGAGCCTACAACAAGGCCAGCGGGTGGAG 3780 QUERY : 7047 TGTCCAGTACCGCTATGATGGCGTAGGACGGCGGGCTTCCTACAAGACCAACCTGGGCCA 7106 111111111111111111111111111111111111111111111111111111111111 SBJCT : 3781 TGTCCAGTACCGCTATGATGGCGTAGGACGGCGGGCTTCCTACAAGACCAACCTGGGCCA 3840 QUERY : 7107 CCACCTGCAGTACTTCTACTCTGACCTCCACAACCCGACGCGCATCACCCATGTCTACAA 7166

111111111111111111111111111111111111111111111111111111111111 SBJCT : 3841 CCACCTGCAGTACTTCTACTCTGACCTCCACAACCCGACGCGCATCACCCATGTCTACAA 3900 QUERY : 7167 TCACTCCAACTCGGAGATTACCTCACTGTACTACGACCTCCAGGGCCACCTCTTTGCCAT 7226 111111111111111111111111111111111111111111111111111111111111 SBJCT : 3901 TCACTCCAACTCGGAGATTACCTCACTGTACTACGACCTCCAGGGCCACCTCTTTGCCAT 3960 SBJCT : 3901 TCACTCCAACTCGGAGATTACCTCACTGTACTACGACCTCCAGGGCCACCTCTTTGCCAT 3960 H N N) H N t Ht H) N !) H ! N H N ! ! N ! U H H H t H H N N H N ! ! t QUERY : 7227 GGAGAGCAGCAGTGGGGAGGAGTACTATGTTGCCTCTGATAACACAGGGACTCCTCTGGC 7286 Illllllllll111111111111111111111111111111111111111111111111 SBJCT : 3961 GGAGAGCAGCAGTGGGGAGGAGTACTATGTTGCCTCTGATAACACAGGGACTCCTCTGGC 4020 QUERY : 7287 TGTGTTCAGCATCAACGGCCTCATGATCAAACAGCTGCAGTACACGGCCTATGGGGAGAT 7346 111111111111111111111111111111111111111111111111111111111111 SBJCT : 4021 TGTGTTCAGCATCAACGGCCTCATGATCAAACAGCTGCAGTACACGGCCTATGGGGAGAT 4080 QUERY : 7347 TTATTATGACTCCAACCCCGACTTCCAGATGGTCATTGGCTTCCATGGGGGACTCTATGA 7406 111111111111111111111111111111111111111111111111111111111111 SBJCT : 4081 TTATTATGACTCCAACCCCGACTTCCAGATGGTCATTGGCTTCCATGGGGGACTCTATGA 4140 QUERY : 7407 CCCCCTGACCAAGCTGGTCCACTTCACTCAGCGTGATTATGATGTGCTGGCAGGACGATG 7466 111111111111111111111111111111111111111111111111111111111111 SBJCT : 4141 CCCCCTGACCAAGCTGGTCCACTTCACTCAGCGTGATTATGATGTGCTGGCAGGACGATG 4200 QUERY : 7467 GACCTCCCCAGACTATACCATGTGGAAAAACGTGGGCAAGGAGCCGGCCCCCTTTAACCT 7526 111111111111111111111111111111111111111111111111111111111111 SBJCT : 4201 GACCTCCCCAGACTATACCATGTGGAAAAACGTGGGCAAGGAGCCGGCCCCCTTTAACCT 4260 QUERY : 7527 GTATATGTTCAAGAGCAACAATCCTCTCAGCAGTGAGCTAGATTTGAAGAACTACGTGAC 7586 111111111111111111111111111111111111111111111111111111111111 SBJCT : 4261 GTATATGTTCAAGAGCAACAATCCTCTCAGCAGTGAGCTAGATTTGAAGAACTACGTGAC 4320 QUERY : 7587 AGATGTGAAAAGCTGGCTTGTGATGTTTGGATTTCAGCTTAGCAACATCATTCCTGGCTT 7646 111111111111111111111111111111111111111111111111111111111111 SBJCT : 4321 AGATGTGAAAAGCTGGCTTGTGATGTTTGGATTTCAGCTTAGCAACATCATTCCTGGCTT 4380 QUERY : 7647 CCCGAGAGCCAAAATGTATTTCGTGCCTCCTCCCTATGAATTGTCAGAGAGTCAAGCAAG 7706 111111111111111111111111111111111111111111111111111111111111 SBJCT : 4381 CCCGAGAGCCAAAATGTATTTCGTGCCTCCTCCCTATGAATTGTCAGAGAGTCAAGCAAG 4440 QUERY : 7707 TGAGAATGGACAGCTCATTACAGGTGTCCAACAGACAACAGAGAGACATAACCAGGCCTT 7766 111111111111111111111111111111111111111111111111111111111111 SBJCT : 4441 TGAGAATGGACAGCTCATTACAGGTGTCCAACAGACAACAGAGAGACATAACCAGGCCTT 4500 QUERY : 7767 CATGGCTCTGGAAGGACAGGTCATTACTAAAAAGCTCCACGCCAGCATCCGAGAGAAAGC 7826 111111111111111111f111111111111111lllllllt111111111111111111 SBJCT : 4501 CATGGCTCTGGAAGGACAGGTCATTACTAAAAAGCTCCACGCCAGCATCCGAGAGAAAGC 4560 QUERY : 7827 AGGTCACTGGTTTGCCACCACCACGCCCATCATTGGCAAAGGCATCATGTTTGCCATCAA 7886 111111111111111|11111111111111111111111111111111111111111111 SBJCT : 4561 AGGTCACTGGTTTGCCACCACCACGCCCATCATTGGCAAAGGCATCATGTTTGCCATCAA 4620 QUERY : 7887 AGAAGGGCGGGTGACCACGGGCGTGTCCAGCATCGCCAGCGAAGATAGCCGCAAGGTGGC 7946 111111111111111111111111111111111111111111111111111111111111 SBJCT : 4621 AGAAGGGCGGGTGACCACGGGCGTGTCCAGCATCGCCAGCGAAGATAGCCGCAAGGTGGC 4680 QUERY : 7947 ATCTGTGCTGAACAACGCCTACTACCTGGACAAGATGCACTACAGCATCGAGGGCAAGGA 8006 111111111111111111111118111111111111111111111111111111111111 SBJCT : 4681 ATCTGTGCTGAACAACGCCTACTACCTGGACAAGATGCACTACAGCATCGAGGGCAAGGA 4740 QUERY : 8007 CACCCACTACTTTGTGAAGATTGGCTCAGCCGATGGCGACCTGGTCACACTAGGCACCAC 8066 llllllllllllllllllllllllllllllllllllllllllllllllllllllllllll SBJCT : 4741 CACCCACTACTTTGTGAAGATTGGCTCAGCCGATGGCGACCTGGTCACACTAGGCACCAC 4800 QUERY : 8067 CATCGGCCGCAAGGTGCTAGAGAGCGGGGTGAACGTGACCGTGTCCCAGCCCACGCTGCT 8126 111111111111111111111111111111111111111111111111111111111111 SBJCT : 4801 CATCGGCCGCAAGGTGCTAGAGAGCGGGGTGAACGTGACCGTGTCCCAGCCCACGCTGCT 4860 QUERY : 8127 GGTCAACGGCAGGACTCGAAGGTTCACGAACATTGAGTTCCAGTACTCCACGCTGCTGCT 8186 1111111111111111111111111111111111111111111|1111111111111111 SBJCT : 4861 GGTCAACGGCAGGACTCGAAGGTTCACGAACATTGAGTTCCAGTACTCCACGCTGCTGCT 4920

QUERY : 8187 CAGCATCCGCTATGGCCTCACCCCCGACACCCTGGACGAAGAGAAGGCCCGCGTCCTGGA 8246 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII SBJCT : 4921 CAGCATCCGCTATGGCCTCACCCCCGACACCCTGGACGAAGAGAAGGCCCGCGTCCTGGA 4980 QUERY : 8247 CCAGGCGAGACAGAGGGCCCTGGGCACGGCCTGGGCCAAGGAGCAGCAGAAAGCCAGGGA 8306 111111111111111111111111111111111111111111111111111111111111 SBJCT : 4981 CCAGGCGAGACAGAGGGCCCTGGGCACGGCCTGGGCCAAGGAGCAGCAGAAAGCCAGGGA 5040 QUERY : 8307 CGGGAGAGAGGGGAGCCGCCTGTGGACTGAGGGCGAGAAGCAGCAGCTTCTGAGCACCGG 8366 1111111111111111111111111111111|111111s111111111111111111111 SBJCT : 5041 CGGGAGAGAGGGGAGCCGCCTGTGGACTGAGGGCGAGAAGCAGCAGCTTCTGAGCACCGG 5100 QUERY : 8367 GCGCGTGCAAGGGTACGAGGGATATTACGTGCTTCCCGTGGAGCAATACCCAGAGCTTGC 8426 Illllllllllllllllllllllllllllllllllllll SBJCT : 5101 GCGCGTGCAAGGGTACGAGGGATATTACGTGCTTCCCGTGGAGCAATACCCAGAGCTTGC 5160 QUERY : 8427 AGACAGTAGCAGCAACATCCAGTTTTTAAGACAGAATGAGATGGGAAAGAGGTAACAAAA 8486 111111111111111111111111111111111111111111111111l11111111111 SBJCT : 5161 AGACAGTAGCAGCAACATCCAGTTTTTAAGACAGAATGAGATGGGAAAGAGGTAACAAAA 5220 QUERY : 8487 TAATCTGCTGCCATTCCTTGTCTGAATGGCTCAGCAGGAGTAACTGTTATCTCCTCTCCT 8546 111111111111111111111111111111111111111111111111111111111111 SBJCT : 5221 TAATCTGCTGCCATTCCTTGTCTGAATGGCTCAGCAGGAGTAACTGTTATCTCCTCTCCT 5280 QUERY : 8547 AAGGAGATGAAGACCTAACAGGGGCACTGCGGCTGGGCTGCTTTAGGAGACCAAGTGGCA 8606 I SBJCT : 5281 AAGGAGATGAAGACCTAACAGGGGCACTGCGGCTGGGCTGCTTTAGGAGACCAAGTGGCA 5340 QUERY : 8607 AGAAAGCTCACATTTTTTGAGTTCAAATGCTACTGTCCAAGCGAGAAGTCCCTCATCCTG 8666 Illllllillllllllllllllllllllllllllllllllllllllllllllllllllll SBJCT : 5341 AGAAAGCTCACATTTTTTGAGTTCAAATGCTACTGTCCAAGCGAGAAGTCCCTCATCCTG 5400 QUERY : 8667 AAGTAGACTAAAGCCCGGCTGAAAATTCCGAGGAAAACAAAACAAACGAATGAATGAACA 8726 111111111111111111111111111111111111111111111111111111111111 SBJCT : 5401 AAGTAGACTAAAGCCCGGCTGAAAATTCCGAGGAAAACAAAACAAACGAATGAATGAACA 5460 QUERY : 8727 GACACACACAATGTTCCAAGTTCCCCTAAAATATGACCCACTTGTTCTGGGTCTACGCAG 8786 111111111111111111111111111111111111111111111111111111111111 SBJCT : 5461 GACACACACAATGTTCCAAGTTCCCCTAAAATATGACCCACTTGTTCTGGGTCTACGCAG 5520 QUERY : 8787 AAAAGAGACGCAAAGTGT 8804 1|1111111111111111 SBJCT : 5521 AAAAGAGACGCAAAGTGT 5538 SCORE = 1362 BITS (687), EXPECT = 0. 0 IDENTITIES = 705/714 (98%) STRAND = PLUS/PLUS QUERY : 8875 CACGGACCGATAAACAAAGAAGCGAAGATAAGAAAGAAGGCCTCATATCCAATTACCTCA 8934 llllllllllllllllllllllllllllllllllllllllllllllllllllllllllll SBJCT : 5609 CACGGACCGATAAACAAAGAAGCGAAGATAAGAAAGAAGGCCTCATATCCAATTACCTCA 5668 QUERY : 8935 CTCATTCACATGTGAGCGACACGCAGACATCCGCGAGGGCCAGCGTCACCAGACCAGCTG 8994 111111111111111111111111111111111111111111111111111111111111 SBJCT : 5669 CTCATTCACATGTGAGCGACACGCAGACATCCGCGAGGGCCAGCGTCACCAGACCAGCTG 5728 QUERY : 8995 CGGGACAAACCACTCAGACTGCTTGTAGGACAAATACTTCTGACATTTTCGTTTAAGCAA 9054 111111111111111111111111111111111111111111111111111111111111 SBJCT : 5729 CGGGACAAACCACTCAGACTGCTTGTAGGACAAATACTTCTGACATTTTCGTTTAAGCAA 5788 QUERY : 9055 ATACAGGTGCATTTAAAACACGACTTTGGGGGTGATTTGTGTGTAGCGCCTGGGGAGGGG 9114 111111111111111111111111111111111111111111111111111111111111 SBJCT : 5789 ATACAGGTGCATTTAAAACACGACTTTGGGGGTGATTTGTGTGTAGCGCCTGGGGAGGGG 5848 QUERY : 9115 GGATAAAAGAGGAGGAGTGAGCACTGGAAATACTTTTTAAAGNNNNNNNNNCATGAGGGA 9174 I SBJCT : 5849 GGATAAAAGAGGAGGAGTGAGCACTGGAAATACTTTTTAAAGAAAAAAAAACATGAGGGA 5908 QUERY : 9175 ATAAAAGAAATTCCTATCAAAAATCAAAGTGAAATAATACCATCCAGCACTTAACTCTCA 9234

mmHNmNmmthnmmHmmmHHHnmmm SBJCT : 5909 ATAAAAGAAATTCCTATCAAAAATCAAAGTGAAATAATACCATCCAGCACTTAACTCTCA 5968 QUERY : 9235 GGTCCCAACTAAGTCTGGCCTGAGCTAATTTATTTGAGCGCAGAGTGTAAAATTTAATTC 9294 SBJCT : 5969 GGTCCCAACTAAGTCTGGCCTGAGCTAATTTATTTGAGCGCAGAGTGTAAAATTTAATTC 6028 QUERY : 9295 AAAATGGTGGCTATAATCACTACAGATAAATTTCATACTCTTTTGTCTTTGGAGATTCCA 9354 11111111111111111llllllllllllllllllllll111111111111111111111 SBJCT : 6029 AAAATGGTGGCTATAATCACTACAGATAAATTTCATACTCTTTTGTCTTTGGAGATTCCA 6088 QUERY : 9355 TTGTGGACAGTAATACGCAGTTACAGGGTGTAGTCTGTTTAGATTCCGTAGTTCGTGGGT 9414 111111111111111111111111111111111111111111111|11111111111111 SBJCT : 6089 TTGTGGACAGTAATACGCAGTTACAGGGTGTAGTCTGTTTAGATTCCGTAGTTCGTGGGT 6148 QUERY : 9415 ATCAGTTTCGGTAGAGGTGCAGCATCGTGACACTTTTGCTAACAGGTACCACTTCTGATC 9474 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII SBJCT : 6149 ATCAGTTTCGGTAGAGGTGCAGCATCGTGACACTTTTGCTAACAGGTACCACTTCTGATC 6208 QUERY : 9475 ACCCTGTACATACATGAGCCGAAAGGCACAATCACTGTTTCAGATTTAAAATTATTAGTG 9534 111111111111111111111111111111111111111111111111111111111111 SBJCT : 6209 ACCCTGTACATACATGAGCCGAAAGGCACAATCACTGTTTCAGATTTAAAATTATTAGTG 6268 QUERY : 9535 TGTTTGTTTGGTCCAGAAACTGAGACAATCACATGACAGTCACCACGAGGAGAG 9588 111111111111111111111111111111111111111111111111111111 SBJCT : 6269 TGTTTGTTTGGTCCAGAAACTGAGACAATCACATGACAGTCACCACGAGGAGAG 6322 SCORE = 349 BITS (176), EXPECT = 2E-92 IDENTITIES = 176/176 (100%) STRAND = PLUS/PLUS QUERY : 9651 GTCTAATAAGAACTTTGGTACAGGAACTTTTTTGTAATATACATGTATGAATTGTTCATC 9710 111111111111111111111111111111111111111111111111111111111111 SBJCT : 6385 GTCTAATAAGAACTTTGGTACAGGAACTTTTTTGTAATATACATGTATGAATTGTTCATC 6444 QUERY : 9711 GAGTTTTTATATTAATTTTAATTTGCTGCTAAGCAAAGACTAGGGACAGGCAAAGATAAT 9770 1111111111111 ! 1111111111111111111111111111111111111111111111 SBJCT : 6445 GAGTTTTTATATTAATTTTAATTTGCTGCTAAGCAAAGACTAGGGACAGGCAAAGATAAT 6504 QUERY : 9771 TTATGGCAAAGTGTTTAAATTGTTTATACATAAATAAAGTCTCTAAAACTCCTGTG 9826 11111111111111111111111111111111111111111111111111111111 SBJCT : 6505 TTATGGCAAAGTGTTTAAATTGTTTATACATAAATAAAGTCTCTAAAACTCCTGTG 6560 In this search it was also found that the FCTR3bod and e nucleic acids had homology to five fragments of Mus musculus mRNA for Ten-m2. It has 5498 of 6108 bases (90%) identical to bases 2504-8610, 1095 of 1196 bases (91%) identical to bases 103-1298, 1000 of 1088 bases (91%) identical to bases 1420-2540, 81 of 89 bases (91%) identical to bases 8655- 8743, and 30 of 32 bases (93%) identical to bases 7-38 of Mus musculus mRNA for Ten-m2 (Table 3M).

Table 3M. BLASTN of FCTR3b, c, d, and e against Mus musculus mRNA for Ten-m2 Mrna (SEQ ID NO : 65) >GIl4760777lDBJlAB025411. 1lAB025411 MUS MUSCULUS MRNA FOR TEN-M2, COMPLETE CDS LENGTH = 8797 SCORE = 7263 BITS (3664), EXPECT = 0. 0 IDENTITIES = 5498/6108 (90%), GAPS = 1/6108 (0%) STRAND = PLUS/PLUS QUERY : 2578 GATGGCTGCCCTGACTTGTGCAACGGTAACGGGAGATGCACACTGGGTCAGAACAGCTGG 2637 ############### #############################################

SBJCT : 2504 GATGGCTGCCCTGATTTGTGCAACGGTAACGGGAGATGCACACTGGGTCAGAACAGCTGG 2563 QUERY : 2638 CAGTGTGTCTGCCAGACCGGCTGGAGAGGGCCCGGATGCAACGTTGCCATGGAAACTTCC 2697 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIIIIIIIIIIIIIIIIIIIII III SBJCT : 2564 CAGTGTGTCTGCCAGACCGGCTGGAGAGGGCCTGGATGCAACGTTGCCATGGAAACCTCC 2623 QUERY : 2698 TGTGCTGATAACAAGGATAATGAGGGAGATGGCCTGGTGGATTGTTTGGACCCTGACTGC 2757 II 11111111111111111111111111111111111111 sl 1|111111111111 SBJCT : 2624 TGCGCTGATAACAAGGATAATGAGGGAGATGGCCTGGTGGACTGCCTGGACCCTGACTGC 2683 QUERY : 2758 TGCCTGCAGTCAGCCTGTCAGAACAGCCTGCTCTGCCGGGGGTCCCGGGACCCACTGGAC 2817 11111 11111111111111111111111111111111111111 11111111 11111 SBJCT : 2684 TGCCTACAGTCAGCCTGTCAGAACAGCCTGCTCTGCCGGGGGTCTCGGGACCCCTTGGAC 2743 QUERY : 2818 ATCATTCAGCAGGGCCAGACGGATTGGCCCGCAGTGAAGTCCTTCTATGACCGTATCAAG 2877 11111111111 11 11111 11 11111 111111111|1111111111111 111111 SBJCT : 2744 ATCATTCAGCAAGGTCAGACAGACTGGCCTGCAGTGAAGTCCTTCTATGACCGCATCAAG 2803 QUERY : 2878 CTCTTGGCAGGCAAGGATAGCACCCACATCATTCCTGGAGAGAACCCTTTCAACAGCAGC 2937 111111111|1111111 11111111|11111111111111 11111 11111 111111 SBJCT : 2804 CTCTTGGCAGGCAAGGACAGCACCCACATCATTCCTGGAGACAACCCCTTCAATAGCAGC 2863 QUERY : 2938 TTGGTTTCTCTCATCCGAGGCCAAGTAGTAACTACAGATGGAACTCCCCTGGTCGGTGTG 2997 1111 11111 11111111111111111111 1 1111E 111111 1111 111111 SBJCT : 2864 CTGGTGTCTCTGATCCGAGGCCAAGTAGTAACCATGGATGGGACTCCCTTGGTGGGTGTG 2923 QUERY : 2998 AACGTGTCTTTTGTCAAGTACCCAAAATACGGCTACACCATCACCCGCCAGGATGGCACG 3057 n m m m mm mm m n) m m N m N) m mm mn SBJCT : 2924 AATGTGTCTTTTGTCAAGTACCCAAAATATGGCTACACCATCACTCGCCAGGATGGCACG 2983 QUERY : 3058 TTCGACCTGATCGCAAATGGAGGTGCTTCCTTGACTCTACACTTTGAGCGAGCCCCGTTC 3117 SBJCT : 29B4 TTTGACCTGATTGCCAATGGGGGTTCTGCCTTGACTCTTCACTTTGAGCGAGCCCCTTTC 3043 QUERY : 3118 ATGAGCCAGGAGCGCACTGTGTGGCTGCCGTGGAACAGCTTTTACGCCATGGACACCCTG 3177 11111111111111111 11111111111 11111111111 11 Illllllllllllll SBJCT : 3044 ATGAGCCAGGAGCGCACAGTGTGGCTGCCATGGAACAGCTTCTATGCCATGGACACCCTG 3103 QUERY : 3178 GTGATGAAGACCGAGGAGAACTCCATCCCCAGCTGTGACCTCAGTGGCTTTGTCCGGCCT 3237 II 11111111111111 11111111111111111111111111111111111111111 SBJCT : 3104 GTAATGAAGACCGAGGAAAACTCCATCCCCAGCTGTGACCTCAGTGGCTTTGTCCGGCCA 3163 QUERY : 3238 GATCCAATCATCATCTCCTCCCCACTGTCCACCTTCTTTAGTGCTGCCCCTGGGCAGAAT 3297 11111111111111111111 11 11111111111111 11 111 111111 111 SBJCT : 3164 GATCCAATCATCATCTCCTCTCCTCTGTCCACCTTCTTCAGCGCTTCCCCTGCCTCGAAC 3223 QUERY : 3298 CCCATCGTGCCTGAGACCCAGGTTCTTCATGAAGAAATCGAGCTCCCTGGTTCCAATGTG 3357 11111 11111111111111111111111111111111 111111111111 11111111 SBJCT : 3224 CCCATTGTGCCTGAGACCCAGGTTCTTCATGAAGAAATTGAGCTCCCTGGTACCAATGTG 3283 QUERY : 3358 AAACTTCGCTATCTGAGCTCTAGAACTGCAGGGTACAAGTCACTGCTGAAGATCACCATG 3417 II II II IIIII IIIIIIIIIIIIIIIIIII ! IIIII Illlllllllllllllll SBJCT : 3284 AAGCTCCGTTATCTCAGCTCTAGAACTGCAGGGTATAAGTCGCTGCTGAAGATCACCATG 3343 QUERY : 3418 ACCCAGTCCACAGTGCCCCTGAACCTCATTAGGGTTCACCTGATGGTGGCTGTCGAGGGG 3477 II Illllllllllllll Illlllllll IIIIIIIII Illllll IIIII Illlll SBJCT : 3344 ACGCAGTCCACAGTGCCCTTGAACCTCATCAGGGTTCACTTGATGGTTGCTGTAGAGGGG 3403 QUERY : 3478 CATCTCTTCCAGAAGTCATTCCAGGCTTCTCCCAACCTGGCCTCCACCTTCATCTGGGAC 3537 11111111111111111111111111111111111111 1111 III IIIIIIIIIIII SBJCT : 3404 CATCTCTTCCAGAAGTCATTCCAGGCTTCTCCCAACCTAGCCTACACATTCATCTGGGAC 3463 QUERY : 3538 AAGACAGATGCGTATGGCCAAAGGGTGTATGGACTCTCAGATGCTGTTGTGTCTGTCGGG 3597 IIIIIIIIIII Illlllllilllll Illll II II IIIIlllllllllllll III SBJCT : 3464 AAGACAGATGCTTATGGCCAAAGGGTTTATGGCCTATCGGATGCTGTTGTGTCTGTTGGG 3523 QUERY : 3598 TTTGAATATGAGACCTGTCCCAGTCTAATTCTCTGGGAGAAAAGGACAGCCCTCCTTCAG 3657 IIIIIIIIIIIIIIIII IIIIIIII II II IIIIIIIIIIIIIIIIIIII IIIIII SBJCT : 3524 TTTGAATATGAGACCTGCCCCAGTCTCATCCTGTGGGAGAAAAGGACAGCCCTGCTTCAG 3583

QUERY : 3658 GGATTCGAGCTGGACCCCTCCAACCTCGGTGGCTGGTCCCTAGACAAACACCACATCCTC 3717 Illllllllllllllll IIIIIIII II IIIIIIIIIII IIIIlllllllll IIII SBJCT : 3584 GGATTCGAGCTGGACCCTTCCAACCTTGGAGGCTGGTCCCTGGACAAACACCACACCCTC 3643 QUERY : 3718 AATGTTAAAAGTGGAATCCTACACAAAGGCACTGGGGAAAACCAGTTCCTGACCCAGCAG 3777 11111 11111 11111 11111111111 11 11111 111111111111111111111 SBJCT : 3644 AATGTGAAAAGCGGAATACTACACAAAGGGACAGGGGAGAACCAGTTCCTGACCCAGCAG 3703 QUERY : 3778 CCTGCCATCATCACCAGCATCATGGGCAATGGTCGCCGCCGGAGCATTTCCTGTCCCAGC 3837 IIIIIIIIIIIII IIIIIIIIIIII IIIIIIII I IIIII I SBJCT : 3704 CCTGCCATCATCACGAGCATCATGGGCAACGGTCGCCGCAGAAGCATCTCCTGTCCCAGC 3763 QUERY : 3838 TGCAACGGCCTTGCTGAAGGCAACAAGCTGCTGGCCCCAGTGGCTCTGGCTGTTGGAATC 3897 IIIII Illllllllllllilillll III I IIIII Illll IIIIIIII II Ill SBJCT : 3764 TGCAATGGCCTTGCTGAAGGCAACAAACTGTTAGCCCCTGTGGCCCTGGCTGTGGGGATC 3823 QUERY : 3898 GATGGGAGCCTCTATGTGGGTGACTTCAATTACATCCGACGCATCTTTCCCTCTCGAAAT 3957 1111111111111 111 11111111111 11 11111 111111111111111111111 SBJCT : 3824 GATGGGAGCCTCTTTGTTGGTGACTTCAACTATATCCGGCGCATCTTTCCCTCTCGAAAT 3883 QUERY : 3958 GTGACCAGCATCTTGGAGTTACGAAATAAAGAGTTTAAACATAGCAACAACCCAGCACAC 4017 IIIIIIII Illllllllllllillllllllllllllllllllllllll IIIII IIII SBJCT : 3884 GTGACCAGTATCTTGGAGTTACGAAATAAAGAGTTTAAACATAGCAACAGCCCAGGACAC 3943 QUERY : 4018 AAGTACTACTTGGCAGTGGACCCCGTGTCCGGCTCGCTCTACGTGTCCGACACCAACAGC 4077 11111111111111 111111111111 1 11111 11111111 11 11111111111 SBJCT : 3944 AAGTACTACTTGGCTGTGGACCCCGTGACTGGCTCACTCTACGTCTCTGACACCAACAGT 4003 QUERY : 4078 AGGAGAATCTACCGCGTCAAGTCTCTGAGTGGAACCAAAGACCTGGCTGGGAATTCGGAA 4137 1 1111111111 11111111111111 111 1111111111111111 111111111 SBJCT : 4004 CGCCGAATCTACCGAGTCAAGTCTCTGAGCGGAGCCAAAGACCTGGCTGGAAATTCGGAA 4063 QUERY : 4138 GTTGTGGCAGGGACGGGAGAGCAGTGTCTACCCTTTGATGAAGCCCGCTGCGGGGATGGA 4197 11111111111111 11 11 11 111111111111111111111111ll Ililill11 SBJCT : 4064 GTTGTGGCAGGGACTGGCGAACAATGTCTACCCTTTGATGAAGCCCGCTGTGGGGATGGA 4123 QUERY : 4198 GGGAAGGCCATAGATGCAACCCTGATGAGCCCGAGAGGTATTGCAGTAGACAAGAATGGG 4257 11111111 1 11 11 11111111111111 111111111111111111111111111 SBJCT : 4124 GGGAAGGCTGTGGACGCCACCCTGATGAGCCCCAGAGGTATTGCAGTAGACAAGAATGGG 4183 QUERY : 4258 CTCATGTACTTTGTCGATGCCACCATGATCCGGAAGGTTGACCAGAATGGAATCATCTCC 4317 II IIIIIIIIIII lllllllllllllllllllllll IIIII II Illlllllllll SBJCT : 4184 CTTATGTACTTTGTTGATGCCACCATGATCCGGAAGGTGGACCAAAACGGAATCATCTCC 4243 QUERY : 4318 ACCCTGCTGGGCTCCAATGACCTCACTGCCGTCCGGCCGCTGAGCTGTGATTCCAGCATG 4377 11111111111111111111111111 1 11111 11 11111111111 11 111111 SBJCT : 4244 ACCCTGCTGGGCTCCAATGACCTCACAGCTGTCCGACCACTGAGCTGTGACTCGAGCATG 4303 QUERY : 4378 GATGTAGCCCAGGTTCGTCTGGAGTGGCCAACAGACCTTGCTGTCAATCCCATGGATAAC 4437 II II IIIIIIII Illll Il IIIII IIIIIIII II IIIII IIIlllll III SBJCT : 4304 GACGTGGCCCAGGTCCGTCTAGAATGGCCGACAGACCTCGCCGTCAACCCCATGGACAAC 4363 QUERY : 4438 TCCTTGTATGTTCTAGAGAACAATGTCATCCTTCGAATCACCGAGAACCACCAAGTCAGC 4497 III IIII IIIII IIIIIIII Illlllli II IIIII IIIIIilifll IIIIII SBJCT : 4364 TCCCTGTACGTTCTGGAGAACAACGTCATCCTGCGGATCACGGAGAACCACCAGGTCAGC 4423 QUERY : 4498 ATCATTGCGGGACGCCCCATGCACTGCCAAGTTCCTGGCATTGACTACTCACTCAGCAAA 4557 SBJCT : 4424 ATCATCGCGGGACGGCCTATGCACTGCCAGGTTCCCGGCATCGACTACTCGCTCAGCAAA 4483 QUERY : 4558 CTAGCCATTCACTCTGCCCTGGAGTCAGCCAGTGCCATTGCCATTTCTCACACTGGGGTC 4617 II 11111 11111111 11111 11111111 11111111111111111111111111 SBJCT : 4484 CTCGCCATCCACTCTGCGCTGGAATCAGCCAGCGCCATTGCCATTTCTCACACTGGGGTG 4543 QUERY : 4618 CTCTACATCACTGAGACAGATGAGAAGAAGATTAACCGTCTACGCCAGGTAACAACCAAC 4677 11111111111111111 11 11111111111 11111 11111111 11 11 11111 SBJCT : 4544 CTCTACATCACTGAGACGGACGAGAAGAAGATCAACCGCCTACGCCAAGTCACCACCAAT 4603 QUERY : 4678 GGGGAGATCTGCCTTTTAGCTGGGGCAGCCTCGGACTGCGACTGCAAAAACGATGTCAAT 4737 Il IIIllllllll lllll IIIII IIIII IIIII IIIIIIIIIIIIIIIIIIII

SBJCT : 4604 GGAGAGATCTGCCTCTTAGCCGGGGCGGCCTCAGACTGTGACTGCAAAAACGATGTCAAC 4663 QUERY : 4738 TGCAACTGCTATTCAGGAGATGATGCCTACGCGACTGATGCCATCTTGAATTCCCCATCA 4797 1111 111111 11 11111111 11 11111 11 11 111111 1111 11 11 11 SBJCT : 4664 TGCATCTGCTACTCGGGAGATGACGCTTACGCCACGGACGCCATCCTGAACTCGCCGTCC 4723 QUERY : 4798 TCCTTAGCTGTAGCTCCAGATGGTACCATTTACATTGCAGACCTTGGAAATATTCGGATC 4857 11111111 11 11111 11111 11111 11111111111111111 11111 111111 SBJCT : 4724 TCCTTAGCCGTGGCTCCGGATGGCACCATCTACATTGCAGACCTTGGGAATATCCGGATC 4783 QUERY : 4858 AGGGCGGTCAGCAAGAACAAGCCTGTTCTTAATGCCTTCAACCAGTATGAGGCTGCATCC 4917 IIIIIIIIIIIIII II II II IIIIIIII II Illllilllllllllllllllll SBJCT : 4784 AGGGCGGTCAGCAAAAATAAACCCGTTCTTAACGCATTCAACCAGTATGAGGCTGCATCT 4843 QUERY : 4918 CCCGGAGAGCAGGAGTTATATGTTTTCAACGCTGATGGCATCCACCAATACACTGTGAGC 4977 II IIIII IIIII ll Il ll IIIIllllllllll lllll II IIIIIIIIIII SBJCT : 4844 CCGGGAGAACAGGAATTGTACGTGTTCAACGCTGATGGTATCCATCAGTACACTGTGAGT 4903 QUERY : 4978 CTGGTGACAGGGGAGTACTTGTACAATTTCACATATAGTACTGACAATGATGTCACTGAA 5037 11111111 11111111111111111111111111 11 1111111111 11111 11 SBJCT : 4904 CTGGTGACTGGGGAGTACTTGTACAATTTCACATACAGCGCTGACAATGACGTCACCGAG 4963 QUERY : 5038 TTGATTGACAATAATGGGAATTCCCTGAAGATCCGTCGGGACAGCAGTGGCATGCCCCGT 5097 11111111111 11 11111111111 11111111 11111111111111111111111 SBJCT : 4964 TTGATTGACAACAACGGGAATTCCCTAAAGATCCGCCGGGACAGCAGTGGCATGCCCCGC 5023 QUERY : 5098 CACCTGCTCATGCCTGACAACCAGATCATCACCCTCACCGTGGGCACCAATGGAGGCCTC 5157 11111111111111 11 11 11111 11111111 11 111111111111111111111 SBJCT : 5024 CACCTGCTCATGCCGGATAATCAGATTATCACCCTTACTGTGGGCACCAATGGAGGCCTC 5083 QUERY : 5158 AAAGTCGTGTCCACACAGAACCTGGAGCTTGGTCTCATGACCTATGATGGCAACACTGGG 5217 ) m n m m) m n n m))) i)) n m n !) n) m i) m m ! SBJCT : 5084 AAAGCCGTGTCCACTCAGAACCTGGAGCTGGGCCTCATGACTTATGATGGGAACACTGGA 5143 QUERY : 5218 CTCCTGGCCACCAAGAGCGATGAAACAGGATGGACGACTTTCTATGACTATGACCACGAA 5277 11111 Illllllllll Illlllll {Illlfll 11111 11111111111111111 SBJCT : 5144 CTCCTAGCCACCAAGAGTGATGAAACCGGATGGACAACTTTTTATGACTATGACCACGAG 5203 QUERY : 5278 GGCCGCCTGACCAACGTGACGCGCCCCACGGGGGTGGTAACCAGTCTGCACCGGGAAATG 5337 IIIII IIIllll IIIII IIIIIIIIII IIII Illllllllllllllll SBJCT : 5204 GGCCGTCTGACCAATGTGACCCGCCCCACGGGCGTGGTGACCAGTCTGCACCGGGAAATG 5263 QUERY : 5338 GAGAAATCTATTACCATTGACATTGAGAACTCCAACCGTGATGATGACGTCACTGTCATC 5397 IIIIIIIIIII IIIIIIIIIIIIIIIIIIIIIIIIII IIIIIIIIIIIIIIIII III SBJCT : 5264 GAGAAATCTATCACCATTGACATTGAGAACTCCAACCGGGATGATGACGTCACTGTGATC 5323 QUERY : 5398 ACCAACCTCTCTTCAGTAGAGGCCTCCTACACAGTGGTACAAGATCAAGTTCGGAACAGC 5457 Illllllllll II II IIIIIIIIIII IIIIIIIIIIIIIIIIIIII II Illlll SBJCT : 5324 ACCAACCTCTCCTCCGTGGAGGCCTCCTATACAGTGGTACAAGATCAAGTGCGAAACAGC 5383 QUERY : 5458 TACCAGCTCTGTAATAATGGTACCCTGAGGGTGATGTATGCTAATGGGATGGGTATCAGC 5517 IIIIIIIIIII IIIIIIII IIIII IIIIII II I SBJCT : 5384 TACCAGCTCTGCAATAATGGAACCCTGCGGGTGATGTACGCCAACGGCATGGCTGTCAGC 5443 QUERY : 5518 TTCCACAGCGAGCCCCATGTCCTAGCGGGCACCATCACCCCCACCATTGGACGCTGCAAC 5577 11111111 11111111 11111 11 11111111111tilil1111 11 111111111 SBJCT : 5444 TTCCACAGTGAGCCCCACGTCCTCGCAGGCACCATCACCCCCACCATCGGGCGCTGCAAC 5503 QUERY : 5578 ATCTCCCTGCCTATGGAGAATGGCTTAAACTCCATTGAGTGGCGCCTAAGAAAGGAACAG 5637 11111 lllll 111111111111 1 Illlllll Illllllllll 11 Illllllll SBJCT : 5504 ATCTCTCTGCCCATGGAGAATGGCCTGAACTCCATCGAGTGGCGCCTGAGGAAGGAACAG 5563 QUERY : 5638 ATTAAAGGCAAAGTCACCATCTTTGGCAGGAAGCTCCGGGTCCATGGAAGAAATCTCTTG 5697 II IIIllllllllllllllllllll IIIIIIII Illlllll IIIII IIIIII II SBJCT : 5564 ATCAAAGGCAAAGTCACCATCTTTGGGAGGAAGCTTCGGGTCCACGGAAGGAATCTCCTG 5623 QUERY : 5698 TCCATTGACTATGATCGAAATATTCGGACTGAAAAGATCTATGATGACCACCGGAAGTTC 5757 IIIIIIII IIIII IIIIIIII II ll II Illlllll IIIlllllllllll III SBJCT : 5624 TCCATTGATTATGACCGAAATATCCGTACGGAGAAGATCTACGATGACCACCGGAAATTC 5683

QUERY : 5758 ACCCTGAGGATCATTTATGACCAGGTGGGCCGCCCCTTCCTCTGGCTGCCCAGCAGCGGG 5817 mm m n m m m m m m mm n m m n n mn m SBJCT : 5684 ACCCTGAGGATCATCTATGACCAGGTGGGCCGCCCCTTCCTGTGGCTCCCGAGCAGTGGG 5743 QUERY : 5818 CTGGCAGCTGTCAACGTGTCATACTTCTTCAATGGGCGCCTGGCTGGGCTTCAGCGTGGG 5877 11111111 11111 11 11 111111111111111111 1111 11 11 11111 111 SBJCT : 5744 CTGGCAGCCGTCAATGTCTCCTACTTCTTCAATGGGCGCTTGGCCGGCCTCCAGCGAGGG 5803 QUERY : 5878 GCCATGAGCGAGAGGACAGACATCGACAAGCAAGGCCGCATCGTGTCCCGCATGTTCGCT 5937 11111111111111111111111 11111111111111 11111111111111111111 SBJCT : 5804 GCCATGAGCGAGAGGACAGACATTGACAAGCAAGGCCGGATCGTGTCCCGCATGTTCGCC 5863 QUERY : 5938 GACGGGAAAGTGTGGAGCTACTCCTACCTTGACAAGTCCATGGTCCTCCTGCTTCAGAGC 5997 11111111111 11111 11 11111 11111111111111111111 11111 111111 SBJCT : 5864 GACGGGAAAGTCTGGAGTTATTCCTATCTTGACAAGTCCATGGTCCTTCTGCTACAGAGC 5923 QUERY : 5998 CAACGTCAGTATATATTTGAGTATGACTCCTCTGACCGCCTCCTTGCCGTCACCATGCCC 6057 Illllllllll IIIlllll Illllllllll Il IIIllll II IIIII IIIIII SBJCT : 5924 CAACGTCAGTACATATTTGAATATGACTCCTCCGATCGCCTCCACGCAGTCACTATGCCC 5983 QUERY : 6058 AGCGTGGCCCGGCACAGCATGTCCACACACACCTCCATCGGCTACATCCGTAATATTTAC 6117 II II llllllllllllllllllll Illllllllll II Illlllil Il Illlll SBJCT : 5984 AGTGTCGCCCGGCACAGCATGTCCACGCACACCTCCATTGGTTACATCCGAAACATTTAC 6043 QUERY : 6118 AACCCGCCTGAAAGCAATGCTTCGGTCATCTTTGACTACAGTGATGACGGCCGCATCCTG 6177 11111 11 11111111111 11111111111111111|11111111111111111111 SBJCT : 6044 AACCCACCCGAAAGCAATGCATCGGTCATCTTTGACTACAGTGATGACGGCCGCATCCTA 6103 QUERY : 6178 AAGACCTCCTTTTTGGGCACCGGACGCCAGGTGTTCTACAAGTATGGGAAACTCTCCAAG 6237 11111 11 11 11111111 11 11111111111111111111111 111111111111 SBJCT : 6104 AAGACATCTTTCTTGGGCACTGGGCGCCAGGTGTTCTACAAGTATGGAAAACTCTCCAAG 6163 QUERY : 6238 TTATCAGAGATTGTCTACGACAGTACCGCCGTCACCTTCGGGTATGACGAGACCACTGGT 6297 11111111111 11111111111 11 11111111111 11111111111111111 111 SBJCT : 6164 TTATCAGAGATAGTCTACGACAGCACAGCCGTCACCTTTGGGTATGACGAGACCACCGGT 6223 QUERY : 6298 GTCTTGAAGATGGTCAACCTCCAAAGTGGGGGCTTCTCCTGCACCATCAGGTACCGGAAG 6357 111 1111111111111 11111111111111111111111 11111111111111 111 SBJCT : 6224 GTCCTGAAGATGGTCAATCTCCAAAGTGGGGGCTTCTCCTGTACCATCAGGTACCGAAAG 6283 QUERY : 6358 ATTGGCCCCCTGGTGGACAAGCAGATCTACAGGTTCTCCGAGGAAGGCATGGTCAATGCC 6417 IIII I SBJCT : 6284 GTTGGGCCCCTTGTGGACAAGCAGATTTACAGGTTCTCTGAGGAAGGAATGATCAACGCC 6343 QUERY : 641B AGGTTTGACTACACCTATCATGACAACAGCTTCCGCATCGCAAGCATCAAGCCCGTCATA 6477 11111111 11 11111111 11111 11111111111 11 11111111 11111111 SBJCT : 6344 AGGTTTGATTATACCTATCACGACAATAGCTTCCGCATTGCCAGCATCAAACCCGTCATT 6403 QUERY : 6478 AGTGAGACTCCCCTCCCCGTTGACCTCTACCGCTATGATGAGATTTCTGGCAAGGTGGAA 6537 I) IIIIlllllll Il Illlllllllllllllllll Illlllll IIIIIIIIIIII SBJCT : 6404 AGCGAGACTCCCCTTCCTGTTGACCTCTACCGCTATGACGAGATTTCCGGCAAGGTGGAA 6463 QUERY : 6538 CACTTTGGTAAGTTTGGAGTCATCTATTATGACATCAACCAGATCATCACCACTGCCGTG 6597 11111 11 11111111 11111111 11 1111111111111|111111111111111 SBJCT : 6464 CACTTCGGCAAGTTTGGGGTCATCTACTACGACATCAACCAGATCATCACCACTGCCGTC 6523 QUERY : 6598 ATGACCCTCAGCAAACACTTCGACACCCATGGGCGGATCAAGGAGGTCCAGTATGAGATG 6657 Illll ll IIIII lllll Illlllllllllll Ililllll II ll IIIllllll SBJCT : 6524 ATGACGCTTAGCAAGCACTTTGACACCCATGGGCGCATCAAGGAAGTGCAATATGAGATG 6583 QUERY : 6658 TTCCGGTCCCTCATGTACTGGATGACGGTGCAATATGACAGCATGGGCAGGGTGATCAAG 6717 )) m t) n mH m m)) i Hi mm m) m ! n m urn mm SBJCT : 6584 TTCCGGTCCCTCATGTACTGGATGACTGTGCAATATGACAGTATGGGTAGGGTCATCAAG 6643 QUERY : 6718 AGGGAGCTAAAACTGGGGCCCTATGCCAATACCACGAAGTACACCTATGACTACGATGGG 6777 11111 11 11111 11111111111111 11111 11111111111111111 11 111 SBJCT : 6644 AGGGAACTGAAACTAGGGCCCTATGCCAACACCACAAAGTACACCTATGACTATGACGGG 6703 QUERY : 6778 GACGGGCAGCTCCAGAGCGTGGCCGTCAATGACCGCCCGACCTGGCGCTACAGCTATGAC 6837 11111 11111111111 11111111111111111 11 11111111111 111111111

SBJCT : 6704 GACGGCCAGCTCCAGAGTGTGGCCGTCAATGACCGGCCTACCTGGCGCTATAGCTATGAC 6763 QUERY : 6838 CTTAATGGGAATCTCCACTTACTGAACCCAGGCAACAGTGTGCGCCTCATGCCCTTGCGC 6897 II Illlllll II III 1 ll IIIIIIII Illllll IIIIIIIIIIIIII III SBJCT : 6764 CTCAATGGGAACCTGCACCTTCTAAACCCAGGAAACAGTGCTCGCCTCATGCCCTTACGC 6823 QUERY : 6898 TATGACCTCCGGGATCGGATAACCAGACTCGGGGATGTGCAGTACAAAATTGACGACGAT 6957 11111111111 11 11111111111 11 11111 11111111111111 11 111111 SBJCT : 6824 TATGACCTCCGTGACCGGATAACCAGGCTAGGGGACGTGCAGTACAAAATCGATGACGAT 6883 QUERY : 6958 GGCTATCTGTGCCAGAGAGGGTCTGACATCTTCGAATACAATTCCAAGGGCCTCCTAACA 7017 111111 1111111111111111 11111111 11111111 11111111111 11 11 SBJCT : 6884 GGCTATTTGTGCCAGAGAGGGTCAGACATCTTTGAATACAACTCCAAGGGCCTTCTGACG 6943 QUERY : 7018 AGAGCCTACAACAAGGCCAGCGGGTGGAGTGTCCAGTACCGCTATGATGGCGTAGGACGG 7077 IIIII IIIIIIIIIIIIIIIII 11111 II illllllllllill II II II II SBJCT : 6944 AGAGCATACAACAAGGCCAGCGGATGGAGCGTGCAGTACCGCTATGACGGAGTGGGCCGC 7003 QUERY : 7078 CGGGCTTCCTACAAGACCAACCTGGGCCACCACCTGCAGTACTTCTACTCTGACCTCCAC 7137 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIIIIIIIIIIII lllllllll SBJCT : 7004 CGGGCTTCCTACAAGACCAACCTGGGCCACCACCTACAGTACTTCTACTCCGACCTCCAC 7063 QUERY : 7138 AACCCGACGCGCATCACCCATGTCTACAATCACTCCAACTCGGAGATTACCTCACTGTAC 7197 IIIII II II Illilllllll IIIII IIIIIIIIIII IIIII IIIII ll III SBJCT : 7064 AACCCCACACGTATCACCCATGTTTACAACCACTCCAACTCTGAGATCACCTCGCTCTAC 7123 QUERY : 7198 TACGACCTCCAGGGCCACCTCTTTGCCATGGAGAGCAGCAGTGGGGAGGAGTACTATGTT 7257 I SBJCT : 7124 TATGACCTCCAGGGCCACCTATTTGCCATGGAGAGCAGTAGTGGTGAAGAATACTATGTC 7183 QUERY : 7258 GCCTCTGATAACACAGGGACTCCTCTGGCTGTGTTCAGCATCAACGGCCTCATGATCAAA 7317 I IIII SBJCT : 7184 GCCTCAGACAACACGGGGACCCCTCTGGCTGTGTACAGTATCAATGGCCTCATGATCAAG 7243 QUERY : 7318 CAGCTGCAGTACACGGCCTATGGGGAGATTTATTATGACTCCAACCCCGACTTCCAGATG 7377 11 11111111111 11111111111111 11 11111111111 11 111111111111 SBJCT : 7244 CAACTGCAGTACACAGCCTATGGGGAGATCTACTATGACTCCAATCCAGACTTCCAGATG 7303 QUERY : 7378 GTCATTGGCTTCCATGGGGGACTCTATGACCCCCTGACCAAGCTGGTCCACTTCACTCAG 7437 IIIIIIIIIIIIII II II IIIIIIIIIIIIII Illlllll Illlllll Illll SBJCT : 7304 GTCATTGGCTTCCACGGAGGCCTCTATGACCCCCTCACCAAGCTCGTCCACTTTACTCAA 7363 QUERY : 7438 CGTGATTATGATGTGCTGGCAGGACGATGGACCTCCCCAGACTATACCATGTGGAAAAAC 7497 Illllilllll IIIIIIIIIIIIII IIIII IIIII IIIII IIIIIIIIII lll SBJCT : 7364 CGTGATTATGACGTGCTGGCAGGACGGTGGACGTCCCCCGACTACACCATGTGGAGGAAC 7423 QUERY : 7498 GTGGGCAAGGAGCCGGCCCCCTTTAACCTGTATATGTTCAAGAGCAACAATCCTCTCAGC 7557 m n m m m mm H mum m m) m mm m m m SBJCT : 7424 GTGGGCAAGGAGCCAGCCCCCTTCAACCTGTACATGTTCAAGAACAACAATCCTCTGAGC 7483 QUERY : 7558 AGTGAGCTAGATTTGAAGAACTACGTGACAGATGTGAAAAGCTGGCTTGTGATGTTTGGA 7617 SBJCT : 7484 AATGAGCTGGACTTAAAGAACTACGTGACAGACGTGAAGAGCTGGCTTGTGATGTTTGGA 7543 QUERY : 7618 TTTCAGCTTAGCAACATCATTCCTGGCTTCCCGAGAGCCAAAATGTATTTCGTGCCTCCT 7677 ! t m m m m m urn m mm m m m Hm m n mm SBJCT : 7544 TTTCAGCTCAGCAACATCATTCCTGGATTCCCGAGAGCCAAAATGTATTTTGTGCCTCCC 7603 QUERY : 7678 CCCTATGAATTGTCAGAGAGTCAAGCAAGTGAGAATGGACAGCTCATTACAGGTGTCCAA 7737 I SBJCT : 7604 CCCTATGAACTGTCAGAGAGTCAAGCAAGCGAGAACGGACAGCTCATTACAGGTGTCCAG 7663 QUERY : 7738 CAGACAACAGAGAGACATAACCAGGCCTTCATGGCTCTGGAAGGACAGGTCATTACTAAA 7797 IIIIIIII lllll IIIIIIIIIIIIIII IIIlllllllllllllllllll IIIIII SBJCT : 7664 CAGACAACTGAGAGGCATAACCAGGCCTTCCTGGCTCTGGAAGGACAGGTCATCACTAAA 7723 QUERY : 7798 AAGCTCCACGCCAGCATCCGAGAGAAAGCAGGTCACTGGTTTGCCACCACCACGCCCATC 7857 IIIIIIII Illllilllllllllllllllll IIIIIIIIIII IIIIIIII III (II SBJCT : 7724 AAGCTCCATGCCAGCATCCGAGAGAAAGCAGGCCACTGGTTTGCTACCACCACACCCATC 7783

QUERY : 7858 ATTGGCAAAGGCATCATGTTTGCCATCAAAGAAGGGCGGGTGACCACGGGCGTGTCCAGC 7917 ll IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII I SBJCT : 7784 ATCGGCAAAGGCATCATGTTTGCCATCAAAGAAGGGCGGGTGACCACAGGAGTGTCTAGC 7843 QUERY : 7918 ATCGCCAGCGAAGATAGCCGCAAGGTGGCATCTGTGCTGAACAACGCCTACTACCTGGAC 7977 SBJCT : 7844 ATCGCCAGTGAGGACAGCCGCAAGGTAGCATCCGTGTTGAACAATGCCTACTACTTAGAC 7903 QUERY : 7978 AAGATGCACTACAGCATCGAGGGCAAGGACACCCACTACTTTGTGAAGATTGGCTCAGCC 8037 111111|11111111|1111111111111111 11111111111111111 111 1 11 SBJCT : 7904 AAGATGCACTACAGCATCGAGGGCAAGGACACACACTACTTTGTGAAGATCGGCGCCGCG 7963 QUERY : 8038 GATGGCGACCTGGTCACACTAGGCACCACCATCGGCCGCAAGGTGCTAGAGAGCGGGGTG 8097 mn nmmm nm mntn ! < nnnm ! !) n n mm SBJCT : 7964 GATGGTGACCTGGTCACGCTAGGAACCACCATTGGGCGCAAGGTGCTGGAGAGTGGGGTG 8023 QUERY : 8098 AACGTGACCGTGTCCCAGCCCACGCTGCTGGTCAACGGCAGGACTCGAAGGTTCACGAAC 8157 Illlllll IIIII IIIIIIIIIIIIIIIII II IIIIIIIIIIIIIIIIIIII III SBJCT : 8024 AACGTGACGGTGTCACAGCCCACGCTGCTGGTGAATGGCAGGACTCGAAGGTTCACCAAC 8083 QUERY : 8158 ATTGAGTTCCAGTACTCCACGCTGCTGCTCAGCATCCGCTATGGCCTCACCCCCGACACC 8217 11111111111111111111111111111111 11111111 11111111111111111 SBJCT : 8084 ATTGAGTTCCAGTACTCCACGCTGCTGCTCAGTATCCGCTACGGCCTCACCCCCGACACG 8143 QUERY : 8218 CTGGACGAAGAGAAGGCCCGCGTCCTGGACCAGGCGAGACAGAGGGCCCTGGGCACGGCC 8277 111111111t1 11111111111111111111 111 lltllll 11111111 11 111 SBJCT : 8144 CTGGACGAAGAAAAGGCCCGCGTCCTGGACCAAGCGGGACAGAGAGCCCTGGGTACTGCC 8203 QUERY : 8278 TGGGCCAAGGAGCAGCAGAAAGCCAGGGACGGGAGAGAGGGGAGCCGCCTGTGGACTGAG 8337 11111111111111111111111111111111111111111 11111111111111 111 SBJCT : 8204 TGGGCCAAGGAGCAGCAGAAAGCCAGGGACGGGAGAGAGGGCAGCCGCCTGTGGACGGAG 8263 QUERY : 8338 GGCGAGAAGCAGCAGCTTCTGAGCACCGGGCGCGTGCAAGGGTACGAGGGATATTACGTG 8397 11111111111111 11 11111111 11 11 11 11111 11 11111 11111111 SBJCT : 8264 GGCGAGAAGCAGCAACTCCTGAGCACGGGACGGGTACAAGGTTATGAGGGCTATTACGTA 8323 QUERY : 8398 CTTCCCGTGGAGCAATACCCAGAGCTTGCAGACAGTAGCAGCAACATCCAGTTTTTAAGA 8457 11111 11111 11 11111 11111 11111111111111111111111111 111111 SBJCT : 8324 CTTCCGGTGGAACAGTACCCGGAGCTGGCAGACAGTAGCAGCAACATCCAGTTCTTAAGA 8383 QUERY : 8458 CAGAATGAGATGGGAAAGAGGTAACAAAATAATCTGCTGCCATTCCTTGTCTGAATGGCT 8517 11111111111111111111111111111111 111111111 111 1111 11111 SBJCT : 8384 CAGAATGAGATGGGAAAGAGGTAACAAAATAACCTGCTGCCACCTCTTCTCTGGGTGGCT 8443 QUERY : 8518 CAGCAGGAGTAACTGTTATCTCCTCTCCTAAGGAGATGAAGACCTAACAGGGGCACTGCG 8577 111111111 111111 1 11111111111111111 11111111111 111111111 1 SBJCT : 8444 CAGCAGGAGCAACTGTGACCTCCTCTCCTAAGGAGACGAAGACCTAAC-GGGGCACTGAG 8502 QUERY : 8578 GCTGGGCTGCTTTAGGAGACCAAGTGGCAAGAAAGCTCACATTTTTTGAGTTCAAATGCT 8637 11 11111111111111 11111111111111111111111111111111111111111 SBJCT : 8503 GCCGGGCTGCTTTAGGATCCCAAGTGGCAAGAAAGCTCACATTTTTTGAGTTCAAATGCT 8562 QUERY : 8638 ACTGTCCAAGCGAGAAGTCCCTCATCCTGAAGTAGACTAAAGCCCGGC 8685 Illlll IIIII IIIIIIIIIIIIIIIIIIIIIIIII IIIIIIII SBJCT : 8563 ACTGTCTAAGCGCAAAGTCCCTCATCCTGAAGTAGACTAGAGCCCGGC 8610 SCORE = 1570 BITS (792), EXPECT = 0. 0 IDENTITIES = 1095/1196 (91%) STRAND = PLUS/PLUS QUERY : 270 ATCTGGAATAATGGATGTAAAGGACCGGCGACACCGCTCTTTGACCAGAGGACGCTGTGG 329 Illllllllllllllllllllllllllllllll 11111111111111 11111 11111 SBJCT : 103 ATCTGGAATAATGGATGTAAAGGACCGGCGACATCGCTCTTTGACCAGGGGACGGTGTGG 162 QUERY :'330 CAAAGAGTGTCGCTACACAAGCTCCTCTCTGGACAGTGAGGACTGCCGGGTGCCCACACA 389 I SBJCT : 163 CAAAGAGTGTCGCTACACCAGCTCCTCTCTGGACAGTGAGGACTGCCGTGTGCCCACTCA 222 QUERY : 390 GAAATCCTACAGCTCCAGTGAGACTCTGAAGGCCTATGACCATGACAGCAGGATGCACTA 449 111 11111111 11111111111 1111111 11111111111111111 11111111

SBJCT : 223 GAAGTCCTACAGTTCCAGTGAGACCTTGAAGGCTTATGACCATGACAGCAGAATGCACTA 282 QUERY : 450 TGGAAACCGAGTCACAGACCTCATCCACCGGGAGTCAGATGAGTTTCCTAGACAAGGAAC 509 111111111111111111111 1 1111111|111 111111|11 1111111111 11 SBJCT : 283 TGGAAACCGAGTCACAGACCTGGTGCACCGGGAGTCCGATGAGTTTTCTAGACAAGGGAC 342 QUERY : 510 CAACTTCACCCTTGCCGAACTGGGCATCTGTGAGCCCTCCCCACACCGAAGCGGCTACTG 569 IIIIIIIIIII II III IIII IIIII IIIIIIIIIIIIIIIIIIII II IIIII SBJCT : 343 AAACTTCACCCTGGCAGAATTGGGAATCTGCGAGCCCTCCCCACACCGAAGTGGTTACTG 402 QUERY : 570 CTCCGACATGGGGATCCTTCACCAGGGCTACTCCCTTAGCACAGGGTCTGACGCCGACTC 629 SBJCT : 403 TTCCGACATGGGTATCCTCCACCAGGGCTACTCCCTGAGCACTGGGTCTGATGCAGACTC 462 QUERY : 630 CGACACCGAGGGAGGGATGTCTCCAGAACACGCCATCAGACTGTGGGGCAGAGGGATAAA 689 Illllllllllllllllllllllllllll IIIIIIIIIIIIIIIII IIIIIIIIII SBJCT : 463 GGACACCGAGGGAGGGATGTCTCCAGAACATGCCATCAGACTGTGGGGACGAGGGATAAA 522 QUERY : 690 ATCCAGGCGCAGTTCCGGCCTGTCCAGTCGTGAAAACTCGGCCCTTACCCTGACTGACTC 749 111111111111 11 111 1111111 11 11 11111111111111 11111111111 SBJCT : 523 ATCCAGGCGCAGCTCTGGCTTGTCCAGCCGCGAGAACTCGGCCCTTACTCTGACTGACTC 582 QUERY : 750 TGACAACGAAAACAAATCAGATGATGAGAACGGTCGTCCCATTCCACCTACATCCTCGCC 809 IIIIII IIIII IIIII illll II II IIIIIIIiiIIIlIlllllllllllll I SBJCT : 583 TGACAATGAAAATAAATCGGATGACGACAATGGTCGTCCCATTCCACCTACATCCTCGTC 642 QUERY : 810 TAGTCTCCTCCCATCTGCTCAGCTGCCTAGCTCCCATAATCCTCCACCAGTTAGCTGCCA 869 111 11111111111111111111111111111111111111111111111111111111 SBJCT : 643 TAGCCTCCTCCCATCTGCTCAGCTGCCTAGCTCCCATAATCCTCCACCAGTTAGCTGCCA 702 QUERY : 870 GATGCCATTGCTAGACAGCAACACCTCCCATCAAATCATGGACACCAACCCTGATGAGGA 929 111111111111111111111111111111111 11111111111111111111111111 SBJCT : 703 GATGCCATTGCTAGACAGCAACACCTCCCATCAGATCATGGACACCAACCCTGATGAGGA 762 ) m m m m m) m m m m m) m m m m m m m m m QUERY : 930 ATTCTCCCCCAATTCATACCTGCTCAGAGCATGCTCAGGGCCCCAGCAAGCCTCCAGCAG 989 111111111111111111111111111111111111111111111111111111111p11 SBJCT : 763 ATTCTCCCCCAATTCATACCTGCTCAGAGCATGCTCAGGGCCCCAGCAAGCCTCCAGCAG 822 QUERY : 990 TGGCCCTCCGAACCACCACAGCCAGTCGACTCTGAGGCCCCCTCTCCCACCCCCTCACAA 1049 I SBJCT : 823 TGGCCCTCCAAACCACCACAGCCAGTCAACACTGAGGCCCCCTCTGCCACCCCCTCATAA 882 QUERY : 1050 CCACACGCTGTCCCATCACCACTCGTCCGCCAACTCCCTCAACAGGAACTCACTGACCAA 1109 111111 11111111 11111111 11 111|1111111111111111111111111111 SBJCT : 883 CCACACCCTGTCCCACCACCACTCCTCGGCCAACTCCCTCAACAGGAACTCACTGACCAA 942 QUERY : 1110 TCGGCGGAGTCAGATCCACGCCCCGGCCCCAGCGCCCAATGACCTGGCCACCACACCAGA 1169 11111t111111 11111111111 11 11 11111111 11111111111111 11111 SBJCT : 943 TCGGCGGAGTCAAATCCACGCCCCAGCTCCTGCGCCCAACGACCTGGCCACCACCCCAGA 1002 QUERY : 1170 GTCCGTTCAGCTTCAGGACAGCTGGGTGCTAAACAGCAACGTGCCACTGGAGACCCGGCA 1229 111 11111111 11111 11111111111 11111 11111 11111111111 11111 SBJCT : 1003 GTCTGTTCAGCTCCAGGATAGCTGGGTGCTGAACAGTAACGTCCCACTGGAGACTCGGCA 1062 QUERY : 1230 CTTCCTCTTCAAGACCTCCTCGGGGAGCACACCCTTGTTCAGCAGCTCTTCCCCGGGATA 1289 IIIIII IIIII I II II II IIIIIIIII IIIIIIIIIIIIIII III SBJCT : 1063 CTTCCTTTTCAAAACGTCGTCTGGAAGCACACCCCTGTTCAGCAGCTCTTCTCCGGGATA 1122 QUERY : 1290 CCCTTTGACCTCAGGAACGGTTTACACGCCCCCGCCCCGCCTGCTGCCCAGGAATACTTT 1349 Illllllllllllli I Ilill II II II llllllllllllll IIIIIII II SBJCT : 1123 CCCTTTGACCTCAGGGACCGTTTATACACCACCACCCCGCCTGCTGCCACGGAATACATT 1182 QUERY : 1350 CTCCAGGAAGGCTTTCAAGCTGAAGAAGCCCTCCAAATACTGCAGCTGGAAATGTGCTGC 1409 111111111111 11111111111111 11111111111111111 1111|1111111|1 SBJCT : 1183 CTCCAGGAAGGCCTTCAAGCTGAAGAAACCCTCCAAATACTGCAGTTGGAAATGTGCTGC 1242 QUERY : 1410 CCTCTCCGCCATTGCCGCGGCCCTCCTCTTGGCTATTTTGCTGGCGTATTTCATAG 1465 III II III IIII IIIIIIIIIIII IIII III SBJCT : 1243 CCTGTCTGCCATCGCCGCCGCCCTCCTCTTGGCCATTTTGCTGGCATATTTCATAG 1298

SCORE = 1455 BITS (734), EXPECT = 0. 0 IDENTITIES = 1000/1088 (91%), GAPS = 3/1088 (0%) STRAND = PLUS/PLUS QUERY : 1464 AGTGCCCTGGTCGTTGAAAAACAGCAGCATAGACAGTGGTGAAGCAGAAGTTGGTCGGCG 1523 111111111111. 11111111111111111111111111 11111111111111111111 SBJCT : 1420 AGTGCCCTGGTCATTGAAAAACAGCAGCATAGACAGTGGCGAAGCAGAAGTTGGTCGGCG 1479 QUERY : 1524 GGTAACACAAGAAGTCCCACCAGGGGTGTTTTGGAGGTCACAAATTCACATCAGTCAGCC 1583 II IIII IIIIIIIIIIIIIIIIIIIIIIIII II IIIIIIIIIII SBJCT : 1480 GGTGACACAGGAAGTCCCACCAGGGGTGTTTTGGAGGTCCCAGATTCACATCAGTCAGCC 1539 QUERY : 1584 CCAGTTCTTAAAGTTCAACATCTCCCTCGGGAAGGACGCTCTCTTTGGTGTTTACATAAG 1643 II 111|1111111111111111111 11 11111 11 11111 11111 11 11111 SBJCT : 1540 TCAATTCTTAAAGTTCAACATCTCCCTGGGCAAGGATGCCCTCTTCGGTGTCTATATAAG 1599 QUERY : 1644 AAGAGGACTTCCACCATCTCATGCCCAGTATGACTTCATGGAACGTCTGGACGGGAAGGA 1703 11111111 11111 11111111111111111111111111111 11111 11 11111 SBJCT : 1600 GAGAGGACTACCACCGTCTCATGCCCAGTATGACTTCATGGAACGCCTGGATGGAAAGGA 1659 QUERY : 1704 GAAGTGGAGTGTGGTTGAGTCTCCCAGGGAACGCCGGAGCATACAGACCTTGGTTCAGAA 1763 III IIIII Illll IIIII IIIIllllllllllllllll IIIII IIII IIIII SBJCT : 1660 GAAATGGAGCGTGGTCGAGTCGCCCAGGGAACGCCGGAGCATCCAGACTCTGGTGCAGAA 1719 QUERY : 1764 TGAAGCCGTGTTTGTGCAGTACCTGGATGTGGGCCTGTGGCATCTGGCCTTCTACAATGA 1823 II 11 111111111111111 1111111111111111111 11111111111111111 SBJCT : 1720 CGAGGCTGTGTTTGTGCAGTACTTGGATGTGGGCCTGTGGCACCTGGCCTTCTACAATGA 1779 QUERY : 1824 TGGAAAAGACAAAGAGATGGTTTCCTTCAATACTGTTGTCCTAGATTCAGTGCAGGACTG 1883 IIIII SBJCT : 1780 CGGCAAGGACAAGGAGATGGTCTCCTTCAACACTGTTGTCTTAGATTCAGTGCAGGACTG 1839 QUERY : 1884 TCCACGTAACTGCCATGGGAATGGTGAATGTGTGTCCGGGGTGTGTCACTGTTTCCCAGG 1943 I SBJCT : 1840 TCCACGGAACTGTCACGGGAACGGTGAATGCGTGTCTGGACTGTGTCACTGTTTCCCAGG 1899 QUERY : 1944 ATTTCTAGGAGCAGACTGTGCTAAAGCTGCCTGCCCTGTCCTGTGCAGTGGGAATGGACA 2003 111 11111 11111111111111111111111111111 11111111 11 11111111 SBJCT : 1900 ATTCCTAGGTGCAGACTGTGCTAAAGCTGCCTGCCCTGTACTGTGCAGCGGAAATGGACA 1959 QUERY : 2004 ATATTCTAAAGGGACGTGCCAGTGCTACAGCGGCTGGAAAGGTGCAGAGTGCGACGTGCC 2063 IIIIIIIIIII IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII Il Illll SBJCT : 1960 GTATTCTAAAGGAACGTGCCAGTGCTACAGCGGCTGGAAAGGTGCAGAGTGTGATGTGCC 2019 QUERY : 2064 CATGAATCAGTGCATCGATCCTTCCTGCGGGGGCCACGGCTCCTGCATTGATGGGAACTG 2123 11111 11 11 11111111111111 11111111 11111111111111111111111 SBJCT : 2020 TATGAACCAATGTATCGATCCTTCCTGTGGGGGCCATGGCTCCTGCATTGATGGGAACTG 2079 QUERY : 2124 TGTCTGCTCTGCTGGCTACAAAGGCGAGCACTGTGAGGAAGTTGATTGCTTGGATCCCAC 2183 II Il lllllllllllll IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII ll SBJCT : 2080 CGTGTGTGCTGCTGGCTACAAGGGCGAGCACTGTGAGGAAGTTGATTGCTTGGATCCTAC 2139 QUERY : 2184 CTGCTCCAGCCACGGAGTCTGTGTGAATGGAGAATGCCTGTGCAGCCCTGGCTGGGGTGG 2243 I SBJCT : 2140 CTGCTCCAGCCATGGTGTCTGTGTGAATGGAGAGTGTCTATGCAGCCCCGGCTGGGGTGG 2199 QUERY : 2244 TCTGAACTGTGAGCTGGCGAGGGTCCAGTGCCCAGACCAGTGCAGTGGGCATGGCACGTA 2303 111 11111111111111111111111111111111111111 11111111111111 11 SBJCT : 2200 TCTCAACTGTGAGCTGGCGAGGGTCCAGTGCCCAGACCAGTGTAGTGGGCATGGCACTTA 2259 QUERY : 2304 CCTGCCTGACACGGGCCTCTGCAGCTGCGATCCCAACTGGATGGGTCCCGACTGCTCTGT 2363 III IIIIII 1 IIIIIIIIIIIIII 11111 11111111111111111111111111 SBJCT : 2260 CCTCCCTGACTCCGGCCTCTGCAGCTGTGATCCGAACTGGATGGGTCCCGACTGCTCTGT 2319 QUERY : 2364 TGAAGTGTGCTCAGTAGACTGTGGCACTCACGGCGTCTGCATCGGGGGAGCCTGCCGCTG 2423 11111111111111111111111111111111111111111111111111111111 SBJCT : 2320 T---GTGTGCTCAGTAGACTGTGGCACTCACGGCGTCTGCATCGGGGGAGCCTGCCGCTG 2376 QUERY : 2424 TGAAGAGGGCTGGACAGGCGCAGCGTGTGACCAGCGCGTGTGCCACCCCCGCTGCATTGA 2483 lillllllllllllllllllllll Illlllllllllllllllllllllllllillllll

SBJCT : 2377 TGAAGAGGGCTGGACAGGCGCAGCTTGTGACCAGCGCGTGTGCCACCCCCGCTGCATTGA 2436 QUERY : 2484 GCACGGGACCTGTAAAGATGGCAAATGTGAATGCCGAGAGGGCTGGAATGGTGAACACTG 2543 II SBJCT : 2437 GCACGGGACCTGTAAAGATGGCAAATGTGAATGCCGAGAGGGCTGGAATGGTGAACACTG 2496 QUERY : 2544 CACCATTG 2551 ######## SBJCT : 2497 CACCATTG 2504 SCORE = 105 BITS (53), EXPECT = 5E-19 IDENTITIES = 81/89 (91%), GAPS = 1/89 (1%) STRAND = PLUS/PLUS QUERY : 8711 AACGAATGAATGAACAGACACACACAATGTTCCAAGTTCCCCTAAAATATGACCCACTTG 8770 iiiiii iiiiiii I liiiiii liiiii SBJCT : 8655 AACGAACGAATGAAAACACACACAAAATGTTTCAAGTTCCCCTAAAATATGACCCACTTG 8714 QUERY : 8771 TTCTGGGTCT-ACGCAGAAAAGAGACGCA 8798 III IIIIII 1 IIIIIIIIIIIIIIII SBJCT : 8715 TTCCGGGTCTAAGGCAGAAAAGAGACGCA 8743 SCORE = 48. 1 BITS (24), EXPECT = 0. 093 IDENTITIES = 30/32 (93%) STRAND = PLUS/PLUS QUERY : 475 CACCGGGAGTCAGATGAGTTTCCTAGACAAGG 506 SBJCT : 7 CACCGGGAGTCCGATGAGTTTTCTAGACAAGG 38 In this search it was also found that the FCTR3bcd and e nucleic acids had homology to three fragments of Rattus norvegicus neurestin alpha. It has 5498 of 6132 bases (89%) identical to bases 2527-8658, 1081 of 1196 bases (90%) identical to bases 123-1318, 996 of 1088 bases (91%) identical to bases 1440-2527 of Rattus norvegcus neurestin alpha (GenBank Acc : NM_020088. 1) (Table 3N).

Table 3N. BLASTN of FCTR3b, c, d, and e against Rattus norvegicus Neurestin alpha mRNA (SEQ ID NO : 66) >GI199103191REFINM 020088. 11 RATTUS NORVEGICUS NEURESTIN ALPHA (LOC56762), MRNA LENGTH = 8689 SCORE = 7129 BITS (3596), EXPECT = 0. 0 IDENTITIES = 5498/6132 (89%) STRAND = PLUS/PLUS QUERY : 2578 GATGGCTGCCCTGACTTGTGCAACGGTAACGGGAGATGCACACTGGGTCAGAACAGCTGG 2637 IIIIIIIIIIIIII Illllllllllllllllllllllllllllllllllllllllllll SBJCT : 2527 GATGGCTGCCCTGATTTGTGCAACGGTAACGGGAGATGCACACTGGGTCAGAACAGCTGG 2586 QUERY : 2638 CAGTGTGTCTGCCAGACCGGCTGGAGAGGGCCCGGATGCAACGTTGCCATGGAAACTTCC 2697 IIIIIIIIIIIIIIIIIIIIIIII. lllllllllllllllllllllillllllllll III SBJCT : 2587 CAGTGTGTCTGCCAGACCGGCTGGAGAGGGCCCGGATGCAACGTTGCCATGGAAACCTCC 2646 QUERY : 2698 TGTGCTGATAACAAGGATAATGAGGGAGATGGCCTGGTGGATTGTTTGGACCCTGACTGC 2757 II 11111111111111111111111111111111111111 11 11111111111111 SBJCT : 2647 TGCGCTGATAACAAGGATAATGAGGGAGATGGCCTGGTGGACTGCCTGGACCCTGACTGC 2706 QUERY : 2758 TGCCTGCAGTCAGCCTGTCAGAACAGCCTGCTCTGCCGGGGGTCCCGGGACCCACTGGAC 2817 11111 11111111111111111111111111111 11111111 11111111 11111 SBJCT : 2707 TGCCTCCAGTCAGCCTGTCAGAACAGCCTGCTCTGTCGGGGGTCTCGGGACCCCTTGGAC 2766 QUERY : 2818 ATCATTCAGCAGGGCCAGACGGATTGGCCCGCAGTGAAGTCCTTCTATGACCGTATCAAG 2877 lllllllllll llllllll II IIIII ll lllllllllllllllll lllllllll SBJCT : 2767 ATCATTCAGCAAGGCCAGACAGACTGGCCTGCGGTGAAGTCCTTCTATGATCGTATCAAG 2826

QUERY : 2878 CTCTTGGCAGGCAAGGATAGCACCCACATCATTCCTGGAGAGAACCCTTTCAACAGCAGC 2937 11111111111111111 11111111111111111111111 11111 11111 111111 SBJCT : 2827 CTCTTGGCAGGCAAGGACAGCACCCACATCATTCCTGGAGACAACCCCTTCAATAGCAGC 2886 QUERY : 2938 TTGGTTTCTCTCATCCGAGGCCAAGTAGTAACTACAGATGGAACTCCCCTGGTCGGTGTG 2997 IIII IIIII IIIIIIIIIIIlIIIIIIII II ! IlII II Illlllll llllll SBJCT : 2887 CTGGTGTCTCTGATCCGAGGCCAAGTAGTAACCACGGATGGGACCCCCCTGGTGGGTGTG 2946 QUERY : 2998 AACGTGTCTTTTGTCAAGTACCCAAAATACGGCTACACCATCACCCGCCAGGATGGCACG 3057 II 11111111111111111111111111 11111111111111 11111111 111111 SBJCT : 2947 AATGTGTCTTTTGTCAAGTACCCAAAATATGGCTACACCATCACTCGCCAGGACGGCACG 3006 QUERY : 3058 TTCGACCTGATCGCAAATGGAGGTGCTTCCTTGACTCTACACTTTGAGCGAGCCCCGTTC 3117 SBJCT : 3007 TTTGACCTGATTGCCAATGGGGGCTCTGCCTTGACTCTTCACTTTGAGCGAGCCCCTTTC 3066 QUERY : 3118 ATGAGCCAGGAGCGCACTGTGTGGCTGCCGTGGAACAGCTTTTACGCCATGGACACCCTG 3177 m ! m m m m N n ! ! n n nnn ! n n ! t t n n m n n m SBJCT : 3067 ATGAGCCGGGAGCGCACAGTATGGCCGCCGTGGAACAGCTTCTATGCCATGGACACCCTG 3126 QUERY : 3178 GTGATGAAGACCGAGGAGAACTCCATCCCCAGCTGTGACCTCAGTGGCTTTGTCCGGCCT 3237 II IIIllll IIIIIIIIIIllllllllllllllllllllllll SBJCT : 3127 GTAATGAAGACGGAGGAGAACTCCATCCCCAGCTGTGACCTCAGTGGCTTTGTCCGGCCT 3186 QUERY : 3238 GATCCAATCATCATCTCCTCCCCACTGTCCACCTTCTTTAGTGCTGCCCCTGGGCAGAAT 3297 Illil IIIIIIIIIIIIII II IIIIIIIIIIIIII II III IIIIII I III SBJCT : 3187 GATCCGATCATCATCTCCTCTCCTCTGTCCACCTTCTTCAGCGCTTCCCCTGCGGCGAAC 3246 QUERY : 3298 CCCATCGTGCCTGAGACCCAGGTTCTTCATGAAGAAATCGAGCTCCCTGGTTCCAATGTG 3357 11111 11111111111111111111111111 11 11111111111111 1111 111 SBJCT : 3247 CCCATTGTGCCTGAGACCCAGGTTCTTCATGAGGAGATCGAGCTCCCTGGCACCAACGTG 3306 QUERY : 3358 AAACTTCGCTATCTGAGCTCTAGAACTGCAGGGTACAAGTCACTGCTGAAGATCACCATG 3417 II II II II II Iilll IIIII IIIIIIIIIIIIIIIIIIIIIIfllllllflll SBJCT : 3307 AAGCTCCGTTACCTCAGCTCCAGAACAGCAGGGTACAAGTCACTGCTGAAGATCACCATG 3366 QUERY : 3418 ACCCAGTCCACAGTGCCCCTGAACCTCATTAGGGTTCACCTGATGGTGGCTGTCGAGGGG 3477 11111111111 111111 1111111111 11111111 1111111 11 11 111111 SBJCT : 3367 ACCCAGTCCACGGTGCCCTTGAACCTCATCCGGGTTCACTTGATGGTTGCCGTGGAGGGG 3426 QUERY : 3478 CATCTCTTCCAGAAGTCATTCCAGGCTTCTCCCAACCTGGCCTCCACCTTCATCTGGGAC 3537 Illlllllllllllill Illllllllllllllllllllllll III IIIIIIIIIIII SBJCT : 3427 CATCTCTTCCAGAAGTCGTTCCAGGCTTCTCCCAACCTGGCCTACACATTCATCTGGGAC 3486 QUERY : 3538 AAGACAGATGCGTATGGCCAAAGGGTGTATGGACTCTCAGATGCTGTTGTGTCTGTCGGG 3597 11111111 11 11111111111111 11111 11 11 11111111111111111 11 SBJCT : 3487 AAGACAGACGCTTATGGCCAAAGGGTTTATGGCCTATCGGATGCTGTTGTGTCTGTTGGA 3546 QUERY : 3598 TTTGAATATGAGACCTGTCCCAGTCTAATTCTCTGGGAGAAAAGGACAGCCCTCCTTCAG 3657 IIIllllll II SBJCT : 3547 TTTGAATATGAGACCTGCCCCAGTCTCATCCTGTGGGAAAAAAGGACAGCCCTACTTCAA 3606 QUERY : 3658 GGATTCGAGCTGGACCCCTCCAACCTCGGTGGCTGGTCCGTAGACAAACACCACATCCTC 3717 lllllllllllllllll IIIIIIII IIIIIIIIIIIIII li II IIIIIII Illl SBJCT : 3607 GGATTCGAGCTGGACCCTTCCAACCTTGGTGGCTGGTCCCTGGATAAGCACCACACCCTC 3666 QUERY : 3718 AATGTTAAAAGTGGAATCCTACACAAAGGCACTGGGGAAAACCAGTTCCTGACCCAGCAG 3777 11111 11111 11111 1111 111111111 11111 111111111111111111111 SBJCT : 3667 AATGTGAAAAGCGGAATACTACTCAAAGGCACAGGGGAGAACCAGTTCCTGACCCAGCAG 3726 QUERY : 3778 CCTGCCATCATCACCAGCATCATGGGCAATGGTCGCCGCCGGAGCATTTCCTGTCCCAGC 3837 II 11111111111111111|11111 11 111111111 1 11111 111111111111 SBJCT : 3727 CCCGCCATCATCACCAGCATCATGGGTAACGGTCGCCGCAGAAGCATCTCCTGTCCCAGC 3786 QUERY : 3838 TGCAACGGCCTTGCTGAAGGCAACAAGCTGCTGGCCCCAGTGGCTCTGGCTGTTGGAATC 3897 II SBJCT : 3787 TGCAATGGCCTTGCTGAAGGCAACAAACTGTTGGCCCCCGTGGCCCTGGCTGTGGGGATC 3846 QUERY : 3898 GATGGGAGCCTCTATGTGGGTGACTTCAATTACATCCGACGCATCTTTCCCTCTCGAAAT 3957

m m m m im m m m m n m n m m n n m m n SBJCT : 3847 GATGGGAGCCTCTTTGTCGGTGACTTCAATTATATCCGGCGCATCTTCCCTTCTCGAAAC 3906 QUERY : 3958 GTGACCAGCATCTTGGAGTTACGAAATAAAGAGTTTAAACATAGCAACAACCCAGCACAC 4017 Illlllll IIIIlllllllllllllllllllllllillllllllllll IIIII Illl SBJCT : 3907 GTGACCAGTATCTTGGAGTTACGAAATAAAGAGTTTAAACATAGCAACAGCCCAGGACAC 3966 QUERY : 4018 AAGTACTACTTGGCAGTGGACCCCGTGTCCGGCTCGCTCTACGTGTCCGACACCAACAGC 4077 11111111111111 IIIIIIII Ill I IIIIIIIIIII II II IIIIIIIIIII SBJCT : 3967 AAGTACTACTTGGCTGTGGACCCTGTGACTGGCTCGCTCTATGTCTCTGACACCAACAGT 4026 QUERY : 4078 AGGAGAATCTACCGCGTCAAGTCTCTGAGTGGAACCAAAGACCTGGCTGGGAATTCGGAA 4137 I 1 11111111 11111111111 11 111 11111111111111111111121111 SBJCT : 4027 CGCCGGATCTACCGAGTCAAGTCTCTAAGCGGAGCCAAAGACCTGGCTGGGAATTCGGAA 4086 QUERY : 4138 GTTGTGGCAGGGACGGGAGAGCAGTGTCTACCCTTTGATGAAGCCCGCTGCGGGGATGGA 4197 m n m m n) i)) n u u) i) n n i) u))) n n i))) u u)) M SBJCT : 4087 GTTGTGGCCGGGACTGGCGAACAATGTCTACCCTTTGATGAAGCCCGCTGTGGGGATGGC 4146 QUERY : 4198 GGGAAGGCCATAGATGCAACCCTGATGAGCCCGAGAGGTATTGCAGTAGACAAGAATGGG 4257 11111111 1 11111 11111111111111 11111111111111111111111 111 SBJCT : 4147 GGGAAGGCTGTGGATGCCACCCTGATGAGCCCTAGAGGTATTGCAGTAGACAAGAACGGG 4206 QUERY : 4258 CTCATGTACTTTGTCGATGCCACCATGATCCGGAAGGTTGACCAGAATGGAATCATCTCC 4317 II 11111 11111 11111111111111111111111 11111 1111111111111} 1 SBJCT : 4207 CTTATGTATTTTGTTGATGCCACCATGATCCGGAAGGTCGACCAAAATGGAATCATCTCC 4266 QUERY : 4318 ACCCTGCTGGGCTCCAATGACCTCACTGCCGTCCGGCCGCTGAGCTGTGATTCCAGCATG 4377 Illlllllllllllllllllllllll 11 Illll 11 11111111111 11 111111 SBJCT : 4267 ACCCTGCTGGGCTCCAATGACCTCACAGCTGTCCGACCACTGAGCTGTGACTCTAGCATG 4326 QUERY : 4378 GATGTAGCCCAGGTTCGTCTGGAGTGGCCAACAGACCTTGCTGTCAATCCCATGGATAAC 4437 II 11 11111111 11111 11 lllll 11111111111 11111 11111111 11 SBJCT : 4327 GACGTGGCCCAGGTCCGTCTAGAATGGCCGACAGACCTTGCGGTCAACCCCATGGACAAT 4386 QUERY : 4438 TCCTTGTATGTTCTAGAGAACAATGTCATCCTTCGAATCACCGAGAACCACCAAGTCAGC 4497 III IIII II II lillllll IIIIIIII II IIIIlllllll Illll Illlll SBJCT : 4387 TCCCTGTACGTCCTGGAGAACAACGTCATCCTGCGGATCACCGAGAATCACCAGGTCAGC 4446 QUERY : 4498 ATCATTGCGGGACGCCCCATGCACTGCCAAGTTCCTGGCATTGACTACTCACTCAGCAAA 4557 11111 11111111 11111111111111 11111 11111 11111111 11111111 SBJCT : 4447 ATCATCGCGGGACGGCCCATGCACTGCCAGGTTCCCGGCATCGACTACTCGCTCAGCAAG 4506 QUERY : 4558 CTAGCCATTCACTCTGCCCTGGAGTCAGCCAGTGCCATTGCCATTTCTCACACTGGGGTC 4617 II 11111 11111111 11111111111111 11111 11111111111111 11111 SBJCT : 4507 CTCGCCATCCACTCTGCTCTGGAGTCAGCCAGCGCCATCGCCATTTCTCACACCGGGGTG 4566 QUERY : 4618 CTCTACATCACTGAGACAGATGAGAAGAAGATTAACCGTCTACGCCAGGTAACAACCAAC 4677 11111111111 11111 11 11111111111 11111 11111111111 11 111111 SBJCT : 4567 CTCTACATCACCGAGACGGACGAGAAGAAGATCAACCGCCTACGCCAGGTCACCACCAAC 4626 QUERY : 4678 GGGGAGATCTGCCTTTTAGCTGGGGCAGCCTCGGACTGCGACTGCAAAAACGATGTCAAT 4737 II 11111111111 11111 11111111111 11111 11111111111 11 11111 SBJCT : 4627 GGAGAGATCTGCCTCTTAGCCGGGGCAGCCTCAGACTGTGACTGCAAAAATGACGTCAAC 4686 QUERY : 4738 TGCAACTGCTATTCAGGAGATGATGCCTACGCGACTGATGCCATCTTGAATTCCCCATCA 4797 IIII IIIIIIIII Illlllll II Illll II IIIIIIIIIIIIII IIIII II SBJCT : 4687 TGCATCTGCTATTCGGGAGATGACGCATACGCCACGGATGCCATCTTGAACTCCCCGTCC 4746 QUERY : 4798 TCCTTAGCTGTAGCTCCAGATGGTACCATTTACATTGCAGACCTTGGAAATATTCGGATC 4857 11111111111 11111 11111 11111 11111 11111111 11 11111 IIIIII SBJCT : 4747 TCCTTAGCTGTGGCTCCGGATGGCACCATCTACATCGCAGACCTCGGGAATATCCGGATC 4806 QUERY : 4858 AGGGCGGTCAGCAAGAACAAGCCTGTTCTTAATGCCTTCAACCAGTATGAGGCTGCATCC 4917 11111111111111 11111 11111111111 11 11111111|11111111111 11 SBJCT : 4807 AGGGCGGTCAGCAAAAACAAACCTGTTCTTAACGCGTTCAACCAGTATGAGGCTGCGTCT 4866 QUERY : 4918 CCCGGAGAGCAGGAGTTATATGTTTTCAACGCTGATGGCATCCACCAATACACTGTGAGC 4977 II IIII IIIII I II II IIIIII III lllll II I SBJCT : 4867 CCGGGAGAACAGGAACTGTACGTGTTCAACGCCGATGGTATCCATCAGTACACCGTGAGC 4926

QUERY : 4978 CTGGTGACAGGGGAGTACTTGTACAATTTCACATATAGTACTGACAATGATGTCACTGAA 5037 IIIIIIII lllllllllll IIIIlllllll II II IIIIIIIIIIIIIIII 11 SBJCT : 4927 CTGGTGACCGGGGAGTACTTATACAATTTCACCTACAGCGCTGACAATGATGTCACCGAG 4986 QUERY : 5038 TTGATTGACAATAATGGGAATTCCCTGAAGATCCGTCGGGACAGCAGTGGCATGCCCCGT 5097 11111111111 11 11111111111 11111111 1111111111|111111111111 SBJCT : 4987 TTGATTGACAACAACGGGAATTCCCTAAAGATCCGCCGGGACAGCAGTGGCATGCCCCGA 5046 QUERY : 5098 CACCTGCTCATGCCTGACAACCAGATCATCACCCTCACCGTGGGCACCAATGGAGGCCTC 5157 11111111111111111 11 11111111111111 11 11111|11111 111111111 SBJCT : 5047 CACCTGCTCATGCCTGATAATCAGATCATCACCCTTACGGTGGGCACCAACGGAGGCCTC 5106 QUERY : 5158 AAAGTCGTGTCCACACAGAACCTGGAGCTTGGTCTCATGACCTATGATGGCAACACTGGG 5217 SBJCT : 5107 AAAGCCGTGTCAACGCAGAACCTGGAGCTGGGCCTCATGACTTATGATGGGAACACTGGA 5166 QUERY : 5218 CTCCTGGCCACCAAGAGCGATGAAACAGGATGGACGACTTTCTATGACTATGACCACGAA 5277 11111 11111111111111111111 11111111 11111 11111111111111111 SBJCT : 5167 CTCCTAGCCACCAAGAGCGATGAAACCGGATGGACAACTTTTTATGACTATGACCACGAG 5226 QUERY : 5278 GGCCGCCTGACCAACGTGACGCGCCCCACGGGGGTGGTAACCAGTCTGCACCGGGAAATG 5337 IIIII Illllill Illll Iillillllllilllll Illll IIIIIIIIIIIIIII SBJCT : 5227 GGCCGTCTGACCAATGTGACTCGCCCCACGGGGGTGGTGACCAGCCTGCACCGGGAAATG 5286 QUERY : 5338 GAGAAATCTATTACCATTGACATTGAGAACTCCAACCGTGATGATGACGTCACTGTCATC 5397 II SBJCT : 5287 GAGAAATCCATCACCGTTGACATTGAGAACTCCAACCGTGATAACGATGTCACTGTGATT 5346 QUERY : 5398 ACCAACCTCTCTTCAGTAGAGGCCTCCTACACAGTGGTACAAGATCAAGTTCGGAACAGC 5457 11111111111111111 11111111111111 11111111111111111 111111111 SBJCT : 5347 ACCAACCTCTCTTCAGTGGAGGCCTCCTACACCGTGGTACAAGATCAAGTGCGGAACAGC 5406 QUERY : 5458 TACCAGCTCTGTAATAATGGTACCCTGAGGGTGATGTATGCTAATGGGATGGGTATCAGC 5517 IIIIIIIIIII 1 ll II IIIIII I II Illll II ll ll IIIII 11111 SBJCT : 5407 TACCAGCTCTGCAGCAACGGGACCCTGCGCGTCATGTACGCCAACGGCATGGGCGTCAGC 5466 QUERY : 5518 TTCCACAGCGAGCCCCATGTCCTAGCGGGCACCATCACCCCCACCATTGGACGCTGCAAC 5577 11111111111111111 11111 1l 111111 1111111111111 11 11111 111 SBJCT : 5467 TTCCACAGCGAGCCCCACGTCCTCGCAGGCACCCTCACCCCCACCATCGGGCGCTGTAAC 5526 QUERY : 5578 ATCTCCCTGCCTATGGAGAATGGCTTAAACTCCATTGAGTGGCGCCTAAGAAAGGAACAG 5637 lllllllllll IIIIIIII III I IIIIIIII IIIIIIIIIII II IIIIIIIII SBJCT : 5527 ATCTCCCTGCCCATGGAGAACGGCCTGAACTCCATCGAGTGGCGCCTGAGGAAGGAACAG 5586 QUERY : 5638 ATTAAAGGCAAAGTCACCATCTTTGGCAGGAAGCTCCGGGTCCATGGAAGAAATCTCTTG 5697 IIIIIIIIIIIIIIIIIIIIIIIIII IIIIIIII IIIIIIII IIIII II III Il SBJCT : 5587 ATTAAAGGCAAAGTCACCATCTTTGGGAGGAAGCTTCGGGTCCACGGAAGGAACCTCCTG 5646 QUERY : 5698 TCCATTGACTATGATCGAAATATTCGGACTGAAAAGATCTATGATGACCACCGGAAGTTC 5757 11111111 11111 11111111 11 11111 11111111111 1111111111s1111 SBJCT : 5647 TCCATTGATTATGACCGAAATATCCGCACTGAGAAGATCTATGACGACCACCGGAAGTTC 5706 QUERY : 5758 ACCCTGAGGATCATTTATGACCAGGTGGGCCGCCCCTTCCTCTGGCTGCCCAGCAGCGGG 5817 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIII II SBJCT : 5707 ACCCTGAGGATCATTTATGACCAGGTGGGCCGCCCCTTCCTGTGGCTCCCCAGCAGTGGA 5766 QUERY : 5818 CTGGCAGCTGTCAACGTGTCATACTTCTTCAATGGGCGCCTGGCTGGGCTTCAGCGTGGG 5877 SBJCT : 5767 CTGGCGGCCGTCAATGTCTCCTACTTCTTCAACGGGCGCCTGGCCGGCCTCCAGCGCGGG 5826 QUERY : 5878 GCCATGAGCGAGAGGACAGACATCGACAAGCAAGGCCGCATCGTGTCCCGCATGTTCGCT 5937 11111111111111111111111 11111111111111 11 11111111 11111111 SBJCT : 5827 GCCATGAGCGAGAGGACAGACATTGACAAGCAAGGCCGGATTGTGTCCCGAATGTTCGCC 5886 QUERY : 5938 GACGGGAAAGTGTGGAGCTACTCCTACCTTGACAAGTCCATGGTCCTCCTGCTTCAGAGC 5997 II SBJCT : 5887 GACGGGAAAGTCTGGAGCTATTCCTACCTTGACAAGTCCATGGTCCTCCTGCTGCAGAGC 5946

QUERY : 5998 CAACGTCAGTATATATTTGAGTATGACTCCTCTGACCGCCTCCTTGCCGTCACCATGCCC 6057 II IIIIIIII IIIIIIII IIIIIIIIIIIIIIIIIIIIII II IIIIIIIIIII SBJCT : 5947 CAGCGTCAGTACATATTTGAATATGACTCCTCTGACCGCCTCCACGCAGTCACCATGCCC 6006 QUERY : 6058 AGCGTGGCCCGGCACAGCATGTCCACACACACCTCCATCGGCTACATCCGTAATATTTAC 6117 Il 11 11111111111111111111 11111111111 lililililil 11 111111 SBJCT : 6007 AGTGTCGCCCGGCACAGCATGTCCACGCACACCTCCATTGGCTACATCCGGAACATTTAC 6066 QUERY : 6118 AACCCGCCTGAAAGCAATGCTTCGGTCATCTTTGACTACAGTGATGACGGCCGCATCCTG 6177 IIIII II lillllll II Illlllllllllllfllllllllllllllllllllllll SBJCT : 6067 AACCCACCGGAAAGCAACGCCTCGGTCATCTTTGACTACAGTGATGACGGCCGCATCCTG 6126 QUERY : 6178 AAGACCTCCTTTTTGGGCACCGGACGCCAGGTGTTCTACAAGTATGGGAAACTCTCCAAG 6237 11111 11 11 1111111111 11111111111111 11111 11 lllll 111111 SBJCT : 6127 AAGACGTCTTTCCTGGGCACCGGGCGCCAGGTGTTCTATAAGTACGGAAAACTGTCCAAG 6186 QUERY : 6238 TTATCAGAGATTGTCTACGACAGTACCGCCGTCACCTTCGGGTATGACGAGACCACTGGT 6297 IIIII IIIII Illllllllll ll IIIIIIIIIIIIII IIIllllllllllllll SBJCT : 6187 TTATCGGAGATCGTCTACGACAGCACTGCCGTCACCTTCGGCTATGACGAGACCACTGGC 6246 QUERY : 6298 GTCTTGAAGATGGTCAACCTCCAAAGTGGGGGCTTCTCCTGCACCATCAGGTACCGGAAG 6357 111} 111111111 11 11111111 11111111111111 11111111111111 111 SBJCT : 6247 GTCCTGAAGATGGTGAATCTCCAAAGCGGGGGCTTCTCCTGTACCATCAGGTACCGAAAG 6306 QUERY : 6358 ATTGGCCCCCTGGTGGACAAGCAGATCTACAGGTTCTCCGAGGAAGGCATGGTCAATGCC 6417 1 11 11111 11111111111111 11111111111 1111|1111111 1111 111 SBJCT : 6307 GTCGGGCCCCTCGTGGACAAGCAGATTTACAGGTTCTCTGAGGAAGGCATGATCAACGCC 6366 QUERY : 6418 AGGTTTGACTACACCTATCATGACAACAGCTTCCGCATCGCAAGCATCAAGCCCGTCATA 6477 IIIII II IIIIlIII II IIIIIIIIIIIIIIIIIIII IIIIIIIIIIIIIIIII SBJCT : 6367 AGGTTCGATTACACCTACCACGACAACAGCTTCCGCATCGCCAGCATCAAGCCCGTCATC 6426 QUERY : 6478 AGTGAGACTCCCCTCCCCGTTGACCTCTACCGCTATGATGAGATTTCTGGCAAGGTGGAA 6537 IIIIIIIIIIIIII IIIlllllllllllllllll IIIIIIIIIIIIIIIIIIIIIIII SBJCT : 6427 AGTGAGACTCCCCTTCCCGTTGACCTCTACCGCTACGATGAGATTTCTGGCAAGGTGGAA 6486 QUERY : 6538 CACTTTGGTAAGTTTGGAGTCATCTATTATGACATCAACCAGATCATCACCACTGCCGTG 6597 11111 11 11111 11 11111111 11 11111111111111111111111111111 SBJCT : 6487 CACTTCGGCAAGTTCGGGGTCATCTACTACGACATCAACCAGATCATCACCACTGCCGTC 6546 QUERY : 6598 ATGACCCTCAGCAAACACTTCGACACCCATGGGCGGATCAAGGAGGTCCAGTATGAGATG 6657 11111 11111111 11111 11111111111111 11111111 11 111111111111 SBJCT : 6547 ATGACACTCAGCAAGCACTTTGACACCCATGGGCGCATCAAGGAAGTGCAGTATGAGATG 6606 QUERY : 6658 TTCCGGTCCCTCATGTACTGGATGACGGTGCAATATGACAGCATGGGCAGGGTGATCAAG 6717 11111111111111111111111111111111111111111 11111111111 111111 SBJCT : 6607 TTCCGGTCCCTCATGTACTGGATGACGGTGCAATATGACAGTATGGGCAGGGTCATCAAG 6666 QUERY : 6718 AGGGAGCTAAAACTGGGGCCCTATGCCAATACCACGAAGTACACCTATGACTACGATGGG 6777 )) m n n m) m) n mm)) m)) m mm) m m m ! m SBJCT : 6667 AGGGAACTGAAACTGGGGCCCTATGCCAACACCACAAAGTACACCTATGACTACGACGGG 6726 QUERY : 6778 GACGGGCAGCTCCAGAGCGTGGCCGTCAATGACCGCCCGACCTGGCGCTACAGCTATGAC 6837 IIIII I SBJCT : 6727 GACGGCCAGCTCCAGAGTGTGGCCGTCAATGACCGGCCTACCTGGCGTTATAGCTATGAC 6786 QUERY : 6838 CTTAATGGGAATCTCCACTTACTGAACCCAGGCAACAGTGTGCGCCTCATGCCCTTGCGC 6897 11 11111111 11 111 1 11 11111111 1111111 11111111111 11 1|1 SBJCT : 6787 CTCAATGGGAACCTGCACCTGCTAAACCCAGGAAACAGTGCTCGCCTCATGCCGTTACGC 6846 QUERY : 6898 TATGACCTCCGGGATCGGATAACCAGACTCGGGGATGTGCAGTACAAAATTGACGACGAT 6957 11111111111 11 11111111111 11 11111 11111111111111 11 11 111 SBJCT : 6B47 TATGACCTCCGTGACCGGATAACCAGGCTAGGGGACGTGCAGTACAAAATCGATGATGAT 6906 QUERY : 6958 GGCTATCTGTGCCAGAGAGGGTCTGACATCTTCGAATACAATTCCAAGGGCCTCCTAACA 7017 IIIIII I Illllllllll IIIIIIIIIII IIIIIIII IIIIIIIIIII IIIII SBJCT : 6907 GGCTATTTATGCCAGAGAGGATCTGACATCTTTGAATACAACTCCAAGGGCCTTCTAACG 6966 QUERY : 7018 AGAGCCTACAACAAGGCCAGCGGGTGGAGTGTCCAGTACCGCTATGATGGCGTAGGACGG 7077

Illll IIIIIIIIIIIIIIIIIIIIIIIIII IIIIIIIIIIIIIIIIIIII I Il SBJCT : 6967 AGAGCGTACAACAAGGCCAGCGGGTGGAGTGTGCAGTACCGCTATGATGGCGTGAGCCGC 7026 QUERY : 7078 CGGGCTTCCTACAAGACCAACCTGGGCCACCACCTGCAGTACTTCTACTCTGACCTCCAC 7137 11|111111111111|11111|1111111111111 11111111111 11 111111111 SBJCT : 7027 CGGGCTTCCTACAAGACCAACCTGGGCCACCACCTACAGTACTTCTATTCCGACCTCCAC 7086 QUERY : 7138 AACCCGACGCGCATCACCCATGTCTACAATCACTCCAACTCGGAGATTACCTCACTGTAC 7197 SBJCT : 7087 CACCCCACACGTATCACCCATGTTTACAACCACTCCAACTCTGAGATCACCTCACTCTAC 7146 QUERY : 7198 TACGACCTCCAGGGCCACCTCTTTGCCATGGAGAGCAGCAGTGGGGAGGAGTACTATGTT 7257 SBJCT : 7147 TATGACCTCCAGGGCCACCTCTTTGCCATGGAGAGCAGTAGTGGGGAAGAGTACTATGTT 7206 QUERY : 7258 GCCTCTGATAACACAGGGACTCCTCTGGCTGTGTTCAGCATCAACGGCCTCATGATCAAA 7317 IIIII Illlllll IIIIIIIIIIIIIIIII II II IIIII IIIlllllllllll SBJCT : 7207 GCCTCAGATAACACCGGGACTCCTCTGGCTGTTTTTAGTATCAATGGCCTCATGATCAAG 7266 QUERY : 7318 CAGCTGCAGTACACGGCCTATGGGGAGATTTATTATGACTCCAACCCCGACTTCCAGATG 7377 II II II IIIII Illllllllllllilll IIIIIIIIIII II lllll IIIIII SBJCT : 7267 CAACTCCAATACACAGCCTATGGGGAGATTTACTATGACTCCAATCCAGACTTTCAGATG 7326 QUERY : 7378 GTCATTGGCTTCCATGGGGGACTCTATGACCCCCTGACCAAGCTGGTCCACTTCACTCAG 7437 IIIII IIIIIIII II II IIIII IIIIIIII IIIIIIII II IIIII II III SBJCT : 7327 GTCATCGGCTTCCACGGAGGCCTCTACGACCCCCTCACCAAGCTCGTTCACTTTACGCAG 7386 QUERY : 7438 CGTGATTATGATGTGCTGGCAGGACGATGGACCTCCCCAGACTATACCATGTGGAAAAAC 7497 11111111111 11111111111111 11111 11111 11111 1111111111 11 SBJCT : 7387 CGTGATTATGACGTGCTGGCAGGACGGTGGACGTCCCCCGACTACACCATGTGGAGGAAT 7446 QUERY : 7498 GTGGGCAAGGAGCCGGCCCCCTTTAACCTGTATATGTTCAAGAGCAACAATCCTCTCAGC 7557 11111111111111 11111111 11111111 1111111111 111111111 11111 SBJCT : 7447 GTGGGCAAGGAGCCAGCCCCCTTCAACCTGTACATGTTCAAGAACAACAATCCACTCAGT 7506 QUERY : 7558 AGTGAGCTAGATTTGAAGAACTACGTGACAGATGTGAAAAGCTGGCTTGTGATGTTTGGA 7617 1 111111 11111 11111111111111111 11111 11111111 111111111111 SBJCT : 7507 AATGAGCTGGATTTAAAGAACTACGTGACAGACGTGAAGAGCTGGCTCGTGATGTTTGGA 7566 QUERY : 7618 TTTCAGCTTAGCAACATCATTCCTGGCTTCCCGAGAGCCAAAATGTATTTCGTGCCTCCT 7677 mm)) m)) !) m m) m mn m m m !) m m mum SBJCT : 7567 TTTCAGCTCAGCAACATCATTCCTGGATTCCCAAGAGCCAAAATGTATTTTGTGCCTCCC 7626 QUERY : 7678 CCCTATGAATTGTCAGAGAGTCAAGCAAGTGAGAATGGACAGCTCATTACAGGTGTCCAA 7737 IIII II SBJCT : 7627 CCCTATGAACTGTCAGAGAGCCAAGCAAGTGAGAATGGACAGCTCATTACAGGTGTCCAG 7686 QUERY : 7738 CAGACAACAGAGAGACATAACCAGGCCTTCATGGCTCTGGAAGGACAGGTCATTACTAAA 7797 11111111111111 11111111111111 1111111 11111111111111 11111 SBJCT : 7687 CAGACAACAGAGAGGCATAACCAGGCCTTTCTGGCTCTAGAAGGACAGGTCATCTCTAAA 7746 QUERY : 7798 AAGCTCCACGCCAGCATCCGAGAGAAAGCAGGTCACTGGTTTGCCACCACCACGCCCATC 7857 IIIlllll Il IIIIIIIIIIIIIIIIIII Illllllllll II IIIIIIIIIIII SBJCT : 7747 AAGCTCCATGCAGGCATCCGAGAGAAAGCAGGCCACTGGTTTGCTACGACCACGCCCATC 7806 QUERY : 7858 ATTGGCAAAGGCATCATGTTTGCCATCAAAGAAGGGCGGGTGACCACGGGCGTGTCCAGC 7917 t) m) m m) m m)) m m m m) m m !) m mum m SBJCT : 7807 ATCGGCAAAGGCATCATGTTCGCCATCAAAGAAGGGCGGGTGACCACAGGCGTGTCTAGC 7866 QUERY : 7918 ATCGCCAGCGAAGATAGCCGCAAGGTGGCATCTGTGCTGAACAACGCCTACTACCTGGAC 7977 11111111 11 11 11111111111 11111 111 11111111111111111 11111 SBJCT : 7867 ATCGCCAGTGAGGACAGCCGCAAGGTAGCATCCGTGTTGAACAACGCCTACTACTTGGAC 7926 QUERY : 7978 AAGATGCACTACAGCATCGAGGGCAAGGACACCCACTACTTTGTGAAGATTGGCTCAGCC 8037 111111111111111111111111111111|1 11111111 11111111 11 1111 SBJCT : 7927 AAGATGCACTACAGCATCGAGGGCAAGGACACACACTACTTCGTGAAGATCGGTGCAGCG 7986 QUERY : 8038 GATGGCGACCTGGTCACACTAGGCACCACCATCGGCCGCAAGGTGCTAGAGAGCGGGGTG 8097 II II llllllll II II II IIIII II IIIIIIIIIII Illlllllllll

SBJCT : 7987 GACGGTGACCTGGTTACGCTGGGGACCACCATTGGGCGCAAGGTGCTGGAGAGCGGGGTG 8046 QUERY : 8098 AACGTGACCGTGTCCCAGCCCACGCTGCTGGTCAACGGCAGGACTCGAAGGTTCACGAAC 8157 11111111111111 11111111111111111 11111111111111111111111 111 SBJCT : 8047 AACGTGACCGTGTCACAGCCCACGCTGCTGGTGAACGGCAGGACTCGAAGGTTCACCAAC B106 QUERY : 8158 ATTGAGTTCCAGTACTCCACGCTGCTGCTCAGCATCCGCTATGGCCTCACCCCCGACACC 8217 IIlII IIIIIIIIIIIIIIIlIIIIIIIIIIIII Illli IIIIIIIIIIIIIIIII SBJCT : 8107 ATTGAATTCCAGTACTCCACGCTGCTGCTCAGCATACGCTACGGCCTCACCCCCGACACA 8166 QUERY : 8218 CTGGACGAAGAGAAGGCCCGCGTCCTGGACCAGGCGAGACAGAGGGCCCTGGGCACGGCC 8277 IIIII IIIIIIIIIIIIIIIIIIIIIIIIII III Illlllllllllllll II III SBJCT : 8167 CTGGATGAAGAGAAGGCCCGCGTCCTGGACCAAGCGCGACAGAGGGCCCTGGGTACTGCC 8226 QUERY : 8278 TGGGCCAAGGAGCAGCAGAAAGCCAGGGACGGGAGAGAGGGGAGCCGCCTGTGGACTGAG 8337 m) m n m m) n mm m num m ! m m n n m m i !) SBJCT : 8227 TGGGCCAAGGAGCAGCAGAAAGCCAGGGACGGGAGAGAGGGCAGCCGTCTGTGGACGGAG 8286 QUERY : 8338 GGCGAGAAGCAGCAGCTTCTGAGCACCGGGCGCGTGCAAGGGTACGAGGGATATTACGTG 8397 ) m) n m n n N mum n)) H m m i !) ! m) !)) m !) SBJCT : 8287 GGCGAGAAGCAGCAACTCCTGAGCACGGGACGGGTGCAAGGTTATGAGGGCTATTACGTG 8346 QUERY : 8398 CTTCCCGTGGAGCAATACCCAGAGCTTGCAGACAGTAGCAGCAACATCCAGTTTTTAAGA 8457 lllll IIIII LI IIIIIIIIIII Illlllllllllllllllllllllll IIIIII SBJCT : 8347 CTTCCGGTGGAACAGTACCCAGAGCTGGCAGACAGTAGCAGCAACATCCAGTTCTTAAGA 8406 QUERY : 8458 CAGAATGAGATGGGAAAGAGGTAACAAAATAATCTGCTGCCATTCCTTGTCTGAATGGCT 8517 ! m m m mm n n m m m m mm m m ! m m n SBJCT : 8407 CAGAATGAGATGGGAAAGAGGTAACAAAATAACCTGCTGCCACCTCTTCTCTGGGTGGCT 8466 QUERY : 8518 CAGCAGGAGTAACTGTTATCTCCTCTCCTAAGGAGATGAAGACCTAACAGGGGCACTGCG 8577 IIIlIIIII IIIIII I IIlIIIlllllllllll lIIIIIIIIlIlIIIIIIIII 1 SBJCT : 8467 CAGCAGGAGCAACTGTGACCTCCTCTCCTAAGGAGACGAAGACCTAACAGGGGCACTGAG 8526 QUERY : 8578 GCTGGGCTGCTTTAGGAGACCAAGTGGCAAGAAAGCTCACATTTTTTGAGTTCAAATGCT 8637 11 11111111111111 11111111111111111111111111111111111111111 SBJCT : 8527 GCCGGGCTGCTTTAGGACCCCAAGTGGCAAGAAAGCTCACATTTTTTGAGTTCAAATGCT 8586 QUERY : 8638 ACTGTCCAAGCGAGAAGTCCCTCATCCTGAAGTAGACTAAAGCCCGGCTGAAAATTCCGA 8697 IIIIIIIIIIII IIIIIIIIIIIIIIIIIIIIIIIII III 1111 IIIIII II SBJCT : 8587 ACTGTCCAAGCGCAAAGTCCCTCATCCTGAAGTAGACTAGAGCTCGGCCACAAATTCTGA 8646 QUERY : 8698 GGAAAACAAAAC 8709 111111111111 SBJCT : 8647 GGAAAACAAAAC 8658 SCORE = 1459 BITS (736), EXPECT = 0. 0 IDENTITIES = 1081/1196 (90%) STRAND = PLUS/PLUS QUERY : 270 ATCTGGAATAATGGATGTAAAGGACCGGCGACACCGCTCTTTGACCAGAGGACGCTGTGG 329 11111 111111111111 11111 11111111 11111111111111 11111 11111 SBJCT : 123 ATCTGCAATAATGGATGTGAAGGATCGGCGACATCGCTCTTTGACCAGGGGACGGTGTGG 182 QUERY : 330 CAAAGAGTGTCGCTACACAAGCTCCTCTCTGGACAGTGAGGACTGCCGGGTGCCCACACA 389 111 1l111111111111 11111111111111111111111111111 11111111 11 SBJCT : 183 CAAGGAGTGTCGCTACACCAGCTCCTCTCTGGACAGTGAGGACTGCCGTGTGCCCACGCA 242 QUERY : 390 GAAATCCTACAGCTCCAGTGAGACTCTGAAGGCCTATGACCATGACAGCAGGATGCACTA 449 111 11111111 111|1111111 11111111 11111111111111111 11111111 SBJCT : 243 GAAGTCCTACAGTTCCAGTGAGACCCTGAAGGCTTATGACCATGACAGCAGAATGCACTA 302 QUERY : 450 TGGAAACCGAGTCACAGACCTCATCCACCGGGAGTCAGATGAGTTTCCTAGACAAGGAAC 509 111111111111111111111 | 11111111111 111111111 1111111111 1 SBJCT : 303 TGGAAACCGAGTCACAGACCTGGTGCACCGGGAGTCCGATGAGTTTTCTAGACAAGGGGC 362 QUERY : 510 CAACTTCACCCTTGCCGAACTGGGCATCTGTGAGCCCTCCCCACACCGAAGCGGCTACTG 569 SBJCT : 363 TAATTTCACCCTGGCAGAATTGGGAATCTGCGAGCCCTCCCCACACCGAAGTGGTTACTG 422

QUERY : 570 CTCCGACATGGGGATCCTTCACCAGGGCTACTCCCTTAGCACAGGGTCTGACGCCGACTC 629 11111111111111111 11111111111111111 11111 11111111 11 11111 SBJCT : 423 TTCCGACATGGGGATCCTCCACCAGGGCTACTCCCTGAGCACTGGGTCTGATGCGGACTC 482 QUERY : 630 CGACACCGAGGGAGGGATGTCTCCAGAACACGCCATCAGACTGTGGGGCAGAGGGATAAA 689 11111111111111111111111111111 11111111111111111 1111111111 SBJCT : 483 GGACACCGAGGGAGGGATGTCTCCAGAACATGCCATCAGACTGTGGGGACGAGGGATAAA 542 QUERY : 690 ATCCAGGCGCAGTTCCGGCCTGTCCAGTCGTGAAAACTCGGCCCTTACCCTGACTGACTC 749 III IIIIIIII II III IIIIIII II I IIIII IIIIIIII IIII I SBJCT : 543 ATCGAGGCGCAGCTCTGGCTTGTCCAGCCGCGAGAACTCAGCCCTTACTCTGACTGATTC 602 QUERY : 750 TGACAACGAAAACAAATCAGATGATGAGAACGGTCGTCCCATTCCACCTACATCCTCGCC 809 IIIIII IIIII IIIII IIIII II II IIIII Illlllllllllllllillll I SBJCT : 603 TGACAATGAAAATAAATCGGATGACGACAATGGTCGACCCATTCCACCTACATCCTCGTC 662 QUERY : 810 TAGTCTCCTCCCATCTGCTCAGCTGCCTAGCTCCCATAATCCTCCACCAGTTAGCTGCCA 869 111 11111111111111111111111111111111111111111111111111111111 SBJCT : 663 TAGCCTCCTCCCATCTGCTCAGCTGCCTAGCTCCCATAATCCTCCACCAGTTAGCTGCCA 722 QUERY : 870 GATGCCATTGCTAGACAGCAACACCTCCCATCAAATCATGGACACCAACCCTGATGAGGA 929 mmmmmmmmmmm mmmmmn mmn SBJCT : 723 GATGCCATTGCTAGACAGCAACACCTCCCATCAGATCATGGACACCAACCCCGATGAGGA 782 QUERY : 930 ATTCTCCCCCAATTCATACCTGCTCAGAGCATGCTCAGGGCCCCAGCAAGCCTCCAGCAG 989 ) N) urn m) m m m m m) m m mm m mm m m)) SBJCT : 783 ATTCTCCCCTAATTCATACCTGCTCAGAGCATGCTCAGGGCCCCAGCAAGCCTCCAGTAG 842 QUERY : 990 TGGCCCTCCGAACCACCACAGCCAGTCGACTCTGAGGCCCCCTCTCCCACCCCCTCACAA 1049 IIIIIIIIIIIIIIIIIIIIIIIIIII ll IIIIIIIIIIIIII IIIII Illll II SBJCT : 843 TGGCCCTCCGAACCACCACAGCCAGTCAACGCTGAGGCCCCCTCTGCCACCTCCTCATAA 902 QUERY : 1050 CCACACGCTGTCCCATCACCACTCGTCCGCCAACTCCCTCAACAGGAACTCACTGACCAA 1109 I SBJCT : 903 CCACACCCTGTCCCACCACCACTCCTCTGCCAACTCCCTCAACAGAAACTCACTGACCAA 962 QUERY : 1110 TCGGCGGAGTCAGATCCACGCCCCGGCCCCAGCGCCCAATGACCTGGCCACCACACCAGA 1169 111111111111 11111111111 11 11 11 11111111111111111111 11 11 SBJCT : 963 TCGGCGGAGTCAAATCCACGCCCCAGCTCCTGCACCCAATGACCTGGCCACCACGCCGGA 1022 QUERY : 1170 GTCCGTTCAGCTTCAGGACAGCTGGGTGCTAAACAGCAACGTGCCACTGGAGACCCGGCA 1229 111111111111 11111111111111|11 11111 11111111 11111111 11111 SBJCT : 1023 GTCCGTTCAGCTCCAGGACAGCTGGGTGCTGAACAGTAACGTGCCGCTGGAGACGCGGCA 1082 QUERY : 1230 CTTCCTCTTCAAGACCTCCTCGGGGAGCACACCCTTGTTCAGCAGCTCTTCCCCGGGATA 1289 IIIIIIIIIIIIIII lilll II Illllliil IIIillllllllllll II Ilill SBJCT : 1083 CTTCCTCTTCAAGACGTCCTCCGGAAGCACACCCCTGTTCAGCAGCTCTTCTCCAGGATA 1142 QUERY : 1290 CCCTTTGACCTCAGGAACGGTTTACACGCCCCCGCCCCGCCTGCTGCCCAGGAATACTTT 1349 IIl IIIIIIIIIII II IIIII ll II II llllllllllllll lllllll II SBJCT : 1143 CCCCTTGACCTCAGGGACCGTTTATACACCACCACCCCGCCTGCTGCCACGGAATACATT 1202 QUERY : 1350 CTCCAGGAAGGCTTTCAAGCTGAAGAAGCCCTCCAAATACTGCAGCTGGAAATGTGCTGC 1409 III IIIIIIII Illlllllllflll IIIIIIIIIIIIIIIII Illlllll If II SBJCT : 1203 CTCTAGGAAGGCCTTCAAGCTGAAGAAACCCTCCAAATACTGCAGTTGGAAATGCGCCGC 1262 QUERY : 1410 CCTCTCCGCCATTGCCGCGGCCCTCCTCTTGGCTATTTTGCTGGCGTATTTCATAG 1465 111 11 11111111111 11111111 1111 11111111111 1111111111 SBJCT : 1263 CCTGTCTGCCATTGCCGCTGCCCTCCTTCTGGCCATTTTGCTGGCCTATTTCATAG 1318 SCORE = 1427 BITS (720), EXPECT = 0. 0 IDENTITIES = 996/1088 (91%) STRAND = PLUS/PLUS QUERY : 1464 AGTGCCCTGGTCGTTGAAAAACAGCAGCATAGACAGTGGTGAAGCAGAAGTTGGTCGGCG 1523 SBJCT : 1440 AGTGCCCTGGTCGTTGAAAAACAGCAGCATAGACAGCGGCGAGGCAGAAGTCGGTCGACG 1499 QUERY : 1524 GGTAACACAAGAAGTCCCACCAGGGGTGTTTTGGAGGTCACAAATTCACATCAGTCAGCC 1583 III IIIII IIIIIIIIIIIIIIIIIIIIIIIIIIIII II Illlllllllillllll

SBJCT : 1500 GGTGACACAGGAAGTCCCACCAGGGGTGTTTTGGAGGTCCCAGATTCACATCAGTCAGCC 1559 QUERY : 1584 CCAGTTCTTAAAGTTCAACATCTCCCTCGGGAAGGACGCTCTCTTTGGTGTTTACATAAG 1643 lllll SBJCT : 1560 TCAGTTCTTAAAGTTCAACATCTCCCTGGGGAAGGATGCCCTCTTCGGCGTCTACATAAG 1619 QUERY : 1644 AAGAGGACTTCCACCATCTCATGCCCAGTATGACTTCATGGAACGTCTGGACGGGAAGGA 1703 111111111 11111111111111 11111111111111111111 11|11111 11111 SBJCT : 1620 AAGAGGACTGCCACCATCTCATGCACAGTATGACTTCATGGAACGCCTGGACGGAAAGGA 1679 QUERY : 1704 GAAGTGGAGTGTGGTTGAGTCTCCCAGGGAACGCCGGAGCATACAGACCTTGGTTCAGAA 1763 SBJCT : 1680 GAAGTGGAGTGTGGTCGAGTCACCCAGGGAACGCCGGAGCATCCAGACCCTGGTGCAGAA 1739 QUERY : 1764 TGAAGCCGTGTTTGTGCAGTACCTGGATGTGGGCCTGTGGCATCTGGCCTTCTACAATGA 1823 11 11 11111 111111111 1111111111111111111 11 11111111111111 SBJCT : 1740 CGAGGCTGTGTTCGTGCAGTACTTGGATGTGGGCCTGTGGCACCTCGCCTTCTACAATGA 1799 QUERY : 1824 TGGAAAAGACAAAGAGATGGTTTCCTTCAATACTGTTGTCCTAGATTCAGTGCAGGACTG 1883 SBJCT : 1800 CGGCAAGGACAAGGAGATGGTCTCCTTCAATACGGTTGTCTTAGATTCAGTGCAGGACTG 1859 QUERY : 1884 TCCACGTAACTGCCATGGGAATGGTGAATGTGTGTCCGGGGTGTGTCACTGTTTCCCAGG 1943 Ililll IIIIIIII IIIiI II IIIII lllll II Illlllllllllillllll SBJCT : 1860 TCCACGAAACTGCCACGGGAACGGCGAATGCGTGTCTGGACTGTGTCACTGTTTCCCAGG 1919 QUERY : 1944 ATTTCTAGGAGCAGACTGTGCTAAAGCTGCCTGCCCTGTCCTGTGCAGTGGGAATGGACA 2003 III IIII III SBJCT : 1920 ATTCCTAGGTGCAGACTGCGCTAAAGCTGCCTGCCCTGTTCTGTGCAGTGGGAATGGACA 1979 QUERY : 2004 ATATTCTAAAGGGACGTGCCAGTGCTACAGCGGCTGGAAAGGTGCAGAGTGCGACGTGCC 2063 11111 11111111 11111111111111 11111111111 11111 11111 11111 SBJCT : 1980 GTATTCCAAAGGGACATGCCAGTGCTACAGTGGCTGGAAAGGAGCAGAATGCGATGTGCC 2039 QUERY : 2064 CATGAATCAGTGCATCGATCCTTCCTGCGGGGGCCACGGCTCCTGCATTGATGGGAACTG 2123 mm n m m m m m m m m m mmmm m N mm SBJCT : 2040 CATGAACCAGTGCATCGATCCTTCCTGTGGGGGCCACGGCTCCTGCATTGATGGGAACTG 2099 QUERY : 2124 TGTCTGCTCTGCTGGCTACAAAGGCGAGCACTGTGAGGAAGTTGATTGCTTGGATCCCAC 2183 11 11 1 11111111111 11111111111 11 11111 11111111111111 11 SBJCT : 2100 CGTGTGTGCAGCTGGCTACAAGGGCGAGCACTGCGAAGAAGTGGATTGCTTGGATCCAAC 2159 QUERY : 2184 CTGCTCCAGCCACGGAGTCTGTGTGAATGGAGAATGCCTGTGCAGCCCTGGCTGGGGTGG 2243 IIIIIIIIIIII IIIIIIIIII IIII II SBJCT : 2160 CTGCTCCAGCCATGGTGTCTGTGTGAACGGAGAGTGTCTATGCAGCCCCGGCTGGGGCGG 2219 QUERY : 2244 TCTGAACTGTGAGCTGGCGAGGGTCCAGTGCCCAGACCAGTGCAGTGGGCATGGCACGTA 2303 II IIIII Illlllllllllllllllllllllllllllll llllllllllllll I ! SBJCT : 2220 GCTCAACTGCGAGCTGGCGAGGGTCCAGTGCCCAGACCAGTGTAGTGGGCATGGCACTTA 2279 QUERY : 2304 CCTGCCTGACACGGGCCTCTGCAGCTGCGATCCCAACTGGATGGGTCCCGACTGCTCTGT 2363 lll Illlll I IIIIIIIIII Ill IIIII II IIIIlllllllllllllllllll SBJCT : 2280 CCTCCCTGACTCTGGCCTCTGCAACTGTGATCCGAATTGGATGGGTCCCGACTGCTCTGT 2339 QUERY : 2364 TGAAGTGTGCTCAGTAGACTGTGGCACTCACGGCGTCTGCATCGGGGGAGCCTGCCGCTG 2423 111111111111111111111111111111111111111111111111111111111111 SBJCT : 2340 TGAAGTGTGCTCAGTAGACTGTGGCACTCACGGCGTCTGCATCGGGGGAGCCTGCCGCTG 2399 QUERY : 2424 TGAAGAGGGCTGGACAGGCGCAGCGTGTGACCAGCGCGTGTGCCACCCCCGCTGCATTGA 2483 111111111111111111111 11 11111111111111111111111111111111111 SBJCT : 2400 TGAAGAGGGCTGGACAGGCGCGGCTTGTGACCAGCGCGTGTGCCACCCCCGCTGCATTGA 2459 QUERY : 2484 GCACGGGACCTGTAAAGATGGCAAATGTGAATGCCGAGAGGGCTGGAATGGTGAACACTG 2543 111111111111111111111111111111111111111111111111111111111111 SBJCT : 2460 GCACGGGACCTGTAAAGATGGCAAATGTGAATGCCGAGAGGGCTGGAATGGTGAACACTG 2519 QUERY : 2544 CACCATTG 2551 IIIIIIII SBJCT : 2520 CACCATTG 2527

In this search it was also found that the FCTR3bcd and e nucleic acid had homology to six fragments of Gallus gallus partial mRNA for teneurin-2. It has 2780 of 3449 bases (80%) identical to bases 3386-6834, 1553 of 1862 bases (83%) identical to bases 1414-3275, 540 of 628 bases (85%) identical to bases 587-1214, 593 of 725 bases (81%) identical to bases 7084- 7808, 429 of 515 bases (83%) identical to bases 7895-8409, and 397 of 475 bases (83%) identical to bases 20-494 of Gallus gallus partial mRNA for teneurin-2. (EMBL Acc : GGA278031) (Table 30).

Table 30. BLASTN of FCTR3b, c, d, and e against Gallus gallus Teneurin-2 mRNA (SEQ ID NO : 67) >GI1102415731EMB1AJ279031. 11GGA279031 GALLUS GALLUS PARTIAL MRNA FOR TENEURIN-2 (TEN2 GENE), LONG SPLICE VARIANT LENGTH = 8409 SCORE = 1532 BITS (773), EXPECT = 0. 0 IDENTITIES = 2780/3449 (80%) STRAND = PLUS/PLUS QUERY : 3458 TGATGGTGGCTGTCGAGGGGCATCTCTTCCAGAAGTCATTCCAGGCTTCTCCCAACCTGG 3517 lllllll II I II IIIIIIII l II I IIIII I III IIIIIIIII III SBJCT : 3386 TGATGGTAGCAGTAGAAGGGCATCTATTTCAAAAATCATTTCTGGCATCTCCCAACTTGG 3445 QUERY : 3518 CCTCCACCTTCATCTGGGACAAGACAGATGCGTATGGCCAAAGGGTGTATGGACTCTCAG 3577 l l 11 11111111111111 11111111 11111 11 1 111 11111 1 1111 SBJCT : 3446 CTTATACATTCATCTGGGACAAAACAGATGCATATGGTCAGAAGGTTTATGGGTTGTCAG 3505 QUERY : 3578 ATGCTGTTGTGTCTGTCGGGTTTGAATATGAGACCTGTCCCAGTCTAATTCTCTGGGAGA 3637 1111111 11 11111 11 11111111111111 111111111 1 11111 1111111 SBJCT : 3506 ATGCTGTAGTTTCTGTGGGTTTTGAATATGAGACTTGTCCCAGTTTGATTCTGTGGGAGA 3565 QUERY : 3638 AAAGGACAGCCCTCCTTCAGGGATTCGAGCTGGACCCCTCCAACCTCGGTGGCTGGTCCC 3697 IIIIIII II II Il II IIIII IIIII II II llll) II II II Illll SBJCT : 3566 AAAGGACTGCGCTGCTGCAAGGATTTGAGCTAGATCCTTCCAATCTAGGAGGATGGTCTT 3625 QUERY : 3698 TAGACAAACACCACATCCTCAATGTTAAAAGTGGAATCCTACACAAAGGCACTGGGGAAA 3757 l 11 11111 11 1 11 11111 11 11111 11 1 1111111111 111 1111 SBJCT : 3626 TGGATAAACATCATGTACTGAATGTCAAGAGTGGTATATTGCACAAAGGCAATGGAGAAA 3685 QUERY : 3758 ACCAGTTCCTGACCCAGCAGCCTGCCATCATCACCAGCATCATGGGCAATGGTCGCCGCC 3817 I Illll II II IIIIIIII II I II IIIIIIII IIIII IIIII IIIII SBJCT : 3686 ATCAGTTTCTAACTCAGCAGCCAGCTGTGATAACCAGCATTATGGGGAATGGGCGCCGAA 3745 QUERY : 3818 GGAGCATTTCCTGTCCCAGCTGCAACGGCCTTGCTGAAGGCAACAAGCTGCTGGCCCCAG 3877 I Ilill IIIIIIII IIIIIIII II IIIII IIIII II IIIII IIIIIII I SBJCT : 3746 GAAGCATATCCTGTCCTAGCTGCAATGGTCTTGCAGAAGGAAATAAGCTTTTGGCCCCTG 3805 QUERY : 3878 TGGCTCTGGCTGTTGGAATCGATGGGAGCCTCTATGTGGGTGACTTCAATTACATCCGAC 3937 I II Iilll li IIIiI Illli IIIIIII III II II II IIIIIIII II I SBJCT : 3806 TAGCACTGGCAGTGGGAATTGATGGAAGCCTCTTTGTTGGAGATTTTAATTACATTCGGC 3865 QUERY : 3938 GCATCTTTCCCTCTCGAAATGTGACCAGCATCTTGGAGTTACGAAATAAAGAGTTTAAAC 3997 I IIIII II II SBJCT : 3866 GTATCTTCCCATCCAGGAATGTGACTAGCATATTGGAGCTGAGAAATAAAGAGTTTAAAC 3925 QUERY : 3998 ATAGCAACAACCCAGCACACAAGTACTACTTGGCAGTGGACCCCGTGTCCGGCTCGCTCT 4057 1111111111 11 11 11111 11111 1111 11111111111 11 11111 11 1 SBJCT : 3926 ATAGCAACAATCCTGCTCACAAATACTATCTGGCCGTGGACCCCGTTTCGGGCTCCCTGT 3985

QUERY : 4058 ACGTGTCCGACACCAACAGCAGGAGAATCTACCGCGTCAAGTCTCTGAGTGGAACCAAAG 4117 1111 11 111111111111 1 1 11 111 11111 11111 1 111 11 1111 SBJCT : 3986 ACGTATCAGACACCAACAGCCGACGGATATACAAAGTCAAATCTCTTACTGGCACGAAAG 4045 QUERY : 4118 ACCTGGCTGGGAATTCGGAAGTTGTGGCAGGGACGGGAGAGCAGTGTCTACCCTTTGATG 4177 1111111111 11111 11111 11 11 1111} 1} 111111 11 11 1111111111 SBJCT : 4046 ACCTGGCTGGTAATTCTGAAGTGGTAGCGGGGACTGGAGAGCAATGCCTGCCCTTTGATG 4105 QUERY : 4178 AAGCCCGCTGCGGGGATGGAGGGAAGGCCATAGATGCAACCCTGATGAGCCCGAGAGGTA 4237 IIIII I 11 ll 11111111111 11 1 11 11111111 11111 11 1111 1 SBJCT : 4106 AAGCCAGATGTGGAGATGGAGGGAAAGCAGTGGACGCAACCCTAATGAGTCCTCGAGGAA 4165 QUERY : 4238 TTGCAGTAGACAAGAATGGGCTCATGTACTTTGTCGATGCCACCATGATCCGGAAGGTTG 4297 1111111 11 111 1111 11111111 11111 11111111 11111 11 11 11 1 SBJCT : 4166 TTGCAGTGGATAAGTATGGACTCATGTATTTTGTTGATGCCACTATGATTCGAAAAGTGG 4225 QUERY : 4298 ACCAGAATGGAATCATCTCCACCCTGCTGGGCTCCAATGACCTCACTGCCGTCCGGCCGC 4357 1 11111111111 11 11 11 11111111111111111111 11111|11i11 11 1 SBJCT : 4226 ATCAGAATGGAATTATATCAACTCTGCTGGGCTCCAATGACCTAACTGCCGTCCGACCTC 4285 QUERY : 4358 TGAGCTGTGATTCCAGCATGGATGTAGCCCAGGTTCGTCTGGAGTGGCCAACAGACCTTG 4417 IIIII SBJCT : 4286 TAAGCTGTGATTCCAGCATGGATGTCAGCCAGGTACGGCTGGAGTGGCCTACTGATCTCG 4345 QUERY : 4418 CTGTCAATCCCATGGATAACTCCTTGTATGTTCTAGAGAACAATGTCATCCTTCGAATCA 4477 IIIII IIIIIIIIII I (III I Iliil Illilllllillll II I II IIII SBJCT : 4346 CTGTCGATCCCATGGACAACTCACTTTATGTCCTAGAGAACAATGTTATTTTACGGATCA 4405 QUERY : 4478 CCGAGAACCACCAAGTCAGCATCATTGCGGGACGCCCCATGCACTGCCAAGTTCCTGGCA 4537 1 11 11111 11111 11111 11111 11111111111111111111 11111111 1 SBJCT : 4406 CAGAAAACCATCAAGTTAGCATTATTGCTGGACGCCCCATGCACTGCCAGGTTCCTGGTA 4465 QUERY : 4538 TTGACTACTCACTCAGCAAACTAGCCATTCACTCTGCCCTGGAGTCAGCCAGTGCCATTG 4597 I SBJCT : 4466 TAGACTACTCTCTTAGCAAACTGGCTATTCATTCCGCACTTGAATCAGCCAGTGCCATTG 4525 QUERY : 4598 CCATTTCTCACACTGGGGTCCTCTACATCACTGAGACAGATGAGAAGAAGATTAACCGTC 4657 1111 11 11111 11 11 11 1111111 1|1111111111 11 11 11111 11 1 SBJCT : 4526 CCATCTCACACACAGGAGTTCTTTACATCAGTGAGACAGATGAAAAAAAAATTAATCGGC 4585 QUERY : 4658 TACGCCAGGTAACAACCAACGGGGAGATCTGCCTTTTAGCTGGGGCAGCCTCGGACTGCG 4717 Illllllllllll IIIII II II II Illlll I II IIIIIIII II IIIII I SBJCT : 4586 TACGCCAGGTAACTACCAATGGAGAAATATGCCTTCTTGCAGGGGCAGCTTCAGACTGTG 4645 QUERY : 4718 ACTGCAAAAACGATGTCAATTGCAACTGCTATTCAGGAGATGATGCCTACGCGACTGATG 4777 I IIIIIIII llllllll II Il IIIIIIlI II'Illlll ! I ! II IIIIIII SBJCT : 4646 ATTGCAAAAATGATGTCAACTGTAATTGCTATTCTGGGGATGATGGGTATGCCACTGATG 4705 QUERY : 4778 CCATCTTGAATTCCCCATCATCCTTAGCTGTAGCTCCAGATGGTACCATTTACATTGCAG 4837 1111111 11111 11111 11111111111 11 11111111111111 11111 11 1 SBJCT : 4706 CCATCTTAAATTCACCATCTTCCTTAGCTGTGGCCCCAGATGGTACCATCTACATAGCTG 4765 QUERY : 4838 ACCTTGGAAATATTCGGATCAGGGCGGTCAGCAAGAACAAGCCTGTTCTTAATGCCTTCA 4897 1 11 11111111 l1 11 11111 11111 11 1111 111 11111111 1 11 1 SBJCT : 4766 ATCTCGGAAATATCCGCATTAGGGCTGTCAGTAAAAACAGGCCCATTCTTAATTCTTTTA 4825 QUERY : 4898 ACCAGTATGAGGCTGCATCCCCCGGAGAGCAGGAGTTATATGTTTTCAACGCTGATGGCA 4957 I SBJCT : 4826 ACCAATATGAAGCTGCATCTCCAGGAGAACAGGAGCTGTATGTCTTCAATGCTGATGGGA 4885 QUERY : 4958 TCCACCAATACACTGTGAGCCTGGTGACAGGGGAGTACTTGTACAATTTCACATATAGTA 5017 I IIIII Illlll I IIIII II II IlIIlllllllllllllllllll IIIII 1 SBJCT : 4886 TTCACCAGTACACTCTCAGCCTTGTTACCGGGGAGTACTTGTACAATTTCACCTATAGCA 4945 QUERY : 5018 CTGACAATGATGTCACTGAATTGATTGACAATAATGGGAATTCCCTGAAGATCCGTCGGG 5077 I IIIIIIIII SBJCT : 4946 GTGATAACGATGTCACCGAGGTGATGGACAGCAATGGCAACTCCTTGAAGGTCCGTCGGG 5005 QUERY : 5078 ACAGCAGTGGCATGCCCCGTCACCTGCTCATGCCTGACAACCAGATCATCACCCTCACCG 5137 I I I III II I

SBJCT : 5006 ATGCCAGCGGAATGCCCCGCCATTTACTGATGCCTGATAATCAGATTGTCACGCTGGCCG 5065 QUERY : 5138 TGGGCACCAATGGAGGCCTCAAAGTCGTGTCCACACAGAACCTGGAGCTTGGTCTCATGA 5197 1 11111 11111 11 111111 1 11 11 11 1111 111111 11111 1 1111 SBJCT : 5066 TTGGCACTAATGGTGGACTCAAACTAGTCTCAACGCAGACCCTGGAACTTGGATTAATGA 5125 QUERY : 5198 CCTATGATGGCAACACTGGGCTCCTGGCCACCAAGAGCGATGAAACAGGATGGACGACTT 5257 l 111 1 11 1111 111 111 1 ll II lllll IIIllllllllllllll II I SBJCT : 5126 CTTATAACGGAAACAGTGGTCTCTTAGCAACGAAGAGTGATGAAACAGGATGGACAACAT 5185 QUERY : 5258 TCTATGACTATGACCACGAAGGCCGCCTGACCAACGTGACGCGCCCCACGGGGGTGGTAA 5317 1 IIIIIIIIIII II IIIII IIIIIIIIIII II II II IIIII II IIIIIII SBJCT : 5186 TTTATGACTATGATCATGAAGGGCGCCTGACCAATGTAACACGTCCCACTGGAGTGGTAA 5245 QUERY : 5318 CCAGTCTGCACCGGGAAATGGAGAAATCTATTACCATTGACATTGAGAACTCCAACCGTG 5377 l 11 11 11 11 11111111 11 11111111111 11111111111 11 11 11 1 SBJCT : 5246 CTAGCCTTCATCGAGAAATGGAAAAGTCTATTACCATCGACATTGAGAATTCTAATCGGG 5305 QUERY : 5378 ATGATGACGTCACTGTCATCACCAACCTCTCTTCAGTAGAGGCCTCCTACACAGTGGTAC 5437 Illllll IIIII IIIlllll II IIIII Il II Illll IIIII lllll II I SBJCT : 5306 ATGATGATGTCACGGTCATCACAAATCTCTCCTCTGTGGAGGCTTCCTATACAGTTGTTC 5365 QUERY : 5438 AAGATCAAGTTCGGAACAGCTACCAGCTCTGTAATAATGGTACCCTGAGGGTGATGTATG 5497 IIIillllll Illllllllllllllllllilllllllllll Illl IIIlllllll SBJCT : 5366 AAGATCAAGTGAGGAACAGCTACCAGCTCTGTAATAATGGTACTTTGAGAGTGATGTATG 5425 QUERY : 5498 CTAATGGGATGGGTATCAGCTTCCACAGCGAGCCCCATGTCCTAGCGGGCACCATCACCC 5557 1 11111 111 1111 11111 11111111 11 11111111 11 11 11 1 11 1 SBJCT : 5426 CCAATGGCATGAGTATTAGCTTTCACAGCGAACCTCATGTCCTGGCTGGGACAGTAACTC 5485 QUERY : 5558 CCACCATTGGACGCTGCAACATCTCCCTGCCTATGGAGAATGGCTTAAACTCCATTGAGT 5617 1111111 11111 11 11 11 11 11 11 11111111111 11 11111 11111 1 SBJCT : 5486 CCACCATAGGACGATGTAATATTTCTCTACCAATGGAGAATGGTTTGAACTCAATTGAAT 5545 QUERY : 5618 GGCGCCTAAGAAAGGAACAGATTAAAGGCAAAGTCACCATCTTTGGCAGGAAGCTCCGGG 5677 ! m n n n m mN mm mm ft t n ! ! ! n ! m n m SBJCT : 5546 GGCGTCTGAGGAAAGAACAGATTAAAGGCAAAGTGACTGTGTTTGGAAGAAAGCTCAGGG 5605 QUERY : 5678 TCCATGGAAGAAATCTCTTGTCCATTGACTATGATCGAAATATTCGGACTGAAAAGATCT 5737 l 11111111 111 1 IIIIIIIIII II II II IIIII II II Illll Illl SBJCT : 5606 TTCATGGAAGGAATTTGCTGTCCATTGATTACGACCGGAATATACGCACAGAAAAAATCT 5665 QUERY : 5738 ATGATGACCACCGGAAGTTCACCCTGAGGATCATTTATGACCAGGTGGGCCGCCCCTTCC 5797 l 11111 11111 11111111111111111 11111 11 111 1111 11 1111111 SBJCT : 5666 ACGATGATCACCGCAAGTTCACCCTGAGGATAATTTACGATCAGCTGGGACGGCCCTTCC 5725 QUERY : 5798 TCTGGCTGCCCAGCAGCGGGCTGGCAGCTGTCAACGTGTCATACTTCTTCAATGGGCGCC 5857 Ilillllllllllllllll lllll II IIIIIIIIIII II IIIIIIII IIIIIII SBJCT : 5726 TCTGGCTGCCCAGCAGCGGCCTGGCTGCCGTCAACGTGTCCTATTTCTTCAACGGGCGCC 5785 QUERY : 5858 TGGCTGGGCTTCAGCGTGGGGCCATGAGCGAGAGGACAGACATCGACAAGCAAGGCCGCA 5917 1111111111111111 11 11111111111 111111111111111111111111 1 1 SBJCT : 5786 TGGCTGGGCTTCAGCGCGGAGCCATGAGCGAAAGGACAGACATCGACAAGCAAGGCAGGA 5845 QUERY : 5918 TCGTGTCCCGCATGTTCGCTGACGGGAAAGTGTGGAGCTACTCCTACCTTGACAAGTCCA 5977 II I II IIIIIIII II II IIIII Il Illll Ill Illllll II Il IIII SBJCT : 5846 TCATATCGCGCATGTTTGCAGATGGGAAGGTTTGGAGTTACACCTACCTAGAAAAATCCA 5905 QUERY : 5978 TGGTCCTCCTGCTTCAGAGCCAACGTCAGTATATATTTGAGTATGACTCCTCTGACCGCC 6037 1111 11 11111111111111 11 11111 11 10111111111 11 11 11111 1 SBJCT : 5906 TGGTACTACTGCTTCAGAGCCAGCGGCAGTACATCTTTGAGTATGATTCTTCAGACCGGC 5965 QUERY : 6038 TCCTTGCCGTCACCATGCCCAGCGTGGCCCGGCACAGCATGTCCACACACACCTCCATCG 6097 111 111 11 11 11111 11 11 11 lilll 11111111 11 11111 11 1 1 SBJCT : 5966 TCCATGCTGTTACTATGCCTAGTGTTGCTCGGCATAGCATGTCAACTCACACGTCTGTTG 6025 QUERY : 6098 GCTACATCCGTAATATTTACAACCCGCCTGAAAGCAATGCTTCGGTCATCTTTGACTACA 6157 IIIIIII I IIIIIIII II II IIIIIIIIIII II II II Il IIIII IIII SBJCT : 6026 GCTACATTAGGAATATTTATAATCCTCCTGAAAGCAACGCATCAGTGATTTTTGATTACA 6085

QUERY : 6158 GTGATGACGGCCGCATCCTGAAGACCTCCTTTTTGGGCACCGGACGCCAGGTGTTCTACA 6217 1111111 11 1 11 1111 11 11 11111 11 11 11 11 11 11 11 1111 SBJCT : 6086 GTGATGATGGGAGGATTTTGAAAACATCATTTTTAGGTACTGGTCGACAAGTCTTTTACA 6145 QUERY : 6218 AGTATGGGAAACTCTCCAAGTTATCAGAGATTGTCTACGACAGTACCGCCGTCACCTTCG 6277 IIIIIII II II IIIII IIIII II IIIII II IIIIIIII Il II II II I SBJCT : 6146 AGTATGGAAAGCTATCCAAATTATCTGAAATTGTTTATGACAGTACTGCGGTTACTTTTG 6205 QUERY : 6278 GGTATGACGAGACCACTGGTGTCTTGAAGATGGTCAACCTCCAAAGTGGGGGCTTCTCCT 6337 I Illll Il II ! 1 IIIIII I II IIIII II 1 IIIIIIII II II II I SBJCT : 6206 GATATGATGAAACTACAGGTGTCCTAAAAATGGTGAATTTGCAAAGTGGAGGATTTTCTT 6265 QUERY : 6338 GCACCATCAGGTACCGGAAGATTGGCCCCCTGGTGGACAAGCAGATCTACAGGTTCTCCG 6397 l 11 111 1 11 11 11 11111111 11 11 11111 11 11111111 11111 1 SBJCT : 6266 GTACAATCCGCTATCGTAAAATTGGCCCTCTTGTTGACAAACAAATCTACAGATTCTCTG 6325 QUERY : 6398 AGGAAGGCATGGTCAATGCCAGGTTTGACTACACCTATCATGACAACAGCTTCCGCATCG 6457 1 11111 11111111111 11111111 11 11 11111 11111 11 11 11111 1 SBJCT : 6326 AAGAAGGTATGGTCAATGCAAGGTTTGATTATACATATCACGACAATAGTTTTCGCATTG 6385 QUERY : 6458 CAAGCATCAAGCCCGTCATAAGTGAGACTCCCCTCCCCGTTGACCTCTACCGCTATGATG 6517 llllllllll III IIIIIIIIIIIIIIII II ll lllll 11 Illll Illllll SBJCT : 6386 CAAGCATCAAACCCATCATAAGTGAGACTCCTCTTCCAGTTGATCTTTACCGTTATGATG 6445 QUERY : 6518 AGATTTCTGGCAAGGTGGAACACTTTGGTAAGTTTGGAGTCATCTATTATGACATCAACC 6577 IIIIIIIIIIIII II II II IIIII II IIIIIIII II IIIIIIII II II I SBJCT : 6446 AGATTTCTGGCAAAGTTGAGCATTTTGGCAAATTTGGAGTTATTTATTATGATATAAATC 6505 QUERY : 6578 AGATCATCACCACTGCCGTGATGACCCTCAGCAAACACTTCGACACCCATGGGCGGATCA 6637 I 11 11 11 11 11 11 11111 11 11 11 11111 11 11111 11 11 ll I SBJCT : 6506 AAATTATTACTACAGCAGTTATGACACTGAGTAAGCACTTTGATACCCACGGACGCATTA 6565 QUERY : 6638 AGGAGGTCCAGTATGAGATGTTCCGGTCCCTCATGTACTGGATGACGGTGCAATATGACA 6697 l 11 11 11 11111111111111 11111 11111111111111 1111111111111 SBJCT : 6566 AAGAAGTTCAATATGAGATGTTCCGATCCCTGATGTACTGGATGACTGTGCAATATGACA 6625 QUERY : 6698 GCATGGGCAGGGTGATCAAGAGGGAGCTAAAACTGGGGCCCTATGCCAATACCACGAAGT 6757 1111111 11 11 1 1 11 11 11 11111 11111 11111111 11 11 1111 SBJCT : 6626 GCATGGGAAGAGTAACTAAAAGAGAACTGAAACTTGGGCCGTATGCCAACACAACCAAGT 6685 QUERY : 6758 ACACCTATGACTACGATGGGGACGGGCAGCTCCAGAGCGTGGCCGTCAATGACCGCCCGA 6817 l IIIIIIII II IIIII II IIIII I ll IIIII II Il IIIII I II I SBJCT : 6686 ATACCTATGATTATGATGGAGATGGGCAATTGCAAAGCGTAGCAGTAAATGATAGGCCTA 6745 QUERY : 6818 CCTGGCGCTACAGCTATGACCTTAATGGGAATCTCCACTTACTGAACCCAGGCAACAGTG 6877 1111111 11111 11111111 11111 11111 111 1 11111 11 11 1111111 SBJCT : 6746 CCTGGCGTTACAGTTATGACCTGAATGGAAATCTTCACCTCCTGAATCCTGGAAACAGTG 6805 QUERY : 6878 TGCGCCTCATGCCCTTGCGCTATGACCTC 6906 )) i ! mm m ! m mm SBJCT : 6806 TTCGATTGATGCCCCTGCGCTACGACCTC 6834 SCORE = 1241 BITS (626), EXPECT = 0. 0 IDENTITIES = 1553/1862 (83%) STRAND = PLUS/PLUS QUERY : 1486 AGCAGCATAGACAGTGGTGAAGCAGAAGTTGGTCGGCGGGTAACACAAGAAGTCCCACCA 1545 SBJCT : 1414 AGCAGCATAGATAGTGGAGAAACAGAAGTTGGCCGCAAGGTCACCCAAGAGGTGCCCCCT 14'73 QUERY : 1546 GGGGTGTTTTGGAGGTCACAAATTCACATCAGTCAGCCCCAGTTCTTAAAGTTCAACATC 1605 II 11111 111 1111 11 11 ll Illll 11111 111111 1 11111111111 SBJCT : 1474 GGAGTGTTCTGGCGGTCTCAGATCCATATCAGCCAGCCACAGTTCCTGAAGTTCAACATA 1533 QUERY : 1606 TCCCTCGGGAAGGACGCTCTCTTTGGTGTTTACATAAGAAGAGGACTTCCACCATCTCAT 1665 11111 11111111 11111 11 11111111 11111111111111 11111111 111 SBJCT : 1534 TCCCTAGGGAAGGATGCTCTTTTCGGTGTTTATATAAGAAGAGGACTCCCACCATCACAT 1593 QUERY : 1666 GCCCAGTATGACTTCATGGAACGTCTGGACGGGAAGGAGAAGTGGAGTGTGGTTGAGTCT 1725 II 11111111 11111111111 1111 11111 1|111 11111111111 11 11

SBJCT : 1594 GCACAGTATGATTTCATGGAACGCTTGGATGGGAAAGAGAAATGGAGTGTGGTGGAATCC 1653 QUERY : 1726 CCCAGGGAACGCCGGAGCATACAGACCTTGGTTCAGAATGAAGCCGTGTTTGTGCAGTAC 1785 II 1111111 11 11 11 11111 1 11111111111 11 11111111 111111 SBJCT : 1654 CCACGGGAACGGCGAAGTATTCAGACTCTTGTTCAGAATGAGGCTGTGTTTGTTCAGTAC 1713 QUERY : 1786 CTGGATGTGGGCCTGTGGCATCTGGCCTTCTACAATGATGGAAAAGACAAAGAGATGGTT 1845 1 SBJCT : 1714 TTGGATGTGGGTTTGTGGCACCTGGCGTTTTACAATGATGGCAAGGACAAAGAAGTGGTC 1773 QUERY : 1846 TCCTTCAATACTGTTGTCCTAGATTCAGTGCAGGACTGTCCACGTAACTGCCATGGGAAT 1905 m) m m m) ! m n m n f tn n f n n n n n tH n n ! SBJCT : 1774 TCCTTCAGTACAGTTATTTTGGATTCAGTGCAAGACTGTCCACGTAATTGTCATGGCAAT 1833 QUERY : 1906 GGTGAATGTGTGTCCGGGGTGTGTCACTGTTTCCCAGGATTTCTAGGAGCAGACTGTGCT 1965 II 11 11111 11 11 11 11 11111111 11 1111111 11111111 111111 SBJCT : 1834 GGCGAGTGTGTTTCTGGTGTCTGCCACTGTTTTCCCGGATTTCATGGAGCAGATTGTGCT 1893 QUERY : 1966 AAAGCTGCCTGCCCTGTCCTGTGCAGTGGGAATGGACAATATTCTAAAGGGACGTGCCAG 2025 IIIIIIIIIIIIII II IIIIIIIIIII Illll II II II IIIII II III I SBJCT : 1894 AAAGCTGCCTGCCCGGTGCTGTGCAGTGGCAATGGTCAGTACTCCAAAGGAACCTGCTTG 1953 QUERY : 2026 TGCTACAGCGGCTGGAAAGGTGCAGAGTGCGACGTGCCCATGAATCAGTGCATCGATCCT 2085 11111111 111111111111 1 11 11 11 11 11111 1 11111 11 11111 SBJCT : 1954 TGCTACAGTGGCTGGAAAGGTCCGGAATGTGATGTACCCATCAGCCAGTGTATTGATCCC 2013 QUERY : 2086 TCCTGCGGGGGCCACGGCTCCTGCATTGATGGGAACTGTGTCTGCTCTGCTGGCTACAAA 2145 II 11 11 11 11 11 11111111 11 11111111111111 11 111111 111 SBJCT : 2014 TCGTGTGGAGGTCATGGTTCCTGCATCGAAGGGAACTGTGTCTGTTCCATTGGCTATAAA 2073 QUERY : 2146 GGCGAGCACTGTGAGGAAGTTGATTGCTTGGATCCCACCTGCTCCAGCCACGGAGTCTGT 2205 SBJCT : 2074 GGAGAAAACTGTGAGGAAGTTGATTGCTTAGATCCAACATGCTCCAATCACGGGGTCTGT 2133 QUERY : 2206 GTGAATGGAGAATGCCTGTGCAGCCCTGGCTGGGGTGGTCTGAACTGTGAGCTGGCGAGG 2265 IIIII llllllll ll IIIIIIII IIIIIIIIIII I IIIIIIIIIII I II SBJCT : 2134 GTGAACGGAGAATGTCTCTGCAGCCCAGGCTGGGGTGGAATAAACTGTGAGCTTCCCAGA 2193 QUERY : 2266 GTCCAGTGCCCAGACCAGTGCAGTGGGCATGGCACGTACCTGCCTGACACGGGCCTCTGC 2325 l 111111111111111111111111111111111 111111 1111111 11 11111 SBJCT : 2194 GCCCAGTGCCCAGACCAGTGCAGTGGGCATGGCACATACCTGTCTGACACCGGTCTCTGT 2253 QUERY : 2326 AGCTGCGATCCCAACTGGATGGGTCCCGACTGCTCTGTTGAAGTGTGCTCAGTAGACTGT 2385 Illlllllllllllllllllllll I SBJCT : 2254 AGCTGCGATCCCAACTGGATGGGTCCCGACTGCTCCGTTGAAGTGTGCTCTGTAGACTGT 2313 QUERY : 2386 GGCACTCACGGCGTCTGCATCGGGGGAGCCTGCCGCTGTGAAGAGGGCTGGACAGGCGCA 2445 IIIII II II II IIIII II IIIII II IIIIIIIIIII ll Illlllll I SBJCT : 2314 GGCACCCATGGGGTGTGCATTGGCGGAGCGTGTCGCTGTGAAGAAGGGTGGACAGGAGTG 2373 QUERY : 2446 GCGTGTGACCAGCGCGTGTGCCACCCCCGCTGCATTGAGCACGGGACCTGTAAAGATGGC 2505 IIIIIIIIIIIIII IIIII II IIIII II I Illlllll II Illllllllll SBJCT : 2374 GCGTGTGACCAGCGTGTGTGTCATCCCCGGTGTACAGAGCACGGAACTTGTAAAGATGGG 2433 QUERY : 2506 AAATGTGAATGCCGAGAGGGCTGGAATGGTGAACACTGCACCATTGGTAGGCAAACGGCA 2565 111111111111 1111111111111111 11 lltlllllllllllllllllllll 11 SBJCT : 2434 AAATGTGAATGCAGAGAGGGCTGGAATGGGGAGCACTGCACCATTGGTAGGCAAACGACA 2493 QUERY : 2566 GGCACCGAAACAGATGGCTGCCCTGACTTGTGCAACGGTAACGGGAGATGCACACTGGGT 2625 11111111111111111111111111111111111 11 11111111 11111 11111 SBJCT : 2494 GGCACCGAAACAGATGGCTGCCCTGACTTGTGCAATGGCAACGGGAGGTGCACGCTGGGC 2553 QUERY : 2626 CAGAACAGCTGGCAGTGTGTCTGCCAGACCGGCTGGAGAGGGCCCGGATGCAACGTTGCC 2685 11111111111111111111111111111111111111111111 111111111111111 SBJCT : 2554 CAGAACAGCTGGCAGTGTGTCTGCCAGACCGGCTGGAGAGGGCCTGGATGCAACGTTGCC 2613 QUERY : 2686 ATGGAAACTTCCTGTGCTGATAACAAGGATAATGAGGGAGATGGCCTGGTGGATTGTTTG 2745 11111111 11111111 111|1111111111 111111111111 1111 11 11 1 SBJCT : 2614 ATGGAAACCTCCTGTGCCGATAACAAGGATAACGAGGGAGATGGCTTGGTTGACTGCCTA 2673

QUERY : 2746 GACCCTGACTGCTGCCTGCAGTCAGCCTGTCAGAACAGCCTGCTCTGCCGGGGGTCCCGG 2805 1 111 11 11111111 11111 1 11111 111111¢1111 11111111 11111 SBJCT : 2674 GTCCCAGATTGCTGCCTCCAGTCCACTTGTCAAAACAGCCTGCTGTGCCGGGGTTCCCGC 2733 QUERY : 2806 GACCCACTGGACATCATTCAGCAGGGCCAGACGGATTGGCCCGCAGTGAAGTCCTTCTAT 2865 II 11 11 11111111 11 111 1111 1 1 11 11 11 11111111 111111 SBJCT : 2734 GATCCTCTTGACATCATACAACAGAGCCATTCTGGTTCACCAGCTGTGAAGTCATTCTAT 2793 QUERY : 2866 GACCGTATCAAGCTCTTGGCAGGCAAGGATAGCACCCACATCATTCCTGGAGAGAACCCT 2925 II 11 11111111111 1 11 11111 11111 11 1111111l 11111 11 11 SBJCT : 2794 GATCGAATCAAGCTCTTAGTGGGGAAGGACAGCACTCATATCATTCCAGGAGAAAATCCC 2853 QUERY : 2926 TTCAACAGCAGCTTGGTTTCTCTCATCCGAGGCCAAGTAGTAACTACAGATGGAACTCCC 2985 111111111111 1 11 11111 11 1111111111 11 Illlllllllllll 11 SBJCT : 2854 TTCAACAGCAGCCTTGTGTCTCTTATAAGAGGCCAAGTGGTGACTACAGATGGAACGCCT 2913 QUERY : 2986 CTGGTCGGTGTGAACGTGTCTTTTGTCAAGTACCCAAAATACGGCTACACCATCACCCGC 3045 SBJCT : 2914 CTAGTTGGGGTCAACGTGTCATTTGTCAAGTATCCAAAGTATGGCTATACCATCACTCGT 2973 QUERY : 3046 CAGGATGGCACGTTCGACCTGATCGCAAATGGAGGTGCTTCCTTGACTCTACACTTTGAG 3105 Illlllllll III lil II I ll II Il II I lll 1 III I llllllll SBJCT : 2974 CAGGATGGCATGTTTGACTTGGTTGCTAACGGTGGATCATCCCTAACTTTGCACTTTGAA 3033 QUERY : 3106 CGAGCCCCGTTCATGAGCCAGGAGCGCACTGTGTGGCTGCCGTGGAACAGCTTTTACGCC 3165 II Iffll II IIIII IIIII I II li IIIIIIIIIIIIIIIIiIII II III SBJCT : 3034 CGGGCCCCATTTATGAGTCAGGAAAGGACAGTATGGCTGCCGTGGAACAGCTTCTATGCC 3093 QUERY : 3166 ATGGACACCCTGGTGATGAAGACCGAGGAGAACTCCATCCCCAGCTGTGACCTCAGTGGC 3225 11111111 11 11 11111 11 111111111l1111 11111111111 111l11111 SBJCT : 3094 ATGGACACGCTTGTAATGAAAACAGAGGAGAACTCCATTCCCAGCTGTGATCTCAGTGGC 3153 QUERY : 3226 TTTGTCCGGCCTGATCCAATCATCATCTCCTCCCCACTGTCCACCTTCTTTAGTGCTGCC 3285 111111 1 111111111 1111111 11 11 11111111 11 11111 1111 111 SBJCT : 3154 TTTGTCAGACCTGATCCAGTCATCATTTCATCACCACTGTCAACTTTCTTCAGTGATGCT 3213 QUERY : 3286 CCTGGGCAGAATCCCATCGTGCCTGAGACCCAGGTTCTTCATGAAGAAATCGAGCTCCCT 3345 11111 1 11111 11 11 11 11 11111111111111111111111 111 11111 SBJCT : 3214 CCTGGCCGAAATCCTATTGTACCAGAAACCCAGGTTCTTCATGAAGAAATTGAGGTCCCT 3273 QUERY : 3346 GG 3347 ICI SBJCT : 3274 GG 3275 SCORE = 547 BITS (276), EXPECT = E-152 IDENTITIES = 540/628 (85%) STRAND = PLUS/PLUS QUERY : 782 GTCGTCCCATTCCACCTACATCCTCGCCTAGTCTCCTCCCATCTGCTCAGCTGCCTAGCT 841 IIIIIIIIIIIIIIIIIIIIIIIIII IIII II IIIIIIIIIIIIIIIIIIII II I SBJCT : 587 GTCGTCCCATTCCACCTACATCCTCGTCTAGCCTTCTCCCATCTGCTCAGCTGCCCAGTT 646 QUERY : 842 CCCATAATCCTCCACCAGTTAGCTGCCAGATGCCATTGCTAGACAGCAACACCTCCCATC 901 l 11111111111111111111111111111111111111111111111 11 1111111 SBJCT : 647 CTCATAATCCTCCACCAGTTAGCTGCCAGATGCCATTGCTAGACAGCAATACGTCCCATC 706 QUERY : 902 AAATCATGGACACCAACCCTGATGAGGAATTCTCCCCCAATTCATACCTGCTCAGAGCAT 961 1111111111111111 11111 11111 11111 11 11111111111 11 1111111 SBJCT : 707 AAATCATGGACACCAATCCTGACGAGGAGTTCTCTCCTAATTCATACCTACTAAGAGCAT 766 QUERY : 962 GCTCAGGGCCCCAGCAAGCCTCCAGCAGTGGCCCTCCGAACCACCACAGCCAGTCGACTC 1021 l 11111111 11111 11 111111111111111 1 11111 11111111111 11 1 SBJCT : 767 GTTCAGGGCCACAGCAGGCATCCAGCAGTGGCCCTTCAAACCATCACAGCCAGTCAACGC 826 QUERY : 1022 TGAGGCCCCCTCTCCCACCCCCTCACAACCACACGCTGTCCCATCACCACTCGTCCGCCA 1081 IIIIIII IIIlllll II IIIIIIIIIIII Illllllllllll IIIIIIII IIII SBJCT : 827 TGAGGCCACCTCTCCCCCCTCCTCACAACCACTCGCTGTCCCATCATCACTCGTCTGCCA 886 QUERY : 1082 ACTCCCTCAACAGGAACTCACTGACCAATCGGCGGAGTCAGATCCACGCCCCGGCCCCAG 1141

m m m m m m n m n n n i m m m n n n n i SBJCT : 887 ACTCCCTCAACAGGAACTCGCTCACCAACCGCCGCAACCAGATCCACGCGCCTGCTCCCG 946 QUERY : 1142 CGCCCAATGACCTGGCCACCACACCAGAGTCCGTTCAGCTTCAGGACAGCTGGGTGCTAA 1201 l 11111111111111 11111 11 11111 11 11111 11111111111111111 1 SBJCT : 947 CTCCCAATGACCTGGCGACCACGCCTGAGTCTGTGCAGCTGCAGGACAGCTGGGTGCTCA 1006 QUERY : 1202 ACAGCAACGTGCCACTGGAGACCCGGCACTTCCTCTTCAAGACCTCCTCGGGGAGCACAC 1261 Iililllllllll IIIIIIIII IIII III I II Ilill II II II I II I SBJCT : 1007 ACAGCAACGTGCCGCTGGAGACCAGGCATTTCTTGTTTAAGACATCTTCTGGAACGACTC 1066 QUERY : 1262 CCTTGTTCAGCAGCTCTTCCCCGGGATACCCTTTGACCTCAGGAACGGTTTACACGCCCC 1321 l 1111111 11111111111 11 11111 1111111111111 11111 11 11 1 SBJCT : 1067 CGCTGTTCAGTAGCTCTTCCCCTGGCTACCCACTGACCTCAGGAACAGTTTATACTCCAC 1126 QUERY : 1322 CGCCCCGCCTGCTGCCCAGGAATACTTTCTCCAGGAAGGCTTTCAAGCTGAAGAAGCCCT 1381 ) m) m i) t n n m i i mum)) m) m m)) mm SBJCT : 1127 CTCCCAGGCTGTTACCTAGAAATACATTTTCCAGGAATGCATTCAAGCTGAAAAAGCCCT 1186 QUERY : 1382 CCAAATACTGCAGCTGGAAATGTGCTGC 1409 Il ll SBJCT : 1187 CCAAGTATTGTAGCTGGAAATGTGCTGC 1214 SCORE = 391 BITS (197), EXPECT = E-105 IDENTITIES = 593/725 (81%) STRAND = PLUS / PLUS QUERY : 7156 CATGTCTACAATCACTCCAACTCGGAGATTACCTCACTGTACTACGACCTCCAGGGCCAC 7215 m m n m m n m)) n n ! n t ! n t n n) !) ! t ! n m) SBJCT : 7084 CATGTCTACAATCATTCCAATTCAGAAATTACCTCTCTGTATTATGATCTGCAAGGCCAC 7143 QUERY : 7216 CTCTTTGCCATGGAGAGCAGCAGTGGGGAGGAGTACTATGTTGCCTCTGATAACACAGGG 7275 11111111 11111111 11111111111 11 11 11111 11111 11111111 11 SBJCT : 7144 CTCTTTGCAATGGAGAGTAGCAGTGGGGAAGAATATTATGTCGCCTCCGATAACACGGGC 7203 QUERY : 7276 ACTCCTCTGGCTGTGTTCAGCATCAACGGCCTCATGATCAAACAGCTGCAGTACACGGCC 7335 I SBJCT : 7204 ACTCCGCTAGCCGTATTCAGCATCAATGGCCTCATGATCAAACAGCTTCAGTACACTGCA 7263 QUERY : 7336 TATGGGGAGATTTATTATGACTCCAACCCCGACTTCCAGATGGTCATTGGCTTCCATGGG 7395 II 11 11111111111111111 11111 11 111111 1111 11111 11111111 SBJCT : 7264 TACGGAGAGATTTATTATGACTCAAACCCTGATTTCCAGCTGGTTATTGGGTTCCATGGA 7323 QUERY : 7396 GGACTCTATGACCCCCTGACCAAGCTGGTCCACTTCACTCAGCGTGATTATGATGTGCTG 7455 SBJCT : 7324 GGGCTGTATGATCCTTTAACCAAACTCGTCCATTTTACCCAAAGGGACTACGATGTCCTT 7383 QUERY : 7456 GCAGGACGATGGACCTCCCCAGACTATACCATGTGGAAAAACGTGGGCAAGGAGCCGGCC 7515 II 11111 11111 11 11 11 11 11 111111111111 1 11 1 11 11 11 SBJCT : 7384 GCTGGACGCTGGACATCTCCTGATTACACAATGTGGAAAAACATTGGTAGAGAACCTGCT 7443 QUERY : 7516 CCCTTTAACCTGTATATGTTCAAGAGCAACAATCCTCTCAGCAGTGAGCTAGATTTGAAG 7575 I III SBJCT : 7444 CCCTTCAATCTGTACATGTTCAAGAGTAACAACCCTCTCAGCAATGAACTGGATCTAAAG 7503 QUERY : 7576 AACTACGTGACAGATGTGAAAAGCTGGCTTGTGATGTTTGGATTTCAGCTTAGCAACATC 7635 II 11 11 11111111 11111111111 11111111 11111111111111111111 SBJCT : 7504 AATTATGTAACAGATGTCAAAAGCTGGCTGGTGATGTTCGGATTTCAGCTTAGCAACATT 7563 QUERY : 7636 ATTCCTGGCTTCCCGAGAGCCAAAATGTATTTCGTGCCTCCTCCCTATGAATTGTCAGAG 7695 11111111111111 11111 11111111 11 111 1 11111 11 11 11 1 111 SBJCT : 7564 ATTCCTGGCTTCCCTAGAGCAAAAATGTACTTTGTGTCACCTCCATACGAGCTGACTGAG 7623 QUERY : 7696 AGTCAAGCAAGTGAGAATGGACAGCTCATTACAGGTGTCCAACAGACAACAGAGAGACAT 7755 SBJCT : 7624 AGTCAAGCGTGTGAAAATGGACAGCTAATTACAGGAGTCCAGCAGACAACAGAAAGACAC 7683 QUERY : 7756 AACCAGGCCTTCATGGCTCTGGAAGGACAGGTCATTACTAAAAAGCTCCACGCCAGCATC 7815 II 11 11 11111111111 11 11111111111 111111 1 11 llull 11 SBJCT : 7684 AATCAAGCTTTCATGGCTCTTGAGGGACAGGTCATATCTAAAAGATTACATGCCAGTATT 7743

QUERY : 7816 CGAGAGAAAGCAGGTCACTGGTTTGCCACCACCACGCCCATCATTGGCAAAGGCATCATG 7875 SBJCT : 7744 AGAGAAAAAGCAGGCCACTGGTTTGCAACAAGCACTCCTATTATTGGGAAAGGAATCATG 7803 QUERY : 7876 TTTGC 7880 ICI SBJCT : 7804 TTTGC 7808 SCORE = 339 BITS (171), EXPECT = 2E-89 IDENTITIES = 429/515 (83%) STRAND = PLUS/PLUS QUERY : 7967 ACTACCTGGACAAGATGCACTACAGCATCGAGGGCAAGGACACCCACTACTTTGTGAAGA 8026 IIIIllllll Il IIIIIIIIIIIIIIIIIIII IIIII II Ilillllllll IIII SBJCT : 7895 ACTACCTGGAAAAAATGCACTACAGCATCGAGGGGAAGGATACTCACTACTTTGTCAAGA 7954 QUERY : 8027 TTGGCTCAGCCGATGGCGACCTGGTCACACTAGGCACCACCATCGGCCGCAAGGTGCTAG 8086 I llllllllllll IIIIIII IIIII II 1 1 IIII lll I lllll II I SBJCT : 7955 TAGGCTCAGCCGATAGCGACCTCGTCACCCTCGCGATGACCAGCGGGAGGAAGGTCCTGG 8014 QUERY : 8087 AGAGCGGGGTGAACGTGACCGTGTCCCAGCCCACGCTGCTGGTCAACGGCAGGACTCGAA 8146 I Illll Il IIIIIIIIIII IIIIIIII II II II IIIIIII IIIIlllll SBJCT : 8015 ACAGCGGAGTAAACGTGACCGTCTCCCAGCCAACCCTCCTTATCAACGGAAGGACTCGAC 8074 QUERY : 8147 GGTTCACGAACATTGAGTTCCAGTACTCCACGCTGCTGCTCAGCATCCGCTATGGCCTCA 8206 IIIIIII IIIII IIIII Illll IIIII IIIIII III IIIIlllll II IIII SBJCT : 8075 GGTTCACAAACATCGAGTTTCAGTATTCCACCCTGCTGATCAACATCCGCTACGGGCTCA 8134 QUERY : 8207 CCCCCGACACCCTGGACGAAGAGAAGGCCCGCGTCCTGGACCAGGCGAGACAGAGGGCCC 8266 II 1111111 11111 11 11111111 11 11 11 11111111 1 111 1 1111 SBJCT : 8135 CCGCCGACACGCTGGATGAGGAGAAGGCACGAGTGCTAGACCAGGCTCGGCAGCGAGCCC 8194 QUERY : 8267 TGGGCACGGCCTGGGCCAAGGAGCAGCAGAAAGCCAGGGACGGGAGAGAGGGGAGCCGCC 8326 III III IIIIII 7 I SBJCT : 8195 TGGGGTCGGCCTGGGCCAAAGAGCAGCAGAAGGCACGGGATGGCCGCGAGGGCAGCCGCG 8254 QUERY : 8327 TGTGGACTGAGGGCGAGAAGCAGCAGCTTCTGAGCACCGGGCGCGTGCAAGGGTACGAGG 8386 1 11111 11 11 11111111 1|11111111 111 11 1 11 11111 1111111 SBJCT : 8255 TATGGACAGACGGAGAGAAGCAACAGCTTCTGAACACGGGAAGGGTTCAAGGTTACGAGG 8314 QUERY : 8387 GATATTACGTGCTTCCCGTGGAGCAATACCCAGAGCTTGCAGACAGTAGCAGCAACATCC 8446 1111111 11 1 11 11111111 11111111111 1111111111111111111111 SBJCT : 8315 GATATTATGTCTTGCCTGTGGAGCAGTACCCAGAGCTAGCAGACAGTAGCAGCAACATCC 8374 QUERY : 8447 AGTTTTTAAGACAGAATGAGATGGGAAAGAGGTAA 8481 1111111111111111111 111111111111111 SBJCT : 8375 AGTTTTTAAGACAGAATGAAATGGGAAAGAGGTAA 8409 SCORE = 323 BITS (163), EXPECT = 1E-84 IDENTITIES = 397/475 (83%) STRAND = PLUS/PLUS QUERY : 299 GACACCGCTCTTTGACCAGAGGACGCTGTGGCAAAGAGTGTCGCTACACAAGCTCCTCTC 358 1111111111111111 11111 11 11 11 11 11111111111 11 11 11 11 1 SBJCT : 20 GACACCGCTCTTTGACGAGAGGCCGGTGCGGGAAGGAGTGTCGCTATACTAGTTCTTCAC 79 QUERY : 359 TGGACAGTGAGGACTGCCGGGTGCCCACACAGAAATCCTACAGCTCCAGTGAGACTCTGA 418 1 11111111 111111 1 11 11 1 11111 11111111111111111111 1111 SBJCT : 80 TCGACAGTGAAGACTGCAGAGTACCAGCTCAGAAGTCCTACAGCTCCAGTGAGACCCTGA 139 QUERY : 419 AGGCCTATGACCATGACAGCAGGATGCACTATGGAAACCGAGTCACAGACCTCATCCACC 478 I II IIII IIIIIIII IIIIIIIIIII IIIII IIIII IIIIIII I III SBJCT : 140 AAGCATATGGCCATGACACGAGGATGCACTACGGAAATCGAGTTTCAGACCTGGTTCACA 199 QUERY : 479 GGGAGTCAGATGAGTTTCCTAGACAAGGAACCAACTTCACCCTTGCCGAACTGGGCATCT 538 IIIIIII IIIIIIIIIII II llllllll Illlllllllllll Illlllll Illl SBJCT : 200 GGGAGTCGGATGAGTTTCCAAGGCAAGGAACGAACTTCACCCTTGCAGAACTGGGAATCT 259 QUERY : 539 GTGAGCCCTCCCCACACCGAAGCGGCTACTGCTCCGACATGGGGATCCTTCACCAGGGCT 598

m m m in n m n m m m n m n n n n n n m n SBJCT : 260 GTGAGCCCTCTCCCCATCGAAGTGGCTACTGCTCGGACATAGGAATACTCCATCAAGGCT 319 QUERY : 599 ACTCCCTTAGCACAGGGTCTGACGCCGACTCCGACACCGAGGGAGGGATGTCTCCAGAAC 658 1 111 1 11111 11 11111 11 11111 11111 11111 11111111111111 1 SBJCT : 320 ATTCCTTGAGCACTGGCTCTGATGCTGACTCAGACACGGAGGGCGGGATGTCTCCAGAGC 379 QUERY : 659 ACGCCATCAGACTGTGGGGCAGAGGGATAAAATCCAGGCGCAGTTCCGGCCTGTCCAGTC 718 t Ht n < n mm n ! m) m m ! m ! n n m mum m ! SBJCT : 380 ACGCGATCAGGCTGTGGGGAAGAGGGATCAAATCCAGCCGAAGTTCTGGCCTGTCAAGTC 439 QUERY : 719 GTGAAAACTCGGCCCTTACCCTGACTGACTCTGACAACGAAAACAAATCAGATGA 773 1111111111111 11 11 11 11111111 11111 11 11111 11111111 SBJCT : 440 GTGAAAACTCGGCTCTCACGCTCACTGACTCCGACAATGAGAACAAGTCAGATGA 494 The full FCTR3a amino acid sequence also has 342 of 383 amino acid residues (89%) identical to, and 342 of 383 residues (89%) positive with, the 276 amino acid residue Odd Oz/ten-m homolog 2 (Drosophila) (GenBank Ace : Nu 035986. 2) (SEQ ID NO : 68) (Table 3P).

Table 3P. BLASTP of FCTR3a against Odd Oz/ten-m homolog 2- (SEQ ID NO : 68) >GI ! 7657415jREFtNP 035986. 2j ODD OZ/TEN-M HOMOLOG 2 (DROSOPHILA) ; ODD OZ/TEN-M HOMOLOG 3 (DROSOPHILA) [MUS MUSCULUS] GI#4760778#DBJ#BAA77397.1# (AB025411) TEN-M2 [MUS MUSCULUS] LENGTH = 2764 SCORE = 495 BITS (1274), EXPECT = E-139 IDENTITIES = 342/383 (89%), POSITIVES = 342/383 (89%), GAPS = 41/383 (10%) QUERY : 37 HNPPPVSCQMPLLDSNTSHQIMDTNPDEEFSPNSYLLRACSGPQQASSSGPPNHHSQSTL 96 111111111111111111111111111111111111111111111111111111111111 SBJCT : 189 HNPPPVSCQMPLLDSNTSHQIMDTNPDEEFSPNSYLLRACSGPQQASSSGPPNHHSQSTL 248 QUERY : 97 RPPLPPPHNHTLSHHHSSANSLNRNSLTNRRSQIHAPAPAPNDLATTPESVQLQDSWVLN 156 111111111111111111111111111111111111111111111111111111111111 SBJCT : 249 RPPLPPPHNHTLSHHHSSANSLNRNSLTNRRSQIHAPAPAPNDLATTPESVQLQDSWVLN 308 QUERY : 157 SNVPLETRHFLFKTSSGSTPLFSSSSPGYPLTSGTVYTPPPRLLPRNTFSRKAFKLKKPS 216 111111111111111111111111111111111111111111111110111111111111 SBJCT : 309 SNVPLETRHFLFKTSSGSTPLFSSSSPGYPLTSGTVYTPPPRLLPRNTFSRKAFKLKKPS 368 QUERY : 217 KYCSWKCAALSAIAAALLLAILLAYFI--------------------------------- 243 111111111111111111111111111 SBJCT : 369 KYCSWKCAALSAIAAALLLAILLAYFIAMHLLGLNWQLQPADGHTFNNGVRTGLPGNDDV 428 QUERY : 244--------VPWSLKNSSIDSGEAEVGRRVTQEVPPGVFWRSQIHISQPQFLKFNISL GKD 295 Illlilillllllllllllillllllllllllllllllllllllllllllll SBJCT : 429 ATVPSGGKVPWSLKNSSIDSGEAEVGRRVTQEVPPGVFWRSQIHISQPQFLKFNISLGKD 488 QUERY : 296 ALFGVYIRRGLPPSHAQYDFMERLDGKEKWSVVESPRERRSIQTLVQNEAVFVQYLDVGL 355 111111111111111111111111111111111111111111111|11111111111111 SBJCT : 489 ALFGVYIRRGLPPSHAQYDFMERLDGKEKWSVVESPRERRSIQTLVQNEAVFVQYLDVGL 548 QUERY : 356 WHLAFYNDGKDKEMVSFNTVVLD 378 11111111111111111111111 SBJCT : 549 WHLAFYNDGKDKEMVSFNTWLD 571

The full FCTR3b amino acid sequence has 2442 of 2802 amino acid residues (87%) identical to, and 2532 of 2802 residues (90%) positive with, the 2802 amino acid residue teneurin-2 [Gallus gallus] (GenBank Ace : AJ279031) (SEQ ID NO : 69) (Table 3Q).

Table 3Q. BLASTP of FCTR3a against Teneurin-2- (SEQ ID NO : 69 >GI#10241574#EMB#CAC09416.1# (AJ279031) TENEURIN-2 [GALLUS GALLUS] LENGTH = 2802 SCORE = 4853 BITS (12589), EXPECT = 0. 0 IDENTITIES = 2510/2802 (87%), POSITIVES = 2600/2802 (90%), GAPS = 69/2802 (2%) QUERY : 1 MDVKDRRHRSLTRGRCGKECRYTSSSLDSEDCRVPTQKSYSSSETLKAYDHDSRMHYGNR 60 +Illl1 IIl +I SBJCT : 1 MDIKDRRHRSLTRGRCGKECRYTSSSLDSEDCRVPAQKSYSSSETLKAYGHDTRMHYGNR 60 QUERY : 61 VTDLIHRESDEFPRQGTNFTLAELGICEPSPHRSGYCSDMGILHQGYSLSTGSDADSDTE 120 1+11+1111111111111111111111111111111111+11111111111111111111 SBJCT : 61 VSDLVHRESDEFPRQGTNFTLAELGICEPSPHRSGYCSDIGILHQGYSLSTGSDADSDTE 120 QUERY : 121 GGMSPEHAIRLWGRGIKSRRSSGLSSRENSALTLTDSDNENKSDDENG------------ 168 IIIIIIIIIIIIIIIIII IIIIIIIIIIIIIIIIIIIIIIIII II SBJCT : 121 GGMSPEHAIRLWGRGIKSSRSSGLSSRENSALTLTDSDNENKSDEENDFHTHLSEKLKDR 180 QUERY : 169----------------RPIPPTSSPSLLPSAQLPSSHNPPPVSCQMPLLDSNTSHQI MDT 212 N m m ! U m n ! m ! N ! H N H m m H ! m ! SBJCT : 181 QTSWQQLAETKNSLIRRPIPPTSSSSLLPSAQLPSSHNPPPVSCQMPLLDSNTSHQIMDT 240 QUERY : 213 NPDEEFSPNSYLLRACSGPQQASSSGPPNHHSQSTLRPPLPPPHNHTLSHHHSSANSLNR 272 IIIIIIIIIIIIIIIII SBJCT : 241 NPDEEFSPNSYLLRACSGPQQASSSGPSNHHSQSTLRPPLPPPHNHSLSHHHSSANSLNR 300 QUERY : 273 XXXXXXXXQIHAPAPAPNDLATTPESVQLQDSWVLNSNVPLETRHFLFKXXXXXXXXXXX 332 N m m m m mm mm m mmm m SBJCT : 301 NSLTNRRNQIHAPAPAPNDLATTPESVQLQDSWVLNSNVPLETRHFLFKTSSGTTPLFSS 360 QUERY : 333 XXXXYPLTSGTVYTPPPRLLPRNTFSRKAFKLKKPSKYCSWKCXXXXXXXXXXXXXXXXX 392 11111111111111111111111 111111111111111 SBJCT : 361 SSPGYPLTSGTVYTPPPRLLPRNTFSRNAFKLKKPSKYCSWKCAALSAIAAAVLLAILLA 420 QUERY : 393 YFIV-----------------------------------------PWSLKNSSIDSGEAE 411 111 11 +11111111 1 SBJCT : 421 YFIAMHLLGLNWQLQPADGHTFSNGLRPGAAGAEDGAAAPPAGRGPWVTRNSSIDSGETE 480 QUERY : 412 VGRRVTQEVPPGVFWRSQIHISQPQFLKFNISLGKDALFGVYIRRGLPPSHAQYDFMERL 471 111+11111111111111111111111111111111111111111111111111111111 SBJCT : 481 VGRKVTQEVPPGVFWRSQIHISQPQFLKFNISLGKDALFGVYIRRGLPPSHAQYDFMERL 540 QUERY : 472 DGKEKWSVVESPRERRSIQTLVQNEAVFVQYLDVGLWHLAFYNDGKDKEMVSFNTWLDS 53l IIIIIIIIIII++II+I SBJCT : 541 DGKEKWSVVESPRERRSIQTLVQNEAVFVQYLDVGLWHLAFYNDGKDKEVVSFSTVILDS 600 QUERY : 532 VQDCPRNCHGNGECVSGVCHCFPGFLGADCAKAACPVLCSGNGQYSKGTCQCYSGWKGAE 591 1111111111111111111111111 111111111111111111111111 1111111 1 SBJCT : 601 VQDCPRNCHGNGECVSGVCHCFPGFHGADCAKAACPVLCSGNGQYSKGTCLCYSGWKGPE 660 QUERY : 592 CDVPMNQCIDPSCGGHGSCIDGNCVCSAGYKGEHCEEVDCLDPTCSSHGVCVNGECLCSP 651 ))) ++) n m m m m-mm m) ! +m m m !)) + ! !) m n ! nn SBJCT : 661 CDVPISQCIDPSCGGHGSCIEGNCVCSIGYKGENCEEVDCLDPTCSNHGVCVNGECLCSP 720 SBJCT : 661 CDVPISQCIDPSCGGHGSCIEGNCVCSIGYKGENCEEVDCLDPTCSNHGVCVNGECLCSP 720 QUERY : 652 GWGGLNCELARVQCPDQCSGHGTYLPDTGLCSCDPNWMGPDCSVEVCSVDCGTHGVCIGG 711 IIIIIIII I IIIIIIIIIIIII IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII SBJCT : 721 GWGGINCELPRAQCPDQCSGHGTYLSDTGLCSCDPNWMGPDCSVEVCSVDCGTHGVCIGG 780 m ! n m ! m n m m n n m) n ! m m m m n n mmm QUERY : 712 ACRCEEGWTGAACDQRVCHPRCIEHGTCKDGKCECREGWNGEHCTIGRQTAGTETDGCPD 771 IIIIIIIIII Illilllllli Ililllllllillilllllllllilll Ilillllil SBJCT : 781 ACRCEEGWTGVACDQRVCHPRCTEHGTCKDGKCECREGWNGEHCTIGRQTTGTETDGCPD 840

QUERY : 772 LCNGNGRCTLGQNSWQCVCQTGWRGPGCNVAMETSCADNKDNEGDGLVDCLDPDCCLQSA 831 SBJCT : 841 LCNGNGRCTLGQNSWQCVCQTGWRGPGCNVAMETSCADNKDNEGDGLVDCLVPDCCLQST 900 QUERY : 832 CQNSLLCRGSRDPLDIIQQGQTDWPAVKSFYDRIKLLAGKDSTHIIPGENPFNSSLVSLI 891 Illllllllllllllllll + Illllllllllll IIIIIIIIIIIIIIIIIIIIII SBJCT : 901 CQNSLLCRGSRDPLDIIQQSHSGSPAVKSFYDRIKLLVGKDSTHIIPGENPFNSSLVSLI 960 QUERY : 892 RGQWTTDGTPLVGVNVSFVKYPKYGYTITRQDGTFDLIANGGASLTLHFERAPFMSQER 951 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII III+IIII+IIIIIIIIIIIIIIII SBJCT : 961 RGQWTTDGTPLVGVNVSFVKYPKYGYTITRQDGMFDLVANGGSSLTLHFERAPFMSQER 1020 QUERY : 952 TVWLPWNSFYAMDTLVMKTEENSIPSCDLSGFVRPDPIIISSPLSTFFSAAPGQNPIVPE 1011 +I SBJCT : 1021 TVWLPWNSFYAMDTLVMKTEENSIPSCDLSGFVRPDPVIISSPLSTFFSDAPGRNPIVPE 1080 QUERY : 1012 TQVLHEEIELPGSNVKLRYLSSRTAGYKSLLKITMTQSTVPLNLIRVHLMVAVEGHLFQK 1071 111111111+111++11 111111111111111 1111 111111+11111111111111 SBJCT : 1081 TQVLHEEIEVPGSSIKLIYLSSRTAGYKSLLKIIMTQSLVPLNLIKVHLMVAVEGHLFQK 1140 SBJCT : 1081 TQVLHEEIEVPGSSIKLIYLSSRTAGYKSLLKIIMTQSLVPLNLIKVHLMVAVEGHLFQK 1140 QUERY : 1072 SFQASPNLASTFIWDKTDAYGQRVYGLSDAWSVGFEYETCPSLILWEKRTALLQGFELD 1131 11 111111 111111111111+1111111111111111111111111111111111111 SBJCT : 1141 SFLASPNLAYTFIWDKTDAYGQKVYGLSDAWSVGFEYETCPSLILWEKRTALLQGFELD 1200 H H hH m n+t H m ! m ! m hm m+m m m m m m m ( QUERY : 1132 PSNLGGWSLDKHHILNVKSGILHKGTGENQFLTQQPAIITSIMGNGRRRSISCPSCNGLA 1191 1111111111111+11111111111 11111111111+1111111111111111111111 SBJCT : 1201 PSNLGGWSLDKHHVLNVKSGILHKGNGENQFLTQQPAVITSIMGNGRRRSISCPSCNGLA 1260 H)) m N ! m m) ! i+m) m m) m m)) ! m) m m ! m m m QUERY : 1192 EGNKLLAPVALAVGIDGSLYVGDFNYIRRIFPSRNVTSILELRNKEFKHSNNPAHKYYLA 1251 IIIIII+IIIIIIIII SBJCT : 1261 EGNKLVAPVALAVGIDGSLFVGDE'NYIRRIEPSRNVTSILELRNECEFKHSNNPAHKYY LA 1320 QUERY : 1252 VDPVSGSLYVSDTNSRRIYRVKSLSGTKDLAGNSEWAGTGEQCLPFDEARCGDGGKAID 1311 +I+I+ SBJCT : 1321 VDPVSGSLYVSDTNSRRIYKVKSLTGTKDLAGNSEWAGTGEQCLPFDEARCGDGGKAVD 1380 QUERY : 1312 ATLMSPRGIAVDKNGLMYFVDATMIRKVDQNGIISTLLGSNDLTAVRPLSCDSSMDVAQV 1371 Il ) IIIllllll SBJCT : 1381 ATLMSPRGIAVDKYGLMYFVDATMIRKVDQNGIISTLLGSNDLTAVRPLSCDSSMDVSQV 1440 QUERY : 1372 RLEWPTDLAVNPMDNSLYVLENNVILRITENHQVSIIAGRPMHCQVPGIDYSLSKXXXXX 1431 1111111111+11111111111111111111111111111111111111111111 SBJCT : 1441 RLEWPTDLAVDPMDNSLYVLENNVILRITENHQVSIIAGRPMHCQVPGIDYSLSKLAIHS 1500 QUERY : 1432 XXXXXXXXXXXXTGVLYITETDEKKINRLRQVTTNGEICLLAGAASXXXXXXXXXXXXYS 1491 111111+111111111111111111111111111 11 SBJCT : 1501 ALESASAIAISHTGVLYISETDEKKINRLRQVTTNGEICLLAGAASDCDCKNDVNCNCYS 1560 QUERY : 1492 GDDAYATDAILNSPSSLAVAPDGTIYIADLGNIRIRAVSKNKPVLNAFNQYEAASPGEQE 1551 111 1111111111111111111111111111111111111+1+11+1111111111111 SBJCT : 1561 GDDGYATDAILNSPSSLAVAPDGTIYIADLGNIRIRAVSKNRPILNSFNQYEAASPGEQE 1620 QUERY : 1552 LYVFNADGIHQYTVSLVTGEYLYNFTYSTDNDVTELIDNNGNSLKIRRDSSGMPRHLLMP 1611 t mm m m+m m m m n+nm ! ++) +< mH+tn+tm n n n SBJCT : 1621 LYVFNADGIHQYTLSLVTGEYLYNFTYSSDNDVTEVMDSNGNSLKVRRDASGMPRHLLMP 1680 QUERY : 1612 DNQIITLTVGTNGGLKWSTQNLELGLMTYDGNTGLLATKSDETGWTTFYDYDHEGRLTN 1671 I+ + +'a'IIIIll SBJCT : 1681 DNQIVTLAVGTNGGLKLVSTQTLELGLMTYNGNSGLLATKSDETGWTTFYDYDHEGRLTN 1740 QUERY : 1672 VTRPTGWTSLHREMEKSITIDIENSNRDDDVTVITNLSSVEASYTWQDQVRNSYQLCN 1731 111111111111111111111111|11|11111111111111111111111111111111 SBJCT : 1741 VTRPTGWTSLHREMEKSITIDIENSNRDDDVTVITNLSSVEASYTWQDQVRNSYQLCN 1800 QUERY : 1732 NGTLRVMYANGMGISFHSEPHVLAGTITPTIGRCNISLPMENGLNSIEWRLRKEQIKGKV 1791 IIIIIIIIIIII lilllllllllll+Illllllllllllllllllllllllllllllll SBJCT : 1801 NGTLRVMYANGMSISFHSEPHVLAGTVTPTIGRCNISLPMENGLNSIEWRLRKEQIKGKV 1860 QUERY : 1792 TIFGRKLRVHGRNLLSIDYDRNIRTEKIYDDHRKFTLRIIYDQVGRPFLWLPSSGLAAVN 1851

(+NHHnHnN ! Hmmmmmnmnh+HNHN ! nNm SBJCT : 1861 TVFGRKLRVHGRNLLSIDYDRNIRTEKIYDDHRKFTLRIIYDQLGRPFLWLPSSGLAAVN 1920 QUERY : 1852 VSYFFNGRLAGLQRGAMSERTDIDKQGRIVSRMFADGKVWSYSYLDKSMVLLLQSQRQYI 1911 SBJCT : 1921 VSYFFNGRLAGLQRGAMSERTDIDKQGRIISRMFADGKVWSYTYLEKSMVLLLQSQRQYI 1980 QUERY : 1912 FEYDSSDRLLAVTMPSVARHSMSTHTSIGYIRNIYNPPESNASVIFDYSDDGRILKTSFL 1971 111111111 11111111111111111+11111111111111111111111111111111 SBJCT : 1981 FEYDSSDRLHAVTMPSVARHSMSTHTSVGYIRNIYNPPESNASVIFDYSDDGRILKTSFL 2040 QUERY : 1972 GTGRQVFYKYGKLSKLSEIVYDSTAVTFGYDETTGVLKMVNLQSGGFSCTIRYRKIGPLV 2031 111111111111111111111111111111111111111111111111111111111111 SBJCT : 2041 GTGRQVFYKYGKLSKLSEIVYDSTAVTFGYDETTGVLKMVNLQSGGFSCTIRYRKIGPLV 2100 QUERY : 2032 DKQIYRFSEEGMVNARFDYTYHDNSFRIASIKPVISETPLPVDLYRYDEISGKVEHFGKF 2091 111111111111111111111111111111111+11111111111111111111111111 SBJCT : 2101 DKQIYRFSEEGMVNARFDYTYHDNSFRIASIKPIISETPLPVDLYRYDEISGKVEHFGKF 2160 QUERY : 2092 GVIYYDINQIITTAVMTLSKHFDTHGRIKEVQYEMFRSLMYWMTVQYDSMGRVIKRELKL 2151 Illlllllllllllllfllllllllllllllllllllllllllllllllllfl lilill SBJCT : 2161 GVIYYDINQIITTAVMTLSKHFDTHGRIKEVQYEMFRSLMYWMTVQYDSMGRVTKRELKL 2220 SBJCT : 2161 GVIYYDINQIITTAVMTLSKHFDTHGRIKEVQYEMFRSLMYWMTVQYDSMGRVTKRELKL 2220 QUERY : 2152 GPYANTTKYTYDYDGDGQLQSVAVNDRPTWRYSYDXXXXXXXXXXXXSVRLMPLRYDLRD 2211 1111111111111} 111111111111111111111 1111111111111 SBJCT : 2221 GPYANTTKYTYDYDGDGQLQSVAVNDRPTWRYSYDLNGNLHLLNPGNSVRLMPLRYDLRD 2280 m) m+ u i n) i+n n) n+) u) n) t Ni H)) i+n+) n H n+n tit i QUERY : 2212 RITRLGDVQYKIDDDGYLCQRGSDIFEYNSKGLLTRAYNKASGWSVQYRYDGVGRRASYK 2271 1111111+ 1111111+1111111+1111111111111111+11+1111111+11111 1 SBJCT : 2281 RITRLGDIPYKIDDDGFLCQRGSDVFEYNSKGLLTRAYNKANGWNVQYRYDGLGRRASCK 2340 QUERY : 2272 TNLGHHLQYFYSDLHNPTRITHVYNHSNSEITSLYYDLQGHLFAMESSSGEEYYVASDNT 2331 11111111111+1111111+1111111111111111111111111111111111111111 SBJCT : 2341 TNLGHHLQYFYADLHNPTRVTHVYNHSNSEITSLYYDLQGELFAMESSSGEEYYVASDNT 2400 QUERY : 2332 GTPLAVFSINGLMIKQLQYTAYGEIYYDSNPDFQMVIGFHGGLYDPLTKLVHFTQRDYDV 2391 IIIIIII11+IIIIII SBJCT : 2401 GTPLAVFSINGLMIKQLQYTAYGEIYYDSNPDFQLVIGFHGGLYDPLTKLVHFTQRDYDV 2460 QUERY : 2392 LAGRWTSPDYTMWKNVGKEPAPFNLYMFKSNNPLSSELDLKNYVTDVKSWLVMFGFQLSN 2451 IIIIIIIIIIIIIII+I+IIIIIIIIIIIIIIIII+IIIlllllllllllllllllllll SBJCT : 2461 LAGRWTSPDYTMWKNIGREPAPFNLYMFKSNNPLSNELDLKNYVTDVKSWLVMFGFQLSN 2520 QUERY : 2452 IIPGFPRAKMYFVPPPYELSESQASENGQLITGVQQTTERHNQAFMALEGQVITKKLHAS 2511 1111111111111 11111+1111 1111111111111111111111111111+1+1111 SBJCT : 2521 IIPGFPRAKMYFVSPPYELTESQACENGQLITGVQQTTERHNQAFMALEGQVISKRLHAS 2580 QUERY : 2512 IREKAGHWFATTTPIIGKGIMFAIKEGRVTTGVSSIASEDSRKVASVLNNAYYLDKMHYS 2571 IIIIIIIIIII+11111111111+I+Illlll+Illl++Illl+Illlf-I+ll+IIIII SBJCT : 2581 IREKAGHWFATSTPIIGKGIMFAVKKGRVTTGISSIATDDSRKIASVLNSAHYLEKMHYS 2640 QUERY : 2572 IEGKDTHYFVKIGSADGDLVTLGTTIGRKVLESGVNVTVSQPTLLVNGRTRRFTNIEFQY 2631 +llll+Illl SBJCT : 2641 IEGKDTHYFVKIGSADSDLVTLAMTSGRKVLDSGVNVTVSQPTLLINGRTRRFTNIEFQY 2700 QUERY : 2632 STLLLSIRYGLTPDTLDEEKARVLDQARQRALGTAWAKEQQKARDGREGSRLWTEGEKQQ 2691 IIII++IIIIII Illlllllllllllllllll+IIIIIIIilllllllll+11+IIIII SBJCT : 2701 STLLINIRYGLTADTLDEEKARVLDQARQRALGSAWAKEQQKARDGREGSRVWTDGEKQQ 2760 QUERY : 2692 LLSTGRVQGYEGYYVLPVEQYPELADSSSNIQFLRQNEMGKR 2733 ll+lllllllllllllllllllllllllllllllllllllll SBJCT : 2761 LLNTGRVQGYEGYYVLPVEQYPELADSSSNIQFLRQNEMGKR 2802 The FCTR3bcde and f arnino acid sequences have 1524 of 2352 amino acid residues (64%) identical to, and 1881 of 2532 residues (79%) positive with, the amino acid residues 429-2771, 93 of 157 residues (59%) identical to and 118 of 157 residues (74%) positive with

amino acid residues 1-155, and 59 of 152 residues (38%) identical to and 68 of 152 residues (43%) positive with amino acid residues 211-361 of Ten-m4 [Mus musculus] (ptnr : GenBank Acc : BAA77399. 1) (SEQ ID NO : 70) (Table 3R).

Table 3R. BLASTP of FCTR3b, c, d, e, and f against Mus musculus Ten-m4- (SEQ ID NO : 70) >GI#4760782#DBJ#BAA77399.1# (AB025413) TEN-M4 [MUS MUSCULUS] LENGTH = 2771 SCORE = 3089 BITS (8008), EXPECT 0 IDENTITIES = 1524/2352 (64%), POSITIVES = 1881/2352 (79%), GAPS = 28/2352 (1%) QUERY : 401 KNSSIDSGEAEVGRRVTQEVPPGVFWRSQIHISQPQFLKFNISLGKDALFGVYIRRGLPP 460 ++1 11111 +1111 +1++111 11111+ 1 1 1111+1111 11 1+1 1+1111 SBJCT : 429 EDSFIDSGEIDVGRRASQKIPPGTFWRSQVFIDHPVHLKFNVSLGKAALVGIYGRKGLPP 488 QUERY : 461 SHAQYDFMERLDGK-----EKWSWESPRERRSIQTLVQNEAVFVQYLDVGLWHLAFYND 515 i 1+11+1 111+ l 1+ 1+ 1 +l 1+1111 1+111111|1 SBJCT : 489 SHTQFDFVELLDGRRLLTQEARSLEGPQRQSRGPVPPSSHETGFIQYLDSGIWHLAFYND 548 QUERY : 516 GKDKEMVSFNTWLDSVQDCPRNCHGNGECVSGVCHCFPGFLGADCAKAACPVLCSGNGQ 575 ll+ 1+111 1 ++11 +11 ll+lll+l+ll 1111 1111 11 +1+1111111111 SBJCT : 549 GKESEVVSFLTTAIESVDNCPSNCYGNGDCISGTCHCFLGFLGPDCGRASCPVLCSGNGQ 608 QUERY : 576 YSKGTCQCYSGWKGAECDVPMNQCIDPSCGGHGSCIDGNCVCSAGYKGEHCEEVDCLDPT 635 1 11 l 11111 +1 ll+il 1 1+1+ liiii llilll+lli SBJCT : 609 YMKGRCLCHSGWKGAECDVPTNQCIDVACSSHGTCIMGTCICNPGYKGESCEEVDCMDPT 668 QUERY : 636 CSSHGVCVNGECLCSPGWGGLNCELARVQCPDQCSGHGTYLPDTGLCSCDPNWMGPDCSV 695 III Illl III ll IIII III I I IIIIIIII+IIIIIII+III+I 1 111+ SBJCT : 669 CSSRGVCVRGECHCSVGWGGTNCETPRATCLDQCSGHGTFLPDTGLCNCDPSWTGHDCSI 728 QUERY : 696 EVCSVDCGTHGVCIGGACRCEEGWTGAACDQRVCHPRCIEHGTCKDGKCECREGWNGEHC 755 ) +) +) N nn+tf nn+n n) Nn nn) nnt+Htin i) n) n SBJCT : 729 EICAADCGGHGVCVGGTCRCEDGWMGAACDQRACHPRCAEHGTCRDGKCECSPGWNGEHC 788 ********* QUERY : 756 TIGRQTAGTETDGCPDLCNGNGRCTLGQNSWQCVCQTGWRGPGCNVAMETSCADNKDNEG 815 II ! +)) !)) H) !)) H)) Hi) tH))) ++ii !)) ! H+i SBJCT : 789 TIAHYLDRVVKEGCPGLCNGNGRCTLDLNGWHCVCQLGWRGTGCDTSMETGCGDGKDNDG 848 QUERY : 816 DGLVDCLDPDCCLQSACQNSLLCRGSRDPLDIIQQGQT--DWPAVKSFYDRIKLLAGKDS 873 ililll+lllllll I + 11 11 illilll+ I + liiiii 1 1+11 SBJCT : 849 DGLVDCMDPDCCLQPLCHVNPLCLGSPDPLDIIQETQAPVSQQNLNPFYDRIKFLVGRDS 908 QUERY : 874 THIIPGENPFNSSLVSLIRGQWTTDGTPLVGVNVSFVKYPKYGYTITRQDGTFDLIANG 933 II IIIIIII+ +11111+1+111111111+11+ 1 +1111+1111+111+ 11 SBJCT : 909 THSIPGENPFDGGHACVIRGQVMTSDGTPLVGVNISFINNPLFGYTISRQDGSFDLVTNG 968 QUERY : 934 GASLTLHFERAPFMSQERTVWLPWNSFYAMDTLVMKTEENSIPSCDLSGFVRPDPIIISS 993 ! 1+ 1 111111++11 1+1111+ 1+ 1+1+11+ 111 1111111 1 ll+l++ I SBJCT : 969 GISIILRFERAPFITQEHTLWLPWDRFFVMETIVMRHEENEIPSCDLSNFARPNPVVSPS 1028 QUERY : 994 PLSTFFSAAPGQNPIVPETQVLHEEIELPGSNVKLRYLSSRTAGYKSLLKITMTQSTVPL 1053 ll++l 1+ + liiii I I III + I ++I IIIIII 1111+1+1++1 1+1 SBJCT : 1029 PLTSFASSCAEKGPIVPEIQALQEEIVIAGCKMRLSYLSSRTPGYKSVLRISLTHPTIPF 1088 QUERY : 1054 NLIRVHLMVAVEGHLFQKSFQASPNLASTFIWDKTDAYGQRVYGLSDAWSVGFEYETCP 1113 ll++lllllllll ll+l I 1+1+1+ 1111111 l 1+1+1 i+l 1lll+lll+ll SBJCT : 1089 NLMKVHLMVAVEGRLFRKWFAAAPDLSYYFIWDKTDVYNQKVFGFSEAFVSVGYEYESCP 1148 QUERY : 1114 SLILWEKRTALLQGFELDPSNLGGWSLDKHHILNVKSGILHKGTGENQFLTQQPAIITSI 1173 ililillll+lll+l+l I iiiiiiiiii ll++Illllll lilll++Ill +1 11 SBJCT : 1149 DLILWEKRTAVLQGYEIDASKLGGWSLDKHHALNIQSGILHKGNGENQFVSQQPPVIGSI 1208

QUERY : 1174 MGNGRRRSISCPSCNGLAEGNKLLAPVALAVGIDGSLYVGDFNYIRRIFPSRNVTSILEL 1233 111111111111111111+1111111111 1 111111111111111111 111+111+ SBJCT : 1209 MGNGRRRSISCPSCNGLADGNKLLAPVALTCGSDGSLYVGDFNYIRRIFPSGNVTNILEM 1268 QUERY : 1234 RNKEFKHSNNPAHKYYLAVDPVSGSLYVSDTNSRRIYRVKSLSGTKDLAGNSEWAGTGE 1293 11+11.... 11+11++++1111111+++111 + 111 111111111+ SBJCT : 1269 RNKDFRHSHSPAHKYYLATDPMSGAVFLSDTNSRRVFKVKSTTWKDLVKNSEWAGTGD 1328 QUERY : 1294 QCLPFDEARCGDGGKAIDATLMSPRGIAVDKNGLMYFVDATMIRKVDQNGIISTLLGSND 1353 IIIIII+ llllllll +lll +IIII Ill ll+Illl IIII+IIIIlllllllllll SBJCT : 1329 QCLPFDDTRCGDGGKATEATLTNPRGITVDKFGLIYFVDGTMIRRVDQNGIISTLLGSND 1388 QUERY : 1354 LTAVRPLSCDSSMDVAQVRLEWPTDLAVNPMDNSLYVLENNVILRITENHQVSIIAGRPM 1413 II+ Illllll I+-+IIIIIIIIIII+IIIIIIIIII+lll+1+I+IIIII I+Illll SBJCT : 1389 LTSARPLSCDSVMEISQVRLEWPTDLAINPMDNSLYVLDNNVVLQISENHQVRIVAGRPM 1448 QUERY : 1414 HCQVPGID-YSLSKXXXXXXXXXXXXXXXXXTGVLYITETDEKKINRLRQVTTNGEICLL 1472 11111111 + 111 11111 111111111+11111+111 1+ SBJCT : 1449 HCQVPGIDHFLLSKVAIHATLESATALAVSHNGVLYIAETDEKKINRIRQVTTSGEISLV 1508 QUERY : 1473 AGAASXXXXXXXXXXXXYSGDDAYATDAILNSPSSLAVAPDGTIYIADLGNIRIRAVSKN 1532 III I n+i ! ! m i +t+n mm) + 11 SBJCT : 1509 AGAPSGCDCKNDANCDCFSGDDGYAKDAKLNTPSSLAVCADGELYVADLGNIRIRFIRKN 1568 QUERY : 1533 KPVLNAFNQYEAASPGEQELYVFNADGIHQYTVSLVTGEYLYNFTYSTDNDVTELIDNNG 1592 un m i +)) +m) +) + !) i ! i) N+m) m+ i m + m) SBJCT : 1569 KPFLNTQNMYELSSPIDQELYLFDTSGKHLYTQSLPTGDYLYNFTYTGDGDITHITDNNG 1628 QUERY : 1593 NSLKIRRDSSGMPRHLLMPDNQIITLTVGTNGGLKVVSTQNLELGLMTYDGNTGLLATKS 1652 1 + +1111+¢ ++ll 1+ +1+111 l+ 1+11 11 +111 11+1t SBJCT : 1629 NMVNVRRDSTGMPLWLWPDGQVYWVTMGTNSALRSVTTQGHELAMMTYHGNSGLLATKS 1688 QUERY : 1653 DETGWTTFYDYDHEGRLTNVTRPTGWTSLHREMEKSITIDIENSNRDDDVTVITNLSSV 1712 +1 111111+11 111|111 111 1+1 + + 1+ + +1 1++ 1111+ 1111+ SBJCT : 1689 NENGWTTFYEYDSFGRLTNVTFPTGQVSSFRSDTDSSVHVQVETSSK-DDVTITTNLSAS 1747 QUERY : 1713 EASYTWQDQVRNSYQLCNNGTLRVMYANGMGISFHSEPHVLAGTITPTIGRCNISLPME 1772 I 11++111 + +1+11++ 1111 ++ +111+1111+ 11+1+ 1++11++ SBJCT : 1748 GAFYTLLQDQVRNSYYIGADGSLRLLLANGMEVALQTEPHLLAGTVNPTVGKRNVTLPID 1807 QUERY : 1773 NGLNSIEWRLRKEQIKGKVTIFGRKLRVHGRNLLSIDYDRNIRTEKIYDDHRKFTLRIIY 1832 1111 +111 1111 +1+11+111+1111 11111+1+11 1111111111111111+1 SBJCT : 1808 NGLNLVEWRQRKEQARGQVTVFGRRLRVHNRNLLSLDFDRVTRTEKIYDDHRKFTLRILY 1867 QUERY : 1833 DQVGRPFLWLPSSGLAAVNVSYFFNGRLAGLQRGAMSERTDIDKQGRIVSRMFADGKVWS 1892 u m i ! m i m+) t +)) +m m ! + t+ m n+u ! ! i+n SBJCT : 1868 DQAGRPSLWSPSSRLNGVNVTYSPGGHIAGIQRGIMSERMEYDQAGRITSRIFADGKMWS 1927 QUERY : 1893 YSYLDKSMVLLLQSQRQYIFEYDSSDRLLAVTMPSVARHSMSTHTSIGYIRNIYNPPESN 1952 1+11+11111 1 11111111+1 +111 +1111+111 ++ 1 1+11 1111 111 1 SBJCT : 1928 YTYLEKSMVLHLHSQRQYIFEFDKNDRLSSVTMPNVARQTLETIRSVGYYRNIYQPPEGN 1987 QUERY : 1953 ASVIFDYSDDGRILKTSFLGTGRQVFYKYGKLSKLSEIVYDSTAVTFGYDETTGVLKMVN 2012 1111 1+++11 +1 1 +11111+1 111110111+1 +11+1 1+1 1111 1+11 11 SBJCT : 1988 ASVIQDFTEDGHLLHTFYLGTGRRVIYKYGKLSKLAETLYDTTKVSFTYDETAGMLKTVN 2047 QUERY : 2013 LQSGGFSCTIRYRKIGPLVDKQIYRFSEEGMVNARFDYTYHDNSFRIASIKPVISETPLP 2072 il+ H+Hmmm+mmmmmm)) mu+ ! ++ n+ ! i ! N SBJCT : 2048 LQNEGFTCTIRYRQIGPLIDRQIFRFTEEGMVNARFDYNY-DNSFRVTSMQAVINETPLP 2106 QUERY : 2073 VDLYRYDEISGKVEHFGKFGVIYYDINQIITTAVMTLSKHFDTHGRIKEVQYEMFRSLMY 2132 +111111++111 1 111111111111111111111 +1111 +11+111111+111111 SBJCT : 2107 IDLYRYDDVSGKTEQFGKFGVIYYDINQIITTAVMTHTKHFDAYGRMKEVQYEIFRSLMY 2166 QUERY : 2133 WMTVQYDSMGRVIKRELKLGPYANTTKYTYDYDGDGQLQSVAVNDRPTWRYSYDXXXXXX 2192 1+1111+1+tll+1 +1+1+1 11+1++1141 SBJCT : 2167 WMTVQYDNMGRVVKKELKVGPYANTTRYSYEYDADGQLQTVSINDKPLWRYSYDLNGNLH 2226 QUERY : 2193 XXXXXXSVRLMPLRYDLRDRITRLGDVQYKIDDDGYLCQRGSDIFEYNSKGLLTRAYNKA 2252 | 1+1+11+ 1+] 1 111 +111+1

SBJCT : 2227 LLSPGNSARLTPLRYDLRDRITRLGDVQYKMDEDGFLRQRGGDVFEYNSAGLLIKAYNRA 2286 QUERY : 2253 SGWSVQYRYDGVGRRASYKTNLGHHLQYFYSDLHNPTRITHVYNHSNSEITSLYYDLQGH 2312 11111+11111+111 1 1++ 1111+11+11 111++11+1111+1111111111111 SBJCT : 2287 SGWSVRYRYDGLGRRVSSKSSHSHHLQFFYADLTNPTKVTHLYNHSSSEITSLYYDLQGH 2346 QUERY : 2313 LFAMESSSGEEYYVASDNTGTPLAVFSINGLMIKQLQYTAYGEIYYDSNPDFQMVIGFHG 2372 IIIII III+I+I+I II IIIIIIII IIIIII+ lIIIIIII ! +II+II++II+ll SBJCT : 2347 LFAMELSSGDEFYIACDNIGTPLAVFSGTGLMIKQILYTAYGEIYMDTNPNFQIIIGYHG 2406 QUERY : 2373 GLYDPLTKLVHFTQRDYDVLAGRWTSPDYTMWKNVGKEP-APFNLYMFKSNNPLSSELDL 2431 SBJCT +11 + 11+111114-111+1+ 1+ SBJCT : 2407 GLYDPLTKLVHMGRRDYDVLAGRWTSPDHELWKRLSSNSIVPFHLYMFKNNNPISNSQDI 2466 QUERY : 2432 KNYVTDVKSWLVMFGFQLSNIIPGFPRAKMYFVPPPYELSESQAS----ENGQLITGVQQ 2487 ++III IIl+ IIIII I+III+I+ + I IIl I +I + I III SBJCT : 2467 KCFMTDVNSWLLTFGFQLHNVIPGYPKPDTDAMEPSYELVHTQMKTQEWDNSKSILGVQC 2526 QUERY : 2488 TTERHNQAFMALE------GQVITKKLHASIREKAGHWFATTTPIIGKGIMFAIKEGRVT 2541 ++ +11+ 11 1 11 1 +l 11++ 1 111+ ll+l+llll SBJCT : 2527 EVQKQLKAFVTLERFDQLYGSTITSCQQAPETKK----FASSGSIFGKGVKFALKDGRVT 2582 QUERY : 2542 TGVSSIASEDSRKVASVLNNAYYLDKMHYSIEGKDTHYFVKIGSADGDLVTLGTTIGRKV 2601 1 + 1+1+il 1++1++1111+11+ +1++1+1 [1 1 ++111 11 + 11+ SBJCT : 2583 TDIISVANEDGRRIAAILNNAHYLENLHFTIDGVDTHYFVKPGPSEGDLAILGLSGGRRT 2642 QUERY : 2602 LESGVNVTVSQPTLLVNGRTRRFTNIEFQYSTLLLSIRYGLTPDTLDEEKARVLDQARQR 2661 11+11111111 +++11111+1+1+ 11 1 1+ 111 1+1111 111+} 111 SBJCT : 2643 LENGVNVTVSQINTMLSGRTRRYTDIQLQYRALCLNTRYG---TTVDEEKVRVLELARQR 2699 QUERY : 2662 ALGTAWAKEQQKARDGREGSRLWTEGEKQQLLSTGRVQGYEGYYVLPVEQYPELADSSSN 2721 1+ 111+111+ 1+1 11 1 11+11111+1+1111111+1++1 1111111+11++1 SBJCT : 2700 AVRQAWAREQQRLREGEEGLRAWTDGEKQQVLNTGRVQGYDGFFVTSVEQYPELSDSANN 2759 QUERY : 2722 IQFLRQNEMGKR 2733 + I 1+11+111+1 SBJCT : 2760 IHFMRQSEMGRR 2771 SCORE = 161 BITS (407), EXPECT = 2E-37 IDENTITIES = 93/157 (59%), POSITIVES = 118/157 (74%), GAPS = 4/157 (2%) QUERY : 1 MDVKDRR-HRSLTRGRCGKECRYTSSSLDSEDCRVPTQKSYSSSETLKAYDHDSRMHYGN 59 llll+l+ +11111 1 1 111111 111+ + I 11111111111111 1+1+ ll+ SBJCT : 1 MDVKERKPYRSLTRRR-DAERRYTSSSADSEEGKGP-QKSYSSSETLKAYDQDARLAYGS 58 QUERY : 60 RVTDLIHRESDEFPRQGTNFTLAELGICEPS-PHRSGYCSDMGILHQGYSLSTGSDADSD 118 II I++ +1++p 1 111111 111+ 1 + 11 + I +1+1+ 1 111+ 1111 + SBJCT : 59 RVKDMVPQEAEEFCRTGTNFTLRELGLGEMTPPHGTLYRTDIGLPHCGYSMGASSDADLE 118 QUERY : 119 TEGGMSPEHAIRLWGRGIKSRRSSGLSSRENSALTLT 155 + +1111 +11111 +1 111 1111 11 1111 SBJCT : 119 ADTVLSPEHPVRLWGRSTRSGRSSCLSSRANSNLTLT 155 SCORE = 72. 1 BITS (176), EXPECT = 8E-11 IDENTITIES = 59/152 (38%), POSITIVES = 68/152 (43%), GAPS = 42/152 (27%) QUERY : 285 PAPAPND--LATTP------ESVQLQDSWVLNSNVPLETR-------------------- 316 1+111 1 1+ 1 1 11+1+1111+11111 SBJCT : 211 PSPAPTDHSLSGEPPAGSAQEPTHAQDNWLLNSNIPLETRNLGKQPFLGTLQDNLIEMDI 270 QUERY : 317-------------HFLFKXXXXXXXXXXXXXXXYPLTSGTVYTPPPRLLPRNTFSRK AFK 363 i 11111 111+1111 111+1111 11 SBJCT : 271 LSASRHDGAYSDGHFLFK-PGGTSPLFCTTSPGYPLTSSTVYSPPPRPLPRSTFSRPAFN 329 QUERY : 364 LKKPSKYCSWKCXXXXXXXXXXXXXXXXXYFI 395 11111111+111 ll+ SBJCT : 330 LKKPSKYCNWKCAALSAILISATLVILLAYFV 361 *FCTR3F DOES NOT CONTAIN THESE AMINO ACIDS

The 997-2733 amino acid fragment of the FCTR3bcde and f protein was also found to have 1695 of 1737 amino acid residues (97%) identical to, and 1695 of 1737 residues (97%) positive with the amino a 1737 amino acid residue protein KIAA1127 protein [Homo sapiens] (GenBank Acc : (AB032953) (SEQ ID NO : 71), (Table 3S).

Table 3S. BLASTP of FCTR3b, c, d, e, and f against Homo sapiens KIAA1127 protein (SEQ ID NO : 71) >GIl6329763lDBJlBAA86441. 1l (AB032953) BAA1127 PROTEIN [HOMO SAPIENS] LENGTH = 1737 SCORE = 3295 BITS (8545), EXPECT = 0. 0 IDENTITIES = 1695/1737 (97%), POSITIVES = 1695/1737 (97%) QUERY : 997 TFFSAAPGQNPIVPETQVLHEEIELPGSNVKLRYLSSRTAGYKSLLKITMTQSTVPLNLI 1056 111111111111111111111111111111111111111111111111111111111111 SBJCT : 1 TFFSAAPGQNPIVPETQVLHEEIELPGSNVKLRYLSSRTAGYKSLLKITMTQSTVPLNLI 60 QUERY : 1057 RVHLMVAVEGHLFQKSFQASPNLASTFIWDKTDAYGQRVYGLSDAWSVGFEYETCPSLI 1116 IIIIIIIIIIIIIIIIIIIIIIII IIIIIIIIIIlIIIIIIIIIIIIIIIIIIIIIIII SBJCT : 61 RVHLMVAVEGHLFQKSFQASPNLAYTFIWDKTDAYGQRVYGLSDAWSVGFEYETCPSLI 120 QUERY : 1117 LWEKRTALLQGFELDPSNLGGWSLDKHHILNVKSGILHKGTGENQFLTQQPAIITSIMGN 1176 111111111111111111111111111111111111111111111111111111111111 SBJCT : 121 LWEKRTALLQGFELDPSNLGGWSLDKHHILNVKSGILHKGTGENQFLTQQPAIITSIMGN 180 QUERY : 1177 GRRRSISCPSCNGLAEGNKLLAPVALAVGIDGSLYVGDFNYIRRIFPSRNVTSILELRNK 1236 11111111111111111111111111111111111111111111111t111111111111 SBJCT : 181 GRRRSISCPSCNGLAEGNKLLAPVALAVGIDGSLYVGDFNYIRRIFPSRNVTSILELRNK 240 QUERY : 1237 EFKHSNNPAHKYYLAVDPVSGSLYVSDTNSRRIYRVKSLSGTKDLAGNSEVVAGTGEQCL 1296 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll SBJCT : 241 EFKHSNNPAHKYYLAVDPVSGSLYVSDTNSRRIYRVKSLSGTKDLAGNSEWAGTGEQCL 300 QUERY : 1297 PFDEARCGDGGKAIDATLMSPRGIAVDKNGLMYFVDATMIRKVDQNGIISTLLGSNDLTA 1356 111111111111111111111111111111111111111111111121111111111111 SBJCT : 301 PFDEARCGDGGKAIDATLMSPRGIAVDKNGLMYFVDATMIRKVDQNGIISTLLGSNDLTA 360 QUERY : 1357 VRPLSCDSSMDVAQVRLEWPTDLAVNPMDNSLYVLENNVILRITENHQVSIIAGRPMHCQ 1416 IIIIIIIC SBJCT : 361 VRPLSCDSSMDVAQVRLEWPTDLAVNPMDNSLYVLENNVILRITENHQVSIIAGRPMHCQ 420 QUERY : 1417 VPGIDYSLSKXXXXXXXXXXXXXXXXXTGVLYITETDEKKINRLRQVTTNGEICLLAGAA 1476 I SBJCT : 421 VPGIDYSLSKLAIHSALESASAIAISHTGVLYITETDEKKINRLRQVTTNGEICLLAGAA 480 QUERY : 1477 SXXXXXXXXXXXXYSGDDAYATDAILNSPSSLAVAPDGTIYIADLGNIRIRAVSKNKPVL 1536 I SBJCT : 481 SDCDCKNDVNCNCYSGDDAYATDAILNSPSSLAVAPDGTIYIADLGNIRIRAVSKNKPVL 540 QUERY : 1537 NAFNQYEAASPGEQELYVFNADGIHQYTVSLVTGEYLYNFTYSTDNDVTELIDNNGNSLK 1596 111111111111111111111111111111111111111111111111111111111111 SBJCT : 541 NAFNQYEAASPGEQELYVFNADGIHQYTVSLVTGEYLYNFTYSTDNDVTELIDNNGNSLK 600 QUERY : 1597 IRRDSSGMPRHLLMPDNQIITLTVGTNGGLKWSTQNLELGLMTYDGNTGLLATKSDETG 1656 111111111111111111111111111111111111111111111111111111111111 SBJCT : 601 IRRDSSGMPRHLLMPDNQIITLTVGTNGGLKVVSTQNLELGLMTYDGNTGLLATKSDETG 660 QUERY : 1657 WTTFYDYDHEGRLTNVTRPTGWTSLHREMEKSITIDIENSNRDDDVTVITNLSSVEASY 1716 11111111111111111} 111111111111111111111111111111111111111111 SBJCT : 661 WTTFYDYDHEGRLTNVTRPTGWTSLHREMEKSITIDIENSNRDDDVTVITNLSSVEASY 720 QUERY : 1717 TWQDQVRNSYQLCNNGTLRVMYANGMGISFHSEPHVLAGTITPTIGRCNISLPMENGLN 1776 SBJCT : 721 TVVQDQVRNSYQLCNNGTLRVMYANGMGISFHSEPHVLAGTITPTIGRCNISLPMENGLN 780

QUERY : 1777 SIEWRLRKEQIKGKVTIFGRKLRVHGRNLLSIDYDRNIRTEKIYDDHRKFTLRIIYDQVG 1836 111111111111111111111111111111111111111111111111111111111111 SBJCT : 781 SIEWRLRKEQIKGKVTIFGRKLRVHGRNLLSIDYDRNIRTEKIYDDHRKFTLRIIYDQVG 840 QUERY : 1837 RPFLWLPSSGLAAVNVSYFFNGRLAGLQRGAMSERTDIDKQGRIVSRMFADGKVWSYSYL 1896 SBJCT : 841 RPFLWLPSSGLAAVNVSYFFNGRIAGLQRGAMSERTDIDKQGRIVSRMFADGKVWSYSYL 900 QUERY : 1897 DKSMVLLLQSQRQYIFEYDSSDRLLAVTMPSVARHSMSTHTSIGYIRNIYNPPESNASVI 1956 111111111111111111111111111111111111111111111111111111111111 SBJCT : 901 DKSMVLLLQSQRQYIFEYDSSDRLLAVTMPSVARHSMSTHTSIGYIRNIYNPPESNASVI 960 QUERY : 1957 FDYSDDGRILKTSFLGTGRQVFYKYGKLSKLSEIVYDSTAVTFGYDETTGVLKMVNLQSG 2016 1111111111111111111111111|1111111111111111111111|11111111111 SBJCT : 961 FDYSDDGRILKTSFLGTGRQVFYKYGKLSKLSEIVYDSTAVTFGYDETTGVLKMVNLQSG 1020 QUERY : 2017 GFSCTIRYRKIGPLVDKQIYRFSEEGMVNARFDYTYHDNSFRIASIKPVISETPLPVDLY 2076 111111111111111111111111111111111111111111111111111111111111 SBJCT : 1021 GFSCTIRYRKIGPLVDKQIYRFSEEGMVNARFDYTYHDNSFRIASIKPVISETPLPVDLY 1080 QUERY : 2077 RYDEISGKVEHFGKFGVIYYDINQIITTAVMTLSKHFDTHGRIKEVQYEMFRSLMYWMTV 2136 111l11111111111111111111111111111111111111111111111111111111 SBJCT : 1081 RYDEISGKVEHFGKFGVIYYDINQIITTAVMTLSKHFDTHGRIKEVQYEMFRSLMYWMTV 1140 QUERY : 2137 QYDSMGRVIKRELKLGPYANTTKYTYDYDGDGQLQSVAVNDRPTWRYSYDXXXXXXXXXX 2196 Illllllililllllilllllllililllllilllllllllllllllill SBJCT : 1141 QYDSMGRVIKRELKLGPYANTTKYTYDYDGDGQLQSVAVNDRPTWRYSYDLNGNLHLLNP 1200 QUERY : 2197 XXSVRLMPLRYDLRDRITRLGDVQYKIDDDGYLCQRGSDIFEYNSKGLLTRAYNKASGWS 2256 1111111111111111111111111111111111111111111111111111111111 SBJCT : 1201 GNSVRLMPLRYDLRDRITRLGDVQYKIDDDGYLCQRGSDIFEYNSKGLLTRAYNKASGWS 1260 QUERY : 2257 VQYRYDGVGRRASYKTNLGHHLQYFYSDLHNPTRITHVYNHSNSEITSLYYDLQGHLFAM 2316 111111111111111111111111111111111111111111111111111111111111 SBJCT : 1261 VQYRYDGVGRRASYKTNLGHHLQYFYSDLHNPTRITHVYNHSNSEITSLYYDLQGHLFAM 1320 QUERY : 2317 ESSSGEEYYVASDNTGTPLAVFSINGLMIKQLQYTAYGEIYYDSNPDFQMVIGFHGGLYD 2376 111111111111111111111111111111111111111111111111111111111111 SBJCT : 1321 ESSSGEEYYVASDNTGTPLAVFSINGLMIKQLQYTAYGEIYYDSNPDFQMVIGFHGGLYD 1380 QUERY : 2377 PLTKLVHFTQRDYDVLAGRWTSPDYTMWKNVGKEPAPFNLYMFKSNNPLSSELDLKNYVT 2436 lltilililililililililililililililililililililililililililill SBJCT : 1381 PLTKLVHFTQRDYDVLAGRWTSPDYTMWKNVGKEPAPFNLYMFKSNNPLSSELDLKNYVT 1440 QUERY : 1381 PLTKLVHFTQRDYDVLAGRWTSPDYTMWKNVGKEPAPFNLYMFKSNNPLSSELDLKNYVT 1440 QUERY : 2437 DVKSWLVMFGFQLSNIIPGFPRAKMYFVPPPYELSESQASENGQLITGVQQTTERHNQAF 2496 111111111111111111111111111111111111111111111111111111111111 SBJCT : 1441 DVKSWLVMFGFQLSNIIPGFPRAKMYFVPPPYELSESQASENGQLITGVQQTTERHNQAF 1500 QUERY : 2497 MALEGQVITKKLHASIREKAGHWFATTTPIIGKGIMFAIKEGRVTTGVSSIASEDSRKVA 2556 llulllllllllllllllllllllllllllllllllllllllllllllllllllllllll SBJCT : 1501 MALEGQVITKKLHASIREKAGHWFATTTPIIGKGIMFAIKEGRVTTGVSSIASEDSRKVA 1560 QUERY : 2557 SVLNNAYYLDKMHYSIEGKDTHYFVKIGSADGDLVTLGTTIGRKVLESGVNVTVSQPTLL 2616 IIIIIIIIIIIIIIIIIIIIIlIIIIIIIIIIIIIIIIIIlIIIIIIlIIIIIIIIIIII SBJCT : 1561 SVZNNAYYLDKIHHYSIEGKDTHYEVKIGSADGDLVTLGTTIGRICVLESGVNVTVSQPT LL 1620 QUERY : 2617 VNGRTRRFTNIEFQYSTLLLSIRYGLTPDTLDEEKARVLDQARQRALGTAWAKEQQKARD 2676 111111111111111111111111111111111111111111111111111111111111 SBJCT : 1621 VNGRTRRFTNIEFQYSTLLLSIRYGLTPDTLDEEKARVLDQARQRALGTAWAKEQQKARD 1680 QUERY : 2677 GREGSRLWTEGEKQQLLSTGRVQGYEGYYVLPVEQYPELADSSSNIQFLRQNEMGKR 2733 111111111111111111111111111111111111111111111111111111111 SBJCT : 1681 GREGSRLWTEGEKQQLLSTGRVQGYEGYYVLPVEQYPELADSSSNIQFLRQNEMGKR 1737 The amino acid sequences of the FCTR3bcde and f proteins were also found to have 2528 of 2774 amino acid residues (91%) identical to, and 2557 of 2774 residues (92%)

positive with, the 2765 amino acid residue protein neurestin alpha [Rattus norvegicus] (GenBank Acc : AF086607) (SEQ ID NO : 72), shown in Table 3T.

Table 3T. BLASTP of FCTR3bcd and f against Rattus norvegicus Neurestin alpha (SEQ ID NO : 72) >GI199103201REFINP 064473. 1l NEURESTIN ALPHA [RATTUS NORVEGICUS] GI#5712201#GB#AAD47383.1#AF086607 1 (AF086607) NEURESTIN ALPHA [RATTUS NORVEGICUS] LENGTH = 2765 SCORE = 4988 BITS (12938), EXPECT = 0. 0 IDENTITIES = 2528/2774 (91%), POSITIVES = 2557/2774 (92%), GAPS = 50/2774 (1%) QUERY : 1 MDVKDRRHRSLTRGRCGKECRYTSSSLDSEDCRVPTQKSYSSSETLKAYDHDSRMHYGNR 60 I SBJCT : 1 MDVKDRRHRSLTRGRCGKECRYTSSSLDSEDCRVPTQKSYSSSETLKAYDHDSRMHYGNR 60 QUERY : 61 VTDLIHRESDEFPRQGTNFTLAELGICEPSPHRSGYCSDMGILHQGYSLSTGSDADSDTE 120 N H+n ! N H (H) NN) HU H !) H n N N ! tH H) N ! N ! N) U) H SBJCT : 61 VTDZVHRESDEFSRQGANFTLAEZGICEPSPHRSGYCSDMGILHQGYSLSTGSDADSDTE 120 QUERY : 121 GGMSPEHAIRLWGRGIKSRRSSGLSSRENSALTLTXXXXXXXXXXXXGRXXXXXXXXXXX 180 I SBJCT : 121 GGMSPEHAIRLWGRGIKSRRSSGLSSRENSALTLTDSDNENKSDDDNGRPIPPTSSSSLL 180 QUERY : 181 XXXXXXXXHNPPPVSCQMPLLDSNTSHQIMDTNPDEEFSPNSYLLRACXXXXXXXXXXXX 240 1111111111111111111111111111111111111111 SBJCT : 181 PSAQLPSSHNPPPVSCQMPLLDSNTSHQIMDTNPDEEFSPNSYLLRACSGPQQASSSGPP 240 QUERY : 241 NHHSQXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXQIHAPAPAPNDLATTPESVQ 300 11111 11111111111111111111 SBJCT : 241 NHHSQSTLRPPLPPPHNHTLSHHHSSANSLNRNSLTNRRSQIHAPAPAPNDLATTPESVQ 300 QUERY : 301 LQDSWVLNSNVPLETRHFLFKXXXXXXXXXXXXXXXYPLTSGTVYTPPPRLLPRNTFSRK 360 SBJCT : 301 ZQDSWVLNSNVPLETRHFZFKTSSGSTPLFSSSSPGYPLTSGTVYTPPPRLLPRNTFSRK 360 QUERY : 361 AFKLKKPSKYCSWKCXXXXXXXXXXXXXXXXXYFI------------------------- 395 111111111111111 111 SBJCT : 361 AFKLKKPSKYCSWKCAALSAIAAALLLAILLAYFIAMHLLGLNWQLQPADGHTFNNGVRT 420 QUERY : 396----------------VPWSLKNSSIDSGEAEVGRRVTQEVPPGVFWRSQIHISQPQ FLK 439 11111111111111111111111111111111111111111111 SBJCT : 421 GLPGNDDVATVPSGGKVPWSLKNSSIDSGEAEVGRRVTQEVPPGVFWRSQIHISQPQFLK 480 QUERY : 440 FNISLGKDALFGVYIRRGLPPSHAQYDFMERLDGKEKWSVVESPRERRSIQTLVQNEAVF 499 111111111111111111111111111111111111111111111111111111111111 SBJCT : 481 FNISLGKDALFGVYIRRGLPPSHAQYDFMERLDGKEKWSVVESPRERRSIQTLVQNEAVF 540 QUERY : 500 VQYLDVGLWHLAFYNDGKDKEMVSFNTWLDSVQDCPRNCHGNGECVSGVCHCFPGFLGA 559 1111111111111111111111111111111111111111111111111+1111111111 SBJCT : 541 VQYLDVGLWHLAFYNDGKDKEMVSFNTWLDSVQDCPRNCHGNGECVSGLCHCFPGFLGA 600 QUERY : 560 DCAKAACPVLCSGNGQYSKGTCQCYSGWKGAECDVPMNQCIDPSCGGHGSCIDGNCVCSA 619 IIIIIIIIIIIlllllllllllllllllllllllllllllllllllllllllllllll+I SBJCT : 601 DCAKAACPVLCSGNGQYSKGTCQCYSGWKGAECDVPMNQCIDPSCGGHGSCIDGNCVCAA 660 QUERY : 620 GYKGEHCEEVDCLDPTCSSHGVCVNGECLCSPGWGGLNCELARVQCPDQCSGHGTYLPDT 679 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII+ SBJCT : 661 GYKGEHCEEVDCLDPTCSSHGVCVNGECLCSPGWGGLNCELARVQCPDQCSGHGTYLPDS 720 QUERY : 680 GLCSCDPNWMGPDCSVEVCSVDCGTHGVCIGGACRCEEGWTGAACDQRVCHPRCIEHGTC 739 IIl+IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII SBJCT : 721 GLCNCDPNWMGPDCSVEVCSVDCGTHGVCIGGACRCEEGWTGAACDQRVCHPRCIEHGTC 780 ********* QUERY : 740 KDGKCECREGWNGEHCTIGRQTAGTETDGCPDLCNGNGRCTLGQNSWQCVCQTGWRGPGC 799 111111111111111111 1111111111111111111111|1111111111

SBJCT : 781 KDGKCECREGWNGEHCTI---------DGCPDLCNGNGRCTLGQNSWQCVCQTGWRGPGC 831 QUERY : 800 NVAMETSCADNKDNEGDGLVDCLDPDCCLQSACQNSLLCRGSRDPLDIIQQGQTDWPAVK 859 111111111111111111111111111111111111111111111111111111111111 SBJCT : 832 NVAMETSCADNKDNEGDGLVDCLDPDCCLQSACQNSLLCRGSRDPLDIIQQGQTDWPAVK 891 QUERY : 860 SFYDRIKLLAGKDSTHIIPGENPFNSSLVSLIRGQWTTDGTPLVGVNVSFVKYPKYGYT 919 11111111|11111111111+1111111111111111111111111111111111|1111 SBJCT : 892 SFYDRIKLLAGKDSTHIIPGDNPFNSSLVSLIRGQVVTTDGTPLVGVNVSFVKYPKYGYT 951 QUERY : 920 ITRQDGTFDLIANGGASLTLHFERAPFMSQERTVWLPWNSFYAMDTLVMKTEENSIPSCD 979 lllllllllllllll++llllllllllll+lllll 111111111111111111111111 SBJCT : 952 ITRQDGTFDLIANGGSALTLHFERAPFMSRERTVWPPWNSFYAMDTLVMKTEENSIPSCD 1011 SBJCT : 952 ITRQDGTFDLIANGGSALTLHFERAPFMSRERTVWPPWNSFYAMDTLVMKTEENSIPSCD 1011 QUERY : 980 LSGFVRPDPIIISSPLSTFFSAAPGQNPIVPETQVLHEEIELPGSNVKLRYLSSRTAGYK 1039 111111111|111111111111+1 111111111111111111+111111111111111 SBJCT : 1012 LSGFVRPDPIIISSPLSTFFSASPAANPIVPETQVLHEEIELPGTNVKLRYLSSRTAGYK 1071 QUERY : 1040 SLLKITMTQSTVPLNLIRVHLMVAVEGHLFQKSFQASPNLASTFIWDKTDAYGQRVYGLS 1099 IIIIIIIIIIIIIIIIIIIIIIillllllllllllllllll IIIIllllllllllllll SBJCT : 1072 SLLKITMTQSTVPLNLIRVHLMVAVEGHLFQKSFQASPNLAYTFIWDKTDAYGQRVYGLS 1131 11 n ! N n N ! ! ! N n ! n H) n n N n t n n H H N n n n n n ! t m QUERY : 1100 DAVVSVGFEYETCPSLILWEKRTALLQGFELDPSNLGGWSLDKHHILNVKSGILHKGTGE 1159 1111111111111111111111111t1111111111111111111 11111111 11111 SBJCT : 1132 DAWSVGFEYETCPSLILWEKRTALLQGFELDPSNLGGWSLDKHHTLNVKSGILLKGTGE 1191 QUERY : 1160 NQFLTQQPAIITSIMGNGRRRSISCPSCNGLAEGNKLLAPVALAVGIDGSLYVGDFNYIR 1219 III+I SBJCT : 1192 NQFLTQQPAIITSIMGNGRRRSISCPSCNGLAEGNKLLAPVALAVGIDGSLFVGDFNYTR 1251 QUERY : 1220 RIFPSRNVTSILELRNKEFKHSNNPAHKYYLAVDPVSGSLYVSDTNSRRIYRVKSLSGTK 1279 + +I I SBJCT : 1252 RIFPSRNVTSILELRNKEFKHSNSPGHKYYLAVDPVTGSLYVSDTNSRRIYRVKSLSGAK 1311 m) N m) n) n) H N !)) n ! n n+H m n)) n n) n n n n !)) m) QUERY : 1280 DLAGNSEVVAGTGEQCLPFDEARCGDGGKAIDATLMSPRGIAVDKNGLMYFVDATMIRKV 1339 IIIIIIIIIIIIIIIIIIIIIIIIIIIIII+IIIIIIIlIIIIIIIIIl11111111111 SBJCT : 1312 DLAGNSEVVAGTGEQCLPFDEARCGDGGKAVDATZMSPRGIAVDKNGLMYFVDATMIRKV 1371 QUERY : 1340 DQNGIISTLLGSNDLTAVRPLSCDSSMDVAQVRLEWPTDLAVNPMDNSLYVLENNVILRI 1399 111111111111111111111111111111111111111111111111111111111111 SBJCT : 1372 DQNGIISTLLGSNDLTAVRPLSCDSSMDVAQVRLEWPTDLAVNPMDNSLYVLENNVILRI 1431 QUERY : 1400 TENHQVSIIAGRPMHCQVPGIDYSLSKXXXXXXXXXXXXXXXXXTGVLYITETDEKKINR 1459 lllllllllllllllllllllll SBJCT : 1432 TENHQVSIIAGRPMHCQVPGIDYSLSKLAIHSALESASAIAISHTGVLYITETDEKKINR 1491 QUERY : 1460 LRQVTTNGEICLLAGAASXXXXXXXXXXXXYSGDDAYATDAILNSPSSLAVAPDGTIYIA 1519 111111111111111111 11111111111111111111111111111 SBJCT : 1492 LRQVTTNGEICLLAGAASDCDCKNDVNCICYSGDDAYATDAILNSPSSLAVAPDGTIYIA 1551 QUERY : 1520 DLGNIRIRAVSKNKPVLNAFNQYEAASPGEQELYVFNADGIHQYTVSLVTGEYLYNFTYS 1579 111111111111111111111111111111111111111111111111111111111111 SBJCT : 1552 DLGNIRIRAVSKNKPVLNAFNQYEAASPGEQELYVFNADGIHQYTVSLVTGEYLYNFTYS 1611 QUERY : 1580 TDNDVTELIDNNGNSLKIRRDSSGMPRHLLMPDNQIITLTVGTNGGLKVVSTQNLELGLM 1639 IIIIIIIIIIIIIIIIIIIIIIIIIIIII SBJCT : 1612 ADNDVTELIDNNGNSLKIRRDSSGMPRHLLMPDNQIITLTVGTNGGLKAVSTQNLELGLM 1671 QUERY : 1640 TYDGNTGLLATKSDETGWTTFYDYDHEGRLTNVTRPTGWTSLHREMEKSITIDIENSNR 1699 IIIIIIII-I SBJCT : 1672 TYDGNTGLLATKSDETGWTTFYDYDHEGRLTNVTRPTGWTSLHREMEKSITVDIENSNR 1731 QUERY : 1700 DDDVTVITNLSSVEASYTWQDQVRNSYQLCNNGTLRVMYANGMGISFHSEPHVLAGTIT 1759 1+11111111111111111111111111111+1111111111111+111111111111+1 SBJCT : 1732 DNDVTVITNLSSVEASYTWQDQVRNSYQLCSNGTLRVMYANGMGVSFHSEPHVLAGTLT 1791 QUERY : 1760 PTIGRCNISLPMENGLNSIEWRLRKEQIKGKVTIFGRKLRVHGRNLLSIDYDRNIRTEKI 1819 111111111111111111111111111111111111111111111111111111111111 SBJCT : 1792 PTIGRCNISLPMENGLNSIEWRLRKEQIKGKVTIFGRKLRVHGRNLLSIDYDRNIRTEKI 1851

QUERY : 1820 YDDHRKFTLRIIYDQVGRPFLWLPSSGLAAVNVSYFFNGRLAGLQRGAMSERTDIDKQGR 1879 111111111111111111111111111111111111111111111111111111111111 SBJCT : 1852 YDDHRKFTLRIIYDQVGRPFLWLPSSGLAAVNVSYFFNGRLAGLQRGAMSERTDIDKQGR 1911 QUERY : 1880 IVSRMFADGKVWSYSYLDKSMVLLLQSQRQYIFEYDSSDRLLAVTMPSVARHSMSTHTSI 1939 Ill 1 SBJCT : 1912 IVSRMFADGKVWSYSYLDKSMVLLLQSQRQYIFEYDSSDRLHAVTMPSVARHSMSTHTSI 1971 QUERY : 1940 GYIRNIYNPPESNASVIFDYSDDGRILKTSFLGTGRQVFYKYGKLSKLSEIVYDSTAVTF 1999 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll SBJCT : 1972 GYIRNIYNPPESNASVIFDYSDDGRILKTSFLGTGRQVFYKYGKLSKLSEIVYDSTAVTF 2031 QUERY : 2000 GYDETTGVLKMVNLQSGGFSCTIRYRKIGPLVDKQIYRFSEEGMVNARFDYTYHDNSFRI 2059 111111111111111111111111111+1111111111111111+111111111111111 SBJCT : 2032 GYDETTGVLKMVNLQSGGFSCTIRYRKVGPLVDKQIYRFSEEGMINARFDYTYHDNSFRI 2091 QUERY : 2060 ASIKPVISETPLPVDLYRYDEISGKVEHFGKFGVIYYDINQIITTAVMTLSKHFDTHGRI 2119 Illlilllllllllllllllllllllllllllllllllllllllllllllllllilllll SBJCT : 2092 ASIKPVISETPLPVDLYRYDEISGKVEHFGKFGVIYYDINQIITTAVMTLSKHFDTHGRI 2151 QUERY : 2120 KEVQYEMFRSLMYWMTVQYDSMGRVIKRELKLGPYANTTKYTYDYDGDGQLQSVAVNDRP 2179 Illllllllllllllllllllllllllllllllllllllllllllllllllllllillll SBJCT : 2152 KEVQYEMFRSLMYWMTVQYDSMGRVIKRELKLGPYANTTKYTYDYDGDGQLQSVAVNDRP 2211 QUERY : 2180 TWRYSYDXXXXXXXXXXXXSVRLMPLRYDLRDRITRLGDVQYKIDDDGYLCQRGSDIFEY 2239 1111111 1 1111ß1111111111111111111111111111111111 SBJCT : 2212 TWRYSYDLNGNLHLLNPGNSARLMPLRYDLRDRITRLGDVQYKIDDDGYLCQRGSDIFEY 2271 QUERY : 2240 NSKGLLTRAYNKASGWSVQYRYDGVGRRASYKTNLGHHLQYFYSDLHNPTRITHVYNHSN 2299 1111111111111111111111111 111111111111111111111+111111111111 SBJCT : 2272 NSKGLLTRAYNKASGWSVQYRYDGVSRRASYKTNLGHHLQYFYSDLHHPTRITEVYNHSN 2331 QUERY : 2300 SEITSLYYDLQGHLFAMESSSGEEYYVASDNTGTPLAVFSINGLMIKQLQYTAYGEIYYD 2359 111111111111111111111111111111111111111111111111111111111111 SBJCT : 2332 SEITSLYYDLQGHLFAMESSSGEEYYVASDNTGTPLAVFSINGLMIKQLQYTAYGEIYYD 2391 QUERY : 2360 SNPDFQMVIGFHGGLYDPLTKLVHFTQRDYDVLAGRWTSPDYTMWKNVGKEPAPFNLYMF 2419 111111111111111111111111111111111111111111111+11111111111111 SBJCT : 2392 SNPDFQMVIGFHGGLYDPLTKLVHFTQRDYDVLAGRWTSPDYTMWRNVGKEPAPFNLYMF 2451 QUERY : 2420 KSNNPLSSELDLKNYVTDVKSWLVMFGFQLSNIIPGFPRAKMYFVPPPYELSESQASENG 2479 ++ SBJCT : 2452 KNNNPLSNELDLKNYVTDVKSWLVMFGFQLSNIIPGFPRAKMYFVPPPYELSESQASENG 2511 QUERY : 2480 QLITGVQQTTERHNQAFMALEGQVITKKLHASIREKAGHWFATTTPIIGKGIMFAIKEGR 2539 11111111111111111+1111111+11111 1111111111111111111111111111 SBJCT : 2512 QLITGVQQTTERHNQAFLALEGQVISKKLHAGIREKAGHWFATTTPIIGKGIMFAIKEGR 2571 SBJCT : 2512 QLITGVQQTTERHNQAFLALEGQVISKKLHAGIREKAGHWFATTTPIIGKGIMFAIKEGR 2571 QUERY : 2540 VTTGVSSIASEDSRKVASVLNNAYYLDKMHYSIEGKDTHYFVKIGSADGDLVTLGTTIGR 2599 111111111111111111111111111111111111111111111+11111111111111 SBJCT : 2572 VTTGVSSIASEDSRKVASVLNNAYYLDKMHYSIEGKDTHYFVKIGAADGDLVTLGTTIGR 2631 n m m m nm m n m m ! mm nm m nm m m m NH QUERY : 2600 KVLESGVNVTVSQPTLLVNGRTRRFTNIEFQYSTLLLSIRYGLTPDTLDEEKARVLDQAR 2659 Illlllilllllllllllllllllllllllllilillllllllllllllllllllllill SBJCT : 2632 KVLESGVNVTVSQPTLLVNGRTRRFTNIEFQYSTLLLSIRYGLTPDTLDEEKARVLDQAR 2691 QUERY : 2660 QRALGTAWAKEQQKARDGREGSRLWTEGEKQQLLSTGRVQGYEGYYVLPVEQYPELADSS 2719 111111111111111111111111111111111111111111111111111111111111 SBJCT : 2692 QRALGTAWAKEQQKARDGREGSRLWTEGEKQQLLSTGRVQGYEGYYVLPVEQYPELADSS 2751 QUERY : 2720 SNIQFLRQNEMGKR 2733 SBJCT : 2752 SNIQFLRQNEMGKR 2765 * = FCTR3F DOES NOT CONTAIN THESE AMINO ACIDS

The amino acid sequences of the FCTR3bcde and f proteins were also found to have 2536 of 2774 amino acid residues (91%) identical to, and 2558 of 2774 residues (91%) positive with, the 2764 amino acid residue protein Odd Oz/ten-m homolog 2 (Drosophila) (GenBank Acc : NP035986. 2) (SEQ ID NO : 65), shown in Table 3U.

Table 3U. BLASTP of FCTR3bcde and f against Odd Oz/ten-m homolog 2 (SEQ ID NO : 65) >GI17657415REFINP 035986. 2 ODD OZ/TEN-M HOMOLOG 2 (DROSOPHILA) ; ODD OZ/TEN-M HOMOLOG 3 (DROSOPHILA) [MUS MUSCULUS] GI#4760778#DBJ#BAA77397.1# (AB025411) TEN-M2 [MUS MUSCULUS] LENGTH = 2764 <BR> <BR> SCORE = 4996 BITS (12961), EXPECT = 0.<BR> <BR> <P> IDENTITIES = 2536/2774 (91%), POSITIVES = 2558/2774 (91%), GAPS = 51/2774 (1%) QUERY : 1 MDVKDRRHRSLTRGRCGKECRYTSSSLDSEDCRVPTQKSYSSSETLKAYDHDSRMHYGNR 60 111111111111111111111111111111111111111111111111111111111111 SBJCT : 1 MDVKDRRHRSLTRGRCGKECRYTSSSLDSEDCRVPTQKSYSSSETLKAYDHDSRMHYGNR 60 QUERY : 61 VTDLIHRESDEFPRQGTNFTLAELGICEPSPHRSGYCSDMGILHQGYSLSTGSDADSDTE 120 llsl+lllllll 11111111111111111111111111111111111111111111111 SBJCT : 61 VTDLVHRESDEFSRQGTNFTLAELGICEPSPHRSGYCSDMGILHQGYSLSTGSDADSDTE 120 QUERY : 121 GGMSPEHAIRLWGRGIKSRRSSGLSSRENSALTLTXXXXXXXXXXXXGRXXXXXXXXXXX 180 11111111111111111111111111111111111 11 SBJCT : 121 GGMSPEHAIRLWGRGIKSRRSSGLSSRENSALTLTDSDNENKSDDDNGRPIPPTSSSSLL 180 QUERY : 181 XXXXXXXXHNPPPVSCQMPLLDSNTSHQIMDTNPDEEFSPNSYLLRACXXXXXXXXXXXX 240 1111111111111111111111111111111111111111 SBJCT : 181 PSAQLPSSHNPPPVSCQMPLLDSNTSHQIMDTNPDEEFSPNSYLLRACSGPQQASSSGPP 240 QUERY : 241 NHHSQXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXQIHAPAPAPNDLATTPESVQ 300 IIIII Illlllllllllllllllll SBJCT : 241 NHHSQSTLRPPLPPPHNHTLSHHHSSANSLNRNSLTNRRSQIHAPAPAPNDLATTPESVQ 300 QUERY : 301 LQDSWVLNSNVPLETRHFLFKXXXXXXXXXXXXXXXYPLTSGTVYTPPPRLLPRNTFSRK 360 Illllllllllllllllllll IIIIIIIIIIIIIIIIIIIIIIII SBJCT : 301LQDSWVLNSNVPLETRHFLFKTSSGSTPLFSSSSPGYPLTSGTVYTPPPRLLPRNTF SRK 360 QUERY : 361 AFKLKKPSKYCSWKCXXXXXXXXXXXXXXXXXYFI------------------------- 395 111111111111111 111 SBJCT : 361 AFKLKKPSKYCSWKCAALSAIARALLLAILLAYFIAMHLLGLNWQLQPADGHTFNNGVRT 420 QUERY : 396----------------VPWSLKNSSIDSGEAEVGRRVTQEVPPGVFWRSQIHISQPQ FLK 439 SBJCT : 421 GLPGNDDVATVPSGGKVPWSLKNSSIDSGEAEVGRRVTQEVPPGVFWRSQIHISQPQFLK 480 QUERY : 440 FNISLGKDALFGVYIRRGLPPSHAQYDFMERLDGKEKWSVVESPRERRSIQTLVQNEAVF 499 111111111111111111111111111111111111111111111111111111111111 SBJCT : 481 FNISLGKDALFGVYIRRGLPPSHAQYDFMERLDGKEKWSWESPRERRSIQTLVQNEAVF 540 QUERY : 500 VQYLDVGLWHLAFYNDGKDKEMVSFNTWLDSVQDCPRNCHGNGECVSGVCHCFPGFLGA 559 1111111111111111111111111111111111111111111111111+1111111111 SBJCT : 541 VQYLDVGLWHLAFYNDGKDKEMVSFNTWLDSVQDCPRNCHGNGECVSGLCHCFPGFLGA 600 QUERY : 560 DCAKAACPVLCSGNGQYSKGTCQCYSGWKGAECDVPMNQCIDPSCGGHGSCIDGNCVCSA 619 m N m m m) m m mm m m m mm)) m m m mm) SBJCT : 601DCAKAACPVLCSGNGQYSKGTCQCYSGWKGAECDVPMNQCIDPSCGGHGSCIDGNCV CAA 660 SBJCT : 601 DCAKAACPVLCSGNGQYSKGTCQCYSGWKGAECDVPMNQCIDPSCGGHGSCIDGNCVCAA 660 QUERY : 620 GYKGEHCEEVDCLDPTCSSHGVCVNGECLCSPGWGGLNCELARVQCPDQCSGHGTYLPDT 679 Illllllllllllllllllllllllllllllllllllllllllllllllllllllllll+ SBJCT : 661 GYKGEHCEEVDCLDPTCSSHGVCVNGECLCSPGWGGLNCELARVQCPDQCSGHGTYLPDS 720

QUERY : 680 GLCSCDPNWMGPDCSVEVCSVDCGTHGVCIGGACRCEEGWTGAACDQRVCHPRCIEHGTC 739 1111111111111111 1111111111111111111111111111111111111111111 SBJCT : 721 GLCSCDPNWMGPDCSV-VCSVDCGTHGVCIGGACRCEEGWTGAACDQRVCHPRCIEHGTC 779 ********* QUERY : 740 KDGKCECREGWNGEHCTIGRQTAGTETDGCPDLCNGNGRCTLGQNSWQCVCQTGWRGPGC 799 111111111111111111 111111111111111111111111111111111 SBJCT : 780 KDGKCECREGWNGEHCTI---------DGCPDLCNGNGRCTLGQNSWQCVCQTGWRGPGC 830 QUERY : 800 NVAMETSCADNKDNEGDGLVDCLDPDCCLQSACQNSLLCRGSRDPLDIIQQGQTDWPAVK 859 N) m m m m m m m m ! N) N m m m m m m) H m m SBJCT : 831 NVAMETSCADNKDNEGDGLVDCLDPDCCLQSACQNSLLCRGSRDPLDIIQQGQTDWPAVK 890 QUERY : 860 SFYDRIKLLAGKDSTHIIPGENPFNSSLVSLIRGQWTTDGTPLVGVNVSFVKYPKYGYT 919 SBJCT : 891 SFYDRIKLLAGKDSTHIIPGDNPFNSSLVSLIRGQWTMDGTPLVGVNVSFVKYPKYGYT 950 QUERY : 920 ITRQDGTFDLIANGGASLTLHFERAPFMSQERTVWLPWNSFYAMDTLVMKTEENSIPSCD 979 711++IIIIII SBJCT : 951 ITRQDGTFDLIANGGSALTLHFERAPFMSQERTVWLPWNSFYAMDTLVMKTEENSIPSCD 1010 QUERY : 980 LSGFVRPDPIIISSPLSTFFSAAPGQNPIVPETQVLHEEIELPGSNVKLRYLSSRTAGYK 1039 )) m n mm)))) m)) +) m !) m m)) m !) +m m !) m m) SBJCT : 1011 LSGFVRPDPIIISSPLSTFFSASPASNPIVPETQVLHEEIELPGTNVKLRYLSSRTAGYK 1070 QUERY : 1040 SLLKITMTQSTVPLNLIRVHLMVAVEGHLFQKSFQASPNLASTFIWDKTDAYGQRVYGLS 1099 11111111111111111111111111111111111111111 111111111111111111 SBJCT : 1071 SLLKITMTQSTVPLNLIRVHLMVAVEGHLFQKSFQASPNLAYTFIWDKTDAYGQRVYGLS 1130 QUERY : 1100 DAWSVGFEYETCPSLILWEKRTALLQGFELDPSNLGGWSLDKHHILNVKSGILHKGTGE 1159 lllllllllllllllllllllllllllllllllllllllllllll IIIIIIIIIIIIII SBJCT : 1131 DAVVSVGFEYETCPSLILWEKRTALLQGFELDPSNLGGWSLDKHHTLNVKSGILHKGTGE 1190 QUERY : 1160 NQFLTQQPAIITSIMGNGRRRSISCPSCNGLAEGNKLLAPVALAVGIDGSLYVGDFNYIR 1219 IIIIIIIIIIIIIII+II SBJCT : 1191 NQFLTQQPAIITSIMGNGRRRSISCPSCNGLAEGNKLLAPVALAVGIDGSLFVGDFNYIR 1250 QUERY : 1220 RIFPSRNVTSILELRNKEFKHSNNPAHKYYLAVDPVSGSLYVSDTNSRRIYRVKSLSGTK 1279 n ! m m m m m) m m < m m m+n ! ! m m n n n n N) ! SBJCT : 1251 RIFPSRNVTSILELRNKEFKHSNSPGHKYYLAVDPVTGSLYVSDTNSRRIYRVKSLSGAK 1310 QUERY : 1280 DLAGNSEWAGTGEQCLPFDEARCGDGGKAIDATLMSPRGIAVDKNGLMYFVDATMIRKV 1339 IIIIIIIIllllllllll+IIII SBJCT : 1311 DLAGNSEVVAGTGEQCLPFDEARCGDGGKAVDATLMSPRGIAVDKNGLMYFVDATMIRKV 1370 QUERY : 1340 DQNGIISTLLGSNDLTAVRPLSCDSSMDVAQVRLEWPTDLAVNPMDNSLYVLENNVILRI 1399 111111111111111111111111111111111111111111111111111111111111 SBJCT : 1371 DQNGIISTLLGSNDLTAVRPLSCDSSMDVAQVRLEWPTDLAVNPMDNSLYVLENNVILRI 1430 QUERY : 1400 TENHQVSIIAGRPMHCQVPGIDYSLSKXXXXXXXXXXXXXXXXXTGVLYITETDEKKINR 1459 SBJCT : 1431 TENHQVSIIAGRPMHCQVPGIDYSLSKLAIHSALESASAIAISHTGVLYITETDEKKINR 1490 QUERY : 1460 LRQVTTNGEICLLAGAASXXXXXXXXXXXXYSGDDAYATDAILNSPSSLAVAPDGTIYIA 1519 IIIIllllllllllllll IIIIIIIIIIIIIIIIIIIIIIIIIIIIII SBJCT : 1491 LRQVTTNGEICLLAGAASDCDCKNDVNCICYSGDDAYATDAILNSPSSLAVAPDGTIYIA 1550 QUERY : 1520 DLGNIRIRAVSKNKPVLNAFNQYEAASPGEQELYVFNADGIHQYTVSLVTGEYLYNFTYS 1579 111111111111111|11111111111111111111111111111111111111111111 SBJCT : 1551 DLGNIRIRAVSKNKPVLNAFNQYEAASPGEQELYVFNADGIHQYTVSLVTGEYLYNFTYS 1610 QUERY : 1580 TDNDVTELIDNNGNSLKIRRDSSGMPRHLLMPDNQIITLTVGTNGGLKVVSTQNLELGLM 1639 illllllllllllllllllllllllllllllllllllllllllllll IIIIIIIIIII SBJCT : 1611 ADNDVTELIDNNGNSLKIRRDSSGMPRHLLMPDNQIITLTVGTNGGLKAVSTQNLELGLM 1670 QUERY : 1640 TYDGNTGLLATKSDETGWTTFYDYDHEGRLTNVTRPTGWTSLHREMEKSITIDIENSNR 1699 111111111111111111111111111111111111111111111111111111111111 SBJCT : 1671 TYDGNTGLLATKSDETGWTTFYDYDHEGRLTNVTRPTGVVTSLHREMEKSITIDIENSNR 1730 QUERY : 1700 DDDVTVITNLSSVEASYTWQDQVRNSYQLCNNGTLRVMYANGMGISFHSEPHVLAGTIT 1759 IIIIIIIIIIIIIIIIIIIIIIJIIIIIIIIIIIIIIIIIIIII +11111111111111

SBJCT : 1731 DDDVTVITNLSSVEASYVVQDQVRNSYQLCNNGTLRVMYANGMAVSFHSEPHVLAGTIT 1790 QUERY : 1760 PTIGRCNISLPMENGLNSIEWRLRKEQIKGKVTIFGRKLRVHGRNLLSIDYDRNIRTEKI 1819 111111111111111111111111|11111111111111111111111111111111111 SBJCT : 1791 PTIGRCNISLPMENGLNSIEWRLRKEQIKGKVTIFGRKLRVHGRNLLSIDYDRNIRTEKI 1850 QUERY : 1820 YDDHRKFTLRIIYDQVGRPFLWLPSSGLAAVNVSYFFNGRLAGLQRGAMSERTDIDKQGR 1879 111|1111111111111111111111|1111111111|1111111111111111111111 SBJCT : 1851 YDDHRKFTLRIIYDQVGRPFLWLPSSGLAAVNVSYFFNGRLAGLQRGAMSERTDIDKQGR 1910 QUERY : 1880 IVSRMFADGKVWSYSYLDKSMVLLLQSQRQYIFEYDSSDRLLAVTMPSVARHSMSTHTSI 1939 SBJCT 111111111111111111 SBJCT : 1911 IVSRMFADGKVWSYSYLDKSMVLLLQSQRQYIFEYDSSDRLHAVTMPSVARHSMSTHTSI 1970 QUERY : 1940 GYIRNIYNPPESNASVIFDYSDDGRILKTSFLGTGRQVFYKYGKLSKLSEIVYDSTAVTF 1999 111111111111111111111111111111111111111111111111111111111111 SBJCT : 1971 GYIRNIYNPPESNASVIFDYSDDGRILKTSFLGTGRQVFYKYGKLSKLSEIVYDSTAVTF 2030 QUERY : 2000 GYDETTGVLKMVNLQSGGFSCTIRYRKIGPLVDKQIYRFSEEGMVNARFDYTYHDNSFRI 2059 111111111111111111111111111+1111111111111111+111111111111111 SBJCT : 2031 GYDETTGVLKMVNLQSGGFSCTIRYRKVGPLVDKQIYRFSEEGMINARFDYTYHDNSFRI 2090 QUERY : 2060 ASIKPVISETPLPVDLYRYDEISGKVEHFGKFGVIYYDINQIITTAVMTLSKHFDTHGRI 2119 IIIfl11 SBJCT : 2091 ASIKPVISETPLPVDLYRYDEISGKVEHFGKFGVIYYDINQIITTAVMTLSKHFDTHGRI 2150 QUERY : 2120 KEVQYEMFRSLMYWMTVQYDSMGRVIKRELKLGPYANTTKYTYDYDGDGQLQSVAVNDRP 2179 I SBJCT : 2151 KEVQYEMFRSLMYWMTVQYDSMGRVIKRELKLGPYANTTKYTYDYDGDGQLQSVAVNDRP 2210 QUERY : 2180 TWRYSYDXXXXXXXXXXXXSVRLMPLRYDLRDRITRLGDVQYKIDDDGYLCQRGSDIFEY 2239 n ! n n ! n m ! m ! ! n ! m ! m n ! ! m nn m u ! ! SBJCT : 2211 TWRYSYDLNGNLHLLNPGNSARLMPLRYDLRDRITRLGDVQYKIDDDGYLCQRGSDIFEY 2270 QUERY : 2240 NSKGLLTRAYNKASGWSVQYRYDGVGRRASYKTNLGHHLQYFYSDLHNPTRITHVYNHSN 2299 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII SBJCT : 2271 NSKGLLTRAYNKASGWSVQYRYDGVGRRASYKTNLGHHLQYFYSDLHNPTRITHVYNHSN 2330 QUERY : 2300 SEITSLYYDLQGHLFAMESSSGEEYYVASDNTGTPLAVFSINGLMIKQLQYTAYGEIYYD 2359 IIIIIIIII+III SBJCT : 2331 SEITSLYYDLQGHLFAMESSSGEEYYVASDNTGTPLAVYSINGLMIKQLQYTAYGEIYYD 2390 QUERY : 2360 SNPDFQMVIGFHGGLYDPLTKLVHFTQRDYDVLAGRWTSPDYTMWKNVGKEPAPFNLYMF 2419 IIIlllll+II SBJCT : 2391 SNPDFQMVIGFHGGLYDPLTKLVHFTQRDYDVLAGRWTSPDYTMWRNVGKEPAPFNLYMF 2450 QUERY : 2420 KSNNPLSSELDLKNYVTDVKSWLVMFGFQLSNIIPGFPRAKMYFVPPPYELSESQASENG 2479 1+11111+1111111111111111111111111111111111111111111111111111 SBJCT : 2451 KNNNPLSNELDLKNYVTDVKSWLVMFGFQLSNIIPGFPRAKMYFVPPPYELSESQASENG 2510 QUERY : 2480 QLITGVQQTTERHNQAFMALEGQVITKKLHASIREKAGHWFATTTPIIGKGIMFAIKEGR 2539 11111111111111111+111111111111111111111111111111111111111111 SBJCT : 2511 QLITGVQQTTERHNQAFLALEGQVITKKLHASIREKAGHWFATTTPIIGKGIMFAIKEGR 2570 QUERY : 2540 VTTGVSSIASEDSRKVASVLNNAYYLDKMHYSIEGKDTHYFVKIGSADGDLVTLGTTIGR 2599 111111111111111111111111111111111111111111111+11111111111111 SBJCT : 2571 VTTGVSSIASEDSRKVASVLNNAYYLDKMHYSIEGKDTHYFVKIGAADGDLVTLGTTIGR 2630 QUERY : 2600 KVLESGVNVTVSQPTLLVNGRTRRFTNIEFQYSTLLLSIRYGLTPDTLDEEKARVLDQAR 2659 SBJCT : 2631 KVLESGVNVTVSQPTLLVNGRTRRFTNIEFQYSTLLLSIRYGLTPDTLDEEKARVLDQAG 2690 QUERY : 2660 QRALGTAWAKEQQKARDGREGSRLWTEGEKQQLLSTGRVQGYEGYYVLPVEQYPELADSS 2719 111111111111111111111111111111111111111111111111111111111111 SBJCT : 2691 QRALGTAWAKEQQKARDGREGSRLWTEGEKQQLLSTGRVQGYEGYYVLPVEQYPELADSS 2750 QUERY : 2720 SNIQFLRQNEMGKR 2733 I SBJCT : 2751 SNIQFLRQNEMGKR 2764

* = FCTR3F DOES NOT CONTAIN THESE AMINO ACIDS FCTR3 is related to rat neurestin, a gene implicated in neuronal development (Otaki JM, Firestein S Dev Biol 1999 Aug 1 ; 212 (1) : 165-81) Neurestin shows homology to human gamma-heregulin, a Drosophila receptor-type pair-rule gene product, Odd Oz (Odz)/Ten (m), and Ten (a). Neurestin has putative roles in synapse formation and brain morphogenesis. A mouse neurestin homolog, DOC4, has independently been isolated from the NIH-3T3 fibroblasts. DOC4 is also known as tenascin M (TNM), a Drosophila pair-rule gene homolog containing extracellular EGF-like repeats. The significant homology to these molecules and in particular, y-heregulin, have important implications regarding the potential contribution of FCTR3 to disease progression. Heregulin is the ligand for HER-2/ErbB2/NEU, a proto- oncogene receptor tyrosine kinase implicated in breast and prostate cancer progression that was originally identified in rat neuro/glioblastoma cell lines. Extopic expression of HER- 2/ErbB2/NEU in MDA-MB-435 breast adenocarcinoma cells confers chemoresistance to Taxol-induced apoptosis relative to vector transfected control cells (Yu et al. Overexpression of ErbB2 blocks Taxol-induced apoptosis by up-regulation of p21 Cip1, which inhibits p34Cdc2 kinase. Molec. Cell 2 : 581-591, 1998).

FCTR3 related tenascins and cancer biology As mentioned, FCTR3 also has significant homology to DOC4, (AKA tenascin M), a Drosophila pair-rule gene homolog containing extracellular EGF-like repeats. The tenascins are a growing family of extracellular matrix proteins that play prominent roles in tissue interactions critical to embryogenesis. Overexpression of tenascins has been described in multiple human solid malignancies.

The role of the tenascin family of related proteins is to regulate epithelial-stromal interactions, participate in fibronectin-dependent cell attachment and interaction. Indeed, tenascin-C (TN) is overexpressed in the stroma of malignant ovarian tumours particularly at the interface between epithelia and stroma leading to suggestions that it may be involved in the process of invasion (Wilson et al (1996) Br J Cancer 74 : 999-1004). Tenascin-C is considered a therapeutic target for certain malignant brain tumors (Gladson CL : J Neuropathol Exp Neurol 1999 Oct ; 58 (10) : 1029-40). Stromal or moderate to strong periductal Tenascin-C expression in DCIS (ductal carcinoma in situ) correlates with tumor cell invasion. (Jahkola et al. Eur J Cancer 1998 Oct ; 34 (11) : 1687-92. Tenascin-C expression at the invasion border of early breast cancer is a useful predictor of local and distant recurrence. Jahkola T, et al. Br J Cancer. 1998 Dec ; 78 (l 1) : 1507-13). Tenascin (TN) is an extracellular matrix protein found in areas of cell migration during development and expressed at high levels in migratory glioma

cells. Treasurywala S, Berens ME Glia 1998 Oct ; 24 (2) : 236-43 Migration arrest in glioma cells is dependent on the alphaV integrin subunit. Phillips GR, Krushel LA, Crossin KL J Cell Sci 1998 Apr ; 111 (Pt 8) : 1095-104 Domains of tenascin involved in glioma migration. Finally, tenascin expression in hormone-dependent tissues of breast and endometrium indicate that Tenascin expression reflects malignant progression and is down-regulated by antiprogestins during terminal differentiation of rat mammary tumors (Vollmer et al. Cancer Res 1992 Sep 1 ; 52 (17) : 4642-8) Potential role of FCTR3 in oncologic disease progression : Based on the bioactivity described in the medical literature for related molecules, FCTR3 may play a role in one or more aspects of tumor cell biology that alter the interactions of tumor epithelial cells with stromal components. In consideration, FCTR3 may play a role in the following malignant properties : Autocrine/paracrine stimulation of tumor cell proliferation Autocrine/paracrine stimulation of tumor cell survival and tumor cell resistance to cytotoxic therapy Local tissue remodeling, paranechmal and basement membrane invasion and motility of tumor cells thereby contributing to metastasis.

Tumor-mediated immunosuppression of T-cell mediated immune effector cells and pathways resulting in tumor escape from immune surveilance.

Therapeutic intervention targeting FCTR3 in oncologic and central nervous system indications : Predicted disease indications from expression profiling in 41 normal human tissues and 55 human cancer cell lines (see Example 2) include a subset of human gliomas, astrocytomas, mixed glioma/astrocytomas, renal cells carcinoma, breast adenocarcinoma, ovarian cancer, melanomas. Targeting of FCTR3 by human or humanized monoclonal antibodies designed to disrupt predicted interactions of FCTR3 with its cognate ligand may result in significant anti- tumor/anti-metastatic activity and the amelioration of associated symptomatology.

Identification of small molecules that specifically/selectively interfere with downstream signaling components engaged by FCTR3/ligandinteractions would also be expected to result in significant anti-tumor/anti-metastatic activity and the amelioration of associated symptomatology. Likewise, modified antisense ribonucleotides or antisense gene expression constructs (plasmids, adenovirus, adeno-associated viruses,"naked"DNA approaches)

designed to diminish the expression of FCTR3 transcripts/messenger RNA (mRNA) would be anticipated based on predicted properties of FCTR3 to have anti-tumor impact.

Based on the relatedness to neurestin and heregulins, as well as its high level expression in brain tissue, FCTR3 may also be used for remyelination in order to promote regeneration/repair/remyleination of injured central nervous system cells resulting from ischemia, brain trauma and various neurodegenerative diseases.. This postulate is based on reports indicating that neuregulin, glial growth factor 2, diminishes autoimmune demyelination and enhances remyelination in a chronic relapsing model for multiple sclerosis (Cannella et al.. Proc. Nat. Acad. Sci. 95 : 10100-10105, 1998). The expression of the related molecule neurestin can be induced in external tufted cells during regeneration of olfactory sensory neurons.

FCTR4 FCTR4 is a plasma membrane protein related to NF-Kappa-B P65delta3 protein. The clone is expressed in fetal liver tissues.

The novel FCTR4 nucleic acid of 609 nucleotides (also referred to as 29692275. 0. 1) is shown in Table 4A. An ORF begins with an ATG initiation codon at nucleotides 99-101 and ends with a TAA codon at nucleotides 522-524. A putative untranslated region upstream from the initiation codon and downstream from the termination codon is underlined in Table 4A, and the start and stop codons are in bold letters.

Table 4A. FCTR4 Nucleotide Sequence (SEQ ID NO : 14) CTGACATACTATATTAGTTGTTTGTTCACTGTCTCCACTCCAGCTAGAATATAAGTTCCA TAGGGCAGAGTTTTTGTTCA CTGCTATATTTTATAAGCATGAATGAATGCATGAACGAATGGACTGATAACCCACAAGCC AAAGACCTCCATGACCTGCC<BR> <BR> <BR> ACTGCCCTCCTTTCATTTTATTCTCACCTCTACCAATACTAAATCACCTAGTTATGTAAA TACGATATGCACTTTCATGG<BR> <BR> <BR> CCCCTTGCTTTGTCATATGCTGTTCCCTTTGCCTGGAATATAAACTCTCAAAATACCATC CACATTTTAAAATCTTCTCC AGAAAGCTTCCTCTGTCCACCCCCACCCTCCCACCCCCATATAGAGTAAGTCAGTCTTTC CTTTGTGCTACATTTGTACC TGTATCTACAGTGGCTCTAATCAAACTGCACTGTGTCTCTCACTTCCTAGATTGTGAACT CTTTGAGGCTGAAGACTACT TATTCATCTCTTTACCTCCAATGCCTAGGACAGGACCTTCATAAAGCAACTACTCTATAA ATGTTGAAACATATGCATGA CTATTCTGTAACAGGAATGAAAATATGGCATTTCAAGAAGTCACTACTC The FCTR4 protein encoded by SEQ ID NO : 14 has 141 amino acid residues and is presented using the one-letter code in Table 4B. The Psort profile for FCTR4 predicts that this sequence has no N-terminal signal peptide and is likely to be localized at the plasma membrane with a certainty of 0. 6000. The most likely cleavage site for a peptide is between amino acids 39 and 40, i. e., at the dash in the amino acid sequence ACT-CCA, based on the SignalP result. The predicted molecular weight of this protein is 16051. 5 Daltons.

Table 4B. Encoded FCTR4 protein sequence (SEQ ID NO : 15). <BR> <BR> <BR> <P>MNECMNEWTDNPQAKDLHDLPLPSFHFILTSTNTKSPSYVNTICTFMAPCF VICCSLCLEYKLSYYHPHFKIFSRKLPLSTPTL<BR> <BR> <BR> PPPYRVSQSFLCATFVPVSTVALIKLECVSHFLDCELFEAEDYLFISLPPMPRTGPS

The predicted amino acid sequence was searched in the publicly available GenBank database FCTR4 protein showed 30 % identities (22 over 72 amino acids) and 43% homologies (3 lover 72 amino acids) with hypothetical 10 kD protein of Trypanosoma cruzi (86 aa ; ACC : Q99233) shown in Table 4C. The best homologies with a human protein were 54 % identities (114 over 343 amino acids) withNF-Kappa-B P65delta3 protein (71 aa fragment ; ACC : Q13313) (SEQ ID NO : 77).

Table 4C. BLASTP of FCTR4 against protein sequences BLAST X search results are shown below : ptnr : SPTREMBL-ACC : Q99233 HYPOTHETICAL 10 KD PROTEIN +3, 68, 0. 60, 1, (SEQ ID NO : 73) ptnr : SPTREMBL-ACC : Q16896 GABA RECEPTOR SUBUNIT-AEDES +3, 66, 0. 81, 4 (SEQ ID NO : 74) ptnr : SPTREMBL-ACC : 076473 GABA RECEPTOR SUBUNIT-LEPTI... +3, 66, 0. 99, 2 (SEQ ID NO : 75) ptnr : TREMBLNEW-ACC : AAD28317 F13J11. 13 PROTEIN-Arabid... +3, 62, 0. 99, 1 (SEQ ID NO : 76) Based upon homology, FCTR4 proteins and each homologous protein or peptide may share at least some activity.

FCTR5 FCTR5 is a protein bearing sequence homology to human complement C1R component precursor. The clone is expressed in breast, heart, lung, fetal lung, salivary gland, adrenal gland, spleen, kidney, and fetal kidney.

The novel FCTR5 nucleic acid of 1667 nucleotides (also referred to as 32125243. 0. 21) is shown in Table SA. An ORF begins with an ATG initiation codon at nucleotides 34-36 and ends with a TGA codon at nucleotides 1495-1497. A putative untranslated region upstream from the initiation codon and downstream from the termination codon is underlined in Table 5A, and the start and stop codons are in bold letters.

Table 5A. FCTR5a Nucleotide Sequence (SEQ ID NO : 16) <BR> <BR> <BR> GTTCTCTCGCAGGTCCCAGATGTCCAGTTCCAGATGCCTGGACCCAGAGTGTGGGGGAAA TATCTCTGGAGAAGCCCTCA<BR> <BR> CTCCAAAGGCTGTCCAGGCGCAATGTGGTGGCTGCTTCTCTGGGGAGTCCTCCAGGCTTG CCCAACCCGGGGCTCCGTCC TCTTGGCCCAAGAGCTACCCCAGCAGCTGACATCCCCCGGGTACCCAGAGCCGTATGGCA AAGGCCAAGAGAGCAGCACG GACATCAAGGCTCCAGAGGGCTTTGCTGTGAGGCTCGTCTTCCAGGACTTCGACCTGGAG CCGTCCCAGGACTGTGCAGG GGACTCTGTCACAATCTCATTCGTCGGTTCGGATCCAAGCCAGTTCTGTGGTCAGCAAGG CTCCCCTCTGGGCAGGCCCC CTGGTCAGAGGGAGTTTGTATCCTCAGGGAGGAGTTTGCGGCTGACCTTCCGCACACAGC CTTCCTCGGAGAACAAGACT

GCCCACCTCCACAAGGGCTTCCTGGCCCTCTACCAAACCGTGGCTGTGAACTATAGTCAG CCCATCAGCGAGGCCAGCAG GGGCTCTGAGGCCATCAACGCACCTGGAGACAACCCTGCCAAGGTCCAGAACCACTGCCA GGAGCCCTATTATCAGGCCG CGGCAGCAGGGGCACTCACCTGTGCAACCCCAGGGACCTGGAAAGACAGACAGGATGGGG AGGAGGTTCTTCAGTGTATG CCTGTCTGCGGACGGCCAGTCACCCCCATTGCCCAGAATCAGACGACCCTCGGTTCTTCC AGAGCCAAGCTGGGCAACTT CCCCTGGCAAGCCTTCACCAGTATCCACGGCCGTGGGGGCGGGGCCCTGCTGGGGGACAG ATGGATCCTCACTGCTGCCC ACACCATCTACCCCAAGGACAGTGTTTCTCTCAGGAAGAACCAGAGTGTGAATGTGTTCT TGGGCCACACAGCCATAGAT GAGATGCTGAAACTGGGGAACCACCCTGTCCACCGTGTCGTTGTGCACCCCGACTACCGT CAGAATGAGTCCCATAACTT TAGCGGGGACATCGCCCTCCTGGAGCTGCAGCACAGCATCCCCCTGGGCCCCAACGTCCT CCCGGTCTGTCTGCCCGATA ATGAGACCCTCTACCGCAGCGGCTTGTTGGGCTACGTCAGTGGGTTTGGCATGGAGATGG GCTGGCTAACTACTGAGCTG <BR> <BR> <BR> AAGTACTCGAGGCTGCCTGTAGCTCCCAGGGAGGCCTGCAACGCCTGGCTCCAAAAGAGA CAGAGACCCGAGGTGTTTTC<BR> <BR> <BR> <BR> TGACAATATGTTCTGTGTTGGGGATGAGACGCAAAGGCACAGTGTCTGCCAGGGGGACAG TGGCAGCCTCTATGTGGTAT<BR> <BR> <BR> <BR> <BR> GGGACAATCATGCCCATCACTGGGTGGCCACGGGCATTGTGTCCTGGGGCATAGGGTGTG GCGAAGGGTATGACTTCTAC<BR> <BR> <BR> <BR> ACCAAGGTGCTCAGCTATGTGGACTGGATCAAGGGAGTGATGAATGGCAAGAATTGACCC TGGGGGCTTGAACAGGGACT GACCAGCACAGTGGAGGCCCCAGGCAACAGAGGGCCTGGAGTGAGGACTGAACACTGGGG TAGGGGGTGGGGGTTTCTCT TGCAGTGGCTTGGTGCAACAGTGATGTGAATAGGATTTCCCTTTTTTTTTTTTTTTTTAA AAAAAAA The FCTRS protein encoded by SEQ ID NO : 16 has 487 amino acid residues, and is presented using the one-letter code in Table 5B. FCTR5 was searched against other databases using SignalPep and PSort search protocols. The FCTR5 protein is most likely microbody (peroxisome) (Certainty=0. 6406) and seems to have no N-terminal signal sequence. The predicted molecular weight of FCTR5 protein is 53511. 9 daltons.

Table 5B. Encoded FCTRSa protein sequence (SEQ ID NO : 17). <BR> <BR> <BR> <BR> <BR> <P> MPGPRVWGKYLWRSPHSKGCPGAMWWLLLWGVLQACPTRGSVLLAQELPQQLTSPGYPEP YGKGQESSTDIKAPEGFAVRLVFQ<BR> <BR> <BR> <BR> <BR> DFDLEPSQDCAGDSVTISFVGSDPSQFCGQQGSPLGRPPGQREFVSSGRSLRLTFRTQPS SENKTAHLHKGFLALYQTVAVNYS<BR> <BR> <BR> <BR> QPISEASRGSEAINAPGDNPAKVQNHCQEPYYQAAAAGALTCATPGTWKDRQDGEEVLQC MPVCGRPVTPIAQNQTTLGSSRAK<BR> <BR> <BR> <BR> <BR> LGNFPWQAFTSIHGRGGGALLGDRWILTAAHTIYPKDSVSLRKNQSVNVFLGHTAIDEML KLGNHPVHRVVVHPDYRQNESHNF<BR> <BR> <BR> <BR> <BR> SGDIALLELQHSIPLGPNVLPVCLPDNETLYRSGLLGYVSGFGMEMGWLTTELKYSRLPV APREACNAWLQKRQRPEVFSDNMF<BR> <BR> <BR> <BR> CVGDETQRHSVCQGDSGSLYWWDNHAHHWVATGIVSWGIGCGEGYDFYTKVLSYVDWIKG VMNGKN An alternative embodiment, FCTR5b, is a 1691 base sequence shown in Table 5C.

Table 5C. FCTR5b Nucleotide Sequence (SEQ ID NO : 18) <BR> <BR> <BR> <BR> <BR> TTTTTTTTT GGGAAATCCTATTCACATCACTGTTGCACCAAGCCACTGCAAGAGAAACCCCCACCCC CTACCCCAGTGTTCAGTCCTCACTCCAGGCCCTCTGTTGCCTGGGGCCTCCACTGTGCTG GTCAGTCCCTGTTCAAGCCCCCAG GGTCAATTCTTGCCATTCATCACTCCCTTGATCCAGTCCACATAGCTGAGCACCTTGGTG TAGAAGTCATACCCTTCGCCACAC CCTATGCCCCAGGACACAATGCCCGTGGCCACCCAGTGATGGGCATGATTGTCCCATACC ACATAGAGGCTGCCACTGTCCCCC <BR> <BR> <BR> TGGCAGRCACTGTGCCTTTGCGTCTCATCCCCAACACAGAACATATTGTCAGAAAACACC TCGGGTCTCTGTCTCTTTTGGAGC<BR> <BR> <BR> <BR> CAGGCGTTGCAGGCCTCCCTGGGAGCTACAGGCAGCCTCGAGTACTTCAGCTCAGTAGTT AGCCAGCCCATCTCCATGCCAAAC CCACTGACGTAGCCCAACAAGCCGCTGCGGTAGAGGGTCTCATTATCGGGCAGACAGACC GGGAGGACGTTGGGGCCCAGGGGG <BR> <BR> <BR> ATGCTGTGCTGCAGCTCCAGGAGGGCGATGTCCCCGCTAAAGTTATGGGACTCATTCTGA CGGTAGTCGGGGTGCACAACGACA CGGTGGACAGGGTGGTTCCCCAGTTTCAGCATCTCATCTATGGCTGTGTGGCCCAAGAAC ACATTCACACTCTGGTTCTTCCTG AGAGAAACACTGTCCTTGGGGTAGATGGTGTGGGCAGCAGTGAGGATCCATCTGTCCCCC AGCAGGGCCCCGCCCCCACGGCCG TGGATACTGGTGAAGGCTTGCCAGGGGAAGTTGCCCAGCTTGGCTCTGGAAGAACCGAGG GTCGTCTGATTCTGGGCAATGGGG GTGACTGGCCGTCCGCAGACAGGCATACACTGAAGAACCTCCTCCCCATCCTGTCTGTCT TTCCAGGTCCCTGGGGTTGCACAG GTGAGTGCCCCTGCTGCCGCGGCCTGATAATAGGGCTCCTGGCAGTGGTTCTGGACCTTG GCAGGGTTGTCTCCAGGTGCGTTG ATGGCCTCAGAGCCCCTGCTGGCCTCGCTGATGGGCTGACTATAGTTCACAGCCACGGTT TGGTAGAGGGCCAGGAAGCCCTTG <BR> <BR> TGGAGGTGGGCAGTCTTGTTCTCCGAGGAAGGCTGTGTGCGGAAGGTCAGCCGCAAACTC CTCCCTGAGGATACAAACTCCCTC<BR> <BR> <BR> <BR> <BR> TGACCAGGGGGCCTGCCCAGAGGGGAGCCTTGCTGACCACAGAACTGGCTTGGATCCGAA CCGACGAATGAGATTGTGACAGAG<BR> <BR> <BR> <BR> TCCCCTGCACAGTCCTGGGACGGCTCCAGGTCGAAGTCCTGGAAGACGAGCCTCACAGCA AAGCCCTCTGGAGCCTTGATGTCC GTGCTGCTCTCTTGGCCTTTGCCATACGGCTCTGGGTACCCGGGGGATGTCAGCTGCTGG GGTAGCTCTTGGGCCAAGAGGACG GAGCCCCGGGTTGGGCAAGCCTGGAGGACTCCCCAGAGAAGCAGCCACCACATTGCGCCT GGACAGCCTTTGGAGTGAGGGCTT CTCCAGAGATATTTCCCCCACACTCTGGGTCCAGGCATCTGGAACTGGACATCTGGGACC TGCGAGAGAACTGGCCCAGGATAG GGAACAAAAGG

The FCTR5b protein encoded by SEQ ID NO : 18 has 487 amino acid residues, and is presented using the one-letter code in Table 5D. FCTR5 was searched against other databases using SignalPep and PSort search protocols. The FCTR5b protein is most likely microbody (peroxisome) (Certainty=0. 6406) and seems to have no N-terminal signal sequence. The predicted molecular weight of FCTR5 protein is 53511. 9 daltons.

Table 5D. Encoded FCTR5b protein sequence (SEQ ID NO : 19). <BR> <BR> <BR> <BR> <P>MPGPRVWGKYLWRSPHSKGCPGAMWWLLLWGVLQACPTRGSVLLAQQLPQQ LTSPGYPEPYGKGQESSTDIKAPEGFAVRLVFQ<BR> <BR> <BR> DFDLEPSQDCAGDSVTISFVGSDPSQFCGQQGSPLGRPPGQREFVSSGRSLRLTFRTQPS SENKTAHLHKGFLALYQTVAVNYS<BR> <BR> <BR> QPISEASRGSEAINAPGDNPAKVQNHCQEPYYQAAAAGALTCATPGTWKDRQDGEEVLQC MPVCGRPVTPIAQNQTTLGSSRAK<BR> <BR> <BR> <BR> LGNFPWQAFTSIHGRGGGALLGDRWILTAAHTIYPKDSVSLRKNQSVNVFLGHTAIDEML KLGNHPVHRVVVHPDYRQNESHNF<BR> <BR> <BR> SGDIALLELQHSIPLGPNVLPVCLPDNETLYRSGLLGYVSGFGMEMGWLTTELKYSRLPV APREACNAWLQKRQRPEVFSDNMF<BR> <BR> <BR> <BR> CVGDETQRHSVCQGDSGSLYWWDNHAHHWVATGIVSWGIGCGEGYDFYTKVLSYVDWIKG VMNGKN The predicted amino acid sequence was searched in the publicly available GenBank database FCTR5a protein showed 58 % identities (177 over 302 amino acids) and 74 % homologies (226 over 302 amino acids) with human complement C1R component precursor (EC 3. 4. 21. 41) (705 aa. ; ACC : P00736). Based upon homology, FCTR5 proteins and each homologous protein or peptide may share at least some activity.

In a search of sequence databases, it was found, for example, that the nucleic acid sequence the nucleotides 17-1594 of FCTR5a have 1575 of 1578 bases (99 %) identical to Homo sapiens complement Clr-like proteinase precursor (GENBANK-ID : XM 007061. 1) (SEQ ID NO : 78) (Table 5E).

Table 5E. BLASTN of FCTR5a against Homo sapiens complement Clr-like proteinase precursor (SEQ ID NO : 78) >GIll1436767lREFlXM_007061. 1l HOMO SAPIENS COMPLEMENT C1R-LIKE PROTEINASE PRECURSOR, (LOC51279), MRNA LENGTH = 3318 SCORE = 3104 BITS (1566), EXPECT = 0. 0 IDENTITIES = 1575/1578 (99%) STRAND = PLUS/PLUS QUERY : 17 CAGATGTCCAGTTCCAGATGCCTGGACCCAGAGTGTGGGGGAAATATCTCTGGAGAAGCC 76 11111|111111111111111111111111111111111111111111111111111111 SBJCT : 1 CAGATGTCCAGTTCCAGATGCCTGGACCCAGAGTGTGGGGGAAATATCTCTGGAGAAGCC 60 QUERY : 77 CTCACTCCAAAGGCTGTCCAGGCGCAATGTGGTGGCTGCTTCTCTGGGGAGTCCTCCAGG 136 111111111111111111111111111111111111111111111111111111111111 SBJCT : 61 CTCACTCCAAAGGCTGTCCAGGCGCAATGTGGTGGCTGCTTCTCTGGGGAGTCCTCCAGG 120 QUERY : 137 CTTGCCCAACCCGGGGCTCCGTCCTCTTGGCCCAAGAGCTACCCCAGCAGCTGACATCCC 196 I SBJCT : 121 CTTGCCCAACCCGGGGCTCCGTCCTCTTGGCCCAAGAGCTACCCCAGCAGCTGACATCCC 180 QUERY : 197 CCGGGTACCCAGAGCCGTATGGCAAAGGCCAAGAGAGCAGCACGGACATCAAGGCTCCAG 256 111111111111111111111111111111111111111111l11111111111111111 SBJCT : 181 CCGGGTACCCAGAGCCGTATGGCAAAGGCCAAGAGAGCAGCACGGACATCAAGGCTCCAG 240 QUERY : 257 AGGGCTTTGCTGTGAGGCTCGTCTTCCAGGACTTCGACCTGGAGCCGTCCCAGGACTGTG 316

111111111111111111111111111111111111111111111111111111111111 SBJCT : 241 AGGGCTTTGCTGTGAGGCTCGTCTTCCAGGACTTCGACCTGGAGCCGTCCCAGGACTGTG 300 QUERY : 317 CAGGGGACTCTGTCACAATCTCATTCGTCGGTTCGGATCCAAGCCAGTTCTGTGGTCAGC 376 SBJCT : 301 CAGGGGACTCTGTCACAATCTCATTCGTCGGTTCGGATCCAAGCCAGTTCTGTGGTCAGC 360 QUERY : 377 AAGGCTCCCCTCTGGGCAGGCCCCCTGGTCAGAGGGAGTTTGTATCCTCAGGGAGGAGTT 436 Illllllllllllllllllllllllllllllllillllllllllllllllllllllllll SBJCT : 361 AAGGCTCCCCTCTGGGCAGGCCCCCTGGTCAGAGGGAGTTTGTATCCTCAGGGAGGAGTT 420 SBJCT : 361 AAGGCTCCCCTCTGGGCAGGCCCCCTGGTCAGAGGGAGTTTGTATCCTCAGGGAGGAGTT 420 QUERY : 437 TGCGGCTGACCTTCCGCACACAGCCTTCCTCGGAGAACAAGACTGCCCACCTCCACAAGG 496 111111111111111111111111111111111111111111111111111111111111 SBJCT : 421 TGCGGCTGACCTTCCGCACACAGCCTTCCTCGGAGAACAAGACTGCCCACCTCCACAAGG 480 QUERY : 497 GCTTCCTGGCCCTCTACCAAACCGTGGCTGTGAACTATAGTCAGCCCATCAGCGAGGCCA 556 I SBJCT : 481 GCTTCCTGGCCCTCTACCAAACCGTGGCTGTGAACTATAGTCAGCCCATCAGCGAGGCCA 540 QUERY : 557 GCAGGGGCTCTGAGGCCATCAACGCACCTGGAGACAACCCTGCCAAGGTCCAGAACCACT 616 11111111111111111111111111111111111111111111|111111111111111 QUERY : 541 GCAGGGGCTCTGAGGCCATCAACGCACCTGGAGACAACCCTGCCAAGGTCCAGAACCACT 600 m m m m m m m m m mm m m m m m m m mm QUERY : 617 GCCAGGAGCCCTATTATCAGGCCGCGGCAGCAGGGGCACTCACCTGTGCAACCCCAGGGA 676 IIIIIIIIIIIII QUERY : 601 GCCAGGAGCCCTATTATCAGGCCGCGGCAGCAGGGGCACTCACCTGTGCAACCCCAGGGA 660 m ! n ! m n m N m mt mmn n ! m m ! N ! m ! m) N mn QUERY : 677 CCTGGAAAGACAGACAGGATGGGGAGGAGGTTCTTCAGTGTATGCCTGTCTGCGGACGGC 736 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIillllllllllllllllllllllll SBJCT : 661 CCTGGAAAGACAGACAGGATGGGGAGGAGGTTCTTCAGTGTATGCCTGTCTGCGGACGGC 720 QUERY : 737 CAGTCACCCCCATTGCCCAGAATCAGACGACCCTCGGTTCTTCCAGAGCCAAGCTGGGCA 796 111111111111111111111111111111111111111111111111111111111111 SBJCT : 721 CAGTCACCCCCATTGCCCAGAATCAGACGACCCTCGGTTCTTCCAGAGCCAAGCTGGGCA 780 QUERY : 797 ACTTCCCCTGGCAAGCCTTCACCAGTATCCACGGCCGTGGGGGCGGGGCCCTGCTGGGGG 856 111111111111111111111111111111111111111111111111111111111111 SBJCT : 781 ACTTCCCCTGGCAAGCCTTCACCAGTATCCACGGCCGTGGGGGCGGGGCCCTGCTGGGGG 840 QUERY : 857 ACAGATGGATCCTCACTGCTGCCCACACCATCTACCCCAAGGACAGTGTTTCTCTCAGGA 916 11111111111111111111111111111 111111111111111111111111111111 SBJCT : 841 ACAGATGGATCCTCACTGCTGCCCACACCGTCTACCCCAAGGACAGTGTTTCTCTCAGGA 900 QUERY : 917 AGAACCAGAGTGTGAATGTGTTCTTGGGCCACACAGCCATAGATGAGATGCTGAAACTGG 976 IIIIIIIIIIII SBJCT : 901 AGAACCAGAGTGTGAATGTGTTCTTGGGCCACACAGCCATAGATGAGATGCTGAAACTGG 960 QUERY : 977 GGAACCACCCTGTCCACCGTGTCGTTGTGCACCCCGACTACCGTCAGAATGAGTCCCATA 1036 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll SBJCT : 961 GGAACCACCCTGTCCACCGTGTCGTTGTGCACCCCGACTACCGTCAGAATGAGTCCCATA 1020 QUERY : 1037 ACTTTAGCGGGGACATCGCCCTCCTGGAGCTGCAGCACAGCATCCCCCTGGGCCCCAACG 1096 111111111111111111111111111111111111111111111111111111111111 SBJCT : 1021 ACTTTAGCGGGGACATCGCCCTCCTGGAGCTGCAGCACAGCATCCCCCTGGGCCCCAACG 1080 QUERY : 1097 TCCTCCCGGTCTGTCTGCCCGATAATGAGACCCTCTACCGCAGCGGCTTGTTGGGCTACG 1156 1111l1111111111111111111111111111111111111111111111111111111 SBJCT : 1081 TCCTCCCGGTCTGTCTGCCCGATAATGAGACCCTCTACCGCAGCGGCTTGTTGGGCTACG 1140 QUERY : 1157 TCAGTGGGTTTGGCATGGAGATGGGCTGGCTAACTACTGAGCTGAAGTACTCGAGGCTGC 1216 111111111111111111111111111111111111111111111111111111111111 SBJCT : 1141 TCAGTGGGTTTGGCATGGAGATGGGCTGGCTAACTACTGAGCTGAAGTACTCGAGGCTGC 1200 QUERY : 1217 CTGTAGCTCCCAGGGAGGCCTGCAACGCCTGGCTCCAAAAGAGACAGAGACCCGAGGTGT 1276 SBJCT : 1201 CTGTAGCTCCCAGGGAGGCCTGCAACGCCTGGCTCCAAAAGAGACAGAGACCCGAGGTGT 1260 SBJCT : 1201 CTGTAGCTCCCAGGGAGGCCTGCAACGCCTGGCTCCAAAAGAGACAGAGACCCGAGGTGT 1260 QUERY : 1277 TTTCTGACAATATGTTCTGTGTTGGGGATGAGACGCAAAGGCACAGTGTCTGCCAGGGGG 1336 I SBJCT : 1261 TTTCTGACAATATGTTCTGTGTTGGGGATGAGACGCAAAGGCACAGTGTCTGCCAGGGGG 1320

QUERY : 1337 ACAGTGGCAGCCTCTATGTGGTATGGGACAATCATGCCCATCACTGGGTGGCCACGGGCA 1396 IIIIIIIIIII IIIIIIIIIIIIIIIIIIIIIIIIIlllllllllllllllllll SBJCT : 1321 ACAGTGGCAGCGTCTATGTGGTATGGGACAATCATGCCCATCACTGGGTGGCCACGGGCA 1380 QUERY : 1397 TTGTGTCCTGGGGCATAGGGTGTGGCGAAGGGTATGACTTCTACACCAAGGTGCTCAGCT 1456 11111111111111111111111111111111111111111111111|1111|1111111 SBJCT : 1381 TTGTGTCCTGGGGCATAGGGTGTGGCGAAGGGTATGACTTCTACACCAAGGTGCTCAGCT 1440 QUERY : 1457 ATGTGGACTGGATCAAGGGAGTGATGAATGGCAAGAATTGACCCTGGGGGCTTGAACAGG 1516 111111111111111111111111111111111111111111111111111111111111 SBJCT : 1441 ATGTGGACTGGATCAAGGGAGTGATGAATGGCAAGAATTGACCCTGGGGGCTTGAACAGG 1500 QUERY : 1517 GACTGACCAGCACAGTGGAGGCCCCAGGCAACAGAGGGCCTGGAGTGAGGACTGAACACT 1576 111111111111111111111111111111111111111111111111111111111111 SBJCT : 1501 GACTGACCAGCACAGTGGAGGCCCCAGGCAACAGAGGGCCTGGAGTGAGGACTGAACACT 1560 QUERY : 1577 GGGGTAGGGGGTGGGGGT 1594 1111111111 1111111 SBJCT : 1561 GGGGTAGGGGTTGGGGGT 1578 In this search it was also found that the FCTR5a nucleic acid had homology to three fragments of Homo sapiens complement component 1, r subcomponent. It has 102 of 117 bases (87%) identical to 1458-1574, 82 of 94 bases (87%) identical to 2052-2145, and 54 of 63 bases (85%) identical to 1678-1740 all fragments of Homo sapiens complement component 1, r subcomponent (GenBank Acc : NM001733. 1) (Table 5F).

Table 5F. BLASTN of FCTR5a against Honzo sapiens complement component 1, r subcomponent (SEQ ID NO : 79) >GI#4502492#REF#NM_001733.1# HOMO SAPIENS COMPLEMENT COMPONENT 1, R SUBCOMPONENT (C1R), MRNA LENGTH = 2386 SCORE = 113 BITS (57), EXPECT = 3E-22 IDENTITIES = 102/117 (87%) STRAND = PLUS/PLUS QUERY : 783 AGCCAAGCTGGGCAACTTCCCCTGGCAAGCCTTCACCAGTATCCACGGCCGTGGGGGCGG 842 SBJCT 1111111111111111111 1 1111111 11111111 11 11111111 SBJCT : 1458 AGCCAAGATGGGCAACTTCCCCTGGCAGGTGTTCACCAACATCCACGGGCGCGGGGGCGG 1517 ! ! ! (N N ! ! N t N ! t ! HN ! N N) N N N N N t t N N N H H QUERY : 843 GGCCCTGCTGGGGGACAGATGGATCCTCACTGCTGCCCACACCATCTACCCCAAGGA 899 Illllllllill III I IIIIIilllll illlllllllll I 11 IIIIIIII SBJCT : 1518 GGCCCTGCTGGGCGACCGCTGGATCCTCACAGCTGCCCACACCCTGTATCCCAAGGA 1574 SCORE = 91. 7 BITS (46), EXPECT = lE-15 IDENTITIES = 82/94 (87%) STRAND = PLUS/PLUS QUERY : 1380 CTGGGTGGCCACGGGCATTGTGTCCTGGGGCATAGGGTGTGGCGAAGGGTATGACTTCTA 1439 IIIIIIIIIIIIIII IIIIIIIIIIIII IIII II I III IIIIII SBJCT : 2052 CTGGGTGGCCACGGGCATCGTGTCCTGGGGCATCGGGTGCAGCAGGGGCTATGGCTTCTA 2111 QUERY : 1440 CACCAAGGTGCTCAGCTATGTGGACTGGATCAAG 1473 iiiiii iiiiiii III SBJCT : 2112 CACCAAAGTGCTCAACTACGTGGACTGGATCAAG 2145 SCORE = 54. 0 BITS (27), EXPECT = 2E-04 IDENTITIES = 54/63 (85%) STRAND = PLUS/PLUS

QUERY : 1006 CACCCCGACTACCGTCAGAATGAGTCCCATAACTTTAGCGGGGACATCGCCCTCCTGGAG 1065 SBJCT : 1678 CACCCGGACTACCGTCAGGATGAGTCCTACAATTTTGAGGGGGACATCGCCCTGCTGGAG 1737 QUERY : 1066 CTG 1068 SBJCT : 1738 CTG 1740 The amino acid sequence of the protein of FCTR5a 485 of 487 amino acid residues (99%) identical to, and 487 of 487 residues (100%) positive with, the 487 amino acid complement Clr-like proteinase precursor from Homo sapiens (GenBank-ACC : AAF44349. 1) (SEQ ID N0 : 80) (Table 5G).

Table 5G. BLASTP of FCTR5a and b against Complement ClR-like proteinase precursor (SEQ ID NO : 80) >GI#7706083#REF#NP_057630.1# COMPLEMENT C1R-LIKE PROTEINASE PRECURSOR, [HOMO SAPIENS] GI|11436768|REFlXP_007061. 1l COMPLEMENT C1R-LIKE PROTEINASE PRECURSOR, [HOMO SAPIENS] GI#7271475#GB#AAF44349.1#AF178985_1 (AF178985) COMPLEMENT C1R-LIKE PROTEINASE PRECURSOR [HOMO SAPIENS] LENGTH = 487 SCORE = 972 BITS (2513), EXPECT = 0. 0 IDENTITIES = 485/487 (99%), POSITIVES = 487/487 (100%) R QUERY : 1 MPGPRVWGKYLWRSPHSKGCPGAMWWLLLWGVLQACPTRGSVLLAQELPQQLTSPGYPEP 60 111111111111111111111111111111111111111111111111111111111111 SBJCT : 1 MPGPRVWGKYLWRSPHSKGCPGAMWWLLLWGVLQACPTRGSVLLAQELPQQLTSPGYPEP 60 QUERY : 61 YGKGQESSTDIKAPEGFAVRLVFQDFDLEPSQDCAGDSVTISFVGSDPSQFCGQQGSPLG 120 llillllliillllllllllili11111111illillllllllllllllllllllllll SBJCT : 61 YGKGQESSTDIKAPEGFAVRLVFQDFDLEPSQDCAGDSVTISFVGSDPSQFCGQQGSPLG 120 QUERY : 121 RPPGQREFVSSGRSLRLTFRTQPSSENKTAHLHKGFLALYQTVAVNYSQPISEASRGSEA 180 111111111111111111111111111111111111111111111111111111111111 SBJCT : 121 RPPGQREFVSSGRSLRLTFRTQPSSENKTAHLHKGFLALYQTVAVNYSQPISEASRGSEA 180 QUERY : 181 INAPGDNPAKVQNHCQEPYYQAAAAGALTCATPGTWKDRQDGEEVLQCMPVCGRPVTPIA 240 111111111111111111111111111111111111111111111111111111111111 SBJCT : 181 INAPGDNPAKVQNHCQEPYYQAAAAGALTCATPGTWKDRQDGEEVLQCMPVCGRPVTPIA 240 QUERY : 241 QNQTTLGSSRAKLGNFPWQAFTSIHGRGGGALLGDRWILTAAHTIYPKDSVSLRKNQSVN 300 + SBJCT : 241 QNQTTLGSSRAKLGNFPWQAFTSIHGRGGGALLGDRWILTAAHTVYPKDSVSLRKNQSVN 300 QUERY : 301 VFLGHTAIDEMLKLGNHPVHRWVHPDYRQNESHNFSGDIALLELQHSIPLGPNVLPVCL 360 111111111111111111111111111111111111111111111111111111111111 SBJCT : 301 VFLGHTAIDEMLKLGNHPVHRWVHPDYRQNESHNFSGDIALLELQHSIPLGPNVLPVCL 360 QUERY : 361 PDNETLYRSGLLGYVSGFGMEMGWLTTELKYSRLPVAPREACNAWLQKRQRPEVFSDNMF 420 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII SBJCT : 361 PDNETLYRSGLLGYVSGFGMEMGWLTTELKYSRLPVAPREACNAWLQKRQRPEVFSDNMF 420 QUERY : 421 CVGDETQRHSVCQGDSGSLYWWDNHAHHWVATGIVSWGIGCGEGYDFYTKVLSYVDWIK 480 m)))))))) mm) +i ! mm m) ! H) m)))) m)))) mm) m) SBJCT : 421CVGDETQRHSVCQGDSGSVYWWDNHAHHWVATGIVSWGIGCGEGYDFYTKVLSYVDW IK 480 QUERY : 481 GVMNGKN 487 1111111 SBJCT : 481 GVMNGKN 487

R = AT RESIDUE 46, FCTR5B DIFFERS FROM FCTR5A IN THAT Q46R. THE REST OF THE HOMOLOGY IS THE SAME.

The full amino acid sequence of the protein of FCTR5 a has 175 of 303 amino acid residues (58%) identical to, and 226 of 303 residues (74%) positive with the 400-701 amino acid segment, 72 of 157 residues (45%) identical and 94 of 157 residues (59%) positive with amino acids 1-155, and 36 of 139 residues (25%) identical and 58 of 139 residues (40%) positive with amino acids 188-312 of the 705 amino acid Complement C1R Component Precursor from Homo sapiens (GenBank-ACC : AAA51851. 1) (SEQ ID N0 : 43) (Table 5H).

Table 5H. BLASTP of FCTR5a and b against Complement C1R Component Precursor (SEQ ID NO : 81) >GI#115204#SP#P00736#C1R_HUMAN COMPLEMENT C1R COMPONENT PRECURSOR GI|67614jPIRllC1HURB COMPLEMENT SUBCOMPONENT C1R (EC 3. 4. 21. 41) PRECURSOR-HUMAN GI#179644#GB#AAA51851.1# (M14058) HUMAN COMPLEMENT C1R [HOMO SAPIENS] LENGTH = 705 SCORE = 361 BITS (928), EXPECT = 8E-99 IDENTITIES = 175/303 (58%), POSITIVES = 226/303 (74%), GAPS = 9/303 (2%) QUERY : 189 AKVQNHCQEPYYQ--------AAAAGALTCATPGTWKDRQDGEEVLQCMPVCGRPVTPIA 240 1++l +1 1111+ 1 11 1 ll+ I ll++ +1+1111+11 1+ SBJCT : 400 ARIQYYCHEPYYKMQTRAGSRESEQGVYTCTAQGIWKNEQKGEKIPRCLPVCGKPVNPVE 459 QUERY : 241 QNQTTLGSSRAKLGNFPWQAFTSIHGRGGGALLGDRWILTAAHTIYPKDSVSLRKNQSVN 300 I I +1 +11+111111 11+111111111111111111111+111+ + + I l++ SBJCT : 460 QRQRIIGGQKAKMGNFPWQVFTNIHGRGGGALLGDRWILTAAHTLYPKEHEA-QSNASLD 518 QUERY : 301 VFLGHTAIDEMLKLGNHPVHRVWHPDYRQNESHNFSGDIALLELQHSIPLGPNVLPVCL 360 iiiiii ++I++Illlll+ 11 ilillll+ll+ll llililll++I+ illl+ll+ll SBJCT : 519 VFLGHTNVEELMKLGNHPIRRVSVHPDYRQDESYNFEGDIALLELENSVTLGPNLLPICL 578 QUERY : 361 PDNETLYRSGLLGYVSGFGMEMGWLTTELKYSRLPVAPREACNAWLQKRQRPEVFSDNMF 420 111+1 1 ll+lllllll+ + +1++ 11111 +11 ll+ + I +111 111 SBJCT : 579 PDNDTFYDLGLMGYVSGFGVMEEKIAHDLRFVRLPVANPQACENWLRGKNRMDVFSQNMF 638 QUERY : 421 CVGDETQRHSVCQGDSGSLYVVWDNHAHHWVATGIVSWGIGCGEGYDFYTKVLSYVDWIK 480 1 1 + + liiiii ++ I I SBJCT : 639 CAGHPSLKQDACQGDSGGVFAVRDPNTDRWVATGIVSWGIGCSRGYGFYTKVLNYVDWIK 698 QUERY : 481 GVM 483 I SBJCT : 699 KEM 701 SCORE = 122 BITS (306), EXPECT = 1E-26 IDENTITIES = 72/157 (45%), POSITIVES = 94/157 (59%), GAPS = 3/157 (1%) R QUERY : 24 MWWLLLWGVLQACPTRGSVLLAQELPQQLTSPGYPEPYGKGQESSTDIKAPEGFAVRLVF 83 If I I I li+ + 1+1 ++111 +1+11 1++1 1 l 1+ 1+111 SBJCT : 1 MWLLYLLVPALFCRAGGSIPIPQKLFGEVTSPLFPKPYPNNFETTTVITVPTGYRVKLVF 60 QUERY : 84 QDFDLEPSQDCAGDSVTISFVGSDPSQFCGQQGSPLGRPPGQREFVSSGRSLRLTFRTQP 143 I IIIIII+ 1 1 1 11 +1111 11111 111++11+1 1 + III I SBJCT : 61 QQFDLEPSEGCFYDYVKISADKKSLGRFCGQLGSPLGNPPGKKEFMSQGNKMLLTFHTDF 120 QUERY : 144 SS-ENKTAHLHKGFLALYQTVAVNYSQPISEASRGSE 179 1+ 11 1 +11111 11 ll+ + I + I I SBJCT : 121 SNEENGTIMFYKGFLAYYQ--AVDLDECASRSKSGEE 155

SCORE = 36. 3 BITS (83), EXPECT = 0. 93 IDENTITIES = 36/139 (25%), POSITIVES = 58/139 (40%), GAPS = 17/139 (12%) R QUERY : 35 ACPTRGSVLLAQELPQQLTSPGYPEPYGKGQESSTDIKAPEGFAVRLVF-QDFDLEPSQD 93 4-1 I I I ++I II I + I+ I + I I + II++ I SBJCT : 188 SCQAECSSELYTEASGYISSLEYPRSYPPDLRCNYSIRVERGLTLHLKFLEPFDIDDHQQ 247 QUERY : 94--CAGDSVTISFVGSDPSQFCGQQGSPLGRPPGQREFVSSGRSLRLTFRTQPSSENKT AH 151 1 1 + I I + +111+1 111 + +1 ++ I I I I ++ SBJCT : 248 VHCPYDQLQIYANGKNIGEFCGKQ-----RPP---DLDTSSNAVDLLFFTDESGDS---- 295 QUERY : 152 LHKGFLALYQTVAVNYSQP 170 zu + SBJCT : 296--RGWKLRYTTEIIKCPQP 312 R = AT RESIDUE 46, FCTR5B DIFFERS FROM FCTR5A IN THAT Q46R. THE REST OF THE HOMOLOGY IS THE SAME.

Based upon homology, FCTR5 proteins and each homologous protein or peptide may share at least some activity.

FCTR6 The novel nucleic acid of 1078 nucleotides FCTR6a (also designated 27455183. 0. 19) encoding a novel human blood coagulation factor XI-like protein is shown in Table 6A. An ORF was identified beginning with an ATG initiation codon at nucleotides 243-245 and ending with a TAA codon at nucleotides 1044-1046. A putative untranslated region upstream from the initiation codon and downstream from the termination codon is underlined in Table 6A, and the start and stop codons are in bold letters.

Table 6A FCTR6a Nucleotide Sequence (SEQ ID NO : 20) TTGATCCGTGCCAAGTGGCTTTTTGTGGGCTCTGTAGAGTGCTCTAAACCCAGCTCGGCC TTTGCTGTATTAGACAGAAGCACC TCATTCATATCCCTGGGGCCCCTGATGGTGCAGTGGTCTGGCTGTGGTCTGCACACCAGC TATTCTGTTTTGTTTTGTTTTGTT TTTTTCCTACCTTTTTCCAATCCTCACACCTTCTGATCAACAGCCCCAGTAGGGTTTAAA GGTCCTAGAGCTACATGGGATTTA GGTTTCTGGGCACAGCCAATTCTGCCACTTTTGAGACTTCCCTTCCCCTTCCACTTGCCC CTCTCTGGTTCTCTGCCACCAGTC CAGAAGAACTGAGTGTCGTGCTGGGGACCAACGACTTAACTAGCCCATCCATGGAAATAA AGGAGGTCGCCAGCATCATTCTTC ACAAAGACTTTAAGAGAGCCAACATGGACAATGACATTGCCTTGCTGCTGCTGGCTTCGC CCATCAAGCTCGATGACCTGAAGG TGCCCATCTGCCTCCCCACGCAGCCCGGCCCTGCCACATGGCGCGAATGCTGGGTGGCAG GTTGGGGCCAGACCAATGCTGCTG <BR> <BR> ACAAAAACTCTGTGAAAACGGATCTGATGAAAGTGCCAATGGTCATCATGGACTGGGAGG AGTGTTCAAAGATGTTTCCAAAAC TTACCAAAAATATGCTGTGTGCCGGATACAAGAATGAGAGCTATGATGCCTGCAAGGGTG ACAGTGGGGGGCCTCTGGTCTGCA CCCCAGAGCCTGGTGAGAAGTGGTACCAGGTGGGCATCATCAGCTGGGGAAAGAGCTGTG GAGATAAGAACACCCCAGGGATAT <BR> <BR> ACACCTCGTTGGTGAACTACAACCTCTGGATCGAGAAAGTGACCCAGCTAGGAGGCAGGC CCTTCAATGCAGAGAAAAGGAGGA<BR> <BR> <BR> <BR> CTTCTGTCAAACAGAAACCTATGGGCTCCCCAGTCTCGGGAGTCCCAGAGCCAGGCAGCC CCAGATCCTGGCTCCTGCTCTGTC<BR> <BR> <BR> CCCTGTCCCATGTGTTGTTCAGAGCTATTTTGTACTGkTAATAAAATAGAGGCTATTCTT TCAACCGAAA The FCTR6a protein encoded by SEQ ID NO : 20 has 267 amino acid residues and is presented using the one-letter code in Table 6B. FCTR6a was searched against other databases using SignalPep and PSort search protocols. The FCTR6a protein is most likely mitochondrial matrix space (Certainty= 0. 4372) and seems to have no N-terminal signal sequence. The predicted molecular weight of FCTR6a protein is 29412. 8 daltons.

Table 6B. Encoded FCTR6a protein sequence (SEQ ID NO : 21). <BR> <BR> <BR> <BR> <P>MGFRFLGTANSATFETSLPLPLAPLWFSATSPEELSVVLGTNDLTSPSMEI KEVASIILHKDFKRANMDNDIALLLLASPIKLD<BR> <BR> <BR> <BR> DLKVPICLPTQPGPATWRECWVAGWGQTNAADKNSVKTDLMKVPMVIMDWEECSKMFPKL TKNMLCAGYKNESYDACKGDSGGP<BR> <BR> <BR> LVCTPEPGEKWYQVGIISWGKSCGDKNTPGIYTSLVNYNLWIEKVTQLGGRPFNAEKRRT SVKQKPMGSPVSGVPEPGSPRSWL<BR> <BR> <BR> LLCPLSHVLFRAILY In an alternative embodiment, FCTR6b (alternatively referred to as 27455183. 0. 145) has the 1334 residue sequence shown in Table 6C. An ORF was identified beginning with an ATG initiation codon at nucleotides 499-501 and ending with a TAA codon at nucleotides 1300-1302. A putative untranslated region upstream from the initiation codon and downstream from the termination codon is underlined in Table 6C, and the start and stop codons are in bold letters.

Table 6C FCTR6b Nucleotide Sequence (SEQ ID NO : 22) GATTTTAGAAGGTTAATCAAAAACCCGGGGACAGTTTCTTCATGGCATAACCACAGACCT TTGTGGCACCCGCTGT <BR> <BR> CGTGGGATATCAAATATCCTCTGGGGTTCGGAATGTGGGCTTATTACTGAAGATCCTGTC TGCTTGGTCAGTGGCAGGTC<BR> <BR> <BR> TAGACTAACTTCTGGTCCTGAGTTTCTAAAGTGCTGGTAGACCAGTTGATACAAAACAGA TATAATAATGAATGCCTTAT<BR> <BR> <BR> <BR> CTATCTGAAGGTCAGTTTGATCCGTGCCAAGTGGCTTTTTGTGGGCTGTGTAGAGTGCTC TAhACCCAGCTCGGCCTTTG<BR> <BR> <BR> CTGTATTAGACAGAAGCACCTCATTCATATCCCTGGGGCCCCTGATGGTGCAGTGGTCTG GCTGTGGTCTGCACACCAGC TATTCTGTTTTGTTTTGTTTTGTTTTGTTTTTTCCTACCTTTTTCCAATCCTCACACCTT CTGATCAACAGCCCCAGTAG GGTTTAAAGGTCCTAGAGCTACATGGGATTTAGGTTTCTGGGCACAGCCAATTCTGCCAC TTTTGAGACTTCCCTTCCCC TTCCACTTGCCCCTCTCTGGTTCTCTGCCACCAGTCCAGAAGAACTGAGTGTCGTGCTGG GGACCAACGACTTAACTAGC CCATCCATGGAAATAAAGGAGGTCGCCAGCATCATTCTTCACAAAGACTTTAAGAGAGCC AACATGGACAATGACATTGC CTTGCTGCTGCTGGCTTCGCCCATCAAGCTCGATGACCTGAAGGTGCCCATCTGCCTCCC CACGCAGCCCGGCCCTGCCA CATGGCGCGAATGCTGGGTGGCAGGTTGGGGCCAGACCAATGCTGCTGACAAAAACTCTG TGAAAACGGATCTGATGAAA GTGCCAATGGTCATCATGGACTGGGAGGAGTGTTCAAAGATGTTTCCAAAACTTACCAAA AATATGCTGTGTGCCGGATA CAAGAATGAGAGCTATGATGCCTGCAAGGGTGACAGTGGGGGGCCTCTGGTCTGCACCCC AGAGCCTGGTGAGAAGTGGT ACCAGGTGGGCATCATCAGCTGGGGAAAGAGCTGTGGAGAGAAGAACACCCCAGGGATAT ACACCTCGTTGGTGAACTAC AACCTCTGGATCGAGAAAGTGACCCAGCTAGAGGGCAGGCCCTTCAATGCAGAGAAAAGG AGGACTTCTGTCAAACAGAA ACCTATGGGCTCCCCAGTCTCGGGAGTCCCAGAGCCAGGCAGCCCCAGATCCTGGCTCCT GCTCTGTCCCCTGTCCCATG TGTTGTTCAGAGCTATTTTGTACTGATAATAAAATAGAGGCTATTCTTTCAACCGAAA The FCTR6b protein encoded by SEQ ID NO : 22 has 267 amino acid residues and is presented using the one-letter code in Table 6B. The Psort profile for FCTR4 predicts that this sequence has no N-terminal signal peptide and is likely to be localized at the mitochondrial matrix space (Certainty=0. 4372). The predicted molecular weight of this protein is 29498. 9 Daltons.

Table 6D. Encoded FCTR6b protein sequence (SEQ ID NO : 23). <BR> <BR> <BR> <BR> <P>MGFRFLGTANSATFETSLPLPLAPLWFSATSPEELSVVLGTNDLTSPSMEI KEVASIILHKDFKRANMDNDIALLLLASPIKLD<BR> <BR> <BR> DLKVPICLPTQPGPATWRECWVAGWGQTNAADKNSVKTDLMKVPMVIMDWEECSKMFPKL TKNMLCAGYKNESYDACKGDSGGP<BR> <BR> <BR> <BR> LVCTPEPGEKWYQVGIISWGKSCGEKNTPGIYTSLVNYNLWIEKVTQLEGRPFNAEKRRT SVKQKPMGSPVSGVPEPGSPRSWL<BR> <BR> <BR> LLCPLSHVLFRAILY In a search of sequence databases, it was found, for example, that the FCTR6a nucleic acid sequence has 853 of 897 bases (95 %) identical to bases 551-1447, and 346 of 388 bases (89%) identical to bases 127-513 of Macacafascicularis brain cDNA, clone QccE-17034 (GENBANK-ID : JAB04665 1) (Table 6E).

Table 6E. BLASTN of FCTR6a against Macacafascicularis brain cDNA, clone QccE- 17034 (SEQ ID NO : 82) >GI) 9651112JDBJJAB046651. 1JAB046651 MACACA FASCICULARIS BRAIN CDNA, CLONE QCCE-17034 LENGTH = 1746 SCORE = 1429 BITS (721), EXPECT = 0. 0 IDENTITIES = 853/897 (95%) STRAND = PLUS/PLUS QUERY : 434 CCTTTTTCCAATCCTCACACCTTCTGATCAACAGCCCCAGTAGGGTTTAAAGGTCCTAGA 493 I SBJCT : 551 CCTTTTTCCAATCCTCACACCTTCTGAGCTACAGCCCCAGTAGGGTCTAAATGTCCTAGA 610 QUERY : 494 GCTACATGGGATTTAGGTTTCTGGGCACAGCCAATTCTGCCACTTTTGAGACTTCCCTTC 553 1111 111 11111111111111 11111111111111 11111111111 111111111 SBJCT : 611 GCTATATGAGATTTAGGTTTCTGAGCACAGCCAATTCTCCCACTTTTGAGGCTTCCCTTC 670 QUERY : 554 CCCTTCCACTTGCCCCTCTCTGGTTCTCTGCCACCAGTCCAGAAGAACTGAGTGTCGTGC 613 IIIII IIII IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIIIIII SBJCT : 671 CCCTTTCACTCGCCCCTCTCTGGTTCTCTGCCACCAGTCCAGAAGAACTGAATGTCGTGC 730 QUERY : 614 TGGGGACCAACGACTTAACTAGCCCATCCATGGAAATAAAGGAGGTCGCCAGCATCATTC 673 lllllllllllllllllllllll IIIlllllllllllllllllllllllllllllllll SBJCT : 731 TGGGGACCAACGACTTAACTAGCTCATCCATGGAAATAAAGGAGGTCGCCAGCATCATTC 790 QUERY : 674 TTCACAAAGACTTTAAGAGAGCCAACATGGACAATGACATTGCCTTGCTGCTGCTGGCTT 733 IIIIIII IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII I SBJCT : 791 TTCACAAGGACTTTAAGAGAGCCAACATGGACAATGACATTGCCTTGCTGCTGCTGGCCT 850 QUERY : 734 CGCCCATCAAGCTCGATGACCTGAAGGTGCCCATCTGCCTCCCCACGCAGCCCGGCCCTG 793 m m m m m mm) m) mm m m m m n n m ! ! !) SBJCT : 851 CGCCCATCACACTCGATGACCTGAAGGTGCCCATCTGCCTCCCTACGCAGCACGGCCCCG 910 QUERY : 794 CCACATGGCGCGAATGCTGGGTGGCAGGTTGGGGCCAGACCAATGCTGCTGACAAAAACT 853 I SBJCT : 911 CCACATGGCACGAATGCTGGGTGGCAGGTTGGGGCCAGACCAATGCTGCTGACAAAAACT 970 QUERY : 854 CTGTGAAAACGGATCTGATGAAAGTGCCAATGGTCATCATGGACTGGGAGGAGTGTTCAA 913 IIIIIIIIIIIIIIIIIIIIIIII III IIIIIIIIIIIIIIIIIIIIIIIIIIIIIII SBJCT : 971 CTGTGAAAACGGATCTGATGAAAGCGCCGATGGTCATCATGGACTGGGAGGAGTGTTCAA 1030 QUERY : 914 AGATGTTTCCAAAACTTACCAAAAATATGCTGTGTGCCGGATACAAGAATGAGAGCTATG 973 II 111111111111 11111111111111111111 11111111 1111111111111 SBJCT : 1031 AGGCGTTTCCAAAACTCACCAAAAATATGCTGTGTGCTGGATACAATAATGAGAGCTATG 1090 QUERY : 974 ATGCCTGCAAGGGTGACAGTGGGGGGCCTCTGGTCTGCACCCCAGAGCCTGGTGAGAAGT 1033 l 111111 1111111111 11111 1111111111111111111111111111111111 SBJCT : 1091 ACGCCTGCCAGGGTGACAGCGGGGGACCTCTGGTCTGCACCCCAGAGCCTGGTGAGAAGT 1150 QUERY : 1034 GGTACCAGGTGGGCATCATCAGCTGGGGAAAGAGCTGTGGAGAGAAGAACACCCCAGGGA 1093 1111111111111 1111111111111111111111111111111111111111111111 SBJCT : 1151 GGTACCAGGTGGGTATCATCAGCTGGGGAAAGAGCTGTGGAGAGAAGAACACCCCAGGGA 1210 QUERY : 1094 TATACACCTCGTTGGTGAACTACAACCTCTGGATCGAGAAAGTGACCCAGCTAGAGGGCA 1153 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIllllllllllllllll SBJCT : 1211 TATACACCTCGTTGGTGAACTACAACCTCTGGATCGAGAAGGTGACCCAGCTAGAGGGCA 1270 QUERY : 1154 GGCCCTTCAATGCAGAGAAAAGGAGGACTTCTGTCAAACAGAAACCTATGGGCTCCCCAG 1213 III II SBJCT : 1271 GGCCCTTCAGTGCGGAGAAAATGAGGACCTCTGTCAAACAGAAACCTATGGGCTCCCGAG 1330 QUERY : 1214 TCTCGGGAGTCCCAGAGCCAGGCAGCCCCAGATCCTGGCTCCTGCTCTGTCCCCTGTCCC 1273 IIIIIII IIIIIIIIIIIIIII Ill Illllllllllllllllllllllllllllill SBJCT : 1331 TCTCGGGGGTCCCAGAGCCAGGCGGCCTCAGATCCTGGCTCCTGCTCTGTCCCCTGTCCC 1390 QUERY : 1274 ATGTGTTGTTCAGAGCTATTTTGTACTGATAATAAAATAGAGGCTATTCTTTCAACC 1330 111111111111111111111111111111111111111111111111 111 llll SBJCT : 1391 ATGTGTTGTTCAGAGCTATTTTGTACTGATAATAAAATAGAGGCTATTTTTTTAACC 1447

SCORE = 428 BITS (216), EXPECT = E-117 IDENTITIES = 346/388 (89%), GAPS = 1/388 (0%) STRAND = PLUS/PLUS QUERY : 1 GATTTTAGAAGGTTAATCAAAAACCCGGGGACAGTTTCTTCATGGCATAACCACAGACCT 60 SBJCT : 127 GATTTTAGAAGGTTAATCAAAAACCCAAGGACAGTTTCATCATGTCATAACCAAAGACCC 186 QUERY : 61 TTGTGGCACCCGCTGTCGTGGGATATCAAATATCCTCTGGGGTTCGGAATGTGGGCTTAT 120 IIIIIIIIII IIIIII IIIIIII IIIIIIII I illlllll IIIIIIII IIIII SBJCT : 187 TTGTGGCACCTGCTGTCATGGGATAACAAATATCTTGTGGGGTTCTGAATGTGGACTTAT 246 QUERY : 121 TACTGAAGATCCTGTCTGCTTGGTCAGTGGCAGGTCTAGACTAACTTCTGGTCCTGAGTT 180 )))) N !) m m) m m ! m m))) m n m m) m) m n m ! SBJCT : 247 TACTGAAGCTCCTGTCTGCTTGGTCAGTGG-TGGTCTAGACTAACTTCTGGTCCTGAGAT 305 QUERY : 181 TCTAAAGTGCTGGTAGACCAGTTGATACAAAACAGATATAATAATGAATGCCTTATCTAT 240 111111111 111111111 11111 1 1111 1 11111111111111111111 1111 SBJCT : 306 TCTAAAGTGTTGGTAGACCGGTTGAGATAAAAGATATATAATAATGAATGCCTTACCTAT 365 QUERY : 241 CTGAAGGTCAGTTTGATCCGTGCCAAGTGGCTTTTTGTGGGCTGTGTAGAGTGCTCTAAA 300 III IIIIIIIIIIIII IIIIIIIIIII IIIIIIIII I SBJCT : 366 CTGAAAACCAGTTTGATCCGTGCCAAGGGGCTTTTTGTGGGCTCTGTAGAGTGCCCTAAA 425 QUERY : 301 CCCAGCTCGGCCTTTGCTGTATTAGACAGAAGCACCTCATTCATATCCCTGGGGCCCCTG 360 11111111 11111111111 11111111111111 111111 111 1111111111 SBJCT : 426 CCCAGCTCTGCCTTTGCTGTGTTAGACAGAAGCACGCCATTCACATCTCTGGGGCCCCCA 485 QUERY : 361 ATGGTGCAGTGGTCTGGCTGTGGTCTGC 388 IIIIIII Iill III lillllllll SBJCT : 486 ATGGTGCCATGGTGTGGTTGTGGTCTGC 513 In a search of sequence databases, it was found, for example, that the FCTR6a nucleic acid sequence has 295 of 378 bases (78 %) identical to bases 410-779 ofMus musculus adult male testis cDNA, RIKEN full-length enriched (GENBANK-ID : AK09660) (Table 6F).

Table 6F. BLASTN of FCTR6a against Mus musculus adult male testis cDNA, RIKEN full-length enriched (SEQ ID NO : 83) >GI#12855429#DBJ#AK016601.1#AK016601 MUS MUSCULUS ADULT MALE TESTIS CDNA, RIKEN FULL-LENGTH ENRICHED LIBRARY, CLONE : 4933401F05, FULL INSERT SEQUENCE LENGTH = 1047 SCORE = 97. 6 BITS (49), EXPECT = 2E-17 IDENTITIES = 295/378 (78%), GAPS = 8/378 (2%) STRAND = PLUS/PLUS QUERY : 697 AACATGGACAATGACATTGCCTTGCTGCTGCTGGCTTCGCCCATCAAGCTCGATGACCTG 756 I SBJCT : 410 AACATGGACAACGACATTGCCTTGTTGCTGCTAGCCAAGCCCTTGACGTTCAATGAGCTG 469 SBJCT : 410 AACATGGACAACGACATTGCCTTGTTGCTGCTAGCCAAGCCCTTGACGTTCAATGAGCTG 469 QUERY : 757 AAGGTGCCCATCTGCCTCCCCACGCAGCCCGGCCCTGCCACATGGCGCGAATGCTGGGTG 816 l 111111111111111 11 11111 1111 111 1111 1111111111111 SBJCT : 470 ACGGTGCCCATCTGCCTTCCTCTCTGGCCCGCCCCTCCCAGCTGGCACGAATGCTGGGTG 529 QUERY : 817 GCAGGTTGGGGCCAGACCAATGCTGCTGACAAAAACTCTGTGAAAACGGATCTGATGAAA 876 IIIII illlll IIIII I IIIIIII I III II IIIIIIIIIIIIIII SBJCT : 530 GCAGGATGGGGCGTAACCAACTCAACTGACAAGGAATCTATGTCAACGGATCTGATGAAG 589 QUERY : 877 GTGCCAATGGTCATCATGGACTGGGAGGAGTGTTCAAAGATGTTTCCAAAACTTACCAAA , 936 11111 111 11111 11 11111111 11 1 1 1111111111 1 11 1111 1 SBJCT : 590 GTGCCCATGCGTATCATAGAGTGGGAGGAATGCTTACAGATGTTTCCCAGCCTCACCACA 649

QUERY : 937 AATATGCTGTGTGCCGGATACAAGAATGAGAGCTATGATGCCTGCAAGGGTGACAGTGGG 996 II 111111111111 111 11111111111 11111 111 1111111 SBJCT : 650 AACATGCTGTGTGCCTCATATGGTAATGAGAGCTACGATGCTTGC--------CAGTGGG 701 QUERY : 997 GGGCCTCTGGTCTGCACCCCAGAGCCTGGTGAGAAGTGGTACCAGGTGGGCATCATCAGC 1056 SBJCT : 702 GGACCGCTTGTCTGCACCACAGATCCTGGCAGTAGGTGGTACCAGGTGGGCATCATCAGC 761 QUERY : 1057 TGGGGAAAGAGCTGTGGA 1074 SBJCT : 762 TGGGGCAAGAGCTGTGGA 779 The FCTR6a amino acid has 247 of 267 amino acid residues (92%) identical to, and 251 of 307 residues (94%) positive with, the 267 amino acid hypothetical protein [Macaca fascicularis] (GenBank : AB046651) (SEQ ID NO : 84) (Table 6G).

Table 6G. BLASTP of FCTR6a and b against hypothetical protein [Macaca fascicularis] (SEQ ID NO : 84) >GIj9651113tDBJ) BAB03569. 1) (AB046651) HYPOTHETICAL PROTEIN [MACACA FASCICULARIS] LENGTH = 267 SCORE = 467 BITS (1202), EXPECT = E-131 IDENTITIES = 247/267 (92%), POSITIVES = 251/267 (94%) QUERY : 1 MGFRFLGTANSATFETSLPLPLAPLWFSATSPEELSVVLGTNDLTSPSMEIKEVASIILH 60 1 1111 1111 111 1111 11111111111111+1111111111 1111111111111 SBJCT : 1 MRFRFLSTANSPTFEASLPLSLAPLWFSATSPEELNVVLGTNDLTSSSMEIKEVASIILH 60 QUERY : 61 KDFKRANMDNDIALLLLASPIKLDDLKVPICLPTQPGPATWRECWVAGWGQTNAADKNSV 120 111111111111111111111 1111111111111 11111 111111111111111111 SBJCT : 61 KDFKRANMDNDIALLLLASPITLDDLKVPICLPTQHGPATWHECWVAGWGQTNAADKNSV 120 QUERY : 121 KTDLMKVPMVIMDWEECSKMFPKLTKNMLCAGYKNESYDACKGDSGGPLVCTPEPGEKWY 180 I llll+II SBJCT : 121 KTDLMKAPMVIMDWEECSKAFPKLTKNMLCAGYNNESYDACQGDSGGPLVCTPEPGEKWY 180 K E QUERY : 181 QVGIISWGKSCGDKNTPGIYTSLVNYNLWIEKVTQLGGRPFNAEKRRTSVKQKPMGSPVS 240 111111111111+11111111111111111111111 1111+111 11111111111 11 SBJCT : 181 QVGIISWGKSCGEKNTPGIYTSLVNYNLWIEKVTQLEGRPFSAEKMRTSVKQKPMGSRVS 240 QUERY : 241 GVPEPGSPRSWLLLCPLSHVLFRAILY 267 SBJCT : 241 GVPEPGGLRSWLLLCPLSHVLFRAILY 267 K AND E ARE RESIDUES THAT DIFFER BETWEEN FCTR6A AND B. D193K, AND G217E.

The FCTR6a amino acid has 80 of 201 amino acid residues (39%) identical to, and 119 of 201 residues (58%) positive with, the 638 amino acid plasma kallikrein B1 precursor (GENBANKW : NP000883. 1) (SEQ ID NO : 85) (Table 6H).

Table 6H. BLASTP of FCTR6a and b against plasma kallikrein B1 precursor (SEQ ID NO : 85) >GI14504877|REFlNP_000883. 11 PLASMA KALLIKREIN B1 PRECURSOR ; KALLIKREIN, PLASMA ; KALLIKREIN B PLASMA ; KALLIKREIN 3, PLASMA ; FLETCHER FACTOR [HOMO SAPIENS]

GIl125184lSPlP03952lKAL HUMAN PLASMA KALLIKREIN PRECURSOR (PLASMA PREKALLIKREIN)<BR> (KININOGENIN) (FLETCHER FACTOR) GI#67591#PIR##KQHUP PLASMA KALLIKREIN (EC 3. 4. 21. 34) PRECURSOR-HUMAN GI#190263#GB#AAA60153. GI#190263#GB#AAA60153.1# (M13143) PLASMA PREKALLIKREIN [HOMO SAPIENS] GI#8809781#GB#AAF79940.1# (AF232742) PLASMA KALLIKREIN PRECURSOR [HOMO SAPIENS] LENGTH = 638 SCORE = 133 BITS (334), EXPECT = 3E-30 IDENTITIES = 80/201 (39%), POSITIVES = 119/201 (58%), GAPS = 18/201 (8%) QUERY : 20 LPLAPLWFSATSPEELSWLGTNDLT--SPSMEIKEVASIILHKDFKRANMDNDIALLLL 77 III +1 1 +1 +1+1 +1 +111 l1+1+++1 + ++11l1+ 1 SBJCT : 439 LPLQDVW------RIYSGILNLSDITKDTPFSQIKE---IIIHQNYKVSEGNHDIALIKL 489 QUERY : 78 ASPIKLDDLKVPICLPTQPGPAT-WRECWVAGWGQTNAADKNSVKTDLMKVPMVIMDWEE 136 +1+ + + lilll++ +1 + III III + +1 ++ I 11 +++ 11 SBJCT : 490 QAPLNYTEFQKPICLPSKGDTSTIYTNCWVTGWGFSK--EKGEIQNILQKVNIPLVTNEE 547 K QUERY : 137 CSKMFP--KLTKNMLCAGYKNESYDACKGDSGGPLVCTPEPGEKWYQVGIISWGKSCGDK 194 i 1 + 1+1+ 1+11111 1111111111111 + I III III+ I + SBJCT : 548 CQKRYQDYKITQRMVCAGYKEGGKDACKGDSGGPLVC--KHNGMWRLVGITSWGEGCARR 605 QUERY : 195 NTPGIYTSLVNYNLWIEKVTQ 215 N+H + I 11 + 11 SBJCT : 606 EQPGVYTKVAEYMDWILEKTQ 626 K IS A RESIDUE THAT DIFFERS BETWEEN FCTR6A AND B. D193K.

The FCTR6a amino acid has 73 of 183 amino acid residues (39%) identical to, and 110 of 183 residues (59%) positive with, the 643 amino acid kallikrein [Sus scrofa] (GENBANK- ID : BAA37147. 1) (SEQ ID NO : 86) (Table 6I).

Table 6I. BLASTP of FCTR6a and b against kallikrein [Sus scrofa] (SEQ ID NO : 86) >GI#4165315#DBJ#BAA37147.1# (AB022425) KALLIKREIN [SUS SCROFA] LENGTH = 643 SCORE = 128 BITS (322), EXPECT = 9E-29 IDENTITIES = 73/183 (39%), POSITIVES = 110/183 (59%), GAPS = 12/183 (6%) QUERY : 38 VLGTNDLT--SPSMEIKEVASIILHKDFKRANMDNDIALLLLASPIKLDDLKVPICLPTQ 95 +l +++l +I ++II 11+1... 1 +11111 1 +1+ 1 + IIIII++ SBJCT : 459 ILNISEITKETPFSQVKE---IIIHQNYKILESGHDIALLKLETPLNYTDFQKPICLPSR 515 QUERY : 96 PGP-ATWRECWVAGWGQTNAADKNSVKTDLMKVPMVIMDWEECSKMFP--KLTKNMLCAG 152 + III III 1 +1 ++ I 11 + ++ If (I + I++I I+III SBJCT : 516 DDTNWYTNCWVTGWGFTE--EKGEIQNILQKVNIPLVSNEECQKSYRDHKISKQMICAG 573 K QUERY : 153 YKNESYDACKGDSGGPLVCTPEPGEKWYQVGIISWGKSCGDKNTPGIYTSLVNYNLWIEK 212 11 ittN+U !)) !) +) +n) !) +) + n+H++i)) + SBJCT : 574 YKEGGKDACKGESGGPLVC--KYNGIWHLVGTTSWGEGCARREQPGVYTKVIEYMDWILE 631 QUERY : 213 VTQ 215 SBJCT : 632 KTQ 634 K IS A RESIDUE THAT DIFFERS BETWEEN FCTR6A AND B. D193K.

The FCTR6a amino acid has 81 of 205 amino acid residues (39%) identical to, and 112 of 205 residues (54%) positive with, the 625 amino acid Coagulation factor XI [Homo sapiens] (embCAA64368. 1) (SEQ ID NO : 87) (Table 6J).

Table 6J. BLASTP of FCTR6a and b against Coagulation factor XI [Homo sapiens] (SEQ ID NO : 87) >GI|180352|GB|AAA51985. 1| (M20218) COAGULATION FACTOR XI [HOMO SAPIENS] LENGTH = 625 SCORE = 127 BITS (320), EXPECT = 1E-28 IDENTITIES = 81/205 (39%), POSITIVES = 112/205 (54%), GAPS = 17/205 (8%) QUERY : 20 LPLAPLWFSATSPEELSWLGTNDLTSPSMEIKE------VASIILHKDFKRANMDNDIA 73 I ! ++ N+ii) ++ UN)) ! +) + i) ! i t SBJCT : 427 LTAAHCFYGVESPKILRVYSGILNQS----EIKEDTSFFGVQEIIIHDQYKMAESGYDIA 482 QUERY : 74 LLLLASPIKLDDLKVPICLPTQPG-PATWRECWVAGWGQTNAADKNSVKTDLMKVPMVIM 132 II I + + I + IIIII++ + +111 111 11 ++ I I + ++ SBJCT : 483 LLKLETTVNYTDSQRPICLPSKGDRNVIYTDCWVTGWGYRKLRDK--IQNTLQKAKIPLV 540 QUERY : 133 DWEECSKMFP--KLTKNMLCAGYKNESYDACKGDSGGPLVCTPEPGEKWYQVGIISWGKS 190 111 1 + 1+1 1+1111+ 11111111111 1 + 1 1+ 111 111+ SBJCT : 541 TNEECQKRYRGHKITHKMICAGYREGGKDACKGDSGGPLSC--KHNEVWHLVGITSWGEG 598 K QUERY : 191 CGDKNTPGIYTSLVNYNLWIEKVTQ 215 i + li+li++l 1 11 + 11 SBJCT : 599 CAQRERPGVYTNWEYVDWILEKTQ 623 K IS A RESIDUE THAT DIFFERS BETWEEN FCTR6A AND B. D193K.

The number of new cases of renal cell carcinoma in the United States in 1996 was projected to be 30, 600 with an estimated 12, 000 deaths. Tumors with a proposed histogenesis from the proximal tubule (clear-cell and chromophilic tumors) amount to 85% of renal cancers, whereas tumors with a proposed histogenesis from the connecting tubule/collecting duct (chromophobic-, oncocytic-, and duct Bellini-type tumors) amount to only 11%.

Adenocarcinomas may be separated into clear cell and granular cell carcinomas, although the 2 cell types may occur together in some tumors. The distinction between well- differentiated renal carcinomas and renal adenomas can be difficult. The diagnosis is usually made arbitrarily on the basis of size of the mass, but size alone should not influence the treatment approach, since metastases can occur with lesions as small as 0. 5 centimeters.

While radical nephrectomy with regional lymphadenectomy, is the accepted, often curative therapy for stage I (localized disease) renal cell cancer, very little therapy is available for advance disease that represent about 70% of the patients. Radiotherapy as a postoperative adjuvant has not been effective, and when used preoperatively, may decrease local recurrence but does not appear to improve 5-yr survival. A chemotherapeutic agent capable of significantly altering the course of metastastic renal cell carcinoma has not been identified.

(Renal Cell Cancer O ? DQO) Treatment-Health Professionals, Cancernet, NCI) There is therefore a need to identify genes that are differentially modulated in renal- cell carcinomas. In addition there is a need for methods to assay candidate therapeutic substances for modulating expression of these genes. These substances might be recombinant

protein expressed by the identified genes or antibodies that bind to the identified proteins.

There is yet additionally a need for an effective method of identifying target molecules or related components. These and related needs and defects are addressed in the present invention.

Novel kallikrein-like/coagulation factor XI-like Proteins and Nucleic Acids Encoding Same FCTR6 is surprisingly found to be differentially expressed in clear cell Renal cell carcinoma tissues vs the normal adjacent kidney tissues. The present invention discloses a novel protein encoded by a cDNA and/or by genomic DNA and proteins similar to it, namely, new proteins bearing sequence similarity to kallikrein-like, nucleic acids that encode these proteins or fragments thereof, and antibodies that bind immunospecifically to a protein of the invention. It may have use as a therapeutic agent in the treatmentof renal cancer and liver cirrhosis.

The utility of kallikrein family members in protein therapy of Renal cancer The treatment of renal cell carcinoma with recombinant kallikrein could improve disease outcome through several potential mechanisms. The literature suggests that members of this protein family are inhibitory to the process of angiogenesis, a process of vital importance to tumor progression. Renal cell carcinoma is known to be a highly angiogenic cancer. Thus, treatment of renal cell carcinoma with kallikrein may effectively shutdown the active recruitment of a blood supply to a tumor. Members of this protein family are known to play a role in vascular coagulation. Similar to anti-angiogenic therapy, a factor produced by cancer cells that is pro-coagulatory may also act to inhibit cancer growth by effectively "clogging"the tumor vascular supply. In addition, through its proteolytic activity, kallikrein may degrade ECM proteins or growth factors necessary for the progressive growth of cancer cells. Following is a relevant reference underlining the importance of Kallikrein in cancer therapy.

The New Human Kallikrein Gene Family : Implications in Carcinogenesis.

Diamandis EP ; Yousef GM ; Luo I ; Magklara I ; Obiezu CV Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.

Trends Endocrinol Metab 2000 Mar ; 11 (2) : 54-60.

ABSTRACT : The traditional human kallikrein gene family consists of three genes, namely KLK1 [encoding human kallikrein 1 (hKl) or pancreatic/renal kallikrein], KLK2 (encoding hK2, previously known as human glandular kallikrein 1) and KLK3 [encoding hK3 or prostate-specific antigen (PSA)]. KLK2 and KLK3 have important applications in prostate cancer diagnostics and, more recently, in breast cancer diagnostics. During the past two to three years, new putative members of the human kallikrein gene family have been identified, including the PRSSL1 gene [encoding normal epithelial cell-specific 1 gene (NES1)], the gene encoding zyme/protease M/neurosin, the gene encoding prostaselKLK-Ll, and the genes encoding neuropsin, stratum corneum chymotryptic enzyme and trypsin-like serine protease. Another five putative kallikrein genes, provisionally named KLK-L2, KLK-L3, KLK-L4, KLK-L5 and KLK-L6, have also been identified. Many of the newly identified kallikrein-like genes are regulated by steroid hormones, and a few kallikreins (NES1, protease M, PSA) are known to be downregulated in breast and possibly other cancers.

NES1 appears to be a novel breast cancer tumor suppressor protein and PSA a potent inhibitor of angiogenesis. This brief review summarizes recent developments and possible applications of the newly defined and expanded human kallikrein gene locus.

The utility of kallikrein-like/coagulation factor XI-like family members in protein therapy of liver cirrosis Results related to inflammation shown below in Example A, Table CC3, panel 4, indicate over-expression of 27455183. 0. 19 in the liver cirrhosis sample, as compared to panel 1 data (Table CC1), where there is little or no expression in normal adult liver. Panel 4 was generated from various human cell lines that were untreated or resting as well as the same cells that were treated with a wide variety of immune modulatory molecules. There are several disease tissues represented as well as organ controls.

Potential Role (s) of FCTR6 in Inflammation : Liver cirrhosis occurs in patients with hepatitis C and also in alcoholics. This protein is 41% related to coagulation factor XI and its potential role in liver cirrhosis may be related to cleavage of kininogen. A reference for this follows : Thromb Haesnost 2000 May ; 83 (5) : 709-14 High molecular weight kininogen is cleaved by FXIa at three sites : Arg409-Arg410, Lys502-Thr503 and Lys325-Lys326. Mauron T, Lammle B, Wuillemin WA Central Hematology Laboratory, University of Bern, Inselspital,

Switzerland.

Abstract : We investigated the cleavage of high molecular weight kininogen (HK) by activated coagulation factor XI (FXIa) in vitro. Incubation of HK with FXIa resulted in the generation of cleavage products which were subjected to SDS-Page and analyzed by silverstaining, ligand-blotting and immunoblotting, respectively. Upon incubation with FXIa, bands were generated at 111, 100, 88 kDa on nonreduced and at 76, 62 and 51 kDa on reduced gels.

Amino acid sequence analysis of the reaction mixtures revealed three cleavage sites at Arg409-Arg410, at Lys502-Thr503 and at Lys325-Lys326. Analysis of HK-samples incubated with FXIa for 3 min, 10 min and 120 min indicated HK to be cleaved first at Arg409-Arg410, followed by cleavage at Lys502-Thr503 and then at Lys325-Lys326. In conclusion, HK is cleaved by FXIa at three sites. Cleavage of HK by FXIa results in the loss of the surface binding site of HK, which may constitute a mechanism of inactivation of HK and of control of contact system activation.

Impact of Therapeutic Targeting of FCTR6 in Inflammation : Therapeutic targeting of FCTR6 with a monoclonal antibody is anticipated to limit or block the extent of breakdown of kininogen and thereby reduce the degradation of liver that occurs in liver cirrhosis. A pertinent reference is : Thromb Haemost 1999 Nov ; 82 (5) : 1428-32 Parallel reduction of plasma levels of high and low molecular weight kininogen in patients with cirrhosis.

Cugno M, Scott CF, Salerno F, Lorenzano E, Muller-Esterl W, Agostoni A, Colman RW Department of Internal Medicine, IRCCS Maggiore Hospital, University of Milan, Italy. massimo. cugno@unimi. it Abstract : Little is known about the regulation of high-molecular-weight-kininogen (HK) and low-molecular-weight-kininogen (LK) or the relationship of each to the degree of liver function impairment in patients with cirrhosis. In this study, we evaluated HK and LK quantitatively by a recently described particle concentration fluorescence immunoassay (PCFIA) and qualitatively by SDS PAGE and immunoblotting analyses in plasma from 33 patients with cirrhosis presenting various degrees of impairment of liver function. Thirty-three healthy subjects served as normal controls. Patients with cirrhosis had significantly lower plasma levels of HK (median 49 microg/ml [range 22-99 microg/ml]) and LK (58 microg/ml [15-100 microg/ml]) than normal subjects (HK 83 microg/ml [65-115 microg/ml] ; LK 80

microg/ml [45-120 microg/ml]) (p<0. 0001). The plasma concentrations of HK and LK were directly related to plasma levels of cholinesterase (P<0. 0001) and albumin (P<0. 0001 and P<0. 001) and inversely to the Child-Pugh score (P<0. 0001) and to prothrombin time ratio (P<0. 0001) (reflecting the clinical and laboratory abnormalities in liver disease). Similar to normal individuals, in patients with cirrhosis, plasma HK and LK levels paralleled one another, suggesting that a coordinate regulation of those proteins persists in liver disease. SDS PAGE and immunoblotting analyses of kininogens in cirrhotic plasma showed a pattern similar to that observed in normal controls for LK (a single band at 66 kDa) with some lower molecular weight forms noted in cirrhotic plasma. A slight increase of cleavage of HK (a major band at 130 kDa and a faint but increased band at 107 kDa) was evident. The increased cleavage of HK was confirmed by the lower cleaved kininogen index (CKI), as compared to normal controls. These data suggest a defect in hepatic synthesis as well as increased destructive cleavage of both kininogens in plasma from patients with cirrhosis. The decrease of important regulatory proteins like kininogens may contribute to the imbalance in coagulation and fibrinolytic systems, which frequently occurs in cirrhotic patients.

In summary, the differential expression of FCTR6 (Kallikrein family) in renal cell carcinoma is an important finding that could have immense potential in renal carcinogenesis.

In additon, overexpression of the above gene in liver cirrhosis demonstrates its anticipated use as an immunotherapeutic target.

FCTR7 The novel nucleic acid of 1498 nucleotides FCTR7 (also designated. 32592466. 0. 64) encoding a novel trypsin inhibitor-like protein is shown in Table 7A. An ORF begins with an ATG initiation codon at nucleotides 470-472 and ends with a TAA codon at nucleotides 1369- 1371. Putative untranslated regions, if any, are found upstream from the initiation codon and downstream from the termination codon.

Table 7A. FCTR7 Nucleotide Sequence (SEQ ID NO : 24) AGGCGCCTGGTTCTGCGCGTACTGGCTGTACGGAGCAGGAGCAAGAGGTCGCCGCCAGCC TCCGCCGCCGAGCCTCGTTCGTGT CCCCGCCCCTCGCTCCTGCAGCTACTGCTCAGAAACGCTGGGGCGCCCACCCTGGCAGAC TAACGAAGCAGCTCCCTTCCCACC CCAACTGCAGGTCTAATTTTGGACGCTTTGCCTGCCATTTCTTCCAGGTTGAGGGAGCCG CAGAGGCGGAGGCTCGCGTATTCC TGCAGTCAGCACCCACGTCGCCCCCGGACGCTCGGTGCTCAGGCCCTTCGCGAGCGGGGC TCTCCGTCTGCGGTCCCTTGTGAA GGCTCTGGGCGGCTGCAGAGGCCGGCCGTCCGGTTTGGCTCACCTCTCCCAGGAAACTTC ACACTGGAGAGCCAAAAGGAGTGG AAGAGCCTGTCTTGGAGATTTTCCTGGGGAAATCCTGAGGTCATTCATTATGAAGTGTAC CGCGCGGGAGTGGCTCAGAGTAAC CACAGTGCTGTTCATGGCTAGAGCAATTCCAGCCATGGTGGTTCCCAATGCCACTTTATT GGAGAAACTTTTGGAAAAATACAT<BR> <BR> GGATGAGGATGGTGAGTGGTGGATAGCCAAACAACGAGGGAAAAGGGCCATCACAGACAA TGACATGCAGAGTATTTTGGACCT<BR> <BR> TCATAATAAATTACGAAGTCAGGTGTATCCAACAGCCTCTAATATGGAGTATATGACATG GGATGTAGAGCTGGAAAGATCTGC AGAATCCAGGGCTGAAATTGCTTGTGGGAACATGGACCTGCAAGCTTGCTTCCATCAATT GGACAGAATTTGGGAGCACACTGG <BR> <BR> GGAAGATATAGGCCCCCGACGTTTCATGTACAATCGTGGTATGATGAAGTGAAAGACTTT AGCTACCCATATGAACATGAATGC

AACCCATATTGTCCATTCAGGTGTTCTGGCCCTGTATGTACACATTATACACAGGTCGTG TGGGCAACTAGTAACAGAATCGGT <BR> <BR> TGTGCCATTAATTTGTGTCATAACATGAACATCTGGGGGCAGATATGGCCCAAAGCTGTC TACCTGGTGTGCAATTACTCCCCA AAGGGAAACTGGTGGGGCCATGCCCCTTACAAACATGGGCGGCCCTGTTCTGCTTGCCCA CCTAGTTTTGGAGGGGGCTGTAGA GAAAATCTGTGCTACAAAGAAGGGTCAGACAGGTATTATCCCCCTCGAGAAGAGGAAACA AATGAAATAGAACGGCAGCAGTCA CAAGTCCATGACACCCATGTCCGGACAAGATCAGATGATAGTAGCAGAAATGAAGTCATT AGCTTTGGGAAAAGTAATGAAAAT <BR> <BR> ATAATGGTTTTAGAAATCCTGTGTTAAATATTGCTATATTTTCTTAGCAGTTATTTCTAC AGTTAATTACATAGTCATGATTGT<BR> <BR> TCTACGTTTCATATATTATATGGTGCTTTGTATATGCCCCTAATAAAATGAATCTAAACA TTGAAAAAAA The FCTR7 protein encoded by SEQ ID NO : 24 has 300 amino acid residues and is presented using the one-letter code in Table 7B. The FCTR7 gene was found to be expressed in : brain ; germ cell tumors. FCTR7 gene maps to Unigene cluster Hs. 182364 which is expressed in the following tissues : brain, breast, ear, germ cell, heart, liver, lung, whole embryo, ovary, pancreas, pooled, prostate, stomach, testis, uterus, vascular. Therefore the FCTR7 protein described in this invention is also expressed in the above tissues.

The Signal, Psort and/or Hydropathy profile for FCTR7 predict that this sequence has a signal peptide and is likely to be localized outside of the cell with a certainty of 0. 4228. The Signal ? shows a cleavage site between amino acids 20 and 21, i. e., at the dash in the sequence amino acid ARA-IP. The predicted molecular weight of FCTR7 is 34739. 9 Daltons.

Hydropathy profile shows an amino terminal hydrophobic region. This region could function as a signal peptide and target the invention to be secreted or plasma membrane localized.

Table 7B. Encoded FCTR7 protein sequence (SEQ ID NO : 25). <BR> <BR> <BR> <BR> <P>MKCTAREWLRVTTVLFMARAIPAMVVPNATLLEKLLEKYMDEDGEWWIAKQ RGKRAITDNDMQSILDLHNKLRSQVYPTASNME<BR> <BR> <BR> YMTWDVELERSAESRAESCLWEHGPASLLPSIGQNLGAHWGRYRPPTFHVQSWYDEVKDF SYPYEHECNPYCPFRCSGPVCTHY<BR> <BR> TQVVWATSNRIGCAINLCHNMNIWGQIWPKAVYLVCNYSPKGNWWGHAPYKHGRPCSACP PSFGGGCRENLCYKEGSDRYYPPR<BR> <BR> <BR> EEETNEIERQQSQVHDTHVRTRSDDSSRNEVISFGKSNENIMVLEILC This gene maps to Unigene cluster Hs. 182364 which has been assigned the following mapping information shown in table 7C. Therefore the chromosomal assignment for this gene is the same as that for Unigene cluster 182364.

Table 7C. Mapping Information.

Chromosome : 8 Gene Map 98 : Marker SHGC-32056, Interval D8S279-D8S526 Gene Map 98 : Marker SGC32056, Interval D8S526-D8S275 Gene Map 98 : Marker sts-G20223, Interval D8S526-D8S275 Gene Map 98 : Marker stSG30385, Interval D8S526-D8S275 Whitehead map : EST67946, Chr. 8 dbSTS entries : G25853, G29349, G20223 The predicted amino acid sequence was searched in the publicly available GenBank database FCTR7 protein showed Score = 743 (261. 5 bits), Expect = 1. 4e-73, P = 1. 4e-73, 54 %

identities (129 over 237 amino acids) and 43% homologies (167 over 237 amino acids) with human 25 kD trypsin inhibitor protein (258 aa ; ACC : 043692) (Table 7D).

Table 7D. BLAST X search results are shown below : ptnr : SPTREMBL-ACC : 043692 25 KDA TRYPSIN INHIBITOR-HO... +2 743 8. 4e-73 1 (SEQ ID NO : 88) ptnr : SPTREMBL-ACC : 044228 HRTT-1-HALOCYNTHIA RORETZI... +2 325 2. 9e-28 1 (SEQ ID NO : 89) ptnr : SWISSPROT-ACC : P48060 GLIOMA PATHOGENESIS-RELATED... +2 314 5. 3e-27 1 (SEQ ID NO : 90) ptnr : PIR-ID : JC4131 glioma pathogenesis-related protein... +2 309 2. 0e-26 1 (SEQ ID NO : 91) ptnr : SWISSNEW-ACC : 019010 CYSTEINE-RICH SECRETORY PROTE... +2 258 9. 4e-21 1 (SEQ ID NO : 92) The nucleotide sequence of FCTR7 has 954 of 957 residues (99 %) identical to the 1- 957 base segment, and 174 of 175 residues (99%) identical to bases 1317-1953 of the 2664 nucleotide Homo sapiens putative secretory protein precursor, mRNA (GenBank-ACC : AF142573) (SEQ ID NO : 93) (Table 7E).

Table 7E. BLASTN of FCTR7 against Putative secretory protein precursor (SEQ ID NO : 93) >gi) 1200231Oj gbjAFl42573. 1jAF142573 Homo sapiens putative secretory protein precursor, mRNA, complete cds Length = 2664 Score = 1865 bits (941), Expect = 0. 0 Identities = 954/957 (99%), Gaps = 1/957 (02) Strand = Plus/Plus Query : 364 gtccggtttggctcacctctcccaggaaacttcacactggagagccaaaaggagtggaag 423 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII Sbjct : 1 gtccggtttggctcacctctcccaggaaacttcacactggagagccaaaaggagtggaag 60 Query : 424 agcctgtcttggagattttcctggggaaatcctgaggtcattcattatgaagtgtaccgc 483 111111111111111111111111111111111111111111111111111111111111 Sbjct : 61 agcctgtcttggagattttcctggggaaatcctgaggtcattcattatgaagtgtaccgc 120 Query : 484 gcgggagtggctcagagtaaccacagtgctgttcatggctagagcaattccagccatggt 543 Illlllllllllllllllllllllllllllll1111111111111111111111111111 Sbjct : 121 gcgggagtggctcagagtaaccacagtgctgttcatggctagagcaattccagccatggt 180 Query : 544 ggttcccaatgccactttattggagaaacttttggaaaaatacatggatgaggatggtga 603 111111111111111111111111111111111111111111111111111111111111 Sbjct : 181 ggttcccaatgccactttattggagaaacttttggaaaaatacatggatgaggatggtga 240 Query : 604 gtggtggatagccaaacaacgagggaaaagggccatcacagacaatgacatgcagagtat 663 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII

Sbjct : 241 gtggtggatagccaaacaacgagggaaaagggccatcacagacaatgacatgcagagtat 300 Query : 664 tttggaccttcataataaattacgaagtcaggtgtatccaacagcctctaatatggagta 723 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII Sbjct : 301 tttggaccttcataataaattacgaagtcaggtgtatccaacagcctctaatatggagta 360 Query : 724 tatgacatgggatgtagagctggaaagatctgcagaatccagggctgaaa-ttgcttgtg 782 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIIIIIII IIIIIIIII Sbjct : 361 tatgacatgggatgtagagctggaaagatctgcagaatcctgggctgaaagttgcttgtg 420 Query : 783 ggaacatggacctgcaagcttgcttccatcaattggacagaatttgggagcacactgggg 842 111111111111111111111111111111111111111111111111111111111111 Sbjct : 421 ggaacatggacctgcaagcttgcttccatcaattggacagaatttgggagcacactgggg 480 Sbjct : 421 ggaacatggacctgcaagcttgcttccatcaattggacagaatttgggagcacactgggg 480 ! m m n)) m n mH)) m ! ! n m) i ! i u) m n m n ! t) ! Query : 843 aagatataggcccccgacgtttcatgtacaatcgtggtatgatgaagtgaaagactttag 902 1111111111111111111111111111111111111111111111|1111111111111 Sbjct : 481 aagatataggcccccgacgtttcatgtacaatcgtggtatgatgaagtgaaagactttag 540 Query : 903 ctacccatatgaacatgaatgcaacccatattgtccattcaggtgttctggccctgtatg 962 Illllllllllllllllllllllllllllllllllllllllllllllllllllllllll Sbjct : 541 ctacccatatgaacatgaatgcaacccatattgtccattcaggtgttctggccctgtatg 600 Query : 963 tacacattatacacaggtcgtgtgggcaactagtaacagaatcggttgtgccattaattt 1022 1022 Sbjct : 601 tacacattatacacaggtcgtgtgggcaactagtaacagaatcggttgtgccattaattt 660 Query : 1023 gtgtcataacatgaacatctgggggcagatatggcccaaagctgtctacctggtgtgcaa 1082 111111111111111111111111111111111111111111111111111111111111 Sbjct : 661 gtgtcataacatgaacatctgggggcagatatggcccaaagctgtctacctggtgtgcaa 720 Query : 1083 ttactccccaaagggaaactggtggggccatgccccttacaaacatgggcggccctgttc 1142 1142 n m)) m) n n H m)) m) n i m m) m m m H) m) m) m Sbjct : 721 ttactccccaaagggaaactggtggggccatgccccttacaaacatgggcggccctgttc 780 Query : 1143 tgcttgcccacctagttttggagggggctgtagagaaaatctgtgctacaaagaagggtc 1202 1202 Sbjct : 781 tgcttgcccacctagttttggagggggctgtagagaaaatctgtgctacaaagaagggtc 840 Query : 1203 agacaggtattatccccctcgagaagaggaaacaaatgaaatagaacggcagcagtcaca 1262 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIIIIIIIII Sbjct : 841 agacaggtattatccccctcgagaagaggaaacaaatgaaatagaacgacagcagtcaca 900 Query : 1263 agtccatgacacccatgtccggacaagatcagatgatagtagcagaaatgaagtcat 1319 111111111111111111111111111111111111111111111111111111111 Sbjct : 901 agtccatgacacccatgtccggacaagatcagatgatagtagcagaaatgaagtcat 957 Score = 339 bits (171), Expect = 3e-90 Identities = 174/175 (99%) Strand = Plus/Plus Query : 1317 cattagctttgggaaaagtaatgaaaatataatggttttagaaatcctgtgttaaatatt 1376 1376 Sbjct : 1779 cattagctttgggaaaagtaatgaaaatataatggttttagaaatcctgtgttaaatatt 1838 Query : 1377 gctatattttcttagcagttatttctacagttaattacatagtcatgattgttctacgtt 1436

m m m m m m m m m m m m m m m m m m m n Sbjct : 1839 gctatattttcttagcagttatttctacagttaattacatagtcatgattgttctacgtt 1898 1898 Query : 1437 tcatatattatatggtgctttgtatatgcccctaataaaatgaatctaaacattg 1491 IIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIIIIIIIIIIIIIIIIIIIIII Sbjct : 1899 tcatatattatatggtgctttgtatatgccactaataaaatgaatctaaacattg 1953 The FCTR7 amino acid has 284 of 285 amino acid residues (99%) identical to, and 284 of 285 amino acid residues (99%) similar to, the 500 amino acid Putative secretory protein precursor [Homo sapiens] (GenBank-Acc No. : AF142573) (SEQ ID NO : 94) (Table 7F).

Table 7F. BLASTP alignments of FCTR7 against Putative secretory protein precursor, (SEQ ID NO : 94) >gill20023111gblAAG43287. 11AF142573 1 (AF142573) putative secretory protein precursor [Homo sapiens] Length = 500 Score = 581 bits (1499), Expect = e-165 Identities = 284/285 (99%), Positives = 284/285 (99%) Query : 1 MKCTAREWLRVTTVLFMARAIPAMVVPNATLLEKLLEKYMDEDGEWWIAKQRGKRAITDN 60 11111111111111111111111111111111111111111111111111111111111 Sbjct : 1 MKCTAREWLRVTTVLFMARAIPAMVVPNATLLEKLLEKYMDEDGEWWIAKQRGKRAITDN 60 Query : 61 DMQSILDLHNKLRSQVYPTASNMEYMTWDVELERSAESRAESCLWEHGPASLLPSIGQNL 120 Sbjct : 61 DMQSILDLHNKLRSQVYPTASNMEYMTWDVELERSAESWAESCLWEHGPASLLPSIGQNL 120 Query : 121 GAHWGRYRPPTFHVQSWYDEVKDFSYPYEHECNPYCPFRCSGPVCTHYTQVVWATSNRIG 180 11111111} 111111111111111111111111111111111111111111111111111 Sbjct : 121 GAHWGRYRPPTFHVQSWYDEVKDFSYPYEHECNPYCPFRCSGPVCTHYTQVVWATSNRIG 180 Query : 181 CAINLCHNMNIWGQIWPKAVYLVCNYSPKGNWWGHAPYKHGRPCSACPPSFGGGCRENLC 240 111111111111111111111111111111111111111111111111111111111111 Sbjct : 181 CAINLCHNMNIWGQIWPKAVYLVCNYSPKGNWWGHAPYKHGRPCSACPPSFGGGCRENLC 240 Query : 241 YKEGSDRYYPPREEETNEIERQQSQVHDTHVRTRSDDSSRNEVIS 285 111111111111111111111111111111111111111111111 Sbjct : 241 YKEGSDRYYPPREEETNEIERQQSQVHDTHVRTRSDDSSRNEVIS 285 The FCTR7 amino acid has 137 of 176 amino acid residues (78%) identical to, and 151 of 176 amino acid residues (86%) similar to, the 188 amino acid Late gestation lung protein 1 [Rattus norvegicus] (GenBank-Acc No. : AF109674) (SEQ ID N0 : 95) (Table 7G).

Table 7G. BLASTP alignments of FCTR7 against Late gestation lung protein 1, (SEQ ID NO : 95) >gil4324682lgblAAD16986. 1l (AF109674) late gestation lung protein 1 [Rattus norvegicus] Length = 188 Score = 277 bits (709), Expect = le-73 Identities = 137/176 (78%), Positives = 151/176 (86%) Query : 68 LHNKLRSQVYPTASNMEYMTWDVELERSAESRAESCLWEHGPASLLPSIGQNLGAHWGRY 127

mm mn mmmn nm i mmm mm mn Sbjct : 2 LHNKLRGQVYPPASNMEYMTWDEELERSAAAWAQRCLWEHGPASLLVSIGQNLAVHWGRY 61 Query : 128 RPPTFHVQSWYDEVKDFSYPYEHECNPYCPFRCSGPVCTHYTQVVWATSNRIGCAINLCH 187 I I I I I I I I I I I I 1 1++1 1 | I | I 1 1+1 1 1 1 1 1 +1 1 1 1 l 1+1 1 l 1+1+1 1 l 1++ 1 Sbjct : !) Ni) Nin++) N !) ! N+) !)) N +NHN+i))) +) + !)) ++) Sbjct : 62 RSPGFHVQSNYDEVKDYTYPYPHECNPMCPERCSGAMCTHYTQMVNATTNKIGCAVHTCR 121 Query : 188 NMNIWGQIWPKAVYLVCNYSPKGNWWGHAPYKHGRPCSACPPSFGGGCRENLCYKE 243 +++II II llllllllllllll I IIIIIIIIII II I+Illll IIII+I Sbjct : 122 SMSVWGDIWENAVYLVCNYSPKGNWIGEAPYKHGRPCSECPSSYGGGCRNNLCYRE 177 The FCTR7 amino acid has 130 of 237 amino acid residues (55%) identical to, and 165 of 237 amino acid residues (70%) similar to, the 258 amino acid R3H domain-containing preproprotein ; 25 kDa trypsin inhibitor [Homo sapiens] (GenBank-Acc No. : D45027) (SEQ ID NO : 96) (Table 7H).

Table 7H. BLASTP alignments of FCTR7 against R3H domain-containing preproprotein, 25 kDa trypsin inhibitor (SEQ ID NO : 96) >gil7705676lreflNP 056970. 11 R3H domain-containing preproprotein ; 25 kDa trypsin inhibitor ; R3H domain (binds single-stranded nucleic acids) containing [Homo sapiens] gi12943716idbjlBAA25066. 11- (D45027) 25 kDa trypsin inhibitor [Homo sapiens] Length = 258 Score = 265 bits (678), Expect = 4e-70 Identities = 130/237 (55%), Positives = 165/237 (70%), Gaps = 3/237 (1%) Query : 12 TTVLFMARAIPAMVVPNATLLEKLLEKYMDEDGEWWIAKQRGKRAITDNDMQSILDLHNK 71 +11+ + + I + +l 1+ +I 1 I I II I+ III +III II+ Sbjct : 20 STVVLLNSTDSSPPTNNFTDIEAALKAQLDSAD---IPKARRKRYISQNDMIAILDYHNQ 76 Query : 72 LRSQVYPTASNMEYMTWDVELERSAESRAESCLWEHGPASLLPSIGQNLGAHWGRYRPPT 131 +1 +1+1 1+11111 11 1 111 1 1+1+111+ 11 +1111 1111 Sbjct : 77 VRGKVFPPAANMEYMVWDENLAKSAEAWAATCIWDHGPSYLLRFLGQNLSVRTGRYRSIL 136 Query : 132 FHVQSWYDEVKDFSYPYEHECNPYCPFRCSGPVCTHYTQVVWATSNRIGCAINLCHNMNI 191 I+ IIIIIII+++y +III II II II+IIIIII+IIIIIIIIIIII+ I III+ Sbjct : 137 QLVKPWYDEVKDYAFPYPQDCNPRCPMRCFGPMCTHYTQMVWATSNRIGCAIHTCQNMNV 196 Query : 192 WGQIWPKAVYLVCNYSPKGNWWGHAPYKHGRPCSACPPSFGGGCRENLCYKEGSDRY 248 II +I +IIIIIIII+IIIII I IIlI I III+IIII+II I +III+ + I Sbjct : 197 WGSVWRRAVYLVCNYAPKGNWIGEAPYKVGVPCSSCPPSYGGSCTDNLCFPGVTSNY 253 The FCTR7 amino acid has 109 of 233 amino acid residues (47%) identical to, and 146 of 233 amino acid residues (63%) similar to, the 253 amino acid Novel protein similar to a trypsin inhibitor [Homo sapiens] 25 kDa trypsin inhibitor (EMBLAcc No. : AL117382) (SEQ ID NO : 97) (Table 7I).

Table 7I. BLASTP alignments of FCTR7 against Novel protein similar to a trypsin inhibitor, (SEQ ID NO : 97) >gi#9885193#emb#CAC04190.1# (AL117382) dJ881L22. 3 (novel protein similar to a trypsin inhibitor) [Homo sapiens] Length = 253 Score = 225 bits (575), Expect = 4e-58 Identities = 109/233 (47%), Positives = 146/233 (63%), Gaps = 8/233 (3%) Query : 10 RVTTVLFMARAIPAMWPNATLLEKLLEKYMDEDGEWWIAKQRGKRAITDNDMQSILDLH 69 + I I 1 i 1 +1 + I ++ + 1 11 1+ 11 ++11 1 Sbjct : 19 QAVNALIMPNATPAPAQPESTAMRLL--------SGLEVPRYRRKRHISVRDMNALLDYH 70 Query : 70 NKLRSQVYPTASNMEYMTWDVELERSAESRAESCLWEHGPASLLPSIGQNLGAHWGRYRP 129 ! +I+ III i+IIIII li I I II I I-I III+ j+ +IIII I I+il Sbjct : 71 NHIRASVYPPAANMEYMVWDKRLARAAEAWATQCIWAHGPSQLMRYVGQNLSIHSGQYRS 130 Query : 130 PTFHVQSWYDEVKDFSYPYEHECNPYCPFRCSGPVCTHYTQVVWATSNRIGCAINLCHNM 189 ++l I + + +II+II+II II I+IIII+III+III+llll+ I ++ Sbjct : 131 VVDLMKSWSEEKWHYLFPAPRDCNPHCPWRCDGPTCSHYTQMVWASSNRLGCAIHTCSSI 190 Query : 190 NIWGQIWPKAVYLVCNYSPKGNWWGHAPYKHGRPCSACPPSFGGGCRENLCYK 242 ++11 I +1 IIIIII+ IIII I +III I+III+IIII+ 1 I I+I+I Sbjct : 191 SVWGNTWHRAAYLVCNYAIKGNWIGESPYKMGKPCSSCPPSYQGSCNSNMCFK 243 The FCTR7 amino acid has 129 of 237 amino acid residues (54%) identical to, and 167 of 237 amino acid residues (70%) similar to, the 258 amino acid 25 kDa Trypsin Inhibitor from Homo sapiens (EMBLAcc No. : 043692) (SEQ ID NO : 88) (Table 7J).

Table 7J. BLASTP alignments of FCTR7 against 25 kDa Trypsin Inhibitor, (SEQ ID NO : 88) ptnr : SPTREMBL-ACC : 043692 25 KDA TRYPSIN INHIBITOR-Homo sapiens (Human), 258 aa.

Score = 743 (261. 5 bits), Expect = 1. 6e-73, P = 1. 6e-73 Identities = 129/237 (54%), Positives = 167/237 (70%) The FCTR7 amino acid has 79 of 193 amino acid residues (40%) identical to, and 110 of 193 amino acid residues (56%) similar to, the 266 amino acid Glioma Pathogenesis-Related Protein (RTVP-1 Protein)-Homo sapiens (SWISSPROT Acc No. : P48060) (SEQ ID NO : 90) (Table 7K).

Table 7K. BLASTP alignments of FCTR7 against Glioma Pathogenesis-Related Protein, (SEQ ID NO : 90) ptnr : SWISSPROT-ACC : P48060 GLIOMA PATHOGENESIS-RELATED PROTEIN (RTVP-1 PROTEIN)-Homo sapiens (Human), 266 aa Score = 314 (110. 5 bits), Expect = 4. 7e-28, P = 4. 7e-28 Identities = 79/193 (40%), Positives = 110/193 (56%) The FCTR7 amino acid has 66 of 186 amino acid residues (35%) identical to, and 91 of 186 amino acid residues (48%) similar to, the 186 amino acid Neutrophil granules matrix glycoprotein SGP28 precursor from Homo sapiens (SWISSPROT Acc No. : S68691) (SEQ ID NO : 98) (Table 7L).

Table 7L. BLASTP alignments of FCTR7 against Neutrophil granules matrix glycoprotein, (SEQ ID NO : 98) ptnr : PIR-ID : S68691 neutrophil granules matrix glycoprotein SGP28 precursor- human Score (89. 4 bits), Expect = l. le-21, P = l. le-21 Identities = 66/186 (35%), Positives = 91/186 (48%) A novel developmentally regulated gene with homology to a tumor derived trypsin inhibitor is expressed in lung mesenchyme, as described in Am. J. Physiol. 0 : 0-0 (1999). cDNA cloning of a novel trypsin inhibitor with similarity to pathogenesis-related proteins, and its frequent expression in human brain cancer cells is disclosed in Biochim. Biophys. Acta 1395 : 202-208 (1998). RTVP-1, a novel human gene with sequence similarity to genes of diverse species, is expressed in tumor cell lines of glial but not neuronal origin, as published in Gene 180 : 125-130 (1996). The human glioma pathogenesis-related protein is structurally related to plan pathogenesis-related proteins and its gene is expressed specifically in brain tumors (Gene 159 : 131-135 (1995)). Structure comparison of human glioma pathogenesis- related protein GliPR and the plant pathogenesis-related protein P14a indicates a functional link between the human immune system and a plant defense system (Proc. Natl. Acad. Sci.

U. S. A. 95 : 2262-2266 (1998)). GliPR is highly expressed in the human brain tumor, glioblastoma multiform/astrocytome, but neither in normal fetal or adult brain tissue, nor in other nervous system tumors. GliPR belongs to a family that groups mammalian SCP/TPX1 ; insects AG3/AG5 ; FUNGI SC7/SC14 and plants PR-1. SGP28, a novel matrix glycoprotein in specific granules of human neutrophils with similarity to a human testis-specific gene product and to a rodent sperm-coating glycoprotein (FEBS Lett. 380, 246-250, 1996). The primary structure and properties of helothermine, a peptide toxin that blocks ryanodine receptors is

described in Biophys. J. 68 : 2280-2288 (1995). As GliPR, Helothermine belongs to a family that groups mammalian SCP/TPX1 ; insects AG3/AG5 ; FUNGI SC7/SC14 and plants PR-1.

Based upon homology, FCTR7 protein and each homologous protein or peptide may share at least some activity.

Therapeutic uses : FCTR7 protein has homology to trypsin inhibitors, Q91055 helothermine, tumor derived tyrpsin inhibitors, glioma pathogenesis-related protein, Q9 Z 0U6 LATE GESTATION LUNG PROTEIN 1, and to the Prosite family which groups mammalian SCP/TPX1 ; INSECTS AG3/AG5 ; FUNGI SC7/SC14 AND PLANTS PR-1 proteins.

Therefore the FCTR7 protein disclosed in this invention could function like the proteins which it has homology to. These functions include tissue development in vitro and in vivo, and cancer pathogenesis.

Based the tissue expression pattern, the gene is implicated in diseases of tissues in which it is expressed. These diseases include but are not limited to : Glioma, * cancer, * lung diseases, * gestation, * male and female reproductive diseases, * deafness, 'neurological disorders, * gastric disorders, and * pancreatic diseases like diabetes.

These materials are further useful in the generation of antibodies that bind immunospecifically to the novel FCTR7 substances for use in therapeutic or diagnostic methods. These antibodies may be generated according to methods known in the art, using prediction from hydrophobicity charts, as described in the"Anti-FCTRX Antibodies"section below. In one embodiment, a contemplated FCTR7 epitope is from aa 40 to 120. In another embodiment, a FCTR7 epitope is from aa 130 to 170. In additional embodiments, FCTR7 epitopes are from aa 210 to 230, and from aa 240 to 280.

TABLE 8A : Summary Of Nucleic Acids And Proteins Of The Invention Name Tables Clone ; Description of Homolog Nucleic Acid Amino Acid SEQ ID NO SEQ ID NO FCTR1 1A, 1B, 58092213. 0. 36 follistatin-like protein 1 2 FCTR2 2A, 2B AC012614 1. 0. 123 ; KIAA1061-like protein 3 4 FCTR3 3A, 3B 10129612. 0. 118 ; neurestin-like protein 5 6 3C, 3D 10129612. 0. 405 ; neurestin-like protein 8 3E 10129612. 0. 154 ; neurestin-like protein 9 3F 10129612. 0. 67 ; neurestin-like protein 10 3G 10129612. 0. 258 ; neurestin-like protein 11 3H, 3I 10129612. 0. 352 ; neurestin-like protein 12 13 FCTR4 4A, 4B 29692275. 0. 1 ; NF-Kappa-B P65delta3-like 14 15 protein FCTR5 SA, 5B 32125243. 0. 21 ; human complement C1R 16 17 component precursor-like protein 5C, 5D 18 19 FCTR6 6A, 6B 27455183. 0. 19 ; novel human blood 20 21 coagulation factor XI-like protein 6C, 6D 27455183. 0. 145 ; novel human blood 22 23 coagulation factor XI-like protein FCTR7 7A, 7B 32592466. 0. 64 ; trypsin inhibitor-like protein 24 25 FCTR1 Example 2 Ag809 Forward 26 FCTR1 Example 2 Ag809 Probe 27 FCTR1 Example 2 Ag809 Reverse 28 FCTR4 Example 2 Ag2773 Forward 29 FCTR4 Example 2 Ag2773 Probe 30 FCTR4 Example 2 Ag2773 Reverse 31 FCTR5 Example 2 Ag427 Forward 32 FCTR5 Example 2 Ag427 Probe 33 FCTR5 Example 2 Ag427 Reverse 34 FCTR6 Example 2 Agl541 Forward 35 FCTR6 Example 2 Agl541 Probe 36 FCTR6 Example 2 Agl541 Reverse 37 TABLE 8B : Summary of Query Sequences Disclosed Table Database Acc. No. Sequence Name Species SEQ ID NO. 1C, 1K remtrEmbl BAA21725 IGFBP-like protein mouse 38 1D sptrEmbl Q61581 Follistatin-like protein-2 Mouse 39 1E SptrEmbl Q07822 Mac25 protein Human 40 1F, 1K SptrEmbl 088812 Mac25 protein Mouse 41 1G, 1K SptrEmbl Q16270 Prostacyclin-stimulating factor Human 42 1H, 1K PIR B40098 Colorectal cancer suppressor Rat 43 1I TrEmblne AAD9360 PTP sigma (brain) precursor Human 44 w 1J SptrEmbl Q13332 PTP sigma precursor Human 45 2C GenBank AB028984 KIAA1061 cDNA Human 46 2D TrEmblne BAA85677 KIAA1263 Human 47 w 2E TrEmblne BAA83013 KIAA1061 protein fragment Human 48 w 2F Embl CAB70877. 1 Hypothetical protein Human 49 DKFzp566D234. 1 2G GenBank Q62632 Follistatin-related protein-1 precursor Rat 50 2H GenBank Q62536 Follistatin-related protein-1 precursor Mouse 51 21 GenBank JG0187 Follistatin related protein African 52 clawed frog 2J GenBank Q12841 Follistatin related protein-1 precursor Human 53 2K Embl CAB42968. 1 Flik protein Chicken 54 2L GenBank T13822 Frazzled gene protein Fruit fly 55 2M GenBank AAC38849. 1 Roundabout 1 Fruit fly 56 2N GenBank 060469 Down Syndrome Cell Adhesion Human 57 Molecule Precursor 20 SwissProt Q 13449 Limbic system-associated membrane Human 58 protein precursor 2P SptrEmbl 070246 Putative neuronal cell adhesion Mouse 59 molecule, short form 2Q SptrEmbl 002869 CHLAMP, G11-isoform precursor Chicken 60 2R SwissProt Q62813 Limbic system-associated membrane Rat 61 protein precursor 3J GenBank NM_011856. 2 Odd Oz/ten-m homology 2 Fruit fly 62 3K Embl AJ245711. 1 Teneurin-2 cDNA, short splice variant Chicken 63 3L GenBank AB032953 KIAA 1127 cDNA Human 64 3M, GenBank AB025411 Ten-m2 cDNA Mouse 65 3U 3N GenBank 020088. 1 Neurestin alpha cDNA Rat 66 30 Embl GGA278031 Teneurin-2 Chicken 67 3PGenBank NP035986. 2 Odd Oz/ten-m homology 2 Fruit fly 68 3Q Embl CAC09416. 1 Teneurin-2 Chicken 69 3R GenBank BAA77399. 1 Ten-m4 Mouse 70 3S GenBank AB032953 KIAA1127 protein Human 71 3T GenBank AF086607 Neurestin alpha Rat 72 4C SptrEmbl Q99233 Hypothetical 10 kD protein Trypanos 73 ome 4C SptrEmbl Q16896 GABA receptor subunit 74 4C SptrEmbl 076473 GABA receptor subunit 75 4C TrEmblne AAD28317 FI3J11. 13 protein 76 w Text p. SptrEmbl Q13313 NF-kappa B P65 delta 3 protein Human 77 90 5E GenBank XM_007061. 1 Complement ClR-like proteinase Human 78 precursor 5FGenBank NM001733. 1 Complement component 1, R Human 79 subcomponent cDNA 5G GenBank AAF44349. 1 Complement ClRlike proteinase Human 80 precursor 5H GenBank AAA5185. 1 Complement C1R component Human 81 precursor 6E GenBank AB046651 Brain cDNA clone Qcc-17034 Macaque 82 6F GenBank AK09660 Adult testis cDNA, RIKEN full length Mouse 83 enriched 6G GenBank AB046651 Hypothetical protein Macaque 84 6HGenBank NP000838. 1 Plasma kallikrein B1 precursor Human 85 61 GenBank BAA37147. 1 Kallikrein Pig 86 6J Embl CAA64368. 1 Coagulation factor XI Human 87 7D, 7J SptrEmbl 043692 25 kDa trypsin inhibitor Human 88 7D SptrEmbl 044228 HRTT-1 89 7D, 7K SptrEmbl P418060 Glioma pathogenesis-related protein Human 90 7D PIR-ID JC4131 Glioma pathogenesis-related protein Human 91 7D SwissProt 019010 Cysteine-rcih secretory protein 92 7E GenBank AF142573 Putatitive secretory protein precursor Human 93 cDNA 7F GenBank AF142573 Putative secretory protein precursor Human 94 7G GenBank AF109674 Late gestation lung protein 1 Rat 95 7H GenBank D45027 R3H domain containing preprotein, 25 Human 96 kDa trypsin inhibitor 71 Embl AL117382 Novel protein similar to a trypsin Human 97 inhibitor 7L PIR-ID S68691 Neutrophil granules matrix Human 98 glycoprotein SGP28 precursor I

FCTRX Nucleic Acids and Polypeptides One aspect of the invention pertains to isolated nucleic acid molecules that encode FCTRX polypeptides or biologically-active portions thereof Also included in the invention are nucleic acid fragments sufficient for use as hybridization probes to identify FCTRX- encoding nucleic acids (e. g., FCTRX mRNAs) and fragments for use as PCR primers for the amplification and/or mutation of FCTRX nucleic acid molecules. As used herein, the term "nucleic acid molecule"is intended to include DNA molecules (e. g., cDNA or genomic DNA), RNA molecules (e. g., mRNA), analogs of the DNA or RNA generated using nucleotide analogs, and derivatives, fragments and homologs thereof. The nucleic acid molecule may be single-stranded or double-stranded, but preferably is comprised double- stranded DNA.

An FCTRX nucleic acid can encode a mature FCTRX polypeptide. As used herein, a "mature"form of a polypeptide or protein disclosed in the present invention is the product of a naturally occurring polypeptide or precursor form or proprotein. The naturally occurring

polypeptide, precursor or proprotein includes, by way of nonlimiting example, the full length gene product, encoded by the corresponding gene. Alternatively, it may be defined as the polypeptide, precursor or proprotein encoded by an ORF described herein. The product "mature"form arises, again by way of nonlimiting example, as a result of one or more naturally occurring processing steps as they may take place within the cell, or host cell, in which the gene product arises. Examples of such processing steps leading to a"mature"form of a polypeptide or protein include the cleavage of the N-terminal methionine residue encoded by the initiation codon of an ORF, or the proteolytic cleavage of a signal peptide or leader sequence. Thus a mature form arising from a precursor polypeptide or protein that has residues 1 to N, where residue 1 is the N-terminal methionine, would have residues 2 through N remaining after removal of the N-terminal methionine. Alternatively, a mature form arising from a precursor polypeptide or protein having residues 1 to N, in which an N-terminal signal sequence from residue 1 to residue M is cleaved, would have the residues from residue M+1 to residue N remaining. Further as used herein, a"mature"form of a polypeptide or protein may arise from a step of post-translational modification other than a proteolytic cleavage event.

Such additional processes include, by way of non-limiting example, glycosylation, myristoylation or phosphorylation. In general, a mature polypeptide or protein may result from the operation of only one of these processes, or a combination of any of them.

The term'probes", as utilized herein, refers to nucleic acid sequences of variable length, preferably between at least about 10 nucleotides (nt), 100 nt, or as many as approximately, e. g., 6, 000 nt, depending upon the specific use. Probes are used in the detection of identical, similar, or complementary nucleic acid sequences. Longer length probes are generally obtained from a natural or recombinant source, are highly specific, and much slower to hybridize than shorter-length oligomer probes. Probes may be single-or double-stranded and designed to have specificity in PCR, membrane-based hybridization technologies, or ELISA-like technologies.

The term"isolated"nucleic acid molecule, as utilized herein, is one which is separated from other nucleic acid molecules which are present in the natural source of the nucleic acid.

Preferably, an"isolated"nucleic acid is free of sequences which naturally flank the nucleic acid (i. e., sequences located at the 5'-and 3'-termini of the nucleic acid) in the genomic DNA of the organism from which the nucleic acid is derived. For example, in various embodiments, the isolated FCTRX nucleic acid molecules can contain less than about 5 kb, 4 kb, 3 kb, 2 kb, 1 kb, 0. 5 kb or 0. 1 kb of nucleotide sequences which naturally flank the nucleic acid molecule in genomic DNA of the cell/tissue from which the nucleic acid is derived (e. g., brain, heart,

liver, spleen, etc.). Moreover, an"isolated"nucleic acid molecule, such as a cDNA molecule, can be substantially free of other cellular material or culture medium when produced by recombinant techniques, or of chemical precursors or other chemicals when chemically synthesized.

A nucleic acid molecule of the invention, e. g., a nucleic acid molecule having the nucleotide sequence of SEQ ID NOS : 1, 3, 5, 7, 9, 10, 11, 12, 14, 16, 18, 20, 22, and 24, or a complement of this aforementioned nucleotide sequence, can be isolated using standard molecular biology techniques and the sequence information provided herein. Using all or a portion of the nucleic acid sequence of SEQ ID NOS : 1, 3, 5, 7, 9, 10, 11, 12, 14, 16, 18, 20, 22, and 24 as a hybridization probe, FCTRX molecules can be isolated using standard hybridization and cloning techniques (e. g., as described in Sambrook, et al., (eds.), MOLECULAR CLONING : A LABORATORY MANUAL 2nd Ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 1989 ; and Ausubel, et al., (eds.), CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, New York, NY, 1993.) A nucleic acid of the invention can be amplified using cDNA, mRNA or alternatively, genomic DNA, as a template and appropriate oligonucleotide primers according to standard PCR amplification techniques. The nucleic acid so amplified can be cloned into an appropriate vector and characterized by DNA sequence analysis. Furthermore, oligonucleotides corresponding to FCTRX nucleotide sequences can be prepared by standard synthetic techniques, e. g., using an automated DNA synthesizer.

As used herein, the term"oligonucleotide"refers to a series of linked nucleotide residues, which oligonucleotide has a sufficient number of nucleotide bases to be used in a PCR reaction. A short oligonucleotide sequence may be based on, or designed from, a genomic or cDNA sequence and is used to amplify, confirm, or reveal the presence of an identical, similar or complementary DNA or RNA in a particular cell or tissue.

Oligonucleotides comprise portions of a nucleic acid sequence having about 10 nt, 50 nt, or 100 nt in length, preferably about 15 nt to 30 nt in length. In one embodiment of the invention, an oligonucleotide comprising a nucleic acid molecule less than 100 nt in length would further comprise at least 6 contiguous nucleotides of SEQ ID NOS : 1, 3, 5, 7, 9, 10, 11, 12, 14, 16, 18, 20, 22, and 24, or a complement thereof. Oligonucleotides may be chemically synthesized and may also be used as probes.

In another embodiment, an isolated nucleic acid molecule of the invention comprises a nucleic acid molecule that is a complement of the nucleotide sequence shown in SEQ ID NOS : 1, 3, 5, 7, 9, 10, 11, 12, 14, 16, 18, 20, 22, and 24, or a portion of this nucleotide

sequence (e. g., a fragment that can be used as a probe or primer or a fragment encoding a biologically-active portion of an FCTRX polypeptide). A nucleic acid molecule that is complementary to the nucleotide sequence shown in SEQ ID NOS : 1, 3, 5, 7, 9, 10, 11, 12, 14, 16, 18, 20, 22, and 24, is one that is sufficiently complementary to the nucleotide sequence shown in SEQ ID NOS : 1, 3, 5, 7, 9, 10, 11, 12, 14, 16, 18, 20, 22, and 24, that it can hydrogen bond with little or no mismatches to the nucleotide sequence shown in SEQ ID NOS : 1, 3, 5, 7, 9, 10, 11, 12, 14, 16, 18, 20, 22, and 24, thereby forming a stable duplex.

As used herein, the term"complementary"refers to Watson-Crick or Hoogsteen base pairing between nucleotides units of a nucleic acid molecule, and the term"binding"means the physical or chemical interaction between two polypeptides or compounds or associated polypeptides or compounds or combinations thereof. Binding includes ionic, non-ionic, van der Waals, hydrophobic interactions, and the like. A physical interaction can be either direct or indirect. Indirect interactions may be through or due to the effects of another polypeptide or compound. Direct binding refers to interactions that do not take place through, or due to, the effect of another polypeptide or compound, but instead are without other substantial chemical intermediates.

Fragments provided herein are defined as sequences of at least 6 (contiguous) nucleic acids or at least 4 (contiguous) amino acids, a length sufficient to allow for specific hybridization in the case of nucleic acids or for specific recognition of an epitope in the case of amino acids, respectively, and are at most some portion less than a full length sequence.

Fragments may be derived from any contiguous portion of a nucleic acid or amino acid sequence of choice. Derivatives are nucleic acid sequences or amino acid sequences formed from the native compounds either directly or by modification or partial substitution. Analogs are nucleic acid sequences or amino acid sequences that have a structure similar to, but not identical to, the native compound but differs from it in respect to certain components or side chains. Analogs may be synthetic or from a different evolutionary origin and may have a similar or opposite metabolic activity compared to wild type. Homologs are nucleic acid sequences or amino acid sequences of a particular gene that are derived from different species.

Derivatives and analogs may be full length or other than full length, if the derivative or analog contains a modified nucleic acid or amino acid, as described below. Derivatives or analogs of the nucleic acids or proteins of the invention include, but are not limited to, molecules comprising regions that are substantially homologous to the nucleic acids or proteins of the invention, in various embodiments, by at least about 70%, 80%, or 95% identity (with a preferred identity of 80-95%) over a nucleic acid or amino acid sequence of

identical size or when compared to an aligned sequence in which the alignment is done by a computer homology program known in the art, or whose encoding nucleic acid is capable of hybridizing to the complement of a sequence encoding the aforementioned proteins under stringent, moderately stringent, or low stringent conditions. See e. g. Ausubel, et al., CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, New York, NY, 1993, and below.

A"homologous nucleic acid sequence"or"homologous amino acid sequence,"or variations thereof, refer to sequences characterized by a homology at the nucleotide level or amino acid level as discussed above. Homologous nucleotide sequences encode those sequences coding for isoforms of FCTRX polypeptides. Isoforms can be expressed in different tissues of the same organism as a result of, for example, alternative splicing of RNA.

Alternatively, isoforms can be encoded by different genes. In the invention, homologous nucleotide sequences include nucleotide sequences encoding for an FCTRX polypeptide of species other than humans, including, but not limited to : vertebrates, and thus can include, e. g., frog, mouse, rat, rabbit, dog, cat cow, horse, and other organisms. Homologous nucleotide sequences also include, but are not limited to, naturally occurring allelic variations and mutations of the nucleotide sequences set forth herein. A homologous nucleotide sequence does not, however, include the exact nucleotide sequence encoding human FCTRX protein.

Homologous nucleic acid sequences include those nucleic acid sequences that encode conservative amino acid substitutions (see below) in SEQ ID NOS : 2, 4, 6, 8, 13, 15, 17, 19, 21, 23, and 25, as well as a polypeptide possessing FCTRX biological activity. Various biological activities of the FCTRX proteins are described below.

An FCTRX polypeptide is encoded by the open reading frame ("ORF") of an FCTRX nucleic acid. An ORF corresponds to a nucleotide sequence that could potentially be translated into a polypeptide. A stretch of nucleic acids comprising an ORF is uninterrupted by a stop codon. An ORF that represents the coding sequence for a full protein begins with an ATG "start"codon and terminates with one of the three"stop"codons, namely, TAA, TAG, or TGA. For the purposes of this invention, an ORF may be any part of a coding sequence, with or without a start codon, a stop codon, or both. For an ORF to be considered as a good candidate for coding for a bonafide cellular protein, a minimum size requirement is often set, e. g., a stretch of DNA that would encode a protein of 50 amino acids or more.

The nucleotide sequences determined from the cloning of the human FCTRX genes allows for the generation of probes and primers designed for use in identifying and/or cloning FCTRX homologues in other cell types, e. g. from other tissues, as well as FCTRX homologues from other vertebrates. The probe/primer typically comprises substantially

purified oligonucleotide. The oligonucleotide typically comprises a region of nucleotide sequence that hybridizes under stringent conditions to at least about 12, 25, 50, 100, 150, 200, 250, 300, 350 or 400 consecutive sense strand nucleotide sequence of SEQ ID NOS : 1, 3, 5, 7, 9, 10, 11, 12, 14, 16, 18, 20, 22, and 24 ; or an anti-sense strand nucleotide sequence of SEQ ID NOS : 1, 3, 5, 7, 9, 10, 11, 12, 14, 16, 18, 20, 22, and 24 ; or of a naturally occurring mutant of SEQ ID NOS : 1, 3, 5, 7, 9, 10, 11, 12, 14, 16, 18, 20, 22, and 24.

Probes based on the human FCTRX nucleotide sequences can be used to detect transcripts or genomic sequences encoding the same or homologous proteins. In various embodiments, the probe further comprises a label group attached thereto, e. g. the label group can be a radioisotope, a fluorescent compound, an enzyme, or an enzyme co-factor. Such probes can be used as a part of a diagnostic test kit for identifying cells or tissues which mis- express an FCTRX protein, such as by measuring a level of an FCTRX-encoding nucleic acid in a sample of cells from a subject e. g., detecting FCTRX mRNA levels or determining whether a genomic FCTRX gene has been mutated or deleted.

"A polypeptide having a biologically-active portion of an FCTRX polypeptide"refers to polypeptides exhibiting activity similar, but not necessarily identical to, an activity of a polypeptide of the invention, including mature forms, as measured in a particular biological assay, with or without dose dependency. A nucleic acid fragment encoding a"biologically- active portion of FCTRX"can be prepared by isolating a portion of SEQ ID NOS : 1, 3, 5, 7, 9, 10, 11, 12, 14, 16, 18, 20, 22, and 24, that encodes a polypeptide having an FCTRX biological activity (the biological activities of the FCTRX proteins are described below), expressing the encoded portion of FCTRX protein (e. g., by recombinant expression in vitro) and assessing the activity of the encoded portion of FCTRX.

FCTRX Nucleic Acid and Polypeptide Variants The invention further encompasses nucleic acid molecules that differ from the nucleotide sequences shown in SEQ ID NOS : 1, 3, 5, 7, 9, 10, 11, 12, 14, 16, 18, 20, 22, and 24, due to degeneracy of the genetic code and thus encode the same FCTRX proteins as that encoded by the nucleotide sequences shown in SEQ ID NO NOS : 1, 3, 5, 7, 9, 10, 11, 12, 14, 16, 18, 20, 22, and 24. In another embodiment, an isolated nucleic acid molecule of the invention has a nucleotide sequence encoding a protein having an amino acid sequence shown in SEQ ID NOS : 2, 4, 6, 8, 13, 15, 17, 19, 21, 23, and 25.

In addition to the human FCTRX nucleotide sequences shown in SEQ ID NOS : 1, 3, 5, 7, 9, 10, 11, 12, 14, 16, 18, 20, 22, and 24, it will be appreciated by those skilled in the art that

DNA sequence polymorphisms that lead to changes in the amino acid sequences of the FCTRX polypeptides may exist within a population (e. g., the human population). Such genetic polymorphism in the FCTRX genes may exist among individuals within a population due to natural allelic variation. As used herein, the terms"gene"and"recombinant gene"refer to nucleic acid molecules comprising an open reading frame (ORF) encoding an FCTRX protein, preferably a vertebrate FCTRX protein. Such natural allelic variations can typically result in 1-5% variance in the nucleotide sequence of the FCTRX genes. Any and all such nucleotide variations and resulting amino acid polymorphisms in the FCTRX polypeptides, which are the result of natural allelic variation and that do not alter the functional activity of the FCTRX polypeptides, are intended to be within the scope of the invention.

Moreover, nucleic acid molecules encoding FCTRX proteins from other species, and thus that have a nucleotide sequence that differs from the human sequence of SEQ ID NOS : 1, 3, 5, 7, 9, 10, 11, 12, 14, 16, 18, 20, 22, and 24, are intended to be within the scope of the invention. Nucleic acid molecules corresponding to natural allelic variants and homologues of the FCTRX cDNAs of the invention can be isolated based on their homology to the human FCTRX nucleic acids disclosed herein using the human cDNAs, or a portion thereof, as a hybridization probe according to standard hybridization techniques under stringent hybridization conditions.

Accordingly, in another embodiment, an isolated nucleic acid molecule of the invention is at least 6 nucleotides in length and hybridizes under stringent conditions to the nucleic acid molecule comprising the nucleotide sequence of SEQ ID NOS : 1, 3, 5, 7, 9, 10, 11, 12, 14, 16, 18, 20, 22, and 24. In another embodiment, the nucleic acid is at least 10, 25, 50, 100, 250, 500, 750, 1000, 1500, or 2000 or more nucleotides in length. In yet another embodiment, an isolated nucleic acid molecule of the invention hybridizes to the coding region. As used herein, the term"hybridizes under stringent conditions"is intended to describe conditions for hybridization and washing under which nucleotide sequences at least 60% homologous to each other typically remain hybridized to each other.

Homologs (i. e., nucleic acids encoding FCTRX proteins derived from species other than human) or other related sequences (e. g., paralogs) can be obtained by low, moderate or high stringency hybridization with all or a portion of the particular human sequence as a probe using methods well known in the art for nucleic acid hybridization and cloning.

As used herein, the phrase"stringent hybridization conditions"refers to conditions under which a probe, primer or oligonucleotide will hybridize to its target sequence, but to no other sequences. Stringent conditions are sequence-dependent and will be different in

different circumstances. Longer sequences hybridize specifically at higher temperatures than shorter sequences. Generally, stringent conditions are selected to be about 5°C lower than the thermal melting point (Tm) for the specific sequence at a defined ionic strength and pH. The Tm is the temperature (under defined ionic strength, pH and nucleic acid concentration) at which 50% of the probes complementary to the target sequence hybridize to the target sequence at equilibrium. Since the target sequences are generally present at excess, at Tm, 50% of the probes are occupied at equilibrium. Typically, stringent conditions will be those in which the salt concentration is less than about 1. 0 M sodium ion, typically about 0. 01 to 1. 0 M sodium ion (or other salts) at pH 7. 0 to 8. 3 and the temperature is at least about 30°C for short probes, primers or oligonucleotides (e. g., 10 nt to 50 nt) and at least about 60°C for longer probes, primers and oligonucleotides. Stringent conditions may also be achieved with the addition of destabilizing agents, such as formamide.

Stringent conditions are known to those skilled in the art and can be found in Ausubel, et al., (eds.), CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, N. Y.

(1989), 6. 3. 1-6. 3. 6. Preferably, the conditions are such that sequences at least about 65%, 70%, 75%, 85%, 90%, 95%, 98%, or 99% homologous to each other typically remain hybridized to each other. A non-limiting example of stringent hybridization conditions are hybridization in a high salt buffer comprising 6X SSC, 50 mM Tris-HCl (pH 7. 5), 1 mM EDTA, 0. 02% PVP, 0. 02% Ficoll, 0. 02% BSA, and 500 mg/ml denatured salmon sperm DNA at 65°C, followed by one or more washes in 0. 2X SSC, 0. 01% BSA at 50°C. An isolated nucleic acid molecule of the invention that hybridizes under stringent conditions to the sequences of SEQ ID NOS : I, 3, 5, 7, 9, 10, 11, 12, 14, 16, 18, 20, 22, and 24, corresponds to a naturally-occurring nucleic acid molecule. As used herein, a"naturally-occurring"nucleic acid molecule refers to an RNA or DNA molecule having a nucleotide sequence that occurs in nature (e. g., encodes a natural protein).

In a second embodiment, a nucleic acid sequence that is hybridizable to the nucleic acid molecule comprising the nucleotide sequence of SEQ ID NOS : 1, 3, 5, 7, 9, 10, 11, 12, 14, 16, 18, 20, 22, and 24, or fragments, analogs or derivatives thereof, under conditions of moderate stringency is provided. A non-limiting example of moderate stringency hybridization conditions are hybridization in 6X SSC, 5X Denhardt's solution, 0. 5% SDS and 100 mg/ml denatured salmon sperm DNA at 55°C, followed by one or more washes in 1X SSC, 0. 1% SDS at 37°C. Other conditions of moderate stringency that may be used are well-known within the art. See, e. g, Ausubel, et al. (eds.), 1993, CURRENT PROTOCOLS IN

MOLECULAR BIOLOGY, John Wiley & Sons, NY, and Kriegler, 1990 ; GENE TRANSFER AND EXPRESSION, A LABORATORY MANUAL, Stockton Press, NY.

In a third embodiment, a nucleic acid that is hybridizable to the nucleic acid molecule comprising the nucleotide sequences of SEQ ID NOS : 1, 3, 5, 7, 9, 10, 11, 12, 14, 16, 18, 20, 22, and 24, or fragments, analogs or derivatives thereof, under conditions of low stringency, is provided. A non-limiting example of low stringency hybridization conditions are hybridization in 35% formamide, 5X SSC, 50 mM Tris-HCl (pH 7. 5), 5 mM EDTA, 0. 02% PVP, 0. 02% Ficoll, 0. 2% BSA, 100 mg/ml denatured salmon sperm DNA, 10% (wt/vol) dextran sulfate at 40°C, followed by one or more washes in 2X SSC, 25 mM Tris-HCl (pH 7. 4), 5 mM EDTA, and 0. 1% SDS at 50°C. Other conditions of low stringency that may be used are well known in the art (e. g., as employed for cross-species hybridizations). See, e. g., Ausubel, et al. (eds.), 1993, CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, NY, and Kriegler, 1990, GENE TRANSFER AND EXPRESSION, A LABORATORY MANUAL, Stockton Press, NY ; Shilo and Weinberg, 1981. Proc Natl Acad Sci USA 78 : 6789-6792.

Conservative Mutations In addition to naturally-occurring allelic variants of FCTRX sequences that may exist in the population, the skilled artisan will further appreciate that changes can be introduced by mutation into the nucleotide sequences of SEQ ID NO NOS : 1, 3, 5, 7, 9, 10, 11, 12, 14, 16, 18, 20, 22, and 24, thereby leading to changes in the amino acid sequences of the encoded FCTRX proteins, without altering the functional ability of said FCTRX proteins. For example, nucleotide substitutions leading to amino acid substitutions at"non-essential"amino acid residues can be made in the sequence of SEQ ID NOS : 2, 4, 6, 8, 13, 15, 17, 19, 21, 23, and 25.. A"non-essential"amino acid residue is a residue that can be altered from the wild-type sequences of the FCTRX proteins without altering their biological activity, whereas an"essential"amino acid residue is required for such biological activity. For example, amino acid residues that are conserved among the FCTRX proteins of the invention are predicted to be particularly non-amenable to alteration. Amino acids for which conservative substitutions can be made are well-known within the art.

Another aspect of the invention pertains to nucleic acid molecules encoding FCTRX proteins that contain changes in amino acid residues that are not essential for activity. Such FCTRX proteins differ in amino acid sequence from SEQ ID NOS : 2, 4, 6, 8, 13, 15, 17, 19, 21, 23, and 25, yet retain biological activity. In one embodiment, the isolated nucleic acid molecule comprises a nucleotide sequence encoding a protein, wherein the protein comprises an amino acid sequence at least about 45% homologous to the amino acid sequences of SEQ

ID NOS : 2, 4, 6, 8, 13, 15, 17, 19, 21, 23, and 25. Preferably, the protein encoded by the nucleic acid molecule is at least about 60% homologous to SEQ ID NOS : 2, 4, 6, 8, 13, 15, 17, 19, 21, 23, and 25 ; more preferably at least about 70% homologous to SEQ ID NOS : 2, 4, 6, 8, 13, 15, 17, 19, 21, 23, and 25 ; still more preferably at least about 80% homologous to SEQ ID NOS : 2, 4, 6, 8, 13, 15, 17, 19, 21, 23, and 25 ; even more preferably at least about 90% homologous to SEQ ID NOS : 2, 4, 6, 8, 13, 15, 17, 19, 21, 23, and 25 ; and most preferably at least about 95% homologous to SEQ ID NOS : 2, 4, 6, 8, 13, 15, 17, 19, 21, 23, and 25.

An isolated nucleic acid molecule encoding an FCTRX protein homologous to the protein of SEQ ID NOS : 2, 4, 6, 8, 13, 15, 17, 19, 21, 23, and 25, can be created by introducing one or more nucleotide substitutions, additions or deletions into the nucleotide sequence of SEQ ID NOS : 1, 3, 5, 7, 9, 10, 11, 12, 14, 16, 18, 20, 22, and 24, such that one or more amino acid substitutions, additions or deletions are introduced into the encoded protein.

Mutations can be introduced into SEQ ID NOS : 2, 4, 6, 8, 13, 15, 17, 19, 21, 23, and 25, by standard techniques, such as site-directed mutagenesis and PCR-mediated mutagenesis.

Preferably, conservative amino acid substitutions are made at one or more predicted, non-essential amino acid residues. A"conservative amino acid substitution"is one in which the amino acid residue is replaced with an amino acid residue having a similar side chain.

Families of amino acid residues having similar side chains have been defined within the art.

These families include amino acids with basic side chains (e. g., lysine, arginine, histidine), acidic side chains (e. g., aspartic acid, glutamic acid), uncharged polar side chains (e. g, glycine, asparagine, glutamin, serine, threonine, tyrosine, cysteine), nonpolar side chains (e. g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), beta-branched side chains (e. g., threonine, valine, isoleucine) and aromatic side chains (e. g., tyrosine, phenylalanine, tryptophan, histidine). Thus, a predicted non-essential amino acid residue in the FCTRX protein is replaced with another amino acid residue from the same side chain family. Alternatively, in another embodiment, mutations can be introduced randomly along all or part of an FCTRX coding sequence, such as by saturation mutagenesis, and the resultant mutants can be screened for FCTRX biological activity to identify mutants that retain activity. Following mutagenesis of SEQ ID NOS : 2, 4, 6, 8, 13, 15, 17, 19, 21, 23, and 25, the encoded protein can be expressed by any recombinant technology known in the art and the activity of the protein can be determined.

The relatedness of amino acid families may also be determined based on side chain interactions. Substituted amino acids may be fully conserved"strong"residues or fully conserved"weak"residues. The"strong"group of conserved amino acid residues may be any

one of the following groups : STA, NEQK, NHQK, NDEQ, QHRK, MILV, MILF, HY, FYW, wherein the single letter amino acid codes are grouped by those amino acids that may be substituted for each other. Likewise, the"weak"group of conserved residues may be any one of the following : CSA, ATV, SAG, STNK, STPA, SGND, SNDEQK, NDEQHK, NEQHRK, VLIM, HFY, wherein the letters within each group represent the single letter amino acid code.

In one embodiment, a mutant FCTRX protein can be assayed for (i) the ability to form protein : protein interactions with other FCTRX proteins, other cell-surface proteins, or biologically-active portions thereof, (ii) complex formation between a mutant FCTRX protein and an FCTRX ligand ; or (iii) the ability of a mutant FCTRX protein to bind to an intracellular target protein or biologically-active portion thereof ; (e. g. avidin proteins).

In yet another embodiment, a mutant FCTRX protein can be assayed for the ability to regulate a specific biological function (e. g., regulation of insulin release).

Antisense Nucleic Acids Another aspect of the invention pertains to isolated antisense nucleic acid molecules that are hybridizable to or complementary to the nucleic acid molecule comprising the nucleotide sequence of SEQ ID NOS : 1, 3, 5, 7, 9, 10, 11, 12, 14, 16, 18, 20, 22, and 24, or fragments, analogs or derivatives thereof. An"antisense"nucleic acid comprises a nucleotide sequence that is complementary to a"sense"nucleic acid encoding a protein (e. g., complementary to the coding strand of a double-stranded cDNA molecule or complementary to an mRNA sequence). In specific aspects, antisense nucleic acid molecules are provided that comprise a sequence complementary to at least about 10, 25, 50, 100, 250 or 500 nucleotides or an entire FCTRX coding strand, or to only a portion thereof. Nucleic acid molecules encoding fragments, homologs, derivatives and analogs of an FCTRX protein of SEQ ID NOS : 2, 4, 6, 8, 13, 15, 17, 19, 21, 23, and 25 ; or antisense nucleic acids complementary to an FCTRX nucleic acid sequence of SEQ ID NOS : 1, 3, 5, 7, 9, 10, 11, 12, 14, 16, 18, 20, 22, and 24, are additionally provided.

In one embodiment, an antisense nucleic acid molecule is antisense to a"coding region"of the coding strand of a nucleotide sequence encoding an FCTRX protein. The term "coding region"refers to the region of the nucleotide sequence comprising codons which are translated into amino acid residues. In another embodiment, the antisense nucleic acid molecule is antisense to a"noncoding region"of the coding strand of a nucleotide sequence encoding the FCTRX protein. The term"noncoding region"refers to 5'and 3'sequences

which flank the coding region that are not translated into amino acids (i. e., also referred to as 5'and 3'untranslated regions).

Given the coding strand sequences encoding the FCTRX protein disclosed herein, antisense nucleic acids of the invention can be designed according to the rules of Watson and Crick or Hoogsteen base pairing. The antisense nucleic acid molecule can be complementary to the entire coding region of FCTRX mRNA, but more preferably is an oligonucleotide that is antisense to only a portion of the coding or noncoding region of FCTRX mRNA. For example, the antisense oligonucleotide can be complementary to the region surrounding the translation start site of FCTRX mRNA. An antisense oligonucleotide can be, for example, about 5, 10, 15, 20, 25, 30, 35, 40, 45 or 50 nucleotides in length. An antisense nucleic acid of the invention can be constructed using chemical synthesis or enzymatic ligation reactions using procedures known in the art. For example, an antisense nucleic acid (e. g, an antisense oligonucleotide) can be chemically synthesized using naturally-occurring nucleotides or variously modified nucleotides designed to increase the biological stability of the molecules or to increase the physical stability of the duplex formed between the antisense and sense nucleic acids (e. g., phosphorothioate derivatives and acridine substituted nucleotides can be used).

Examples of modified nucleotides that can be used to generate the antisense nucleic acid include : 5-fluorouracil, 5-bromouracil, 5-chlorouracil, 5-iodouracil, hypoxanthine, xanthine, 4-acetylcytosine, 5-(carboxyhydroxylmethyl) uracil, 5-carboxymethylaminomethyl- 2-thiouridine, 5-carboxymethylaminomethyluracil, dihydrouracil, beta-D-galactosylqueosine, inosine, N6-isopentenyladenine, 1-methylguanine, 1-methylinosine, 2, 2-dimethylguanine, 2-methyladenine, 2-methylguanine, 3-methylcytosine, 5-methylcytosine, N6-adenine, 7-methylguanine, 5-methylaminomethyluracil, 5-methoxyaminomethyl-2-thiouracil, beta-D-malmosylqueosine, 5'-methoxycarboxymethyluracil, 5-methoxyuracil, 2-methylthio-N6-isopentenyladenine, uracil-5-oxyacetic acid (v), wybutoxosine, pseudouracil, queosine, 2-thiocytosine, 5-methyl-2-thiouracil, 2-thiouracil, 4-thiouracil, 5-methyluracil, uracil-5-oxyacetic acid methylester, uracil-5-oxyacetic acid (v), 5-methyl-2-thiouracil, 3- (3-amino-3-N-2-carboxypropyl) uracil, (acp3) w, and 2, 6-diaminopurine. Alternatively, the antisense nucleic acid can be produced biologically using an expression vector into which a nucleic acid has been subcloned in an antisense orientation (i. e., RNA transcribed from the inserted nucleic acid will be of an antisense orientation to a target nucleic acid of interest, described further in the following subsection).

The antisense nucleic acid molecules of the invention are typically administered to a subject or generated in situ such that they hybridize with or bind to cellular mRNA and/or

genomic DNA encoding an FCTRX protein to thereby inhibit expression of the protein (e. g., by inhibiting transcription and/or translation). The hybridization can be by conventional nucleotide complementarity to form a stable duplex, or, for example, in the case of an antisense nucleic acid molecule that binds to DNA duplexes, through specific interactions in the major groove of the double helix. An example of a route of administration of antisense nucleic acid molecules of the invention includes direct injection at a tissue site. Alternatively, antisense nucleic acid molecules can be modified to target selected cells and then administered systemically. For example, for systemic administration, antisense molecules can be modified such that they specifically bind to receptors or antigens expressed on a selected cell surface (e. g., by linking the antisense nucleic acid molecules to peptides or antibodies that bind to cell surface receptors or antigens). The antisense nucleic acid molecules can also be delivered to cells using the vectors described herein. To achieve sufficient nucleic acid molecules, vector constructs in which the antisense nucleic acid molecule is placed under the control of a strong pol II or pol III promoter are preferred.

In yet another embodiment, the antisense nucleic acid molecule of the invention is an a-anomeric nucleic acid molecule. An a-anomeric nucleic acid molecule forms specific double-stranded hybrids with complementary RNA in which, contrary to the usual p-units, the strands run parallel to each other. See, e. g., Gaultier, et al., 1987. Nucl. Acids Res. 15 : 6625-6641. The antisense nucleic acid molecule can also comprise a 2'-o-methylribonucleotide (see, e. g., Inoue, et al. 1987. Nucl. Acids Res. 15 : 6131-6148) or a chimeric RNA-DNA analogue (see, e. g., Inoue, et al., 1987. FEBS Lett. 215 : 327-330.

Ribozymes and PNA Moieties Nucleic acid modifications include, by way of non-limiting example, modified bases, and nucleic acids whose sugar phosphate backbones are modified or derivatized. These modifications are carried out at least in part to enhance the chemical stability of the modified nucleic acid, such that they may be used, for example, as antisense binding nucleic acids in therapeutic applications in a subject.

In one embodiment, an antisense nucleic acid of the invention is a ribozyme.

Ribozymes are catalytic RNA molecules with ribonuclease activity that are capable of cleaving a single-stranded nucleic acid, such as an mRNA, to which they have a complementary region. Thus, ribozymes (e. g., hammerhead ribozymes as described in Haselhoff and Gerlach 1988. Nature 334 : 585-591) can be used to catalytically cleave FCTRX mRNA transcripts to thereby inhibit translation of FCTRX MARNA. A ribozyme having specificity for an FCTRX-encoding nucleic acid can be designed based upon the nucleotide

sequence of an FCTRX cDNA disclosed herein (i. e., SEQ ID NOS : 1, 3, 5, 7, 9, 10, 11, 12, 14, 16, 18, 20, 22, and 24). For example, a derivative of a Tetrahymena L-19 IVS RNA can be constructed in which the nucleotide sequence of the active site is complementary to the nucleotide sequence to be cleaved in an FCTRX-encoding MARNA. See, e. g., U. S. Patent 4, 987, 071 to Cech, et al. and U. S. Patent 5, 116, 742 to Cech, et al. FCTRX MARNA can also be used to select a catalytic RNA having a specific ribonuclease activity from a pool of RNA molecules. See, e. g., Bartel et al., (1993) Science 261 : 1411-1418.

Alternatively, FCTRX gene expression can be inhibited by targeting nucleotide sequences complementary to the regulatory region of the FCTRX nucleic acid (e. g., the FCTRX promoter and/or enhancers) to form triple helical structures that prevent transcription of the FCTRX gene in target cells. See, e. g., Helene, 199 1. Anticancer Drug Des. 6 : 569-84 ; Helene, et al. 1992. Ann. N. Y. Acad. Sci. 660 : 27-36 ; Maher, 1992. Bioassays 14 : 807-15.

In various embodiments, the FCTRX nucleic acids can be modified at the base moiety, sugar moiety or phosphate backbone to improve, e. g., the stability, hybridization, or solubility of the molecule. For example, the deoxyribose phosphate backbone of the nucleic acids can be modified to generate peptide nucleic acids. See, e. g., Hyrup, et al., 1996. Bioorg Med Chem 4 : 5-23. As used herein, the terms"peptide nucleic acids"or"PNAs"refer to nucleic acid mimics (e. g., DNA mimics) in which the deoxyribose phosphate backbone is replaced by a pseudopeptide backbone and only the four natural nucleobases are retained. The neutral backbone of PNAs has been shown to allow for specific hybridization to DNA and RNA under conditions of low ionic strength. The synthesis of PNA oligomers can be performed using standard solid phase peptide synthesis protocols as described in Hyrup, et al., 1996. supra ; Perry-O'Keefe, et al., 1996. Proc. Natl. Acad. Sci. USA 93 : 14670-14675.

PNAs of FCTRX can be used in therapeutic and diagnostic applications. For example, PNAs can be used as antisense or antigene agents for sequence-specific modulation of gene expression by, e. g., inducing transcription or translation arrest or inhibiting replication. PNAs of FCTRX can also be used, for example, in the analysis of single base pair mutations in a gene (e. g., PNA directed PCR clamping ; as artificial restriction enzymes when used in combination with other enzymes, e. g., Si nucleases (see, Hyrup, et al., 1996. supra) ; or as probes or primers for DNA sequence and hybridization (see, Hyrup, et al., 1996, supra ; Perry-O'Keefe, et al., 1996. supra).

In another embodiment, PNAs of FCTRX can be modified, e. g., to enhance their stability or cellular uptake, by attaching lipophilic or other helper groups to PNA, by the formation of PNA-DNA chimeras, or by the use of liposomes or other techniques of drug

delivery known in the art. For example, PNA-DNA chimeras of FCTRX can be generated that may combine the advantageous properties of PNA and DNA. Such chimeras allow DNA recognition enzymes (e. g., RNase H and DNA polymerases) to interact with the DNA portion while the PNA portion would provide high binding affinity and specificity. PNA-DNA chimeras can be linked using linkers of appropriate lengths selected in terms of base stacking, number of bonds between the nucleobases, and orientation (see, Hyrup, etal., 1996. supra).

The synthesis of PNA-DNA chimeras can be performed as described in Hyrup, et al., 1996. supra and Finn, et al., 1996. Nucl Acids Res 24 : 3357-3363. For example, a DNA chain can be synthesized on a solid support using standard phosphoramidite coupling chemistry, and modified nucleoside analogs, e. g., 5'- (4-methoxytrityl) amino-5'-deoxy-thymidine phosphoramidite, can be used between the PNA and the 5'end of DNA. See, e. g., Mag, et al., 1989. Nucl Acid Res 17 : 5973-5988. PNA monomers are then coupled in a stepwise manner to produce a chimeric molecule with a 5'PNA segment and a 3'DNA segment. See, e. g., Finn, et al., 1996. supra. Alternatively, chimeric molecules can be synthesized with a 5'DNA segment and a 3'PNA segment. See, e. g., Petersen, et al., 1975. Bioorg. Med. Chem. Lett. 5 : 1119-11124.

In other embodiments, the oligonucleotide may include other appended groups such as peptides (e. g., for targeting host cell receptors in vivo), or agents facilitating transport across the cell membrane (see, e. g., Letsinger, et al., 1989. Proc. Natl. Acad. Sci. U. S. A. 86 : 6553-6556 ; Lemaitre, et al., 1987. Proc. Natl. Acad. Sci. 84 : 648-652 ; PCT Publication No.

W088/09810) or the blood-brain barrier (see, e. g, PCT Publication No. WO 89/10134). In addition, oligonucleotides can be modified with hybridization triggered cleavage agents (see, e. g., Krol, et al., 1988. BioTechniques 6 : 958-976) or intercalating agents (see, e. g., Zon, 1988.

Pharm. Res. 5 : 539-549). To this end, the oligonucleotide may be conjugated to another molecule, e. g., a peptide, a hybridization triggered cross-linking agent, a transport agent, a hybridization-triggered cleavage agent, and the like.

FCTRX Polypeptides A polypeptide according to the invention includes a polypeptide including the amino acid sequence of FCTRX polypeptides whose sequences are provided in SEQ ID NOS : 2, 4, 6, 8, 13, 15, 17, 19, 21, 23, and 25. The invention also includes a mutant or variant protein any of whose residues may be changed from the corresponding residues shown in SEQ ID NOS : 2, 4, 6, 8, 13, 15, 17, 19, 21, 23, and 25, while still encoding a protein that maintains its FCTRX activities and physiological functions, or a functional fragment thereof.

In general, an FCTRX variant that preserves FCTRX-like function includes any variant in which residues at a particular position in the sequence have been substituted by other amino acids, and further include the possibility of inserting an additional residue or residues between two residues of the parent protein as well as the possibility of deleting one or more residues from the parent sequence. Any amino acid substitution, insertion, or deletion is encompassed by the invention. In favorable circumstances, the substitution is a conservative substitution as defined above.

One aspect of the invention pertains to isolated FCTRX proteins, and biologically- active portions thereof, or derivatives, fragments, analogs or homologs thereof. Also provided are polypeptide fragments suitable for use as immunogens to raise anti-FCTRX antibodies. In one embodiment, native FCTRX proteins can be isolated from cells or tissue sources by an appropriate purification scheme using standard protein purification techniques. In another embodiment, FCTRX proteins are produced by recombinant DNA techniques. Alternative to recombinant expression, an FCTRX protein or polypeptide can be synthesized chemically using standard peptide synthesis techniques.

An"isolated"or"purified"polypeptide or protein or biologically-active portion thereof is substantially free of cellular material or other contaminating proteins from the cell or tissue source from which the FCTRX protein is derived, or substantially free from chemical precursors or other chemicals when chemically synthesized. The language"substantially free of cellular material"includes preparations of FCTRX proteins in which the protein is separated from cellular components of the cells from which it is isolated or recombinantly- produced. In one embodiment, the language"substantially free of cellular material"includes preparations of FCTRX proteins having less than about 30% (by dry weight) of non-FCTRX proteins (also referred to herein as a"contaminating protein"), more preferably less than about 20% of non-FCTRX proteins, still more preferably less than about 10% of non-FCTRX proteins, and most preferably less than about 5% of non-FCTRX proteins. When the FCTRX protein or biologically-active portion thereof is recombinantly-produced, it is also preferably substantially free of culture medium, i. e., culture medium represents less than about 20%, more preferably less than about 10%, and most preferably less than about 5% of the volume of the FCTRX protein preparation.

The language"substantially free of chemical precursors or other chemicals"includes preparations of FCTRX proteins in which the protein is separated from chemical precursors or other chemicals that are involved in the synthesis of the protein. In one embodiment, the language"substantially free of chemical precursors or other chemicals"includes preparations

of FCTRX proteins having less than about 30% (by dry weight) of chemical precursors or non-FCTRX chemicals, more preferably less than about 20% chemical precursors or non-FCTRX chemicals, still more preferably less than about 10% chemical precursors or non-FCTRX chemicals, and most preferably less than about 5% chemical precursors or non-FCTRX chemicals.

Biologically-active portions of FCTRX proteins include peptides comprising amino acid sequences sufficiently homologous to or derived from the amino acid sequences of the FCTRX proteins (e. g., the amino acid sequence shown in SEQ ID NOS : 2, 4, 6, 8, 13, 15, 17, 19, 21, 23, and 25) that include fewer amino acids than the full-length FCTRX proteins, and exhibit at least one activity of an FCTRX protein. Typically, biologically-active portions comprise a domain or motif with at least one activity of the FCTRX protein. A biologically- active portion of an FCTRX protein can be a polypeptide which is, for example, 10, 25, 50, 100 or more amino acid residues in length.

Moreover, other biologically-active portions, in which other regions of the protein are deleted, can be prepared by recombinant techniques and evaluated for one or more of the functional activities of a native FCTRX protein.

In an embodiment, the FCTRX protein has an amino acid sequence shown in SEQ ID NOS : 2, 4, 6, 8, 13, 15, 17, 19, 21, 23, and 25. In other embodiments, the FCTRX protein is substantially homologous to SEQ ID NOS : 2, 4, 6, 8, 13, 15, 17, 19, 21, 23, and 25, and retains the functional activity of the protein of SEQ ID NOS : 2, 4, 6, 8, 13, 15, 17, 19, 21, 23, and 25, yet differs in amino acid sequence due to natural allelic variation or mutagenesis, as described in detail, below. Accordingly, in another embodiment, the FCTRX protein is a protein that comprises an amino acid sequence at least about 45% homologous to the amino acid sequence of SEQ ID NOS : 2, 4, 6, 8, 13, 15, 17, 19, 21, 23, and 25, and retains the functional activity of the FCTRX proteins of SEQ ID NOS : 2, 4, 6, 8, 13, 15, 17, 19, 21, 23, and 25.

Determining Homology Between Two or More Sequences To determine the percent homology of two amino acid sequences or of two nucleic acids, the sequences are aligned for optimal comparison purposes (e. g., gaps can be introduced in the sequence of a first amino acid or nucleic acid sequence for optimal alignment with a second amino or nucleic acid sequence). The amino acid residues or nucleotides at corresponding amino acid positions or nucleotide positions are then compared. When a position in the first sequence is occupied by the same amino acid residue or nucleotide as the corresponding position in the second sequence, then the molecules are homologous at that

position (i. e., as used herein amino acid or nucleic acid"homology"is equivalent to amino acid or nucleic acid"identity").

The nucleic acid sequence homology may be determined as the degree of identity between two sequences. The homology may be determined using computer programs known in the art, such as GAP software provided in the GCG program package. See, Needleman and Wunsch, 1970. JMol Biol 48 : 443-453. Using GCG GAP software with the following settings for nucleic acid sequence comparison : GAP creation penalty of 5. 0 and GAP extension penalty of 0. 3, the coding region of the analogous nucleic acid sequences referred to above exhibits a degree of identity preferably of at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 99%, with the CDS (encoding) part of the DNA sequence shown in SEQ ID NOS : 1, 3, 5, 7, 9, 10, 11, 12, 14, 16, 18, 20, 22, and 24.

The tenn"sequence identity"refers to the degree to which two polynucleotide or polypeptide sequences are identical on a residue-by-residue basis over a particular region of comparison. The term"percentage of sequence identity"is calculated by comparing two optimally aligned sequences over that region of comparison, determining the number of positions at which the identical nucleic acid base (e. g., A, T, C, G, U, or I, in the case of nucleic acids) occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the region of comparison (i. e., the window size), and multiplying the result by 100 to yield the percentage of sequence identity. The term"substantial identity"as used herein denotes a characteristic of a polynucleotide sequence, wherein the polynucleotide comprises a sequence that has at least 80 percent sequence identity, preferably at least 85 percent identity and often 90 to 95 percent sequence identity, more usually at least 99 percent sequence identity as compared to a reference sequence over a comparison region.

Chimeric and Fusion Proteins The invention also provides FCTRX chimeric or fusion proteins. As used herein, an FCTRX"chimeric protein"or"fusion protein"comprises an FCTRX polypeptide operatively- linked to a non-FCTRX polypeptide. An"FCTRX polypeptide"refers to a polypeptide having an amino acid sequence corresponding to an FCTRX protein (SEQ ID NOS : 2, 4, 6, 8, 13, 15, 17, 19, 21, 23, and 25), whereas a"non-FCTRX polypeptide"refers to a polypeptide having an amino acid sequence corresponding to a protein that is not substantially homologous to the FCTRX protein, e. g., a protein that is different from the FCTRX protein and that is derived from the same or a different organism. Within an FCTRX fusion protein the FCTRX polypeptide can correspond to all or a portion of an FCTRX protein. In one embodiment, an

FCTRX fusion protein comprises at least one biologically-active portion of an FCTRX protein. In another embodiment, an FCTRX fusion protein comprises at least two biologically-active portions of an FCTRX protein. In yet another embodiment, an FCTRX fusion protein comprises at least three biologically-active portions of an FCTRX protein.

Within the fusion protein, the term"operatively-linked"is intended to indicate that the FCTRX polypeptide and the non-FCTRX polypeptide are fused in-frame with one another.

The non-FCTRX polypeptide can be fused to the N-terminus or C-terminus of the FCTRX polypeptide.

In one embodiment, the fusion protein is a GST-FCTRX fusion protein in which the FCTRX sequences are fused to the C-terminus of the GST (glutathione S-transferase) sequences. Such fusion proteins can facilitate the purification of recombinant FCTRX polypeptides.

In another embodiment, the fusion protein is an FCTRX protein containing a heterologous signal sequence at its N-terminus. In certain host cells (e. g., mammalian host cells), expression and/or secretion of FCTRX can be increased through use of a heterologous signal sequence.

In yet another embodiment, the fusion protein is an FCTRX-immunoglobulin fusion protein in which the FCTRX sequences are fused to sequences derived from a member of the immunoglobulin protein family. The FCTRX-immunoglobulin fusion proteins of the invention can be incorporated into pharmaceutical compositions and administered to a subject to inhibit an interaction between an FCTRX ligand and an FCTRX protein on the surface of a cell, to thereby suppress FCTRX-mediated signal transduction in vivo. The FCTRX- immunoglobulin fusion proteins can be used to affect the bioavailability of an FCTRX cognate ligand. Inhibition of the FCTRX ligand/FCTRX interaction may be useful therapeutically for both the treatment of proliferative and differentiative disorders, as well as modulating (e. g. promoting or inhibiting) cell survival. Moreover, the FCTRX-immunoglobulin fusion proteins of the invention can be used as immunogens to produce anti-FCTRX antibodies in a subject, to purify FCTRX ligands, and in screening assays to identify molecules that inhibit the interaction of FCTRX with an FCTRX ligand.

An FCTRX chimeric or fusion protein of the invention can be produced by standard recombinant DNA techniques. For example, DNA fragments coding for the different polypeptide sequences are ligated together in-frame in accordance with conventional techniques, e. g., by employing blunt-ended or stagger-ended termini for ligation, restriction enzyme digestion to provide for appropriate termini, filling-in of cohesive ends as appropriate,

alkaline phosphatase treatment to avoid undesirable joining, and enzymatic ligation. In another embodiment, the fusion gene can be synthesized by conventional techniques including automated DNA synthesizers. Alternatively, PCR amplification of gene fragments can be carried out using anchor primers that give rise to complementary overhangs between two consecutive gene fragments that can subsequently be annealed and reamplified to generate a chimeric gene sequence (see, e. g., Ausubel, et al. (eds.) CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, 1992). Moreover, many expression vectors are commercially available that already encode a fusion moiety (e. g., a GST polypeptide). An FCTRX-encoding nucleic acid can be cloned into such an expression vector such that the fusion moiety is linked in-frame to the FCTRX protein.

FCTRXAgonists and Antagonists The invention also pertains to variants of the FCTRX proteins that function as either FCTRX agonists (i. e., mimetics) or as FCTRX antagonists. Variants of the FCTRX protein can be generated by mutagenesis (e. g., discrete point mutation or truncation of the FCTRX protein). An agonist of the FCTRX protein can retain substantially the same, or a subset of, the biological activities of the naturally occurring form of the FCTRX protein. An antagonist of the FCTRX protein can inhibit one or more of the activities of the naturally occurring form of the FCTRX protein by, for example, competitively binding to a downstream or upstream member of a cellular signaling cascade which includes the FCTRX protein. Thus, specific biological effects can be elicited by treatment with a variant of limited function. In one embodiment, treatment of a subject with a variant having a subset of the biological activities of the naturally occurring form of the protein has fewer side effects in a subject relative to treatment with the naturally occurring form of the FCTRX proteins.

Variants of the FCTRX proteins that function as either FCTRX agonists (i. e., mimics) or as FCTRX antagonists can be identified by screening combinatorial libraries of mutants (e. g., truncation mutants) of the FCTRX proteins for FCTRX protein agonist or antagonist activity. In one embodiment, a variegated library of FCTRX variants is generated by combinatorial mutagenesis at the nucleic acid level and is encoded by a variegated gene library. A variegated library of FCTRX variants can be produced by, for example, enzymatically ligating a mixture of synthetic oligonucleotides into gene sequences such that a degenerate set of potential FCTRX sequences is expressible as individual polypeptides, or alternatively, as a set of larger fusion proteins (e. g., for phage display) containing the set of FCTRX sequences therein. There are a variety of methods which can be used to produce libraries of potential FCTRX variants from a degenerate oligonucleotide sequence. Chemical

synthesis of a degenerate gene sequence can be performed in an automatic DNA synthesizer, and the synthetic gene then ligated into an appropriate expression vector. Use of a degenerate set of genes allows for the provision, in one mixture, of all of the sequences encoding the desired set of potential FCTRX sequences. Methods for synthesizing degenerate oligonucleotides are well-known within the art. See, e. g., Narang, 1983. Tetrahedron 39 : 3 ; Itakura, et al., 1984. Annu. Rev. Biochem. 53 : 323 ; Itakura, et al., 1984. Science 198 : 1056 ; Ike, et al., 1983. Nucl. Acids Res. 11 : 477.

Polypeptide Libraries In addition, libraries of fragments of the FCTRX protein coding sequences can be used to generate a variegated population of FCTRX fragments for screening and subsequent selection of variants of an FCTRX protein. In one embodiment, a library of coding sequence fragments can be generated by treating a double stranded PCR fragment of an FCTRX coding sequence with a nuclease under conditions wherein nicking occurs only about once per molecule, denaturing the double stranded DNA, renaturing the DNA to form double-stranded DNA that can include sense/antisense pairs from different nicked products, removing single stranded portions from reformed duplexes by treatment with Si nuclease, and ligating the resulting fragment library into an expression vector. By this method, expression libraries can be derived which encodes N-terminal and internal fragments of various sizes of the FCTRX proteins.

Various techniques are known in the art for screening gene products of combinatorial libraries made by point mutations or truncation, and for screening cDNA libraries for gene products having a selected property. Such techniques are adaptable for rapid screening of the gene libraries generated by the combinatorial mutagenesis of FCTRX proteins. The most widely used techniques, which are amenable to high throughput analysis, for screening large gene libraries typically include cloning the gene library into replicable expression vectors, transforming appropriate cells with the resulting library of vectors, and expressing the combinatorial genes under conditions in which detection of a desired activity facilitates isolation of the vector encoding the gene whose product was detected. Recursive ensemble mutagenesis (REM), a new technique that enhances the frequency of functional mutants in the libraries, can be used in combination with the screening assays to identify FCTRX variants.

See, e. g., Arkin and Yourvan, 1992. Proc. Natl. Acad. Sci. USA 89 : 7811-7815 ; Delgrave, et al., 1993. Protein Engineering 6 : 327-331.

Anti-FCTRX Antibodies The invention encompasses antibodies and antibody fragments, such as Fab or (Fab) 2, that bind immunospecifically to any of the FCTRX polypeptides of said invention.

An isolated FCTRX protein, or a portion or fragment thereof, can be used as an immunogen to generate antibodies that bind to FCTRX polypeptides using standard techniques for polyclonal and monoclonal antibody preparation. The full-length FCTRX proteins can be used or, alternatively, the invention provides antigenic peptide fragments of FCTRX proteins for use as immunogens. The antigenic FCTRX peptides comprises at least 4 amino acid residues of the amino acid sequence shown in SEQ ID NO NOS : 2, 4, 6, 8, 13, 15, 17, 19, 21, 23, and 25, and encompasses an epitope of FCTRX such that an antibody raised against the peptide forms a specific immune complex with FCTRX. Preferably, the antigenic peptide comprises at least 6, 8, 10, 15, 20, or 30 amino acid residues. Longer antigenic peptides are sometimes preferable over shorter antigenic peptides, depending on use and according to methods well known to someone skilled in the art.

In certain embodiments of the invention, at least one epitope encompassed by the antigenic peptide is a region of FCTRX that is located on the surface of the protein (e. g., a hydrophilic region). As a means for targeting antibody production, hydropathy plots showing regions of hydrophilicity and hydrophobicity may be generated by any method well known in the art, including, for example, the Kyte Doolittle or the Hopp Woods methods, either with or without Fourier transformation (see, e. g., Hopp and Woods, 1981. Proc. Nat. Acad. Sci. USA 78 : 3824-3828 ; Kyte and Doolittle, 1982. J. Mol. Biol. 157 : 105-142, each incorporated herein by reference in their entirety).

As disclosed herein, FCTRX protein sequences of SEQ ID NOS : 2, 4, 6, 8, 13, 15, 17, 19, 21, 23, and 25, or derivatives, fragments, analogs or homologs thereof, may be utilized as immunogens in the generation of antibodies that immunospecifically-bind these protein components. The term"antibody"as used herein refers to immunoglobulin molecules and immunologically-active portions of immunoglobulin molecules, i. e., molecules that contain an antigen binding site that specifically-binds (immunoreacts with) an antigen, such as FCTRX.

Such antibodies include, but are not limited to, polyclonal, monoclonal, chimeric, single chain, Fab and F (ab') 2 fragments, and an Fab expression library. In a specific embodiment, antibodies to human FCTRX proteins are disclosed. Various procedures known within the art may be used for the production of polyclonal or monoclonal antibodies to an FCTRX protein sequence of SEQ ID NOS : 2, 4, 6, 8, 13, 15, 17, 19, 21, 23, and 25, or a derivative, fragment, analog or homolog thereof. Some of these proteins are discussed below.

For the production of polyclonal antibodies, various suitable host animals (e. g., rabbit, goat, mouse or other mammal) may be immunized by injection with the native protein, or a synthetic variant thereof, or a derivative of the foregoing. An appropriate immunogenic preparation can contain, for example, recombinantly-expressed FCTRX protein or a chemically-synthesized FCTRX polypeptide. The preparation can further include an adjuvant.

Various adjuvants used to increase the immunological response include, but are not limited to, Freund's (complete and incomplete), mineral gels (e. g., aluminum hydroxide), surface active substances (e. g., lysolecithin, pluronic polyols, polyanions, peptides, oil emulsions, dinitrophenol, etc.), human adjuvants such as Bacille Calmette-Guerin and Corynebacterium parvum, or similar immunostimulatory agents. If desired, the antibody molecules directed against FCTRX can be isolated from the mammal (e. g., from the blood) and further purified by well known techniques, such as protein A chromatography to obtain the IgG fraction.

The term"monoclonal antibody"or"monoclonal antibody composition", as used herein, refers to a population of antibody molecules that contain only one species of an antigen binding site capable of immunoreacting with a particular epitope of FCTRX. A monoclonal antibody composition thus typically displays a single binding affinity for a particular FCTRX protein with which it immunoreacts. For preparation of monoclonal antibodies directed towards a particular FCTRX protein, or derivatives, fragments, analogs or homologs thereof, any technique that provides for the production of antibody molecules by continuous cell line culture may be utilized. Such techniques include, but are not limited to, the hybridoma technique (see, e. g., Kohler & Milstein, 1975. Nature 256 : 495-497) ; the trioma technique ; the human B-cell hybridoma technique (see, e. g., Kozbor, et al., 1983. Immunol. Today 4 : 72) and the EBV hybridoma technique to produce human monoclonal antibodies (see, e. g., Cole, et al., 1985. In : MONOCLONAL ANTIBODIES AND CANCER THERAPY, Alan R. Liss, Inc., pp. 77-96).

Human monoclonal antibodies may be utilized in the practice of the invention and may be produced by using human hybridomas (see, e. g., Cote, et al., 1983. Proc Natl Acad Sci USA 80 : 2026-2030) or by transforming human B-cells with Epstein Barr Virus in vitro (see, e. g., Cole, et al., 1985. In : MONOCLONAL ANTIBODIES AND CANCER THERAPY, Alan R. Liss, Inc., pp. 77-96). Each of the above citations is incorporated herein by reference in their entirety.

According to the invention, techniques can be adapted for the production of single-chain antibodies specific to an FCTRX protein (see, e. g., U. S. Patent No. 4, 946, 778).

In addition, methods can be adapted for the construction of Fab expression libraries (see, e. g., Huse, et al., 1989. Science 246 : 1275-1281) to allow rapid and effective identification of monoclonal Fab fragments with the desired specificity for an FCTRX protein or derivatives,

fragments, analogs or homologs thereof. Non-human antibodies can be"humanized"by techniques well known in the art. See, e. g., U. S. Patent No. 5, 225, 539. Antibody fragments that contain the idiotypes to an FCTRX protein may be produced by techniques known in the art including, but not limited to : (i) all Fab') 2 fragment produced by pepsin digestion of an antibody molecule ; (ii) an Fab fragment generated by reducing the disulfide bridges of an F (ab') 2 fragment ; (iii) an Fab fragment generated by the treatment of the antibody molecule with papain and a reducing agent ; and (iv) F, fragments.

Additionally, recombinant anti-FCTRX antibodies, such as chimeric and humanized monoclonal antibodies, comprising both human and non-human portions, which can be made using standard recombinant DNA techniques, are within the scope of the invention. Such chimeric and humanized monoclonal antibodies can be produced by recombinant DNA techniques known in the art, for example using methods described in International Application No. PCT/US86/02269 ; European Patent Application No. 184, 187 ; European Patent Application No. 171, 496 ; European Patent Application No. 173, 494 ; PCT International Publication No. WO 86/01533 ; U. S. Patent No. 4, 816, 567 ; U. S. Pat. No. 5, 225, 539 ; European Patent Application No. 125, 023 ; Better, et al., 1988. Science 240 : 1041-1043 ; Liu, et al., 1987.

Proc. Natl. Acad. Sci. USA 84 : 3439-3443 ; Liu, et al., 1987. J. Immunol. 139 : 3521-3526 ; Sun, et al., 1987. Proc. Natl. Acad. Sci. USA 84 : 214-218 ; Nishimura, et al., 1987. Cancer Res. 47 : 999-1005 ; Wood, et al., 1985. Nature 314 : 446-449 ; Shaw, et al., 1988. J. Natl. Cancer Inst.

80 : 1553-1559) ; Morrison (1985) Science 229 : 1202-1207 ; Oi, et al. (1986) BioTechniques 4 : 214 ; Jones, et al., 1986. Nature 321 : 552-525 ; Verhoeyan, et al., 1988. Science 239 : 1534 ; and Beidler, et al., 1988. J. Immunol. 141 : 4053-4060. Each of the above citations are incorporated herein by reference in their entirety.

In one embodiment, methods for the screening of antibodies that possess the desired specificity include, but are not limited to, enzyme-linked immunosorbent assay (ELISA) and other immunologically-mediated techniques known within the art. In a specific embodiment, selection of antibodies that are specific to a particular domain of an FCTRX protein is facilitated by generation of hybridomas that bind to the fragment of an FCTRX protein possessing such a domain. Thus, antibodies that are specific for a desired domain within an FCTRX protein, or derivatives, fragments, analogs or homologs thereof, are also provided herein.

Anti-FCTRX antibodies may be used in methods known within the art relating to the localization and/or quantitation of an FCTRX protein (e. g., for use in measuring levels of the FCTRX protein within appropriate physiological samples, for use in diagnostic methods, for

use in imaging the protein, and the like). In a given embodiment, antibodies for FCTRX proteins, or derivatives, fragments, analogs or homologs thereof, that contain the antibody derived binding domain, are utilized as pharmacologically-active compounds (hereinafter "Therapeutics").

An anti-FCTRX antibody (e. g., monoclonal antibody) can be used to isolate an FCTRX polypeptide by standard techniques, such as affinity chromatography or immunoprecipitation. An anti-FCTRX antibody can facilitate the purification of natural FCTRX polypeptide from cells and of recombinantly-produced FCTRX polypeptide expressed in host cells. Moreover, an anti-FCTRX antibody can be used to detect FCTRX protein (e. g., in a cellular lysate or cell supernatant) in order to evaluate the abundance and pattern of expression of the FCTRX protein. Anti-FCTRX antibodies can be used diagnostically to monitor protein levels in tissue as part of a clinical testing procedure, e. g., to, for example, determine the efficacy of a given treatment regimen. Detection can be facilitated by coupling (i. e., physically linking) the antibody to a detectable substance. Examples of detectable substances include various enzymes, prosthetic groups, fluorescent materials, luminescent materials, bioluminescent materials, and radioactive materials. Examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, p-galactosidase, or acetylcholinesterase ; examples of suitable prosthetic group complexes include streptavidin/biotin and avidin/biotin ; examples of suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin ; an example of a luminescent material includes luminol ; examples of bioluminescent materials include luciferase, luciferin, and aequorin, and examples of suitable radioactive material include 1, 1, S or H.

FCTRX Recombinant Expression Vectors and Host Cells Another aspect of the invention pertains to vectors, preferably expression vectors, containing a nucleic acid encoding an FCTRX protein, or derivatives, fragments, analogs or homologs thereof. As used herein, the term"vector"refers to a nucleic acid molecule capable of transporting another nucleic acid to which it has been linked. One type of vector is a "plasmid", which refers to a circular double stranded DNA loop into which additional DNA segments can be ligated. Another type of vector is a viral vector, wherein additional DNA segments can be ligated into the viral genome. Certain vectors are capable of autonomous replication in a host cell into which they are introduced (e. g., bacterial vectors having a bacterial origin of replication and episomal mammalian vectors). Other vectors (e. g.,

non-episomal mammalian vectors) are integrated into the genome of a host cell upon introduction into the host cell, and thereby are replicated along with the host genome.

Moreover, certain vectors are capable of directing the expression of genes to which they are operatively-linked. Such vectors are referred to herein as"expression vectors". In general, expression vectors of utility in recombinant DNA techniques are often in the form of plasmids.

In the present specification,"plasmid"and"vector"can be used interchangeably as the plasmid is the most commonly used form of vector. However, the invention is intended to include such other forms of expression vectors, such as viral vectors (e. g., replication defective retroviruses, adenoviruses and adeno-associated viruses), which serve equivalent functions.

The recombinant expression vectors of the invention comprise a nucleic acid of the invention in a form suitable for expression of the nucleic acid in a host cell, which means that the recombinant expression vectors include one or more regulatory sequences, selected on the basis of the host cells to be used for expression, that is operatively-linked to the nucleic acid sequence to be expressed. Within a recombinant expression vector,"operably-linked"is intended to mean that the nucleotide sequence of interest is linked to the regulatory sequence (s) in a manner that allows for expression of the nucleotide sequence (e. g., in an in vitro transcription/translation system or in a host cell when the vector is introduced into the host cell).

The term"regulatory sequence"is intended to includes promoters, enhancers and other expression control elements (e. g., polyadenylation signals). Such regulatory sequences are described, for example, in Goeddel, GENE EXPRESSION TECHNOLOGY : METHODS IN ENZYMOLOGY 185, Academic Press, San Diego, Calif. (1990). Regulatory sequences include those that direct constitutive expression of a nucleotide sequence in many types of host cell and those that direct expression of the nucleotide sequence only in certain host cells (e. g., tissue-specific regulatory sequences). It will be appreciated by those skilled in the art that the design of the expression vector can depend on such factors as the choice of the host cell to be transformed, the level of expression of protein desired, etc. The expression vectors of the invention can be introduced into host cells to thereby produce proteins or peptides, including fusion proteins or peptides, encoded by nucleic acids as described herein (e. g., FCTRX proteins, mutant forms of FCTRX proteins, fusion proteins, etc.).

The recombinant expression vectors of the invention can be designed for expression of FCTRX proteins in prokaryotic or eukaryotic cells. For example, FCTRX proteins can be expressed in bacterial cells such as Escherichia coli, insect cells (using baculovirus expression vectors) yeast cells or mammalian cells. Suitable host cells are discussed further in Goeddel,

GENE EXPRESSION TECHNOLOGY : METHODS IN ENZYMOLOGY 185, Academic Press, San Diego, Calif. (1990). Alternatively, the recombinant expression vector can be transcribed and translated in vitro, for example using T7 promoter regulatory sequences and T7 polymerase.

Expression of proteins in prokaryotes is most often carried out in Escherichia coli with vectors containing constitutive or inducible promoters directing the expression of either fusion or non-fusion proteins. Fusion vectors add a number of amino acids to a protein encoded therein, usually to the amino terminus of the recombinant protein. Such fusion vectors typically serve three purposes : (i) to increase expression of recombinant protein ; (ii) to increase the solubility of the recombinant protein ; and (iii) to aid in the purification of the recombinant protein by acting as a ligand in affinity purification. Often, in fusion expression vectors, a proteolytic cleavage site is introduced at the junction of the fusion moiety and the recombinant protein to enable separation of the recombinant protein from the fusion moiety subsequent to purification of the fusion protein. Such enzymes, and their cognate recognition sequences, include Factor Xa, thrombin and enterokinase. Typical fusion expression vectors include pGEX (Pharmacia Biotech Inc ; Smith and Johnson, 1988. Gene 67 : 31-40), pMAL (New England Biolabs, Beverly, Mass.) and pRIT5 (Pharmacia, Piscataway, N. J.) that fuse glutathione S-transferase (GST), maltose E binding protein, or protein A, respectively, to the target recombinant protein.

Examples of suitable inducible non-fusion E. coli expression vectors include pTrc (Amrann et al., (1988) Gene 69 : 301-315) and pET l ld (Studier et al., GENE EXPRESSION TECHNOLOGY : METHODS IN ENZYMOLOGY 185, Academic Press, San Diego, Calif. (1990) 60-89).

One strategy to maximize recombinant protein expression in E. coli is to express the protein in a host bacteria with an impaired capacity to proteolytically cleave the recombinant protein. See, e. g., Gottesman, GENE EXPRESSION TECHNOLOGY : METHODS IN ENZYMOLOGY 185, Academic Press, San Diego, Calif. (1990) 119-128. Another strategy is to alter the nucleic acid sequence of the nucleic acid to be inserted into an expression vector so that the individual codons for each amino acid are those preferentially utilized in E. coli (see, e. g., Wada, et al., 1992. Nucl. Acids Res. 20 : 2111-2118). Such alteration of nucleic acid sequences of the invention can be carried out by standard DNA synthesis techniques.

In another embodiment, the FCTRX expression vector is a yeast expression vector.

Examples of vectors for expression in yeast Saccharomyces cerivisae include pYepSecl (Baldari, et al., 1987. EMBO J. 6 : 229-234), pMFa (Kurjan and Herskowitz, 1982. Cell 30 :

933-943), pJRY88 (Schultz et al., 1987. Gene 54 : 113-123), pYES2 (Invitrogen Corporation, San Diego, Calif.), and picZ (InVitrogen Corp, San Diego, Calif.).

Alternatively, FCTRX can be expressed in insect cells using baculovirus expression vectors. Baculovirus vectors available for expression of proteins in cultured insect cells (e. g., SF9 cells) include the pAc series (Smith, et al., 1983. Mol. Cell. Biol. 3 : 2156-2165) and the pVL series (Lucklow and Summers, 1989. Virology 170 : 31-39).

In yet another embodiment, a nucleic acid of the invention is expressed in mammalian cells using a mammalian expression vector. Examples of mammalian expression vectors include pCDM8 (Seed, 1987. Nature 329 : 840) and pMT2PC (Kaufman, et al., 1987. EMBO J 6 : 187-195). When used in mammalian cells, the expression vector's control functions are often provided by viral regulatory elements. For example, commonly used promoters are derived from polyoma, adenovirus 2, cytomegalovirus, and simian virus 40. For other suitable expression systems for both prokaryotic and eukaryotic cells see, e. g., Chapters 16 and 17 of Sambrook, et al., MOLECULAR CLONING : A LABORATORY MANUAL. 2nd ed., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N. Y., 1989.

In another embodiment, the recombinant mammalian expression vector is capable of directing expression of the nucleic acid preferentially in a particular cell type (e. g., tissue-specific regulatory elements are used to express the nucleic acid). Tissue-specific regulatory elements are known in the art. Non-limiting examples of suitable tissue-specific promoters include the albumin promoter (liver-specific ; Pinkert, et al., 1987. Genes Dev. 1 : 268-277), lymphoid-specific promoters (Calame and Eaton, 1988. Adv. Immunol. 43 : 235-275), in particular promoters of T cell receptors (Winoto and Baltimore, 1989. EMBO J.

8 : 729-733) and immunoglobulins (Banerji, et al., 1983. Cell 33 : 729-740 ; Queen and Baltimore, 1983. Cell 33 : 741-748), neuron-specific promoters (e. g., the neurofilament promoter ; Byme and Ruddle, 1989. Proc. Natl. Acad. Sci. USA 86 : 5473-5477), pancreas-specific promoters (Edlund, et al., 1985. Science 230 : 912-916), and mammary gland-specific promoters (e. g., milk whey promoter ; U. S. Pat. No. 4, 873, 316 and European Application Publication No. 264, 166). Developmentally-regulated promoters are also encompassed, e. g, the murine hox promoters (Kessel and Gruss, 1990. Science 249 : 374-379) and the oc-fetoprotein promoter (Campes and Tilghman, 1989. Genes Dev. 3 : 537-546).

The invention further provides a recombinant expression vector comprising a DNA molecule of the invention cloned into the expression vector in an antisense orientation. That is, the DNA molecule is operatively-linked to a regulatory sequence in a manner that allows for expression (by transcription of the DNA molecule) of an RNA molecule that is antisense to

FCTRX mRNA. Regulatory sequences operatively linked to a nucleic acid cloned in the antisense orientation can be chosen that direct the continuous expression of the antisense RNA molecule in a variety of cell types, for instance viral promoters and/or enhancers, or regulatory sequences can be chosen that direct constitutive, tissue specific or cell type specific expression of antisense RNA. The antisense expression vector can be in the form of a recombinant plasmid, phagemid or attenuated virus in which antisense nucleic acids are produced under the control of a high efficiency regulatory region, the activity of which can be determined by the cell type into which the vector is introduced. For a discussion of the regulation of gene expression using antisense genes see, e. g., Weintraub, et al.,"Antisense RNA as a molecular tool for genetic analysis,"Reviews-Trehds in Genetics, Vol. 1 (1) 1986.

Another aspect of the invention pertains to host cells into which a recombinant expression vector of the invention has been introduced. The terms"host cell"and "recombinant host cell"are used interchangeably herein. It is understood that such terms refer not only to the particular subject cell but also to the progeny or potential progeny of such a cell. Because certain modifications may occur in succeeding generations due to either mutation or environmental influences, such progeny may not, in fact, be identical to the parent cell, but are still included within the scope of the term as used herein.

A host cell can be any prokaryotic or eukaryotic cell. For example, FCTRX protein can be expressed in bacterial cells such as E. coli, insect cells, yeast or mammalian cells (such as Chinese hamster ovary cells (CHO) or COS cells). Other suitable host cells are known to those skilled in the art.

Vector DNA can be introduced into prokaryotic or eukaryotic cells via conventional transformation or transfection techniques. As used herein, the terms"transformation"and "transfection"are intended to refer to a variety of art-recognized techniques for introducing foreign nucleic acid (e. g., DNA) into a host cell, including calcium phosphate or calcium chloride co-precipitation, DEAE-dextran-mediated transfection, lipofection, or electroporation. Suitable methods for transforming or transfecting host cells can be found in Sambrook, et al. (MOLECULAR CLONING : A LABORATORY MANUAL. 2nd ed., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N. Y., 1989), and other laboratory manuals.

For stable transfection of mammalian cells, it is known that, depending upon the expression vector and transfection technique used, only a small fraction of cells may integrate the foreign DNA into their genome. In order to identify and select these integrants, a gene that encodes a selectable marker (e. g., resistance to antibiotics) is generally introduced into the

host cells along with the gene of interest. Various selectable markers include those that confer resistance to drugs, such as G418, hygromycin and methotrexate. Nucleic acid encoding a selectable marker can be introduced into a host cell on the same vector as that encoding FCTRX or can be introduced on a separate vector. Cells stably transfected with the introduced nucleic acid can be identified by drug selection (e. g., cells that have incorporated the selectable marker gene will survive, while the other cells die).

A host cell of the invention, such as a prokaryotic or eukaryotic host cell in culture, can be used to produce (i. e., express) FCTRX protein. Accordingly, the invention further provides methods for producing FCTRX protein using the host cells of the invention. In one embodiment, the method comprises culturing the host cell of invention (into which a recombinant expression vector encoding FCTRX protein has been introduced) in a suitable medium such that FCTRX protein is produced. In another embodiment, the method further comprises isolating FCTRX protein from the medium or the host cell.

Transgenic FCTRX Animals The host cells of the invention can also be used to produce non-human transgenic animals. For example, in one embodiment, a host cell of the invention is a fertilized oocyte or an embryonic stem cell into which FCTRX protein-coding sequences have been introduced.

Such host cells can then be used to create non-human transgenic animals in which exogenous FCTRX sequences have been introduced into their genome or homologous recombinant animals in which endogenous FCTRX sequences have been altered. Such animals are useful for studying the function and/or activity of FCTRX protein and for identifying and/or evaluating modulators of FCTRX protein activity. As used herein, a"transgenic animal"is a non-human animal, preferably a mammal, more preferably a rodent such as a rat or mouse, in which one or more of the cells of the animal includes a transgene. Other examples of transgenic animals include non-human primates, sheep, dogs, cows, goats, chickens, amphibians, etc. A transgene is exogenous DNA that is integrated into the genome of a cell from which a transgenic animal develops and that remains in the genome of the mature animal, thereby directing the expression of an encoded gene product in one or more cell types or tissues of the transgenic animal. As used herein, a"homologous recombinant animal"is a non-human animal, preferably a mammal, more preferably a mouse, in which an endogenous FCTRX gene has been altered by homologous recombination between the endogenous gene and an exogenous DNA molecule introduced into a cell of the animal, e. g., an embryonic cell of the animal, prior to development of the animal.

A transgenic animal of the invention can be created by introducing FCTRX-encoding nucleic acid into the male pronuclei of a fertilized oocyte (e. g., by microinjection, retroviral infection) and allowing the oocyte to develop in a pseudopregnant female foster animal. The human FCTRX cDNA sequences of SEQ ID NOS : 1, 3, 5, 7, 9, 10, 11, 12, 14, 16, 18, 20, 22, and 24, can be introduced as a transgene into the genome of a non-human animal.

Alternatively, a non-human homologue of the human FCTRX gene, such as a mouse FCTRX gene, can be isolated based on hybridization to the human FCTRX cDNA (described further supra) and used as a transgene. Intronic sequences and polyadenylation signals can also be included in the transgene to increase the efficiency of expression of the transgene. A tissue-specific regulatory sequence (s) can be operably-linked to the FCTRX transgene to direct expression of FCTRX protein to particular cells. Methods for generating transgenic animals via embryo manipulation and microinjection, particularly animals such as mice, have become conventional in the art and are described, for example, in U. S. Patent Nos. 4, 736, 866 ; 4, 870, 009 ; and 4, 873, 191 ; and Hogan, 1986. In : MANIPULATING THEMousE EMBRYO, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N. Y. Similar methods are used for production of other transgenic animals. A transgenic founder animal can be identified based upon the presence of the FCTRX transgene in its genome and/or expression of FCTRX mRNA in tissues or cells of the animals. A transgenic founder animal can then be used to breed additional animals carrying the transgene. Moreover, transgenic animals carrying a transgene- encoding FCTRX protein can further be bred to other transgenic animals carrying other transgenes.

To create a homologous recombinant animal, a vector is prepared which contains at least a portion of an FCTRX gene into which a deletion, addition or substitution has been introduced to thereby alter, e. g., functionally disrupt, the FCTRX gene. The FCTRX gene can be a human gene (e. g., the cDNA of SEQ ID NOS : 1, 3, 5, 7, 9, 10, 11, 12, 14, 16, 18, 20, 22, and 24), but more preferably, is a non-human homologue of a human FCTRX gene. For example, a mouse homologue of human FCTRX gene of SEQ ID NOS : 1, 3, 5, 7, 9, 10, 11, 12, 14, 16, 18, 20, 22, and 24, can be used to construct a homologous recombination vector suitable for altering an endogenous FCTRX gene in the mouse genome. In one embodiment, the vector is designed such that, upon homologous recombination, the endogenous FCTRX gene is functionally disrupted (i. e., no longer encodes a functional protein ; also referred to as a "knock out"vector).

Alternatively, the vector can be designed such that, upon homologous recombination, the endogenous FCTRX gene is mutated or otherwise altered but still encodes functional

protein (e. g., the upstream regulatory region can be altered to thereby alter the expression of the endogenous FCTRX protein). In the homologous recombination vector, the altered portion of the FCTRX gene is flanked at its 5'-and 3'-termini by additional nucleic acid of the FCTRX gene to allow for homologous recombination to occur between the exogenous FCTRX gene carried by the vector and an endogenous FCTRX gene in an embryonic stem cell. The additional flanking FCTRX nucleic acid is of sufficient length for successful homologous recombination with the endogenous gene. Typically, several kilobases of flanking DNA (both at the 5'-and 3'-termini) are included in the vector. See, e. g, Thomas, et al., 1987. Cell 51 : 503 for a description of homologous recombination vectors. The vector is ten introduced into an embryonic stem cell line (e. g., by electroporation) and cells in which the introduced FCTRX gene has homologously-recombined with the endogenous FCTRX gene are selected.

See, e. g., Li, et al., 1992. Cell 69 : 915.

The selected cells are then injected into a blastocyst of an animal (e. g., a mouse) to form aggregation chimeras. See, e. g., Bradley, 1987. In : TERATOCARCINOMAS AND EMBRYONIC STEM CELLS : A PRACTICAL APPROACH, Robertson, ed. IRL, Oxford, pp. 113-152.

A chimeric embryo can then be implanted into a suitable pseudopregnant female foster animal and the embryo brought to term. Progeny harboring the homologously-recombined DNA in their germ cells can be used to breed animals in which all cells of the animal contain the homologously-recombined DNA by germline transmission of the transgene. Methods for constructing homologous recombination vectors and homologous recombinant animals are described further in Bradley, 1991. Curr. Opin. Biotechnol. 2 : 823-829 ; PCT International Publication Nos. : WO 90/11354 ; WO 91/01140 ; WO 92/0968 ; and WO 93/04169.

In another embodiment, transgenic non-humans animals can be produced that contain selected systems that allow for regulated expression of the transgene. One example of such a system is the cre/loxP recombinase system of bacteriophage Pl. For a description of the cre/loxP recombinase system, See, e. g., Lakso, et al., 1992. Proc. Natl. Acad Sci. USA 89 : 6232-6236. Another example of a recombinase system is the FLP recombinase system of Saccharomyces cerevisiae. See, O'Gorman, et al., 1991. Science 251 : 1351-1355. If a cre/loxP recombinase system is used to regulate expression of the transgene, animals containing transgenes encoding both the Cre recombinase and a selected protein are required. Such animals can be provided through the construction of"double"transgenic animals, e. g., by mating two transgenic animals, one containing a transgene encoding a selected protein and the other containing a transgene encoding a recombinase.

Clones of the non-human transgenic animals described herein can also be produced according to the methods described in Wilmut, et al., 1997. Nature 385 : 810-813. In brief, a cell (e. g., a somatic cell) from the transgenic animal can be isolated and induced to exit the growth cycle and enter Go phase. The quiescent cell can then be fused, e. g., through the use of electrical pulses, to an enucleated oocyte from an animal of the same species from which the quiescent cell is isolated. The reconstructed oocyte is then cultured such that it develops to morula or blastocyte and then transferred to pseudopregnant female foster animal. The offspring borne of this female foster animal will be a clone of the animal from which the cell (e. g., the somatic cell) is isolated.

Pharmaceutical Compositions The FCTRX nucleic acid molecules, FCTRX proteins, and anti-FCTRX antibodies (also referred to herein as"active compounds") of the invention, and derivatives, fragments, analogs and homologs thereof, can be incorporated into pharmaceutical compositions suitable for administration. Such compositions typically comprise the nucleic acid molecule, protein, or antibody and a pharmaceutically acceptable carrier. As used herein,"pharmaceutically acceptable carriers intended to include any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like, compatible with pharmaceutical administration. Suitable carriers are described in the most recent edition of Remington's Pharmaceutical Sciences, a standard reference text in the field, which is incorporated herein by reference. Preferred examples of such carriers or diluents include, but are not limited to, water, saline, finger's solutions, dextrose solution, and 5% human serum albumin. Liposomes and non-aqueous vehicles such as fixed oils may also be used. The use of such media and agents for pharmaceutically active substances is well known in the art. Except insofar as any conventional media or agent is incompatible with the active compound, use thereof in the compositions is contemplated. Supplementary active compounds can also be incorporated into the compositions.

A pharmaceutical composition of the invention is formulated to be compatible with its intended route of administration. Examples of routes of administration include parenteral, e. g., intravenous, intradermal, subcutaneous, oral (e. g., inhalation), transdermal (i. e., topical), transmucosal, and rectal administration. Solutions or suspensions used for parenteral, intradermal, or subcutaneous application can include the following components : a sterile diluent such as water for injection, saline solution, fixed oils, polyethylene glycols, glycerine, propylene glycol or other synthetic solvents ; antibacterial agents such as benzyl alcohol or

methyl parabens ; antioxidants such as ascorbic acid or sodium bisulfite ; chelating agents such as ethylenediaminetetraacetic acid (EDTA) ; buffers such as acetates, citrates or phosphates, and agents for the adjustment of tonicity such as sodium chloride or dextrose. The pH can be adjusted with acids or bases, such as hydrochloric acid or sodium hydroxide. The parenteral preparation can be enclosed in ampoules, disposable syringes or multiple dose vials made of glass or plastic.

Pharmaceutical compositions suitable for injectable use include sterile aqueous solutions (where water soluble) or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersion. For intravenous administration, suitable carriers include physiological saline, bacteriostatic water, Cremophor ELTM (BASF, Parsippany, N. J.) or phosphate buffered saline (PBS). In all cases, the composition must be sterile and should be fluid to the extent that easy syringeability exists. It must be stable under the conditions of manufacture and storage and must be preserved against the contaminating action of microorganisms such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), and suitable mixtures thereof.

The proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants. Prevention of the action of microorganisms can be achieved by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, ascorbic acid, thimerosal, and the like. In many cases, it will be preferable to include isotonic agents, for example, sugars, polyalcohols such as manitol, sorbitol, sodium chloride in the composition. Prolonged absorption of the injectable compositions can be brought about by including in the composition an agent which delays absorption, for example, aluminum monostearate and gelatin.

Sterile injectable solutions can be prepared by incorporating the active compound (e. g., an FCTRX protein or anti-FCTRX antibody) in the required amount in an appropriate solvent with one or a combination of ingredients enumerated above, as required, followed by filtered sterilization. Generally, dispersions are prepared by incorporating the active compound into a sterile vehicle that contains a basic dispersion medium and the required other ingredients from those enumerated above. In the case of sterile powders for the preparation of sterile injectable solutions, methods of preparation are vacuum drying and freeze-drying that yields a powder of the active ingredient plus any additional desired ingredient from a previously sterile-filtered solution thereof.

Oral compositions generally include an inert diluent or an edible carrier. They can be enclosed in gelatin capsules or compressed into tablets. For the purpose of oral therapeutic administration, the active compound can be incorporated with excipients and used in the form of tablets, troches, or capsules. Oral compositions can also be prepared using a fluid carrier for use as a mouthwash, wherein the compound in the fluid carrier is applied orally and swished and expectorated or swallowed. Pharmaceutically compatible binding agents, and/or adjuvant materials can be included as part of the composition. The tablets, pills, capsules, troches and the like can contain any of the following ingredients, or compounds of a similar nature : a binder such as microcrystalline cellulose, gum tragacanth or gelatin ; an excipient such as starch or lactose, a disintegrating agent such as alginic acid, Primogel, or corn starch ; a lubricant such as magnesium stearate or Sterotes ; a glidant such as colloidal silicon dioxide ; a sweetening agent such as sucrose or saccharin ; or a flavoring agent such as peppermint, methyl salicylate, or orange flavoring.

For administration by inhalation, the compounds are delivered in the form of an aerosol spray from pressured container or dispenser which contains a suitable propellant, e. g., a gas such as carbon dioxide, or a nebulizer.

Systemic administration can also be by transmucosal or transdermal means. For transmucosal or transdermal administration, penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art, and include, for example, for transmucosal administration, detergents, bile salts, and fusidic acid derivatives. Transmucosal administration can be accomplished through the use of nasal sprays or suppositories. For transdermal administration, the active compounds are formulated into ointments, salves, gels, or creams as generally known in the art.

The compounds can also be prepared in the form of suppositories (e. g., with conventional suppository bases such as cocoa butter and other glycerides) or retention enemas for rectal delivery.

In one embodiment, the active compounds are prepared with carriers that will protect the compound against rapid elimination from the body, such as a controlled release formulation, including implants and microencapsulated delivery systems. Biodegradable, biocompatible polymers can be used, such as ethylene vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters, and polylactic acid. Methods for preparation of such formulations will be apparent to those skilled in the art. The materials can also be obtained commercially from Alza Corporation and Nova Pharmaceuticals, Inc. Liposomal suspensions (including liposomes targeted to infected cells with monoclonal antibodies to viral

antigens) can also be used as pharmaceutically acceptable carriers. These can be prepared according to methods known to those skilled in the art, for example, as described in U. S.

Patent No. 4, 522, 811.

It is especially advantageous to formulate oral or parenteral compositions in dosage unit form for ease of administration and uniformity of dosage. Dosage unit form as used herein refers to physically discrete units suited as unitary dosages for the subject to be treated ; each unit containing a predetermined quantity of active compound calculated to produce the desired therapeutic effect in association with the required pharmaceutical carrier. The specification for the dosage unit forms of the invention are dictated by and directly dependent on the unique characteristics of the active compound and the particular therapeutic effect to be achieved, and the limitations inherent in the art of compounding such an active compound for the treatment of individuals.

The nucleic acid molecules of the invention can be inserted into vectors and used as gene therapy vectors. Gene therapy vectors can be delivered to a subject by, for example, intravenous injection, local administration (see, e. g., U. S. Patent No. 5, 328, 470) or by stereotactic injection (see, e. g., Chen, et al., 1994. Proc. Natl. Acad. Sci. USA 91 : 3054-3057).

The pharmaceutical preparation of the gene therapy vector can include the gene therapy vector in an acceptable diluent, or can comprise a slow release matrix in which the gene delivery vehicle is imbedded. Alternatively, where the complete gene delivery vector can be produced intact from recombinant cells, e. g., retroviral vectors, the pharmaceutical preparation can include one or more cells that produce the gene delivery system.

The pharmaceutical compositions can be included in a container, pack, or dispenser together with instructions for administration.

Screening and Detection Methods The isolated nucleic acid molecules of the invention can be used to express FCTRX protein (e. g., via a recombinant expression vector in a host cell in gene therapy applications), to detect FCTRX mRNA (e. g., in a biological sample) or a genetic lesion in an FCTRX gene, and to modulate FCTRX activity, as described further, below. In addition, the FCTRX proteins can be used to screen drugs or compounds that modulate the FCTRX protein activity or expression as well as to treat disorders characterized by insufficient or excessive production of FCTRX protein or production of FCTRX protein forms that have decreased or aberrant activity compared to FCTRX wild-type protein (e. g. ; diabetes (regulates insulin release) ; obesity (binds and transport lipids) ; metabolic disturbances associated with obesity, the

metabolic syndrome X as well as anorexia and wasting disorders associated with chronic diseases and various cancers, and infectious disease (possesses anti-microbial activity) and the various dyslipidemias. In addition, the anti-FCTRX antibodies of the invention can be used to detect and isolate FCTRX proteins and modulate FCTRX activity. In yet a further aspect, the invention can be used in methods to influence appetite, absorption of nutrients and the disposition of metabolic substrates in both a positive and negative fashion.

The invention further pertains to novel agents identified by the screening assays described herein and uses thereof for treatments as described, supra.

Screenizlg Assays The invention provides a method (also referred to herein as a"screening assay") for identifying modulators, i. e., candidate or test compounds or agents (e. g., peptides, peptidomimetics, small molecules or other drugs) that bind to FCTRX proteins or have a stimulatory or inhibitory effect on, e. g, FCTRX protein expression or FCTRX protein activity.

The invention also includes compounds identified in the screening assays described herein.

In one embodiment, the invention provides assays for screening candidate or test compounds which bind to or modulate the activity of the membrane-bound form of an FCTRX protein or polypeptide or biologically-active portion thereof. The test compounds of the invention can be obtained using any of the numerous approaches in combinatorial library methods known in the art, including : biological libraries ; spatially addressable parallel solid phase or solution phase libraries ; synthetic library methods requiring deconvolution ; the "one-bead one-compound"library method ; and synthetic library methods using affinity chromatography selection. The biological library approach is limited to peptide libraries, while the other four approaches are applicable to peptide, non-peptide oligomer or small molecule libraries of compounds. See, e. g., Lam, 1997. Anticancer Drug Design 12 : 145.

A"small molecule"as used herein, is meant to refer to a composition that has a molecular weight of less than about 5 kD and most preferably less than about 4 kD. Small molecules can be, e. g., nucleic acids, peptides, polypeptides, peptidomimetics, carbohydrates, lipids or other organic or inorganic molecules. Libraries of chemical and/or biological mixtures, such as fungal, bacterial, or algal extracts, are known in the art and can be screened with any of the assays of the invention.

Examples of methods for the synthesis of molecular libraries can be found in the art, for example in : DeWitt, et al., 1993. Proc. Natl. Acad. Sci. U. S. A. 90 : 6909 ; Erb, et al., 1994.

Proc. Natl. Acad. Sci. U. S. A. 91 : 11422 ; Zuckermann, et al., 1994. J. Med. Chem. 37 : 2678 ; Cho, et al., 1993. Science 261 : 1303 ; Carrell, et al., 1994. Angew. Chem. Int. Ed. Engl. 33 :

2059 ; Carell, et al., 1994. Angew. Chem. Int. Ed. Engl. 33 : 2061 ; and Gallop, et al., 1994. J.

Med. Chem. 37 : 1233.

Libraries of compounds may be presented in solution (e. g., Houghten, 1992.

Biotechniques 13 : 412-421), or on beads (Lam, 1991. Nature 354 : 82-84), on chips (Fodor, 1993. Nature 364 : 555-556), bacteria (Ladner, U. S. Patent No. 5, 223, 409), spores (Ladner, U. S. Patent 5, 233, 409), plasmids (Cull, et al., 1992. Proc. Natl. Acad. Sci. USA 89 : 1865-1869) or on phage (Scott and Smith, 1990. Science 249 : 386-390 ; Devlin, 1990. Science 249 : 404-406 ; Cwirla, et al., 1990. Proc. Natl. Acad. Sci. U. S. A. 87 : 6378-6382 ; Felici, 1991.

J ; Mol. Biol. 222 : 301-310 ; Ladner, U. S. Patent No. 5, 233, 409.).

In one embodiment, an assay is a cell-based assay in which a cell which expresses a membrane-bound form of FCTRX protein, or a biologically-active portion thereof, on the cell surface is contacted with a test compound and the ability of the test compound to bind to an FCTRX protein determined. The cell, for example, can of mammalian origin or a yeast cell.

Determining the ability of the test compound to bind to the FCTRX protein can be accomplished, for example, by coupling the test compound with a radioisotope or enzymatic label such that binding of the test compound to the FCTRX protein or biologically-active portion thereof can be determined by detecting the labeled compound in a complex. For example, test compounds can be labeled with 125I, 35S, I4C, or 3H, either directly or indirectly, and the radioisotope detected by direct counting of radioemission or by scintillation counting.

Alternatively, test compounds can be enzymatically-labeled with, for example, horseradish peroxidase, alkaline phosphatase, or luciferase, and the enzymatic label detected by determination of conversion of an appropriate substrate to product. In one embodiment, the assay comprises contacting a cell which expresses a membrane-bound form of FCTRX protein, or a biologically-active portion thereof, on the cell surface with a known compound which binds FCTRX to form an assay mixture, contacting the assay mixture with a test compound, and determining the ability of the test compound to interact with an FCTRX protein, wherein determining the ability of the test compound to interact with an FCTRX protein comprises determining the ability of the test compound to preferentially bind to FCTRX protein or a biologically-active portion thereof as compared to the known compound.

In another embodiment, an assay is a cell-based assay comprising contacting a cell expressing a membrane-bound form of FCTRX protein, or a biologically-active portion thereof, on the cell surface with a test compound and determining the ability of the test compound to modulate (e. g., stimulate or inhibit) the activity of the FCTRX protein or biologically-active portion thereof. Determining the ability of the test compound to modulate

the activity of FCTRX or a biologically-active portion thereof can be accomplished, for example, by determining the ability of the FCTRX protein to bind to or interact with an FCTRX target molecule. As used herein, a"target molecule"is a molecule with which an FCTRX protein binds or interacts in nature, for example, a molecule on the surface of a cell which expresses an FCTRX interacting protein, a molecule on the surface of a second cell, a molecule in the extracellular milieu, a molecule associated with the internal surface of a cell membrane or a cytoplasmic molecule. An FCTRX target molecule can be a non-FCTRX molecule or an FCTRX protein or polypeptide of the invention. In one embodiment, an FCTRX target molecule is a component of a signal transduction pathway that facilitates transduction of an extracellular signal (e. g. a signal generated by binding of a compound to a membrane-bound FCTRX molecule) through the cell membrane and into the cell. The target, for example, can be a second intercellular protein that has catalytic activity or a protein that facilitates the association of downstream signaling molecules with FCTRX.

Determining the ability of the FCTRX protein to bind to or interact with an FCTRX target molecule can be accomplished by one of the methods described above for determining direct binding. In one embodiment, determining the ability of the FCTRX protein to bind to or interact with an FCTRX target molecule can be accomplished by determining the activity of the target molecule. For example, the activity of the target molecule can be determined by detecting induction of a cellular second messenger of the target (i. e. intracellular Ca2+, diacylglycerol, IP3, etc.), detecting catalytic/enzymatic activity of the target an appropriate substrate, detecting the induction of a reporter gene (comprising an FCTRX-responsive regulatory element operatively linked to a nucleic acid encoding a detectable marker, e. g., luciferase), or detecting a cellular response, for example, cell survival, cellular differentiation, or cell proliferation.

In yet another embodiment, an assay of the invention is a cell-free assay comprising contacting an FCTRX protein or biologically-active portion thereof with a test compound and determining the ability of the test compound to bind to the FCTRX protein or biologically- active portion thereof. Binding of the test compound to the FCTRX protein can be determined either directly or indirectly as described above. In one such embodiment, the assay comprises contacting the FCTRX protein or biologically-active portion thereof with a known compound which binds FCTRX to form an assay mixture, contacting the assay mixture with a test compound, and determining the ability of the test compound to interact with an FCTRX protein, wherein determining the ability of the test compound to interact with an FCTRX

protein comprises determining the ability of the test compound to preferentially bind to FCTRX or biologically-active portion thereof as compared to the known compound.

In still another embodiment, an assay is a cell-free assay comprising contacting FCTRX protein or biologically-active portion thereof with a test compound and determining the ability of the test compound to modulate (e. g. stimulate or inhibit) the activity of the FCTRX protein or biologically-active portion thereof. Determining the ability of the test compound to modulate the activity of FCTRX can be accomplished, for example, by determining the ability of the FCTRX protein to bind to an FCTRX target molecule by one of the methods described above for determining direct binding. In an alternative embodiment, determining the ability of the test compound to modulate the activity of FCTRX protein can be accomplished by determining the ability of the FCTRX protein further modulate an FCTRX target molecule. For example, the catalytic/enzymatic activity of the target molecule on an appropriate substrate can be determined as described, supra.

In yet another embodiment, the cell-free assay comprises contacting the FCTRX protein or biologically-active portion thereof with a known compound which binds FCTRX protein to form an assay mixture, contacting the assay mixture with a test compound, and determining the ability of the test compound to interact with an FCTRX protein, wherein determining the ability of the test compound to interact with an FCTRX protein comprises determining the ability of the FCTRX protein to preferentially bind to or modulate the activity of an FCTRX target molecule.

The cell-free assays of the invention are amenable to use of both the soluble form or the membrane-bound form of FCTRX protein. In the case of cell-free assays comprising the membrane-bound form of FCTRX protein, it may be desirable to utilize a solubilizing agent such that the membrane-bound form of FCTRX protein is maintained in solution. Examples of such solubilizing agents include non-ionic detergents such as n-octylglucoside, n-dodecylglucoside, n-dodecylmaltoside, octanoyl-N-methylglucamide, decanoyl-N-methylglucamide, TritonQ'X-100, Tritons X-114, Thesitt, Isotridecypoly (ethylene glycol ether) n, N-dodecyl--N, N-dimethyl-3-ammonio-1-propane sulfonate, 3- (3-cholamidopropyl) dimethylamminiol-1-propane sulfonate (CHAPS), or 3- (3-cholamidopropyl) dimethylamminiol-2-hydroxy-1-propane sulfonate (CHAPSO).

In more than one embodiment of the above assay methods of the invention, it may be desirable to immobilize either FCTRX protein or its target molecule to facilitate separation of complexed from uncomplexed forms of one or both of the proteins, as well as to accommodate automation of the assay. Binding of a test compound to FCTRX protein, or interaction of

FCTRX protein with a target molecule in the presence and absence of a candidate compound, can be accomplished in any vessel suitable for containing the reactants. Examples of such vessels include microtiter plates, test tubes, and micro-centrifuge tubes. In one embodiment, a fusion protein can be provided that adds a domain that allows one or both of the proteins to be bound to a matrix. For example, GST-FCTRX fusion proteins or GST-target fusion proteins can be adsorbed onto glutathione sepharose beads (Sigma Chemical, St. Louis, MO) or glutathione derivatized microtiter plates, that are then combined with the test compound or the test compound and either the non-adsorbed target protein or FCTRX protein, and the mixture is incubated under conditions conducive to complex formation (e. g., at physiological conditions for salt and pH). Following incubation, the beads or microtiter plate wells are washed to remove any unbound components, the matrix immobilized in the case of beads, complex determined either directly or indirectly, for example, as described, supra.

Alternatively, the complexes can be dissociated from the matrix, and the level of FCTRX protein binding or activity determined using standard techniques.

Other techniques for immobilizing proteins on matrices can also be used in the screening assays of the invention. For example, either the FCTRX protein or its target molecule can be immobilized utilizing conjugation of biotin and streptavidin. Biotinylated FCTRX protein or target molecules can be prepared from biotin-NHS (N-hydroxy-succinimide) using techniques well-known within the art (e. g., biotinylation kit, Pierce Chemicals, Rockford, 111.), and immobilized in the wells of streptavidin-coated 96 well plates (Pierce Chemical). Alternatively, antibodies reactive with FCTRX protein or target molecules, but which do not interfere with binding of the FCTRX protein to its target molecule, can be derivatized to the wells of the plate, and unbound target or FCTRX protein trapped in the wells by antibody conjugation. Methods for detecting such complexes, in addition to those described above for the GST-immobilized complexes, include immunodetection of complexes using antibodies reactive with the FCTRX protein or target molecule, as well as enzyme-linked assays that rely on detecting an enzymatic activity associated with the FCTRX protein or target molecule.

In another embodiment, modulators of FCTRX protein expression are identified in a method wherein a cell is contacted with a candidate compound and the expression of FCTRX mRNA or protein in the cell is determined. The level of expression of FCTRX mRNA or protein in the presence of the candidate compound is compared to the level of expression of FCTRX mRNA or protein in the absence of the candidate compound. The candidate compound can then be identified as a modulator of FCTRX mRNA or protein expression

based upon this comparison. For example, when expression of FCTRX mRNA or protein is greater (i. e., statistically significantly greater) in the presence of the candidate compound than in its absence, the candidate compound is identified as a stimulator of FCTRX mRNA or protein expression. Alternatively, when expression of FCTRX mRNA or protein is less (statistically significantly less) in the presence of the candidate compound than in its absence, the candidate compound is identified as an inhibitor of FCTRX mRNA or protein expression.

The level of FCTRX MRNA or protein expression in the cells can be determined by methods described herein for detecting FCTRX MARNA or protein.

In yet another aspect of the invention, the FCTRX proteins can be used as"bait proteins"in a two-hybrid assay or three hybrid assay (see, e. g., U. S. Patent No. 5, 283, 317 ; Zervos, et al., 1993. Cell 72 : 223-232 ; Madura, et al., 1993. J. Biol. Chem. 268 : 12046-12054 ; Bartel, et al., 1993. Biotechniques 14 : 920-924 ; Iwabuchi, et al., 1993. Oncogene 8 : 1693-1696 ; and Brent WO 94/10300), to identify other proteins that bind to or interact with FCTRX ("FCTRX-binding proteins"or"FCTRX-bp") and modulate FCTRX activity. Such FCTRX-binding proteins are also likely to be involved in the propagation of signals by the FCTRX proteins as, for example, upstream or downstream elements of the FCTRX pathway.

The two-hybrid system is based on the modular nature of most transcription factors, which consist of separable DNA-binding and activation domains. Briefly, the assay utilizes two different DNA constructs. In one construct, the gene that codes for FCTRX is fused to a gene encoding the DNA binding domain of a known transcription factor (e. g., GAL-4). In the other construct, a DNA sequence, from a library of DNA sequences, that encodes an unidentified protein ("prey"or"sample") is fused to a gene that codes for the activation domain of the known transcription factor. If the"bait"and the"prey"proteins are able to interact, ira vivo, forming an FCTRX-dependent complex, the DNA-binding and activation domains of the transcription factor are brought into close proximity. This proximity allows transcription of a reporter gene (e. g., LacZ) that is operably linked to a transcriptional regulatory site responsive to the transcription factor. Expression of the reporter gene can be detected and cell colonies containing the functional transcription factor can be isolated and used to obtain the cloned gene that encodes the protein which interacts with FCTRX.

The invention further pertains to novel agents identified by the aforementioned screening assays and uses thereof for treatments as described herein.

Detection Assays Portions or fragments of the cDNA sequences identified herein (and the corresponding complete gene sequences) can be used in numerous ways as polynucleotide reagents. By way of example, and not of limitation, these sequences can be used to : (i) map their respective genes on a chromosome ; and, thus, locate gene regions associated with genetic disease ; (ii) identify an individual from a minute biological sample (tissue typing) ; and (iii) aid in forensic identification of a biological sample. Some of these applications are described in the subsections, below.

Chromosome Mapping Once the sequence (or a portion of the sequence) of a gene has been isolated, this sequence can be used to map the location of the gene on a chromosome. This process is called chromosome mapping. Accordingly, portions or fragments of the FCTRX sequences, SEQ ID NOS : 1, 3, 5, 7, 9, 10, 11, 12, 14, 16, 18, 20, 22, and 24, or fragments or derivatives thereof, can be used to map the location of the FCTRX genes, respectively, on a chromosome. The mapping of the FCTRX sequences to chromosomes is an important first step in correlating these sequences with genes associated with disease.

Briefly, FCTRX genes can be mapped to chromosomes by preparing PCR primers (preferably 15-25 bp in length) from the FCTRX sequences. Computer analysis of the FCTRX, sequences can be used to rapidly select primers that do not span more than one exon in the genomic DNA, thus complicating the amplification process. These primers can then be used for PCR screening of somatic cell hybrids containing individual human chromosomes.

Only those hybrids containing the human gene corresponding to the FCTRX sequences will yield an amplified fragment.

Somatic cell hybrids are prepared by fusing somatic cells from different mammals (e. g., human and mouse cells). As hybrids of human and mouse cells grow and divide, they gradually lose human chromosomes in random order, but retain the mouse chromosomes. By using media in which mouse cells cannot grow, because they lack a particular enzyme, but in which human cells can, the one human chromosome that contains the gene encoding the needed enzyme will be retained. By using various media, panels of hybrid cell lines can be established. Each cell line in a panel contains either a single human chromosome or a small number of human chromosomes, and a full set of mouse chromosomes, allowing easy mapping of individual genes to specific human chromosomes. See, e. g., D'Eustachio, et al., 1983. Science 220 : 919-924. Somatic cell hybrids containing only fragments of human

chromosomes can also be produced by using human chromosomes with translocations and deletions.

PCR mapping of somatic cell hybrids is a rapid procedure for assigning a particular sequence to a particular chromosome. Three or more sequences can be assigned per day using a single thermal cycler. Using the FCTRX sequences to design oligonucleotide primers, sub- localization can be achieved with panels of fragments from specific chromosomes.

Fluorescence in situ hybridization (FISH) of a DNA sequence to a metaphase chromosomal spread can further be used to provide a precise chromosomal location in one step. Chromosome spreads can be made using cells whose division has been blocked in metaphase by a chemical like colcemid that disrupts the mitotic spindle. The chromosomes can be treated briefly with trypsin, and then stained with Giemsa. A pattern of light and dark bands develops on each chromosome, so that the chromosomes can be identified individually.

The FISH technique can be used with a DNA sequence as short as 500 or 600 bases.

However, clones larger than 1, 000 bases have a higher likelihood of binding to a unique chromosomal location with sufficient signal intensity for simple detection. Preferably 1, 000 bases, and more preferably 2, 000 bases, will suffice to get good results at a reasonable amount of time. For a review of this technique, see, Verma, et al., HUMAN CHROMOSOMES : A MANUAL OF BASIC TECHNIQUES (Pergamon Press, New York 1988).

Reagents for chromosome mapping can be used individually to mark a single chromosome or a single site on that chromosome, or panels of reagents can be used for marking multiple sites and/or multiple chromosomes. Reagents corresponding to noncoding regions of the genes actually are preferred for mapping purposes. Coding sequences are more likely to be conserved within gene families, thus increasing the chance of cross hybridizations during chromosomal mapping.

Once a sequence has been mapped to a precise chromosomal location, the physical position of the sequence on the chromosome can be correlated with genetic map data. Such data are found, e. g., in McKusick, MENDELIAN INHERITANCE IN MAN, available on-line through Johns Hopkins University Welch Medical Library). The relationship between genes and disease, mapped to the same chromosomal region, can then be identified through linkage analysis (co-inheritance of physically adjacent genes), described in, e. g., Egeland, et al., 1987.

Nature, 325 : 783-787.

Moreover, differences in the DNA sequences between individuals affected and unaffected with a disease associated with the FCTRX gene, can be determined. If a mutation is observed in some or all of the affected individuals but not in any unaffected individuals,

then the mutation is likely to be the causative agent of the particular disease. Comparison of affected and unaffected individuals generally involves first looking for structural alterations in the chromosomes, such as deletions or translocations that are visible from chromosome spreads or detectable using PCR based on that DNA sequence. Ultimately, complete sequencing of genes from several individuals can be performed to confirm the presence of a mutation and to distinguish mutations from polymorphisms.

Tissue Typing The FCTRX sequences of the invention can also be used to identify individuals from minute biological samples. In this technique, an individual's genomic DNA is digested with one or more restriction enzymes, and probed on a Southern blot to yield unique bands for identification. The sequences of the invention are useful as additional DNA markers for RFLP ("restriction fragment length polymorphisms,"described in U. S. Patent No. 5, 272, 057).

Furthermore, the sequences of the invention can be used to provide an alternative technique that determines the actual base-by-base DNA sequence of selected portions of an individual's genome. Thus, the FCTRX sequences described herein can be used to prepare two PCR primers from the 5'-and 3'-termini of the sequences. These primers can then be used to amplify an individual's DNA and subsequently sequence it.

Panels of corresponding DNA sequences from individuals, prepared in this manner, can provide unique individual identifications, as each individual will have a unique set of such DNA sequences due to allelic differences. The sequences of the invention can be used to obtain such identification sequences from individuals and from tissue. The FCTRX sequences of the invention uniquely represent portions of the human genome. Allelic variation occurs to some degree in the coding regions of these sequences, and to a greater degree in the noncoding regions. It is estimated that allelic variation between individual humans occurs with a frequency of about once per each 500 bases. Much of the allelic variation is due to single nucleotide polymorphisms (SNPs), which include restriction fragment length polymorphisms (RFLPs).

Each of the sequences described herein can, to some degree, be used as a standard against which DNA from an individual can be compared for identification purposes. Because greater numbers of polymorphisms occur in the noncoding regions, fewer sequences are necessary to differentiate individuals. The noncoding sequences can comfortably provide positive individual identification with a panel of perhaps 10 to 1, 000 primers that each yield a noncoding amplified sequence of 100 bases. If predicted coding sequences, such as those in

SEQ ID NOS : 1, 3, 5, 7, 9, 10, 11, 12, 14, 16, 18, 20, 22, and 24, are used, a more appropriate number of primers for positive individual identification would be 500-2, 000.

Predictive Medicine The invention also pertains to the field of predictive medicine in which diagnostic assays, prognostic assays, pharmacogenomics, and monitoring clinical trials are used for prognostic (predictive) purposes to thereby treat an individual prophylactically. Accordingly, one aspect of the invention relates to diagnostic assays for determining FCTRX protein and/or nucleic acid expression as well as FCTRX activity, in the context of a biological sample (e. g., blood, serum, cells, tissue) to thereby determine whether an individual is afflicted with a disease or disorder, or is at risk of developing a disorder, associated with aberrant FCTRX expression or activity. The disorders include Also within the scope of the invention is the use of a Therapeutic in the manufacture of a medicament for treating or preventing disorders or syndromes including, e. g., Colorectal cancer, adenomatous polyposis coli, myelogenous leukemia, congenital ceonatal alloimmune thrombocytopenia, multiple human solid malignancies, malignant ovarian tumours particularly at the interface between epithelia and stroma, malignant brain tumors, mammary tumors, human gliomas, astrocytomas, mixed glioma/astrocytomas, renal cells carcinoma, breast adenocarcinoma, ovarian cancer, melanomas, renal cell carcinoma, clear cell and granular cell carcinomas, autocrine/paracrine stimulation of tumor cell proliferation, autocrine/paracrine stimulation of tumor cell survival and tumor cell resistance to cytotoxic therapy, paranechmal and basement membrane invasion and motility of tumor cells thereby contributing to metastasis, tumor-mediated immunosuppression of T-cell mediated immune effector cells and pathways resulting in tumor escape from immune surveilance, neurological disorders, neurodegenerative disorders, nerve trauma, familial myelodysplastic syndrome, Charcot-Marie-Tooth neuropathy, demyelinating Gardner syndrome, familial myelodysplastic syndrome ; mental health conditions, immunological disorders, allergy and infection, asthma, bronchial asthma, Avellino type eosinophilia, lung diseases, reproductive disorders, male infertility, female reproductive system disorders, male and female reproductive diseases, hemangioma, deafness, glycoprotein la deficiency, desmoid disease, turcot syndrome, liver cirrhosis, hepatitis C, gastric disorders, pancreatic diseases like diabetes, Schistosoma mansoni infection, Spinocerebellar ataxia, Plasmodium falciparum parasitemia, Corneal dystrophy-Groenouw type I, Corneal dystrophy -lattice type I, and Reis-Bucklers corneal dystrophy. The invention also provides for prognostic (or predictive) assays for determining whether an individual is at risk of developing a disorder associated with FCTRX protein, nucleic acid expression or activity. For example,

mutations in an FCTRX gene can be assayed in a biological sample. Such assays can be used for prognostic or predictive purpose to thereby prophylactically treat an individual prior to the onset of a disorder characterized by or associated with FCTRX protein, nucleic acid expression, or biological activity.

Another aspect of the invention provides methods for determining FCTRX protein, nucleic acid expression or activity in an individual to thereby select appropriate therapeutic or prophylactic agents for that individual (referred to herein as"pharmacogenomics").

Phannacogenomics allows for the selection of agents (e. g., drugs) for therapeutic or prophylactic treatment of an individual based on the genotype of the individual (e. g., the genotype of the individual examined to determine the ability of the individual to respond to a. particular agent.) Yet another aspect of the invention pertains to monitoring the influence of agents (e. g., drugs, compounds) on the expression or activity of FCTRX in clinical trials.

These and other agents are described in further detail in the following sections.

Diagnostic Assays An exemplary method for detecting the presence or absence of FCTRX in a biological sample involves obtaining a biological sample from a test subject and contacting the biological sample with a compound or an agent capable of detecting FCTRX protein or nucleic acid (eg., mRNA, genomic DNA) that encodes FCTRX protein such that the presence of FCTRX is detected in the biological sample. An agent for detecting FCTRX mRNA or genomic DNA is a labeled nucleic acid probe capable of hybridizing to FCTRX mRNA or genomic DNA. The nucleic acid probe can be, for example, a full-length FCTRX nucleic acid, such as the nucleic acid of SEQ ID NOS : 1, 3, 5, 7, 9, 10, 11, 12, 14, 16, 18, 20, 22, and 24, or a portion thereof, such as an oligonucleotide of at least 15, 30, 50, 100, 250 or 500 nucleotides in length and sufficient to specifically hybridize under stringent conditions to FCTRX mRNA or genomic DNA. Other suitable probes for use in the diagnostic assays of the invention are described herein.

An agent for detecting FCTRX protein is an antibody capable of binding to FCTRX protein, preferably an antibody with a detectable label. Antibodies can be polyclonal, or more preferably, monoclonal. An intact antibody, or a fragment thereof (e. g., Fab or F (ab') 2) can be used. The term"labeled", with regard to the probe or antibody, is intended to encompass direct labeling of the probe or antibody by coupling (i. e., physically linking) a detectable substance to the probe or antibody, as well as indirect labeling of the probe or antibody by reactivity with another reagent that is directly labeled. Examples of indirect labeling include

detection of a primary antibody using a fluorescently-labeled secondary antibody and end-labeling of a DNA probe with biotin such that it can be detected with fluorescently- labeled streptavidin. The term"biological sample"is intended to include tissues, cells and biological fluids isolated from a subject, as well as tissues, cells and fluids present within a subject. That is, the detection method of the invention can be used to detect FCTRX mRNA, protein, or genomic DNA in a biological sample in vitro as well as in vivo. For example, in vitro techniques for detection of FCTRX mRNA include Northern hybridizations and in situ hybridizations. In vitro techniques for detection of FCTRX protein include enzyme linked immunosorbent assays (ELISAs), Western blots, immunoprecipitations, and immunofluorescence. In vitro techniques for detection of FCTRX genomic DNA include Southern hybridizations. Furthermore, in vivo techniques for detection of FCTRX protein include introducing into a subject a labeled anti-FCTRX antibody. For example, the antibody can be labeled with a radioactive marker whose presence and location in a subject can be detected by standard imaging techniques.

In one embodiment, the biological sample contains protein molecules from the test subject. Alternatively, the biological sample can contain MARNA molecules from the test subject or genomic DNA molecules from the test subject. A preferred biological sample is a peripheral blood leukocyte sample isolated by conventional means from a subject.

In another embodiment, the methods further involve obtaining a control biological sample from a control subject, contacting the control sample with a compound or agent capable of detecting FCTRX protein, mRNA, or genomic DNA, such that the presence of FCTRX protein, mRNA or genomic DNA is detected in the biological sample, and comparing the presence of FCTRX protein, mRNA or genomic DNA in the control sample with the presence of FCTRX protein, MARNA or genomic DNA in the test sample.

The invention also encompasses kits for detecting the presence of FCTRX in a biological sample. For example, the kit can comprise : a labeled compound or agent capable of detecting FCTRX protein or mRNA in a biological sample ; means for determining the amount of FCTRX in the sample ; and means for comparing the amount of FCTRX in the sample with a standard. The compound or agent can be packaged in a suitable container. The kit can further comprise instructions for using the kit to detect FCTRX protein or nucleic acid.

Prognostic Assays The diagnostic methods described herein can furthermore be utilized to identify subjects having or at risk of developing a disease or disorder associated with aberrant FCTRX expression or activity. For example, the assays described herein, such as the preceding

diagnostic assays or the following assays, can be utilized to identify a subject having or at risk of developing a disorder associated with FCTRX protein, nucleic acid expression or activity.

Alternatively, the prognostic assays can be utilized to identify a subject having or at risk for developing a disease or disorder. Thus, the invention provides a method for identifying a disease or disorder associated with aberrant FCTRX expression or activity in which a test sample is obtained from a subject and FCTRX protein or nucleic acid (e. g., mRNA, genomic DNA) is detected, wherein the presence of FCTRX protein or nucleic acid is diagnostic for a subject having or at risk of developing a disease or disorder associated with aberrant FCTRX expression or activity. As used herein, a"test sample"refers to a biological sample obtained from a subject of interest. For example, a test sample can be a biological fluid (e. g., serum), cell sample, or tissue.

Furthermore, the prognostic assays described herein can be used to determine whether a subject can be administered an agent (e. g., an agonist, antagonist, peptidomimetic, protein, peptide, nucleic acid, small molecule, or other drug candidate) to treat a disease or disorder associated with aberrant FCTRX expression or activity. For example, such methods can be used to determine whether a subject can be effectively treated with an agent for a disorder.

Thus, the invention provides methods for determining whether a subject can be effectively treated with an agent for a disorder associated with aberrant FCTRX expression or activity in which a test sample is obtained and FCTRX protein or nucleic acid is detected (e. g., wherein the presence of FCTRX protein or nucleic acid is diagnostic for a subject that can be administered the agent to treat a disorder associated with aberrant FCTRX expression or activity).

The methods of the invention can also be used to detect genetic lesions in an FCTRX gene, thereby determining if a subject with the lesioned gene is at risk for a disorder characterized by aberrant cell proliferation and/or differentiation. In various embodiments, the methods include detecting, in a sample of cells from the subject, the presence or absence of a genetic lesion characterized by at least one of an alteration affecting the integrity of a gene encoding an FCTRX-protein, or the misexpression of the FCTRX gene. For example, such genetic lesions can be detected by ascertaining the existence of at least one of : (i) a deletion of one or more nucleotides from an FCTRX gene ; (ii) an addition of one or more nucleotides to an FCTRX gene ; (iii) a substitution of one or more nucleotides of an FCTRX gene, (iv) a chromosomal rearrangement of an FCTRX gene ; (v) an alteration in the level of a messenger RNA transcript of an FCTRX gene, (vi) aberrant modification of an FCTRX gene, such as of the methylation pattern of the genomic DNA, (vii) the presence of a non-wild-type splicing

pattern of a messenger RNA transcript of an FCTRX gene, (viii) a non-wild-type level of an FCTRX protein, (ix) allelic loss of an FCTRX gene, and (x) inappropriate post-translational modification of an FCTRX protein. As described herein, there are a large number of assay techniques known in the art which can be used for detecting lesions in an FCTRX gene. A preferred biological sample is a peripheral blood leukocyte sample isolated by conventional means from a subject. However, any biological sample containing nucleated cells may be used, including, for example, buccal mucosal cells.

In certain embodiments, detection of the lesion involves the use of a probe/primer in a polymerase chain reaction (PCR) (see, e. g., U. S. Patent Nos. 4, 683, 195 and 4, 683, 202), such as anchor PCR or RACE PCR, or, alternatively, in a ligation chain reaction (LCR) (see, e. g., Landegran, et al., 1988. Science 241 : 1077-1080 ; and Nakazawa, et al., 1994. Proc. Natl.

Acad. Sci. USA 91 : 360-364), the latter of which can be particularly useful for detecting point mutations in the FCTRX-gene (see, Abravaya, et al., 1995. Nucl. Acids Res. 23 : 675-682).

This method can include the steps of collecting a sample of cells from a patient, isolating nucleic acid (e. g., genomic, mRNA or both) from the cells of the sample, contacting the nucleic acid sample with one or more primers that specifically hybridize to an FCTRX gene under conditions such that hybridization and amplification of the FCTRX gene (if present) occurs, and detecting the presence or absence of an amplification product, or detecting the size of the amplification product and comparing the length to a control sample. It is anticipated that PCR and/or LCR may be desirable to use as a preliminary amplification step in conjunction with any of the techniques used for detecting mutations described herein.

Alternative amplification methods include : self sustained sequence replication (see, Guatelli, et al., 1990. Proc. Natl. Acad. Sci. USA 87 : 1874-1878), transcriptional amplification system (see, Kwoh, et al., 1989. Proc. Natl. Acad. Sci. USA 86 : 1173-1177) ; QP Replicase (see, Lizardi, et al, 1988. BioTechnology 6 : 1197), or any other nucleic acid amplification method, followed by the detection of the amplified molecules using techniques well known to those of skill in the art. These detection schemes are especially useful for the detection of nucleic acid molecules if such molecules are present in very low numbers.

In an alternative embodiment, mutations in an FCTRX gene from a sample cell can be identified by alterations in restriction enzyme cleavage patterns. For example, sample and control DNA is isolated, amplified (optionally), digested with one or more restriction endonucleases, and fragment length sizes are determined by gel electrophoresis and compared.

Differences in fragment length sizes between sample and control DNA indicates mutations in the sample DNA. Moreover, the use of sequence specific ribozymes (see, e. g., U. S. Patent

No. 5, 493, 531) can be used to score for the presence of specific mutations by development or loss of a ribozyme cleavage site.

In other embodiments, genetic mutations in FCTRX can be identified by hybridizing a sample and control nucleic acids, e. g., DNA or RNA, to high-density arrays containing hundreds or thousands of oligonucleotides probes. See, e. g, Cronin, et al., 1996. Human Mutation 7 : 244-255 ; Kozal, et al., 1996. Nat. Med. 2 : 753-759. For example, genetic mutations in FCTRX can be identified in two dimensional arrays containing light-generated DNA probes as described in Cronin, et al., supra. Briefly, a first hybridization array of probes can be used to scan through long stretches of DNA in a sample and control to identify base changes between the sequences by making linear arrays of sequential overlapping probes.

This step allows the identification of point mutations. This is followed by a second hybridization array that allows the characterization of specific mutations by using smaller, specialized probe arrays complementary to all variants or mutations detected. Each mutation array is composed of parallel probe sets, one complementary to the wild-type gene and the other complementary to the mutant gene.

In yet another embodiment, any of a variety of sequencing reactions known in the art can be used to directly sequence the FCTRX gene and detect mutations by comparing the sequence of the sample FCTRX with the corresponding wild-type (control) sequence.

Examples of sequencing reactions include those based on techniques developed by Maxim and Gilbert, 1977. Proc. Natl. Acad. Sci. USA 74 : 560 or Sanger, 1977. Proc. Natl. Acad. Sci. USA 74 : 5463. It is also contemplated that any of a variety of automated sequencing procedures can be utilized when performing the diagnostic assays (see, e. g., Naeve, et al., 1995.

Biotechniques 19 : 448), including sequencing by mass spectrometry (see, e. g., PCT International Publication No. WO 94/16101 ; Cohen, et al., 1996. Adv. Chromatography 36 : 127-162 ; and Griffin, et al., 1993. Appl. Biochem. BiotechnoL 38 : 147-159).

Other methods for detecting mutations in the FCTRX gene include methods in which protection from cleavage agents is used to detect mismatched bases in RNA/RNA or RNA/DNA heteroduplexes. See, e. g., Myers, et al., 1985. Science 230 : 1242. In general, the art technique of"mismatch cleavage"starts by providing heteroduplexes of formed by hybridizing (labeled) RNA or DNA containing the wild-type FCTRX sequence with potentially mutant RNA or DNA obtained from a tissue sample. The double-stranded duplexes are treated with an agent that cleaves single-stranded regions of the duplex such as which will exist due to basepair mismatches between the control and sample strands. For instance, RNA/DNA duplexes can be treated with RNase and DNA/DNA hybrids treated with

Si nuclease to enzymatically digesting the mismatched regions. In other embodiments, either DNA/DNA or RNA/DNA duplexes can be treated with hydroxylamine or osmium tetroxide and with piperidine in order to digest mismatched regions. After digestion of the mismatched regions, the resulting material is then separated by size on denaturing polyacrylamide gels to determine the site of mutation. See, e. g., Cotton, et al., 1988. Proc. Natl. Acad. Sci. USA 85 : 4397 ; Saleeba, et al., 1992. Methods Enzymol. 217 : 286-295. In an embodiment, the control DNA or RNA can be labeled for detection.

In still another embodiment, the mismatch cleavage reaction employs one or more proteins that recognize mismatched base pairs in double-stranded DNA (so called"DNA mismatch repair"enzymes) in defined systems for detecting and mapping point mutations in FCTRX cDNAs obtained from samples of cells. For example, the mutY enzyme of E. coli cleaves A at G/A mismatches and the thymidine DNA glycosylase from HeLa cells cleaves T at G/T mismatches. See, e. g., Hsu, et al., 1994. Carciraogenesis 15 : 1657-1662. According to an exemplary embodiment, a probe based on an FCTRX sequence, e. g., a wild-type FCTRX sequence, is hybridized to a cDNA or other DNA product from a test cell (s). The duplex is treated with a DNA mismatch repair enzyme, and the cleavage products, if any, can be detected from electrophoresis protocols or the like. See, e. g., U. S. Patent No. 5, 459, 039.

In other embodiments, alterations in electrophoretic mobility will be used to identify mutations in FCTRX genes. For example, single strand conformation polymorphism (SSCP) may be used to detect differences in electrophoretic mobility between mutant and wild type nucleic acids. See, e. g., Orita, et al., 1989. Proc. Natl. Acad. Sci. USA : 86 : 2766 ; Cotton, 1993. Mutat. Res. 285 : 125-144 ; Hayashi, 1992. Genet. Anal. Tech. Appl. 9 : 73-79.

Single-stranded DNA fragments of sample and control FCTRX nucleic acids will be denatured and allowed to nature. The secondary structure of single-stranded nucleic acids varies according to sequence, the resulting alteration in electrophoretic mobility enables the detection of even a single base change. The DNA fragments may be labeled or detected with labeled probes. The sensitivity of the assay may be enhanced by using RNA (rather than DNA), in which the secondary structure is more sensitive to a change in sequence. In one embodiment, the subject method utilizes heteroduplex analysis to separate double stranded heteroduplex molecules on the basis of changes in electrophoretic mobility. See, e. g., Keen, et al., 1991.

Trends Genet. 7 : 5.

In yet another embodiment, the movement of mutant or wild-type fragments in polyacrylamide gels containing a gradient of denaturant is assayed using denaturing gradient gel electrophoresis (DGGE). See, e. g., Myers, et al., 1985. Nature 313 : 495. When DGGE is

used as the method of analysis, DNA will be modified to insure that it does not completely denature, for example by adding a GC clamp of approximately 40 bp of high-melting GC-rich DNA by PCR. In a further embodiment, a temperature gradient is used in place of a denaturing gradient to identify differences in the mobility of control and sample DNA. See, e. g., Rosenbaum and Reissner, 1987. Biophys. Chem. 265 : 12753.

Examples of other techniques for detecting point mutations include, but are not limited to, selective oligonucleotide hybridization, selective amplification, or selective primer extension. For example, oligonucleotide primers may be prepared in which the known mutation is placed centrally and then hybridized to target DNA under conditions that permit hybridization only if a perfect match is found. See, e. g., Saiki, et al., 1986. Nature 324 : 163 ; Saiki, et al., 1989. Proc. Natl. Acad. Sci. USA 86 : 6230. Such allele specific oligonucleotides are hybridized to PCR amplified target DNA or a number of different mutations when the oligonucleotides are attached to the hybridizing membrane and hybridized with labeled target DNA.

Alternatively, allele specific amplification technology that depends on selective PCR amplification may be used in conjunction with the instant invention. Oligonucleotides used as primers for specific amplification may carry the mutation of interest in the center of the molecule (so that amplification depends on differential hybridization ; see, e. g., Gibbs, et al., 1989. Nucl. Acids Res. 17 : 2437-2448) or at the extreme 3'-terminus of one primer where, under appropriate conditions, mismatch can prevent, or reduce polymerase extension (see, e. g., Prossner, 1993. Tibtech. 11 : 238). In addition it may be desirable to introduce a novel restriction site in the region of the mutation to create cleavage-based detection. See, e. g., Gasparini, et al., 1992. Mol. Cell Probes 6 : 1. It is anticipated that in certain embodiments amplification may also be performed using Taq ligase for amplification. See, e. g., Barany, 1991. Proc. Natl. Acad. Sci. USA 88 : 189. In such cases, ligation will occur only if there is a perfect match at the 3'-terminus of the 5'sequence, making it possible to detect the presence of a known mutation at a specific site by looking for the presence or absence of amplification.

The methods described herein may be performed, for example, by utilizing pre-packaged diagnostic kits comprising at least one probe nucleic acid or antibody reagent described herein, which may be conveniently used, e. g., in clinical settings to diagnose patients exhibiting symptoms or family history of a disease or illness involving an FCTRX gene.

Furthermore, any cell type or tissue, preferably peripheral blood leukocytes, in which FCTRX is expressed may be utilized in the prognostic assays described herein. However, any

biological sample containing nucleated cells may be used, including, for example, buccal mucosal cells.

Pharmacogexlomics Agents, or modulators that have a stimulatory or inhibitory effect on FCTRX activity (e. g., FCTRX gene expression), as identified by a screening assay described herein can be administered to individuals to treat (prophylactically or therapeutically) disorders (The disorders include metabolic disorders, Also within the scope of the invention is the use of a Therapeutic in the manufacture of a medicament for treating or preventing disorders or syndromes including, e. g., Colorectal cancer, adenomatous polyposis coli, myelogenous leukemia, congenital ceonatal alloimmune thrombocytopenia, multiple human solid malignancies, malignant ovarian tumours particularly at the interface between epithelia and stroma, malignant brain tumors, mammary tumors, human gliomas, astrocytomas, mixed glioma/astrocytomas, renal cells carcinoma, breast adenocarcinoma, ovarian cancer, melanomas, renal cell carcinoma, clear cell and granular cell carcinomas, autocrine/paracrine stimulation of tumor cell proliferation, autocrine/paracrine stimulation of tumor cell survival and tumor cell resistance to cytotoxic therapy, paranechmal and basement membrane invasion and motility of tumor cells thereby contributing to metastasis, tumor-mediated immunosuppression of T-cell mediated immune effector cells and pathways resulting in tumor escape from immune surveilance, neurological disorders, neurodegenerative disorders, nerve trauma, familial myelodysplastic syndrome, Charcot-Marie-Tooth neuropathy, demyelinating Gardner syndrome, familial myelodysplastic syndrome ; mental health conditions, immunological disorders, allergy and infection, asthma, bronchial asthma, Avellino type eosinophilia, lung diseases, reproductive disorders, male infertility, female reproductive system disorders, male and female reproductive diseases, hemangioma, deafness, glycoprotein Ia deficiency, desmoid disease, turcot syndrome, liver cirrhosis, hepatitis C, gastric disorders, pancreatic diseases like diabetes, Schistosoma mansoni infection, Spinocerebellar ataxia, Plasmodium falciparum parasitemia, Corneal dystrophy-Groenouw type I, Corneal dystrophy -lattice type I, and Reis-Bucklers corneal dystrophy) In conjunction with such treatment, the pharmacogenomics (i. e., the study of the relationship between an individual's genotype and that individual's response to a foreign compound or drug) of the individual may be considered.

Differences in metabolism of therapeutics can lead to severe toxicity or therapeutic failure by altering the relation between dose and blood concentration of the pharmacologically active drug. Thus, the pharmacogenomics of the individual permits the selection of effective agents (e. g., drugs) for prophylactic or therapeutic treatments based on a consideration of the

individual's genotype. Such pharmacogenomics can further be used to determine appropriate dosages and therapeutic regimens. Accordingly, the activity of FCTRX protein, expression of FCTRX nucleic acid, or mutation content of FCTRX genes in an individual can be determined to thereby select appropriate agent (s) for therapeutic or prophylactic treatment of the individual.

Pharmacogenomics deals with clinically significant hereditary variations in the response to drugs due to altered drug disposition and abnormal action in affected persons. See e. g., Eichelbaum, 1996. Clin. Exp. Pharmacol. Physiol., 23 : 983-985 ; Linder, 1997. Clin.

Chenu., 43 : 254-266. In general, two types of pharmacogenetic conditions can be differentiated. Genetic conditions transmitted as a single factor altering the way drugs act on the body (altered drug action) or genetic conditions transmitted as single factors altering the way the body acts on drugs (altered drug metabolism). These pharmacogenetic conditions can occur either as rare defects or as polymorphisms. For example, glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common inherited enzymopathy in which the main clinical complication is hemolysis after ingestion of oxidant drugs (anti-malarials, sulfonamides, analgesics, nitrofurans) and consumption of fava beans.

As an illustrative embodiment, the activity of drug metabolizing enzymes is a major determinant of both the intensity and duration of drug action. The discovery of genetic polymorphisms of drug metabolizing enzymes (e. g., N-acetyltransferase 2 (NAT 2) and cytochrome P450 enzymes CYP2D6 and CYP2C19) has provided an explanation as to why some patients do not obtain the expected drug effects or show exaggerated drug response and serious toxicity after taking the standard and safe dose of a drug. These polymorphisms are expressed in two phenotypes in the population, the extensive metabolizer (EM) and poor metabolizer (PM). The prevalence of PM is different among different populations. For example, the gene coding for CYP2D6 is highly polymorphic and several mutations have been identified in PM, which all lead to the absence of functional CYP2D6. Poor metabolizers of CYP2D6 and CYP2C19 quite frequently experience exaggerated drug response and side effects when they receive standard doses. If a metabolite is the active therapeutic moiety, PM show no therapeutic response, as demonstrated for the analgesic effect of codeine mediated by its CYP2D6-formed metabolite morphine. At the other extreme are the so called ultra-rapid metabolizers who do not respond to standard doses. Recently, the molecular basis of ultra-rapid metabolism has been identified to be due to CYP2D6 gene amplification.

Thus, the activity of FCTRX protein, expression of FCTRX nucleic acid, or mutation content of FCTRX genes in an individual can be determined to thereby select appropriate

agent (s) for therapeutic or prophylactic treatment of the individual. In addition, pharmacogenetic studies can be used to apply genotyping of polymorphic alleles encoding drug-metabolizing enzymes to the identification of an individual's drug responsiveness phenotype. This knowledge, when applied to dosing or drug selection, can avoid adverse reactions or therapeutic failure and thus enhance therapeutic or prophylactic efficiency when treating a subject with an FCTRX modulator, such as a modulator identified by one of the exemplary screening assays described herein.

Monitoring of Effects During Clinical Trials Monitoring the influence of agents (e. g., drugs, compounds) on the expression or activity of FCTRX (e. g., the ability to modulate aberrant cell proliferation and/or differentiation) can be applied not only in basic drug screening, but also in clinical trials. For example, the effectiveness of an agent determined by a screening assay as described herein to increase FCTRX gene expression, protein levels, or regulate FCTRX activity, can be monitored in clinical trails of subjects exhibiting decreased FCTRX gene expression, protein levels, or downregulated FCTRX activity. Alternatively, the effectiveness of an agent determined by a screening assay to decrease FCTRX gene expression, protein levels, or downregulate FCTRX activity, can be monitored in clinical trails of subjects exhibiting increased FCTRX gene expression, protein levels, or upregulated FCTRX activity. In such clinical trials, the expression or activity of FCTRX and, preferably, other genes that have been implicated in, for example, a cellular proliferation or immune disorder can be used as a"read out"or markers of the immune responsiveness of a particular cell.

By way of example, and not of limitation, genes, including FCTRX, that are modulated in cells by treatment with an agent (e. g., compound, drug or small molecule) that modulates FCTRX activity (e. g., identified in a screening assay as described herein) can be identified.

Thus, to study the effect of agents on cellular proliferation disorders, for example, in a clinical trial, cells can be isolated and RNA prepared and analyzed for the levels of expression of FCTRX and other genes implicated in the disorder. The levels of gene expression (i. e., a gene expression pattern) can be quantified by Northern blot analysis or RT-PCR, as described herein, or alternatively by measuring the amount of protein produced, by one of the methods as described herein, or by measuring the levels of activity of FCTRX or other genes. In this manner, the gene expression pattern can serve as a marker, indicative of the physiological response of the cells to the agent. Accordingly, this response state may be determined before, and at various points during, treatment of the individual with the agent.

In one embodiment, the invention provides a method for monitoring the effectiveness of treatment of a subject with an agent (e. g., an agonist, antagonist, protein, peptide, peptidomimetic, nucleic acid, small molecule, or other drug candidate identified by the screening assays described herein) comprising the steps of (i) obtaining a pre-administration sample from a subject prior to administration of the agent ; (M) detecting the level of expression of an FCTRX protein, mRNA, or genomic DNA in the preadministration sample ; (iii) obtaining one or more post-administration samples from the subject ; (iv) detecting the level of expression or activity of the FCTRX protein, mRNA, or genomic DNA in the post-administration samples ; (v) comparing the level of expression or activity of the FCTRX protein, mRNA, or genomic DNA in the pre-administration sample with the FCTRX protein, mRNA, or genomic DNA in the post administration sample or samples ; and (vi) altering the administration of the agent to the subject accordingly. For example, increased administration of the agent may be desirable to increase the expression or activity of FCTRX to higher levels than detected, i. e., to increase the effectiveness of the agent. Alternatively, decreased administration of the agent may be desirable to decrease expression or activity of FCTRX to lower levels than detected, i. e., to decrease the effectiveness of the agent.

Methods of Treatment The invention provides for both prophylactic and therapeutic methods of treating a subject at risk of (or susceptible to) a disorder or having a disorder associated with aberrant FCTRX expression or activity. The disorders include cardiomyopathy, atherosclerosis, hypertension, congenital heart defects, aortic stenosis, atrial septal defect (ASD), atrioventricular (A-V) canal defect, ductus arteriosus, pulmonary stenosis, subaortic stenosis, ventricular septal defect (VSD), valve diseases, tuberous sclerosis, scleroderma, obesity, transplantation, adrenoleukodystrophy, congenital adrenal hyperplasia, prostate cancer, neoplasm ; adenocarcinoma ; lymphoma, uterus cancer, fertility, hemophilia, hypercoagulation, idiopathic thrombocytopenic purpura, immunodeficiencies, graft versus host disease, AIDS, bronchial asthma, Crohn's disease ; multiple sclerosis, treatment of Albright Hereditary Ostoeodystrophy, and other diseases, disorders and conditions of the like.

These methods of treatment will be discussed more fully, below.

Disease and Disorders Diseases and disorders that are characterized by increased (relative to a subject not suffering from the disease or disorder) levels or biological activity may be treated with Therapeutics that antagonize (i. e., reduce or inhibit) activity. Therapeutics that antagonize

activity may be administered in a therapeutic or prophylactic manner. Therapeutics that may be utilized include, but are not limited to : (i) an aforementioned peptide, or analogs, derivatives, fragments or homologs thereof, (ii) antibodies to an aforementioned peptide ; (iii) nucleic acids encoding an aforementioned peptide ; (iv) administration of antisense nucleic acid and nucleic acids that are"dysfunctional" (i. e., due to a heterologous insertion within the coding sequences of coding sequences to an aforementioned peptide) that are utilized to "knockout"endoggenous function of an aforementioned peptide by homologous recombination (see, e. g., Capecchi, 1989. Science 244 : 1288-1292) ; or (v) modulators (i. e., inhibitors, agonists and antagonists, including additional peptide mimetic of the invention or antibodies specific to a peptide of the invention) that alter the interaction between an aforementioned peptide and its binding partner.

Diseases and disorders that are characterized by decreased (relative to a subject not suffering from the disease or disorder) levels or biological activity may be treated with Therapeutics that increase (i. e., are agonists to) activity. Therapeutics that upregulate activity may be administered in a therapeutic or prophylactic manner. Therapeutics that may be utilized include, but are not limited to, an aforementioned peptide, or analogs, derivatives, fragments or homologs thereof ; or an agonist that increases bioavailability.

Increased or decreased levels can be readily detected by quantifying peptide and/or RNA, by obtaining a patient tissue sample (e. g., from biopsy tissue) and assaying it in vitro for RNA or peptide levels, structure and/or activity of the expressed peptides (or mRNAs of an aforementioned peptide). Methods that are well-known within the art include, but are not limited to, immunoassays (e. g., by Western blot analysis, immunoprecipitation followed by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis, immunocytochemistry, etc.) and/or hybridization assays to detect expression of mRNAs (e. g, Northern assays, dot blots, in situ hybridization, and the like).

Prophylactic Methods In one aspect, the invention provides a method for preventing, in a subject, a disease or condition associated with an aberrant FCTRX expression or activity, by administering to the subject an agent that modulates FCTRX expression or at least one FCTRX activity. Subjects at risk for a disease that is caused or contributed to by aberrant FCTRX expression or activity can be identified by, for example, any or a combination of diagnostic or prognostic assays as described herein. Administration of a prophylactic agent can occur prior to the manifestation of symptoms characteristic of the FCTRX aberrancy, such that a disease or disorder is prevented or, alternatively, delayed in its progression. Depending upon the type of FCTRX

aberrancy, for example, an FCTRX agonist or FCTRX antagonist agent can be used for treating the subject. The appropriate agent can be determined based on screening assays described herein. The prophylactic methods of the invention are further discussed in the following subsections.

Therapeutic Methods Another aspect of the invention pertains to methods of modulating FCTRX expression or activity for therapeutic purposes. The modulatory method of the invention involves contacting a cell with an agent that modulates one or more of the activities of FCTRX protein activity associated with the cell. An agent that modulates FCTRX protein activity can be an agent as described herein, such as a nucleic acid or a protein, a naturally-occurring cognate ligand of an FCTRX protein, a peptide, an FCTRX peptidomimetic, or other small molecule.

In one embodiment, the agent stimulates one or more FCTRX protein activity. Examples of such stimulatory agents include active FCTRX protein and a nucleic acid molecule encoding FCTRX that has been introduced into the cell. In another embodiment, the agent inhibits one or more FCTRX protein activity. Examples of such inhibitory agents include antisense FCTRX nucleic acid molecules and anti-FCTRX antibodies. These modulatory methods can be performed in vitro (e. g., by culturing the cell with the agent) or, alternatively, in vivo (e. g., by administering the agent to a subject). As such, the invention provides methods of treating an individual afflicted with a disease or disorder characterized by aberrant expression or activity of an FCTRX protein or nucleic acid molecule. In one embodiment, the method involves administering an agent (e. g., an agent identified by a screening assay described herein), or combination of agents that modulates (e. g., up-regulates or down-regulates) FCTRX expression or activity. In another embodiment, the method involves administering an FCTRX protein or nucleic acid molecule as therapy to compensate for reduced or aberrant FCTRX expression or activity.

Stimulation of FCTRX activity is desirable in situations in which FCTRX is abnormally downregulated and/or in which increased FCTRX activity is likely to have a beneficial effect. One example of such a situation is where a subject has a disorder characterized by aberrant cell proliferation and/or differentiation (e. g., cancer or immune associated disorders). Another example of such a situation is where the subject has a gestational disease (e. g., preclampsia).

Determination of the Biological Effect of the Therapeutic In various embodiments of the invention, suitable in vitro or in vivo assays are performed to determine the effect of. a specific Therapeutic and whether its administration is indicated for treatment of the affected tissue.

In various specific embodiments, in vitro assays may be performed with representative cells of the type (s) involved in the patient's disorder, to determine if a given Therapeutic exerts the desired effect upon the cell type (s). Compounds for use in therapy may be tested in suitable animal model systems including, but not limited to rats, mice, chicken, cows, monkeys, rabbits, and the like, prior to testing in human subjects. Similarly, for in vivo testing, any of the animal model system known in the art may be used prior to administration to human subjects.

Prophylactic and Therapeutic Uses of the Compositions of the Invention The FCTRX nucleic acids and proteins of the invention are useful in potential prophylactic and therapeutic applications implicated in a variety of disorders including, but not limited to : Also within the scope of the invention is the use of a Therapeutic in the manufacture of a medicament for treating or preventing disorders or syndromes including, e. g., Colorectal cancer, adenomatous polyposis coli, myelogenous leukemia, congenital ceonatal alloimmune thrombocytopenia, multiple human solid malignancies, malignant ovarian tumours particularly at the interface between epithelia and stroma, malignant brain tumors, mammary tumors, human gliomas, astrocytomas, mixed glioma/astrocytomas, renal cells carcinoma, breast adenocarcinoma, ovarian cancer, melanomas, renal cell carcinoma, clear cell and granular cell carcinomas, autocrine/paracrine stimulation of tumor cell proliferation, autocrine/paracrine stimulation of tumor cell survival and tumor cell resistance to cytotoxic therapy, paranechmal and basement membrane invasion and motility of tumor cells thereby contributing to metastasis, tumor-mediated immunosuppression of T-cell mediated immune effector cells and pathways resulting in tumor escape from immune surveilance, neurological disorders, neurodegenerative disorders, nerve trauma, familial myelodysplastic syndrome, Charcot-Marie-Tooth neuropathy, demyelinating Gardner syndrome, familial myelodysplastic syndrome ; mental health conditions, immunological disorders, allergy and infection, asthma, bronchial asthma, Avellino type eosinophilia, lung diseases, reproductive disorders, male infertility, female reproductive system disorders, male and female reproductive diseases, hemangioma, deafness, glycoprotein Ia deficiency, desmoid disease, turcot syndrome, liver cirrhosis, hepatitis C, gastric disorders, pancreatic diseases like

diabetes, Schistosoma mansoni infection, Spinocerebellar ataxia, Plasmodium falciparum parasitemia, Corneal dystrophy-Groenouw type I, Corneal dystrophy-lattice type I, and Reis- Bucklers corneal dystrophy.

As an example, a cDNA encoding the FCTRX protein of the invention may be useful in gene therapy, and the protein may be useful when administered to a subject in need thereof.

By way of non-limiting example, the compositions of the invention will have efficacy for treatment of patients suffering from : Also within the scope of the invention is the use of a Therapeutic in the manufacture of a medicament for treating or preventing disorders or syndromes including, e. g., Colorectal cancer, adenomatous polyposis coli, myelogenous leukemia, congenital ceonatal alloimmune thrombocytopenia, multiple human solid malignancies, malignant ovarian tumours particularly at the interface between epithelia and stroma, malignant brain tumors, mammary tumors, human gliomas, astrocytomas, mixed glibma/astrocytomas, renal cells carcinoma, breast adenocarcinoma, ovarian cancer, melanomas, renal cell carcinoma, clear cell and granular cell carcinomas, autocrine/paracrine stimulation of tumor cell proliferation, autocrine/paracrine stimulation of tumor cell survival and tumor cell resistance to cytotoxic therapy, paranechmal and basement membrane invasion and motility of tumor cells thereby contributing to metastasis, tumor-mediated immunosuppression of T-cell mediated immune effector cells and pathways resulting in tumor escape from immune surveilance, neurological disorders, neurodegenerative disorders, nerve trauma, familial myelodysplastic syndrome, Charcot-Marie-Tooth neuropathy, demyelinating Gardner syndrome, familial myelodysplastic syndrome ; mental health conditions, immunological disorders, allergy and infection, asthma, bronchial asthma, Avellino type eosinophilia, lung diseases, reproductive disorders, male infertility, female reproductive system disorders, male and female reproductive diseases, hemangioma, deafness, glycoprotein la deficiency, desmoid disease, turcot syndrome, liver cirrhosis, hepatitis C, gastric disorders, pancreatic diseases like diabetes, Schistosoma mansoni infection, Spinocerebellar ataxia, Plasmodium falciparum parasitemia, Corneal dystrophy-Groenouw type I, Corneal dystrophy -lattice type I, and Reis-Bucklers corneal dystrophy.

Both the novel nucleic acid encoding the FCTRX protein, and the FCTRX protein of the invention, or fragments thereof, may also be useful in diagnostic applications, wherein the presence or amount of the nucleic acid or the protein are to be assessed. A further use could be as an anti-bacterial molecule (i. e., some peptides have been found to possess anti-bacterial properties). These materials are further useful in the generation of antibodies which

immunospecifically-bind to the novel substances of the invention for use in therapeutic or diagnostic methods.

EXAMPLES The following examples illustrate by way of non-limiting example various aspects of the invention.

The following examples illustrate by way of non-limiting example various aspects of the invention.

Example 1 : Method of Identifying the Nucleic Acids The novel nucleic acids of the invention were identified by TblastN using a proprietary sequence file, run against the Genomic Daily Files made available by GenBank. The nucleic acids were further predicted by the proprietary software program GenScanTM, including selection of exons. These were further modified by means of similarities using BLAST searches. The sequences were then manually corrected for apparent inconsistencies, thereby obtaining the sequences encoding the full-length proteins.

Example 2. Quantitative expression analysis of FCTR2 in various cells and tissues The quantitative expression of various clones was assessed using microtiter plates containing RNA samples from a variety of normal and pathology-derived cells, cell lines and tissues using real time quantitative PCR (RTQ PCR ; TAQMAN). RTQ PCR was performed on a Perkin-Elmer Biosystems ABI PRISM@ 7700 Sequence Detection System. Various collections of samples are assembled on the plates, and referred to as Panel 1 (containing cells and cell lines from normal and cancer sources), Panel 2 (containing samples derived from tissues, in particular from surgical samples, from normal and cancer sources), Panel 3 (containing samples derived from a wide variety of cancer sources) and Panel 4 (containing cells and cell lines from normal cells and cells related to inflammatory conditions).

First, the RNA samples were normalized to constitutively expressed genes such as ß- actin and GAPDH. RNA (-50 ng total or-1 ng polyA+) was converted to cDNA using the TAQMAN Reverse Transcription Reagents Kit (PE Biosystems, Foster City, CA ; Catalog No. N808-0234) and random hexamers according to the manufacturer's protocol. Reactions were performed in 20 ul and incubated for 30 min. at 48°C. cDNA (5 ul) was then transferred to a separate plate for the TAQMAN@ reaction using p-actin and GAPDH TAQMAN (D Assay Reagents (PE Biosystems ; Catalog Nos. 4310881E and 4310884E, respectively) and

TAQMAN universal PCR Master Mix (PE Biosystems ; Catalog No. 4304447) according to the manufacturer's protocol. Reactions were performed in 25 ul using the following parameters : 2 min. at 50°C ; 10 min. at 95°C ; 15 sec. at 95°C/1 min. at 60°C (40 cycles).

Results were recorded as CT values (cycle at which a given sample crosses a threshold level of fluorescence) using a log scale, with the difference in RNA concentration between a given sample and the sample with the lowest CT value being represented as 2 to the power of delta CT. The percent relative expression is then obtained by taking the reciprocal of this RNA difference and multiplying by 100. The average CT values obtained for B-actin and GAPDH were used to normalize RNA samples. The RNA sample generating the highest CT value required no further diluting, while all other samples were diluted relative to this sample according to their ß-actin/GAPDH average CT values.

Normalized RNA (5 ul) was converted to cDNA and analyzed via TAQMAN using One Step RT-PCR Master Mix Reagents (PE Biosystems ; Catalog No. 4309169) and gene- specific primers according to the manufacturer's instructions. Probes and primers were designed for each assay according to Perkin Elmer Biosystem's Primer Express Software package (version I for Apple Computer's Macintosh Power PC) or a similar algorithm using the target sequence as input. Default settings were used for reaction conditions and the following parameters were set before selecting primers : primer concentration = 250 nM, primer melting temperature (Tm) range = 58°-60° C, primer optimal Tm = 59° C, maximum primer difference = 2° C, probe does not have 5'G, probe Tm must be 10° C greater than primer Tm, amplicon size 75 bp to 100 bp. The probes and primers selected (see below) were synthesized by Synthegen (Houston, TX, USA). Probes were double purified by HPLC to remove uncoupled dye and evaluated by mass spectroscopy to verify coupling of reporter and quencher dyes to the 5'and 3'ends of the probe, respectively. Their final concentrations were : forward and reverse primers, 900 nM each, and probe, 200nM.

PCR conditions : Normalized RNA from each tissue and each cell line was spotted in each well of a 96 well PCR plate (Perkin Elmer Biosystems). PCR cocktails including two probes (a probe specific for the target clone and another gene-specific probe multiplexed with the target probe) were set up using 1X TaqMan PCR Master Mix for the PE Biosystems 7700, with 5 mM MgC12, dNTPs (dA, G, C, U at 1 : 1 : 1 : 2 ratios), 0. 25 U/ml AmpliTaq Gold (PE Biosystems), and 0. 4 Fuzz RNase inhibitor, and 0. 25 U/, ul reverse transcriptase. Reverse transcription was performed at 48° C for 30 minutes followed by amplification/PCR cycles as follows : 95° C 10 min, then 40 cycles of 95° C for 15 seconds, 60° C for 1 minute.

In the results for Panel 1, the following abbreviations are used : ca. = carcinoma, * = established from metastasis, met = metastasis, s cell var= small cell variant, non-s = non-sm =non-small, squam = squamous, pl. eff = pl effusion = pleural effusion, glio = glioma, astro = astrocytoma, and neuro = neuroblastoma.

Panel 2 The plates for Panel 2 generally include 2 control wells and 94 test samples composed of RNA or cDNA isolated from human tissue procured by surgeons working in close cooperation with the National Cancer Institute's Cooperative Human Tissue Network (CHTN) or the National Disease Research Initiative (NDRI). The tissues are derived from human malignancies and in cases where indicated many malignant tissues have"matched margins" obtained from noncancerous tissue just adjacent to the tumor. These are termed normal adjacent tissues and are denoted"NAT"in the results below. The tumor tissue and the "matched margins"are evaluated by two independent pathologists (the surgical pathologists and again by a pathologists at NDRI or CHTN). This analysis provides a gross histopathological assessment of tumor differentiation grade. Moreover, most samples include the original surgical pathology report that provides information regarding the clinical stage of the patient. These matched margins are taken from the tissue surrounding (i. e. immediately proximal) to the zone of surgery (designated"NAT", for normal adjacent tissue, in Table RR).

In addition, RNA and cDNA samples were obtained from various human tissues derived from autopsies performed on elderly people or sudden death victims (accidents, etc.). These tissue were ascertained to be free of disease and were purchased from various commercial sources such as Clontech (Palo Alto, CA), Research Genetics, and Invitrogen.

RNA integrity from all samples is controlled for quality by visual assessment of agarose gel electropherograms using 28S and 18S ribosomal RNA staining intensity ratio as a

guide (2 : 1 to 2. 5 : 1 28s : 18s) and the absence of low molecular weight RNAs that would be indicative of degradation products. Samples are controlled against genomic DNA contamination by RTQ PCR reactions run in the absence of reverse transcriptase using probe and primer sets designed to amplify across the span of a single exon.

Panel 4 Panel 4 includes samples on a 96 well plate (2 control wells, 94 test samples) composed of RNA (Panel 4r) or cDNA (Panel 4d) isolated from various human cell lines or tissues related to inflammatory conditions. Total RNA from control normal tissues such as colon and lung (Stratagene, La Jolla, CA) and thymus and kidney (Clontech) were employed.

Total RNA from liver tissue from cirrhosis patients and kidney from lupus patients was obtained from BioChain (Biochain Institute, Inc., Hayward, CA). Intestinal tissue for RNA preparation from patients diagnosed as having Crohn's disease and ulcerative colitis was obtained from the National Disease Research Interchange (NDRI) (Philadelphia, PA).

Astrocytes, lung fibroblasts, dermal fibroblasts, coronary artery smooth muscle cells, small airway epithelium, bronchial epithelium, microvascular dermal endothelial cells, microvascular lung endothelial cells, human pulmonary aortic endothelial cells, human umbilical vein endothelial cells were all purchased from Clonetics (Walkersville, MD) and grown in the media supplied for these cell types by Clonetics. These primary cell types were activated with various cytokines or combinations of cytokines for 6 and/or 12-14 hours, as indicated. The following cytokines were used ; IL-1 beta at approximately 1-5 ng/ml, TNF alpha at approximately 5-10 ng/ml, IFN gamma at approximately 20-50 ng/ml, IL-4 at approximately 5-10 ng/ml, IL-9 at approximately 5-10 ng/ml, IL-13 at approximately 5-10 ng/ml. Endothelial cells were sometimes starved for various times by culture in the basal media from Clonetics with 0. 1% serum.

Mononuclear cells were prepared from blood of employees at CuraGen Corporation, using Ficoll. LAK cells were prepared from these cells by culture in DMEM 5% FCS (Hyclone), 100 p. M non essential amino acids (Gibco/Life Technologies, Rockville, MD), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5. 5 x 10-5 M (Gibco), and 10 mM Hepes (Gibco) and Interleukin 2 for 4-6 days. Cells were then either activated with 10-20 ng/ml PMA and 1-2 llg/ml ionomycin, IL-12 at 5-10 ng/ml, IFN gamma at 20-50 ng/ml and IL-18 at

5-10 ng/ml for 6 hours. In some cases, mononuclear cells were cultured for 4-5 days in DMEM 5% FCS (Hyclone), 100 pM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5. 5 x 10-5 M (Gibco), and 10 mM Hepes (Gibco) with PHA (phytohemagglutinin) or PWM (pokeweed mitogen) at approximately 5 g/ml. Samples were taken at 24, 48 and 72 hours for RNA preparation. MLR (mixed lymphocyte reaction) samples were obtained by taking blood from two donors, isolating the mononuclear cells using Ficoll and mixing the isolated mononuclear cells 1 : 1 at a final concentration of approximately 2x106 cells/ml in DMEM 5% FCS (Hyclone), 100 uM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol (5. 5 x 10-5 M) (Gibco), and 10 mM Hepes (Gibco). The MLR was cultured and samples taken at various time points ranging from 1-7 days for RNA preparation.

Monocytes were isolated from mononuclear cells using CD14 Miltenyi Beads, +ve VS selection columns and a Vario Magnet according to the manufacturer's instructions.

Monocytes were differentiated into dendritic cells by culture in DMEM 5% fetal calf serum (FCS) (Hyclone, Logan, UT), 100 1M non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5. 5 x 10-5 M (Gibco), and 10 mM Hepes (Gibco), 50 ng/ml GMCSF and 5 ng/ml IL-4 for 5-7 days. Macrophages were prepared by culture of monocytes for 5-7 days in DMEM 5% FCS (Hyclone), 100 uM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5. 5 x 10-5 M (Gibco), 10 mM Hepes (Gibco) and 10% AB Human Serum or MCSF at approximately 50 ng/ml. Monocytes, macrophages and dendritic cells were stimulated for 6 and 12-14 hours with lipopolysaccharide (LPS) at 100 ng/ml. Dendritic cells were also stimulated with anti-CD40 monoclonal antibody (Pharmingen) at 10 ug/ml for 6 and 12-14 hours.

CD4 lymphocytes, CD8 lymphocytes and NK cells were also isolated from mononuclear cells using CD4, CD8 and CD56 Miltenyi beads, positive VS selection columns and a Vario Magnet according to the manufacturer's instructions. CD45RA and CD45RO CD4 lymphocytes were isolated by depleting mononuclear cells of CD8, CD56, CD14 and CD19 cells using CD8, CD56, CD14 and CD19 Miltenyi beads and +ve selection. Then CD45RO beads were used to isolate the CD45RO CD4 lymphocytes with the remaining cells being CD45RA CD4 lymphocytes. CD45RA CD4, CD45RO CD4 and CD8 lymphocytes were placed in DMEM 5% FCS (Hyclone), 100 IlM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5. 5 x 10-5 M (Gibco), and 10 mM Hepes (Gibco)

and plated at 106 cells/ml onto Falcon 6 well tissue culture plates that had been coated overnight with 0. 5 Fg/ml anti-CD28 (Pharmingen) and 3 ug/ml anti-CD3 (OKT3, ATCC) in PBS. After 6 and 24 hours, the cells were harvested for RNA preparation. To prepare chronically activated CD8 lymphocytes, we activated the isolated CD8 lymphocytes for 4 days on anti-CD28 and anti-CD3 coated plates and then harvested the cells and expanded them in DMEM 5% FCS (Hyclone), 100 RM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5. 5 x 10-5 M (Gibco), and 10 mM Hepes (Gibco) and IL-2.

The expanded CD8 cells were then activated again with plate bound anti-CD3 and anti-CD28 for 4 days and expanded as before. RNA was isolated 6 and 24 hours after the second activation and after 4 days of the second expansion culture. The isolated NK cells were cultured in DMEM 5% FCS (Hyclone), 100 uM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5. 5 x 10-5 M (Gibco), and 10 mM Hepes (Gibco) and IL-2 for 4-6 days before RNA was prepared.

To obtain B cells, tonsils were procured from NDRI. The tonsil was cut up with sterile dissecting scissors and then passed through a sieve. Tonsil cells were then spun down and resupended at 106 cells/ml in DMEM 5% FCS (Hyclone), 100 M non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5. 5 x 10-5 M (Gibco), and 10 mM Hepes (Gibco). To activate the cells, we used PWM at 5 jug/ml or anti-CD40 (Pharmingen) at approximately 10 J. gel and IL-4 at 5-10 ng/ml. Cells were harvested for RNA preparation at 24, 48 and 72 hours.

To prepare the primary and secondary Thl/Th2 and Trl cells, six-well Falcon plates were coated overnight with 10 llg/ml anti-CD28 (Pharmingen) and 2 ug/ml OKT3 (ATCC), and then washed twice with PBS. Umbilical cord blood CD4 lymphocytes (Poietic Systems, 5 6 German Town, MD) were cultured at 10-10 cells/ml in DMEM 5% FCS (Hyclone), 100 LM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5. 5 x 10 5 M (Gibco), 10 mM Hepes (Gibco) and IL-2 (4 ng/ml). IL-12 (5 ng/ml) and anti-IL4 (1 tig/ml) were used to direct to Thl, while IL-4 (5 ng/ml) and anti-IFN gamma (1 gg/ml) were used to direct to Th2 and IL-10 at 5 ng/ml was used to direct to Trl. After 4-5 days, the activated Thl, Th2 and Trl lymphocytes were washed once in DMEM and expanded for 4-7 days in DMEM 5% FCS (Hyclone), 100 tM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5. 5 x 10-5 M (Gibco), 10 mM Hepes (Gibco) and IL-2 (1

ng/ml). Following this, the activated Thl, Th2 and Trl lymphocytes were re-stimulated for 5 days with anti-CD28/OKT3 and cytokines as described above, but with the addition of anti- CD95L (1, ug/ml) to prevent apoptosis. After 4-5 days, the Thl, Th2 and Trl lymphocytes were washed and then expanded again with IL-2 for 4-7 days. Activated Thl and Th2 lymphocytes were maintained in this way for a maximum of three cycles. RNA was prepared from primary and secondary Thl, Th2 and Trl after 6 and 24 hours following the second and third activations with plate bound anti-CD3 and anti-CD28 mAbs and 4 days into the second and third expansion cultures in Interleukin 2.

The following leukocyte cells lines were obtained from the ATCC : Ramos, EOL-1, KU-812. EOL cells were further differentiated by culture in 0. 1 mM dbcAMP at 5 x105 cells/ml for 8 days, changing the media every 3 days and adjusting the cell concentration to 5 x105 cells/ml. For the culture of these cells, we used DMEM or RPMI (as recommended by the ATCC), with the addition of 5% FCS (Hyclone), 100 ßM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5. 5 x 10-5 M (Gibco), 10 mM Hepes (Gibco). RNA was either prepared from resting cells or cells activated with PMA at 10 ng/ml and ionomycin at 1, ug/ml for 6 and 14 hours. Keratinocyte line CCD106 and an airway epithelial tumor line NCI-H292 were also obtained from the ATCC. Both were cultured in DMEM 5% FCS (Hyclone), 100 pM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5. 5 x 10-5 M (Gibco), and 10 mM Hepes (Gibco).

CCD1106 cells were activated for 6 and 14 hours with approximately 5 ng/ml TNF alpha and 1 ng/ml IL-1 beta, while NCI-H292 cells were activated for 6 and 14 hours with the following cytokines : 5 ng/ml IL-4, 5 ng/ml IL-9, 5 ng/ml IL-13 and 25 ng/ml IFN gamma.

For these cell lines and blood cells, RNA was prepared by lysing approximately 10 cells/ml using Trizol (Gibco BRL). Briefly, 1/10 volume of bromochloropropane (Molecular Research Corporation) was added to the RNA sample, vortexed and after 10 minutes at room temperature, the tubes were spun at 14, 000 rpm in a Sorvall SS34 rotor. The aqueous phase was removed and placed in a 15 ml Falcon Tube. An equal volume of isopropanol was added and left at-20 degrees C overnight. The precipitated RNA was spun down at 9, 000 rpm for 15 min in a Sorvall SS34 rotor and washed in 70% ethanol. The pellet was redissolved in 300 jj. l ofRNAse-free water and 35 J, 1 buffer (Promega) 5 111 DTT, 7, ul RNAsin and 8 u. l DNAse were added. The tube was incubated at 37 degrees C for 30 minutes to remove contaminating genomic DNA, extracted once with phenol chloroform and re-

precipitated with 1/10 volume of 3 M sodium acetate and 2 volumes of 100% ethanol. The RNA was spun down and placed in RNAse free water. RNA was stored at-80 degrees C.

The above detailed procedures were carried out to obtain the taqman profiles of the clones in question.

Given below are the Primers and the Taqman results for the following clones : 58092213. 0. 36-Probe Name : Ag809 (Table 9 and Table 10) 29692275. 0. 1-Probe Name : Ag2773 (Table 11 and Table 12) 32125243. 0. 21-Probe Name : Ag427 (Table 13 and Table 14) 27455183. 0. 19-Probe Name : Agl541 (Table 15 and Table 16, 17, 18) Table 8 : Primer Design for Probe Ag809 (FCTR1) Primer Sequences TM Length Start Pos SEQID NO Forward 5'-ATGTGATCTTTGGCTGTGAAGT-3'58. 7 22 337 24 Probe FAM-5'-CTACCCCATGGCCTCCATCGAGT-3'-TAMRA 69. 4 23 365 25 Reverse 59. 919 393 26 5'-GGATGTCCAAGCCATCCTT-3'

TABLE 9 : TAQMAN RESULTS FOR FCTR1 Panel Panel Tissue Name Panel 1 Tissue Name 2D Tissue Name 4D Liver Normal Colon 93768Secondary Th1anti- adenocarcinoma 79. 6 GENPAK 061003 6. 8 CD28/anti-CD3 2. 0 83219 CC Well to Mod Diff 93769Secondary Th2anti- Heart (fetal) 43. 8 (OD03866) 6. 1 CD28/anti-CD3 1. 5 83220 CC NAT 93770Secondary Tr1 anti- Pancreas 2. 1 (OD03866) 2. 5 CD28/anti-CD3 2. 5 83221 CC Gr. 2 Pancreatic ca. rectosigmoid 93573 Secondary Th1_resting day CAPAN 2 4. 7 (OD03868) 0. 9 4-6 in IL-2 1. 0 83222 CC NAT 93572Secondary Th2resting day Adrenal gland 2. 3 (OD03868) 1. 2 4-6 in IL-2 3. 0 83235 CC Mod 93571_Secondary Tr1_resting day Thyroid 6. 5 Diff (OD03920) 3. 8 4-6 in IL-2 1. 7 83236 CC NAT 93568primary Th1anti- Salivary gland 12. 3 (OD03920) 1. 3 CD28/anti-CD3 0. 4 83237 CC Gr. 2 ascend colon 93569_primary Th2anti- Pituitary gland 8. 7 (OD03921) 6. 9 CD28/anti-CD3 1. 5 83238 CC NAT 93570_primary Tr1anti-CD28/anti- Brain (fetal) 0. 0 (OD03921) 4. 0 CD3 2. 0 Brain (whole) 3. 0 83241 CC from 1. 2 93565_primary Th1_resting dy 4-6 5. 4 Partial in IL-2 Hepatectomy (OD04309) Brain 83242 Liver NAT 93566_primary Th2 resting dy 4-6 (amygdala) 2. 4 (OD04309) 0. 6 in IL-2 3. 1 87472 Colon mets Brain to lung (OD04451-93567primary Tr1resting dy 4-6 (cerebellum) 0. 0 01) 4. 4 in IL-2 0. 0 Brain 87473 Lung NAT 93351 CD45RA CD4 (hippocampus) 13. 0 (OD04451-02) 1. 2 lymphocyte anti-CD28/anti-CD3 11. 2 Normal Prostate Clontech As 93352_CD45RO CD4 Brain (thalamus) 3. 0 6546-1 10. 2 lymphocyte anti-CD28/anti-CD3 1. 2 84140 Prostate Cancer 93251 CD8 Lymphocytes anti- Cerebral Cortex 2. 3 (OD04410) 41. 8 CD28/anti-CD8 0. 9 84141 Prostate 93353_chronic CD8 Lymphocytes Spinal cord 2. 6 NAT (OD04410) 25. 7 2ry_resting dy 4-6 in IL-2 0. 0 CNS ca. 87073 Prostate (glio/astro) U87-Cancer 93574 chronic CD8 Lymphocytes MG 12. 1 (OD04720-01) 11. 0 2ry_activated CD3/CD28 0. 6 CNS ca. 87074 Prostate (glio/astro) U-NAT (OD04720- 118-MG 100. 0 02) 10. 0 93354 CD4 none 1. 1 CNS ca. (astro) Normal Lung 93252 Secondary SW1783 6. 5 GENPAK 061010 7. 9 Th1/Th2/Tr1_anti-CD95 CH11 0. 0 83239 Lung Met CNS ca. * (neuro ; to Muscle met) SK-N-AS 52. 1 (OD04286) 6. 5 93103_LAK cells_resting 0.5 CNS ca. (astro) 83240 Muscle SF-539 12. 6 NAT (OD04286) 2. 6 93788 LAK cells_IL-2 0.0 84136 Lung CNS ca. (astro) Malignant Cancer SNB-75 11. 9 (OD03126) 14. 8 93787 LAK cells IL-2+IL-12 0. 7 CNS ca. 84137 Lung NAT (glio) SNB-19 0. 0 (OD03126) 3. 2 93789 LAK cells IL-2+IFN gamma 1. 1 84871 Lung CNS ca. Cancer (glio) U251 0. 9 (OD04404) 2. 1 93790 LAK cells IL-2+ IL-18 0. 3 CNS ca. (glio) 84872 Lung NAT 93104_LAK cells_PMA/ionomycin SF-295 12. 6 (OD04404) 1. 9 and IL-18 0. 0 84875 Lung Cancer Heart 13. 9 (OD04565) 0. 3 93578 NK Cells IL-2 resting 1. 3 85950 Lung Cancer 93109_Mixed Lymphocyte Skeletal muscle 3. 2 (OD04237-01) 1. 3 Reaction Two Way MLR 0. 5 85970 Lung NAT 93110Mixed Lymphocyte Bone marrow 3. 6 (OD04237-02) 2. 6 Reaction Two Way MLR 0. 5 83255 OcularMel Met to Liver 93111_Mixed Lymphocyte Thymus 4. 2 (OD04310) 0. 1 Reaction Two Way MLR 2. 7 83256 Liver NAT 93112 Mononuclear Cells Spleen 61. 6 (OD04310) 0. 6 (PBMCs) _resting 0. 0 84139 Melanoma Mets to Lung 93113_Mononuclear Cells Lymph node 3. 3 (OD04321) 2. 5 (PBMCs) PWM 1. 3 84138 Lung NAT 93114 Mononuclear Cells Colorectal 11. 9 (OD04321) 2. 6 (PBMCs) _PHA-L 1. 0 Normal Kidney Stomach 28. 3 GENPAK 061008 5. 6 93249 Ramos (B cell)_none 1. 2 83786 Kidney Ca, Nuclear grade Small intestine 4. 5 2 (OD04338) 0. 6 93250 Ramos (B cell) ionomycin 2. 3 Colon ca. 83787 Kidney SW480 46. 7 NAT (OD04338) 3. 7 93349 B lymphocytes PWM 4. 3 Colon ca. * 83788 Kidney Ca (SW480 Nuclear grade 1/2 93350_B lymphoytes_CD40L and met) SW620 19. 0 (OD04339) 0. 8 IL-4 1. 4 83789 Kidney 92665 EOL-1 Colon ca. HT29 5. 3 NAT (OD04339) 3. 1 (Eosinophil) dbcAMP differentiated 7. 2 83790 Kidney Ca, 93248 EOL-1 Colon ca. HCT-Clear cell type (Eosinophil) dbcAMP/PMAionomyc 116 5. 0 (OD04340) 1. 5 in 3. 0 Colon ca. CaCo-83791 Kidney 2 49. 3 NAT (OD04340) 5. 1 93356 Dendritic Cells none 1. 5 83219 CC Well 83792 Kidney Ca, to Mod Diff. Nuclear grade 3 93355 Dendritic Cells LPS 100 (OD03866) 3. 0 (OD04348) 14. 5 ng/ml 0. 7 Colon ca. HCC-83793 Kidney 2998 27. 7 NAT (OD04348) 2. 5 93775_Dendritic Cells_anti-CD40 0. 5 Gastric ca. * 87474 Kidney (liver met) NCI-Cancer N87 10. 5 (OD04622-01) 1. 7 93774 Monocytes resting 0. 5 87475 Kidney NAT (OD04622- Bladder 3. 7 03) 2. 0 93776 Monocytes_LPS 50 ng/ml 0. 0 85973 Kidney Cancer Trachea 23. 5 (OD04450-01) 0. 3 93581 Macrophages resting 1. 3 85974 Kidney NAT (OD04450-93582MacrophagesLPS 100 Kidney 1. 8 03) 2. 0 ng/ml 1. 8 Kidney Cancer Kidney (fetal) 1. 9 Clontech 8120607 7. 0 93098 HUVEC (Endothelial) none 2. 3 Kidney NAT 93099 HUVEC Renal ca. 786-0 7. 0 Clontech 8120608 1. 5 (Endothelial) starved 9. 0 Kidney Cancer Renal ca. A498 6. 8 Clontech 8120613 2. 0 93100 HUVEC (Endothelial) IL-1b 1. 2 Renal ca. RXF Kidney NAT 93779_HUVEC (Endothelial) IFN 393 4. 7 Clontech 8120614 4. 1 gamma 1. 4 Kidney Cancer 93102 HUVEC (Endothelial) _TNF Renal ca. ACHN 9. 8 Clontech 9010320 2. 2 alpha + IFN gamma 0. 8 Kidney NAT 93101 HUVEC (Endothelial) TNF Renal ca. UO-31 1. 3 Clontech 9010321 3. 5 alpha + IL4 1. 1 Normal Uterus Renal ca. TK-10 0. 6 GENPAK 061018 3. 1 93781 HUVEC (Endothelial) IL-11 3. 0 Uterus Cancer 93583 Lung Microvascular Liver 0. 8 GENPAK 064011 17. 6 Endothelial Cells none 0. 8 Normal Thyroid 93584Lung Microvascutar Clontech A+ Endothelial Cells TNFa (4 ng/ml) Liver (fetal) 1. 1 6570-1 3.7 and IL1b (1 ng/ml) 0. 5 Liver ca. (hepatoblast) Thyroid Cancer 92662 Microvascular Dermal HepG2 54. 0 GENPAK 064010 1. 2 endothelium none 1. 1 Thyroid Cancer 92663 Microsvasular Derma) INVITROGEN endothelium_TNFa (4 ng/ml) and Lung 3.9 A302152 0.6 IL1b (1 ng/ml) 1. 0 Thyroid NAT INVITROGEN 93773 Bronchial epithelium TNFa Lung (fetal) 9. 0 A302153 2. 6 (4 ng/ml) and IL1b (1 ng/ml) ** 0. 0 Lung ca. (small Normal Breast 93347 Small Airway cell) LX-1 34. 4 GENPAK 061019 3. 4 Epithelium_none 0.4 84877 Breast 93348 Small Airway Lung ca. (small Cancer Epithelium TNFa (4 ng/ml) and cell) NCI-H69 3. 0 (OD04566) 0. 9 IL1 b (1 ng/ml) 0. 5 85975 Breast Lung ca. (s. cell Cancer 92668_Coronery Artery var.) SHP-77 13. 0 (OD04590-01) 67. 8 SMC resting 5. 8 85976 Breast 92669 Coronery Artery Lung ca. (large Cancer Mets SMC_TNFa (4 ng/ml) and IL1b (1 cell) NCI-H460 6. 8 (OD04590-03) 51. 1 ng/ml) 2. 3 87070 Breast Cancer Lung ca. (non-Metastasis sm. cell) A549 3. 4 (OD04655-05) 12. 7 93107 astrocytes_resting 2. 7 Lung ca. (non-GENPAK Breast 93108 astrocytes TNFa (4 ng/ml) s. cell) NCI-H23 34. 4 Cancer 064006 8. g and IL1b (1 ng/ml) 0. 0 Lung ca (non-Breast Cancer s. cell) HOP-62 10. 5 Clontech 9100266 6. 2 92666_KU-812 (Basophil)_resting 6. 8 Lung ca. (non-Breast NAT 92667 KU-812 s. cl) NCI-H522 47. 6 Clontech 9100265 3. 3 (Basophil) PMA/ionoycin 8. 4 Lung ca. Breast Cancer (squam.) SW INVITROGEN 93579_CCD1106 900 4. 7 A209073 3. 4 (Keratinocytes)_none 1. 6 Lung ca. Breast NAT (squam.) NCI-INVITROGEN 93580_CCD1106 H596 0. 7 A2090734 8. 7 (Keratinocytes) TNFa and IFNg ** 1. 4 Normal Liver Mammary gland 9. 9 GENPAK 061009 1. 1 93791_Liver Cirrhosis 4. 2 Breast ca. * (pl. Liver Cancer effusion) MCF-7 5. 6 GENPAK 064003 0. 6 93792_Lupus Kidney 1.9 Liver Cancer Breast ca. * Research (pl. ef) MDA-MB-Genetics RNA 231 21. 3 1025 0. 6 93577 NCI-H292 39. 5 Liver Cancer Research Breast ca. * (pl. Genetics RNA effusion) T47D 66. 0 1026 1.4 93358_NCl-H292_IL-4 39. 0 Paired Liver Cancer Tissue Research Breast ca. BT-Genetics RNA 549 7.6 6004-T 1.3 93360_NCl-H292_IL-9 65. 5 Paired Liver Tissue Research Breast ca. MDA- Genetics RNA N 18. 7 6004-N 1. 3 93359 NCI-H292 IL-13 37. 1 Paired Liver Cancer Tissue Research Genetics RNA Ovary 12. 1 6005-T 1. 1 93357 NCI-H292 IFN gamma 31. 9 Paired Liver Tissue Research Ovarian Genetics RNA ca. OVCAR-3 3. 5 6005-N 0. 3 93777 HPAEC-0. 5 Ovarian Normal Bladder 93778_HPAEC_IL-1 beta/TNA ca. OVCAR-4 4. 0 GENPAK 061001 5. 9 alpha 1. 2 Ovarian ca. Bladder Cancer 93254 Normal Human Lung OVCAR-5 9. 1 Research 1.7 Fibroblast none 42. 3 Genetics RNA 1023 Bladder Cancer 93253 Normal Human Lung Ovarian ca. INVITROGEN Fibrobiast TNFa (4 ng/ml) and IL- OVCAR-8 12. 7 A302173 1. 9 1 b (1 ng/ml) 17. 8 87071 Bladder Ovarian Cancer 93257 Normal Human Lung ca. IGROV-1 9. 8 (OD04718-01) 2. 0 Fibroblast IL-4 100. 0 Ovarian ca. * 87072 Bladder (ascites) SK-OV-Normal Adjacent 93256 Normal Human Lung 3 0. 4 (OD04718-03) 3. 3 Fibroblast IL-9 72. 7 Normal Ovary 93255 Normal Human Lung Uterus 6.9 Res. Gen. 2. 2 Fibroblast IL-13 60. 7 Ovarian Cancer 93258 Normal Human Lung Placenta 4. 6 GENPAK 064008 29. 1 Fibroblast IFN gamma 81. 8 87492 Ovary Cancer 93106_Dermal Fibroblasts Prostate 15. 7 (OD04768-07) 100. 0 CCD1070 resting 76. 8 Prostate ca. * 87493 Ovary NAT 93361 Dermal Fibroblasts (bone met) PC-3 35. 9 (OD04768-08) 2. 2 CCD1070 TNF alpha 4 ng/ml 30. 2 Normal Stomach 93105 Dermal Fibroblasts Testis 14. 6 GENPAK 061017 13. 1 CCD1070 IL-1 beta 1 ng/ml 38. 2 Melanoma NAT Stomach 93772 dermal fibroblast IFN Hs688 (A). T 13. 5 Clontech 9060359 8. 8 gamma 34. 2 Melanoma* Gastric Cancer (met) Clontech Hs688 (B). T 71. 2 9060395 2. 5 93771 dermal fibroblast IL-4 80. 7 Melanoma NAT Stomach UACC-62 1. 7 Clontech 9060394 9. 7 93259 IBD Colitis 1** 0. 0 Gastric Cancer Clontech Melanoma M14 9. 5 9060397 15. 9 93260 IBD Colitis 2 0. 3 Melanoma LOX NAT Stomach IMVI 2. 4 Clontech 9060396 12. 9 93261 IBD Crohns 1. 4 Melanoma* Gastric Cancer (met) SK-MEL-5 3. 4 GENPAK 064005 12. 1 735010 Colon normal 35. 6 Adipose 5. 9 735019 Lung none 11. 0 64028-1 Thymus none 5. 8 64030-1_Kidney_none 9. 7

Taqman results shown in Table 9 demonstrates that cFCTR1 is highly expressed by tumor cell lines and also overexpressed in tumor tissues, specifically breast and ovarian tumor compared to Normal Adjacent Tissues (NAT). There are reports that follistatin can act as a modulator of tumor growth and its expression also correlate with polycystic ovary syndrome, a benign form of ovarian tumor.

Table 10 : Primer Design for Probe Ag2773 (FCTR4) Primer Sequences TM Length Start Pos SEQ ID NO Forward 5'-CCTTGCTTTGTCATATGCTGTT-3' 59.3 22 243 29 Probe FAM-5'-CCCTTTGCCTGGAATATAAACTCTCA-3'-TAMRA 64. 6 26 265 30 Reverse 5'-AGAGGAAGCTTTCTGGAGAAGA-3'58. 9 22 313 31 TABLE 11 : TAQMAN RESULTS FOR CLONE FCTR4 Panel Panel Panel Tissue Name 1 D Tissue Name 2D Tissue Name 4D Liver Normal Colon 93768_Secondary Th1_anti-CD28/anti- adenocarcinoma 18. 3 GENPAK 061003 41. 2 CD3 12. 7 83219 CC Well to Mod Diff 93769 Secondary Th2^anti-CD28/anti- Heart (fetal) 4. 3 (OD03866) 5. 2 CD3 14. 2 83220 CC NAT 93770Secondary Tr1anti-CD28/anti- Pancreas 3. 1 (OD03866) 2. 5 CD3 14. 7 83221 CC Gr. 2 Pancreatic rectosigmoid 93573_Secondary Th1_resting day 4-6 ca. CAPAN 2 20. 0 (OD03868) 0. 7 in IL-2 4. 7 83222 CC NAT 93572Secondary Th2resting day 4-6 Adrenal gland 7. 4 (OD03868) 1. 4 in IL-2 3. 5 83235 CC Mod 93571 Secondary Tr1_resting day 4-6 Thyroid 6. 8 Diff (OD03920) 14. 0 in IL-2 7. 0 83236 CC NAT 93568_primary Th1anti-CD28/anti- Salivary gland 2. 5 (OD03920) 13. 9 CD3 22. 4 83237 CC Gr. 2 ascend colon 93569_primary Th2_anti-CD28/anti- Pituitary gland 5. 7 (OD03921) 16. 2 CD3 16. 3 83238 CC NAT 93570_primary Tr1 anti-CD28/anti- Brain (fetal) 14. 4 (OD03921) 5. 2 CD3 21. 8 83241 CC from Partial Hepatectomy 93565_primary Th1 resting dy 4-6 in Brain (whole) 19. 6 (OD04309) 13. 9 IL-2 30. 2 Brain 83242 Liver NAT 93566_primary Th2 resting dy 4-6 in (amygdala) 3. 7 (OD04309) 12. 7 IL-2 14. 4 87472 Colon mets Brain to lung (OD04451-93567_primary Tr1_1resting dy 4-6 in IL- (cerebellum) 2. 1 01) 3. 4 2 7. 4 Brain 87473 Lung NAT 93351 CD45RA CD4 lymphocyte anti- (hippocampus) 22.7 (OD04451-02) 1.5 CD28/anti-CD3 7.6 Normal Prostate Clontech A+ 93352 CD45RO CD4 lymphocyte anti- Brain (thalamus) 7. 4 6546-1 1. 0 CD28/anti-CD3 11. 1 84140 Prostate Cancer 93251 CD8 Lymphocytes anti- Cerebral Cortex 47. 3 (OD04410) 3. 1 CD28/anti-CD3 9. 6 84141 Prostate 93353_chronic CD8 Lymphocytes Spinal cord 8. 3 NAT (OD04410) 10. 6 2ry resting dy 4-6 in IL-2 9. 7 CNS ca. 87073 Prostate (glio/astro) U87- Cancer 93574 chronic CD8 Lymphocytes MG 19. 9 (OD04720-01) 9. 7 2ry_activated CD3/CD28 6. 2 CNS ca. 87074 Prostate (glio/astro) U-NAT (OD04720- 118-MG 57. 0 02) 8. 3 93354 CD4 none 6. 4 CNS ca. (astro) Normal Lung 93252Secondary Th1/Th2/Tr1anti- SW1783 10. 0 GENPAK 061010 36. 6 CD95 CH11 9. 3 83239 Lung Met CNS ca. * (neuro ; to Muscle met) SK-N-AS 44. 8 (OD04286) 11. 7 93103 LAK cells resting 11. 0 CNS ca. (astro) 83240 Muscle SF-539 37. 4 NAT (OD04286) 3. 4 93788 LAK cells IL-2 10. 4 84136 Lung CNS ca. (astro) Malignant Cancer SNB-75 62. 0 (OD03126) 15. 1 93787_LAK cells_lL-2+1 L-12 7. 4 CNS ca. (glio) 84137 Lung NAT SNB-19 24. 8 (OD03126) 17. 4 93789 LAK cells IL-2+IFN gamma 11. 6 84871 Lung CNS ca. (glio) Cancer U251 40. 3 (OD04404) 5. 0 93790_LAK cells_IL-2+ IL-18 13. 3 CNS ca. (glio) 84872 Lung NAT 93104_LAK cells_PMA/ionomycin and SF-295 100. 0 (OD04404) 6. 3 IL-18 4. 8 84875 Lung Cancer Heart 0. 0 (OD04565) 3. 2 93578 NK Cells IL-2 resting 6. 2 85950 Lung Cancer 93109 Mixed Lymphocyte Skeletal muscle 0. 0 (OD04237-01) 15. 8 Reaction Two Way MLR 12. 3 85970 Lung NAT 93110Mixed Lymphocyte Bone marrow 33. 7 (OD04237-02) 10. 5 Reaction_Two Way MLR 8. 7 83255 Ocular Mel Met to Liver 93111 Mixed Lymphocyte Thymus 12. 4 (OD04310) 5. 9 Reaction Two Way MLR 3. 5 83256 Liver NAT 93112 Mononuclear Cells Spleen 21. 3 (ODO4310) 3. 6 (PBMCs) _resting 4. 5 84139 Melanoma Mets to Lung 93113 Mononuclear Cells Lymph node 13. 4 (OD04321) 10. 6 (PBMCs) _PWM 21. 2 84138 Lung NAT 93114_Mononuclear Cells Colorectal 38. 2 (OD04321) 10. 6 (PBMCs) _PHA-L 8. 9 Normal Kidney Stomach 9. 9 GENPAK 061008 26. 2 93249 Ramos (B cell) none 100. 0 83786 Kidney Ca, Nuclear grade Small intestine 17. 9 2 (OD04338) 22. 2 93250_Ramos (B cell)_ionomycin 28. 7 83787 Kidney Colon ca. SW480 27. 7 NAT (OD04338) 11. 7 93349 B lymphocytes PWM 20. 0 Colon ca. * 83788 Kidney Ca (SW480 Nuclear grade 1/2 met) SW620 30. 8 (OD04339) 45. 1 93350_B lymphoytes_CD40L and IL-4 7. 8 83789 Kidney 92665EOL-1 (Eosinophil) _dbcAMP Colon ca. HT29 8. 1 NAT (OD04339) 14. 8 differentiated8. 0 83790 Kidney Ca, Colon ca. HCT- Clear cell type 93248EOL-1 116 35. 4 (OD04340) 26. 6 (Eosinophil) _dbcAMP/PMAionomycin 3. 8 Colon ca. CaCo-83791 Kidney 2 37. 6 NAT (OD04340) 10. 4 93356 Dendritic Cells none 6. 8 83219 CC Well 83792 Kidney Ca, to Mod Diff Nuclear grade 3 (OD03866) 17. 8 (OD04348) 2. 4 93355 Dendritic Cells LPS 100 ng/ml 3. 3 Colon ca. HCC- 83793 Kidney 2998 19. 9 NAT (OD04348) 18. 8 93775 Dendritic Cells anti-CD40 6. 3 Gastric ca. * 87474 Kidney (liver met) NCI-Cancer N87 73. 2 (OD04622-01) 5. 6 93774 Monocytes resting 10. 6 87475 Kidney NAT (OD04622- Bladder 43. 2 03) 0. 5 93776 Monocytes LPS 50 ng/ml 3. 5 85973 Kidney Cancer Trachea 10. 3 (OD04450-01) 21. 2 93581 Macrophages resting 7. 6 85974 Kidney NAT (OD04450- Kidney 9. 2 03) 9. 3 93582 Macrophages LPS 100 ng/ml 3. 9 Kidney Cancer Kidney (fetal) 0. 0 Clontech 8120607 0. 0 93098_HUVEC (Endothelial) _none 8. 5 Kidney NAT Renal ca. 786-0 53. 6 Clontech 8120608 0. 9 93099_HUVEC (Endothelia)_starved 17. 9 Kidney Cancer Renal ca. A498 36. 1 Clontech 8120613 0. 0 93100_HUVEC (Endothelial)_IL-1b 6. 0 Renal ca. RXF Kidney NAT 93779 HUVEC (Endothelial) IFN 393 31. 6 Clontech 8120614 0. 9 gamma 7. 8 Kidney Cancer 93102 HUVEC (Endothelial) TNF Renal ca. ACHN 21. 6 Clontech 9010320 2. 7 alpha + IFN gamma 5. 7 Kidney NAT 93101 HUVEC (Endothelial) TNF Renal ca. UO-31 28. 7 Clontech 9010321 5. 0 alpha + IL4 5. 6 Normal Uterus Renal ca. TK-10 7. 0 GENPAK 061018 5. 3 93781 HUVEC (Endothelial) IL-11 4. 9 Uterus Cancer 93583_Lung Microvascular Endothelial Liver 14. 2 GENPAK 064011 9. 0 Cells none 4. 9 Normal Thyroid 93584 Lung Microvascular Endothelial Clontech A+ Cells_TNFa (4 ng/ml) and IL1b (1 Liver (fetal) 14. 5 6570-1 3. 4 ng/ml) 4. 9 Liver ca. (hepatoblast) Thyroid Cancer 92662 Microvascular Dermal HepG2 59. 9 GENPAK 064010 1. 8 endothelium-none 8. 6 Thyroid Cancer 92663 Microsvasular Dermal INVITROGEN endothelium_TNFa (4 ng/ml) and IL1b Lung 17. 8 A302152 3. 6 (1 ng/ml) 6. 0 Thyroid NAT INVITROGEN 93773_Bronchial epithelium_TNFa (4 Lung (fetal) 9. 6 A302153 4. 9 ng/ml) and ! L1 b (1 ng/ml) ** 0. 9 Lung ca. (small Normal Breast cell) LX-1 70. 2 GENPAK 061019 8. 5 93347 Small Airway Epithelium none 1. 3 84877 Breast Lung ca. (small Cancer 93348_Small Airway Epithelium_TNFa cell) NCI-H69 29. 9 (OD04566) 1. 5 (4 ng/ml) and IL1b (1 ng/ml) 13. 2 85975 Breast Lung ca. (s. cell Cancer var.) SHP-77 3. 9 (OD04590-01) 23. 8 92668 Coronery Artery SMC_resting 3. 4 85976 Breast Lung ca. (large Cancer Mets 92669 Coronery Artery SMC TNFa (4 cell) NCI-H460 2. 0 (OD04590-03) 24. 5 ng/ml) and IL1 b (1 ng/ml) 2. 0 87070 Breast Cancer Lung ca. (non-Metastasis sm. cell) A549 28. 5 (OD04655-05) 12. 9 93107_astrocytes_resting 4.7 Lung ca. (non-GENPAK Breast 93108astrocytesTNFa (4 ng/ml) and s. cell) NCI-H23 36. 1 Cancer 064006 11. 8 IL1b (1 ng/ml) 1. 9 Lung ca (non-Breast Cancer s. cell) HOP-62 29. 9 Clontech 9100266 3. 2 92666_KU-812 (Basophil)_resting 5. 8 Lung ca. (non-Breast NAT 92667KU-812 s. cl) NCI-H522 17. 2 Clontech 9100265 1. 8 (Basophil) PMA/ionocycin 12. 0 Lung ca. Breast Cancer (squam.) SW INVITROGEN 900 63. 7 A209073 11. 0 93579 CCD1106 (Keratinocytes) none 4. 9 Lung ca. Breast NAT (squam.) NCI- INVITROGEN 93580_CCD1106 H596 10. 0 A2090734 7. 1 (Keratinocytes) TNFa and IFNg** 0. 3 Normal Liver Mammary gland 4. 6 GENPAK 061009 8. 8 93791 Liver Cirrhosis 1. 8 Breast ca. * (pl. Liver Cancer effusion) MCF-7 0. 0 GENPAK 064003 4. 9 93792 Lupus Kidney 1. 6 Liver Cancer Breast ca. * Research (pl. ef) MDA-MB-Genetics RNA 231 38. 7 1025 1.0 93577_NCI-H292 11. 1 Liver Cancer Research Breast ca. * (pl. Genetics RNA effusion) T47D 0. 0 1026 0.8 93358_NCI-H292_IL-4 12. 2 Paired Liver Cancer Tissue Research Breast ca. BT- Genetics RNA 549 4.6 6004-T 3.0 93360_NCI-H292_IL-9 7. 6 Paired Liver Tissue Research Breast ca. MDA- Genetics RNA N 19. 0 6004-N 7.3 93359_NCI-H292_IL-13 6.1 Paired Liver Cancer Tissue Research Genetics RNA Ovary 1. 7 6005-T 0. 2 93357 NCI-H292 IFN gamma 5. 8 Paired Liver Tissue Research Ovarian Genetics RNA ca. OVCAR-3 4. 8 6005-N 0. 0 93777 HPAEC-6. 8 Ovarian Normal Bladder ca. OVCAR-4 0. 0 GENPAK 061001 19. 8 93778 HPAEC IL-1 beta/TNA alpha 5. 4 Bladder Cancer Research Ovarian Genetics RNA 93254 Normal Human Lung ca. OVCAR-5 39. 0 1023 3. 1 Fibroblast none 2. 1 Bladder Cancer 93253 Normal Human Lung Ovarian INVITROGEN Fibroblast TNFa (4 ng/ml) and IL-1b (1 ca. OVCAR-8 36. 6 A302173 9. 9 ng/ml) 1. 9 87071 Bladder Ovarian Cancer 93257 Normal Human Lung ca. IGROV-1 0. 0 (OD04718-01) 6. 6 Fibroblast IL-4 3. 6 Ovarian ca. * 87072 Bladder (ascites) SK-OV-Normal Adjacent 93256_Normal Human Lung 3 65. 5 (OD04718-03) 4. 0 Fibroblast IL-9 3. 3 Normal Ovary 93255 Normal Human Lung Uterus 1. 6 Res. Gen. 0. 3 Fibroblast IL-13 2. 3 Ovarian Cancer 93258 Normal Human Lung Placenta 8. 9 GENPAK 064008 6. 8 Fibroblast IFN gamma 2. 9 87492 Ovary Cancer 93106 Dermal Fibroblasts Prostate 0. 0 (OD04768-07) 100. 0 CCD 1 070_resting 5. 6 Prostate ca. * 87493 Ovary NAT 93361 Dermal Fibroblasts (bone met) PC-3 9. 2 (OD04768-08) 3. 6 CCD1070_TNF alpha 4 ng/ml 17. 4 Normal Stomach 93105 Dermal Fibroblasts Testis 29. 5 GENPAK 061017 8. 6 CCD1070 IL-1 beta 1 ng/ml 3. 8 Melanoma NAT Stomach Hs688 (A). T 14. 3 Clontech 9060359 0. 7 93772 dermal fibroblast IFN gamma 2. 6 Melanoma* Gastric Cancer (met) Clontech Hs688 (B). T 22. 9 9060395 3. 9 93771_dermal fibroblast_IL-4 3. 4 Melanoma NAT Stomach UACC-62 9. 7 Clontech 9060394 5. 3 93259 IBD Colitis 1** 0. 2 Gastric Cancer Clontech Melanoma M14 12. 7 9060397 13. 2 93260_IBD Colitis 2 0. 4 Melanoma LOX NAT Stomach IMVI 4. 5 Clontech 9060396 1. 1 93261_IBD Crohns 0. 3 Melanoma* 21. 8 Gastric Cancer 23. 0 735010 Colon normal 3. 3 (met) SK-MEL-5 GENPAK 064005 Adipose 6.7 735019_Lung_none 3. 9 64028-1_Thymus_none 7. 7 64030-1_Kidney_none 21. 8 Table 12 shows the taqman results of clone FCTR4 indicating overexpression in ovarian cancer as compared to Normal Adjacent Tissue (NAT). In addition, increased expression is demonstrated by ovarian tumor cell line suggesting that antibodies could be used to treat ovarian tumors.

Table 13 : Primer Design for Probe Ag427 (FCTR5) Primer Sequences Length Start Po SEQ ID NO Forward 5'-GAGCTACAGGCAGCCTCGAGT-3'21 443 32 Probe TET-5'-TGGCCCAGCTGACCCTGCTCA-3'-TAMRA 21 33 Reverse 20 449 34 5'-GGCTACGTCAGTGGGTTTGG-3'

Table 14 : Taqman results for FCTR5 Tissue Name Panel I Panel 4D Endothelial cells 10. 7 93768_Secondary Th1_anti-CD28Aanti-CD3 15. 9 Endothelial cells (treated) 15. 2 93769_Secondary Th2_anti-CD28/anti-CD3 14. 7 Pancreas 16. 2 93770_Secondary Tr1_anti-CD28/anti-CD3 21. 9 93573_Secondary Th1_resting day 4-6 in IL- Pancreatic ca. CAPAN 2 10. 5 2 12. 3 93572 Secondary Th2_resting day 4-6 in IL- Adipose 45. 1 2 16. 2 Adrenal gland 61. 6 93571_Secondary Tr1_resting day 4-6 in IL-2 16. 2 Thyroid 13. 1 93568 primary Th1 anti-CD28/anti-CD3 13. 9 Salavary gland 33. 7 93569_primary Th2 anti-CD28/anti-CD3 14. 6 Pituitary gland 15. 8 93570 primary Tr1 anti-CD28/anti-CD3 26. 2 Brain (fetal) 7. 2 93565_primary Th1_resting dy 4-6 in IL-2 56. 3 Brain (whole) 6. 3 93566_primary Th2 resting dy 4-6 in IL-2 27. 7 Brain (amygdala) 8. 4 93567_primary Tr1_resting dy 4-6 in IL-2 31. 6 93351_CD45RA CD4 lymphocyte_anti- Brain (cerebellum) 6. 8 CD28/anti-CD3 12. 1 93352 CD45RO CD4 lymphocyte anti- Brain (hippocampus) 7. 9 CD28/anti-CD3 17. 1 93251 CD8 Lymphocytes anti-CD28/anti- Brain (substantia nigra) 9. 5 CD3 9. 1 93353 chronic CD8 Lymphocytes 2resting Brain (thalamus) 7. 9 dy 4-6 in IL-2 13. 4 93574 chronic CD8 Lymphocytes Brain (hypothalamus) 23. 0 2ry activated CD3/CD28 9. 2 Spinal cord 9. 5 93354_CD4 none 7. 6 CNS ca. (glio/astro) U87-93252_Secondary Th1/Th2/Tr1 anti-CD95 MG 12. 6 CH11 20. 2 CNS ca. (glio/astro) U- 118-MG 11. 6 93103 LAK cells resting 57. 0 CNS ca. (astro) SW1783 4. 3 93788_LAK cells_IL-2 18. 8 CNS ca. * (neuro ; met) SK- N-AS 10. 4 93787_LAK cells_IL-2+IL-12 14.2 CNS ca. (astro) SF-539 11. 6 93789_LAK cells_IL-2+IFN gamma 20. 9 CNS ca. (astro) SNB-75 4. 4 93790 LAK cells IL-2+ IL-18 14. 8 CNS ca. (glio) SNB-19 31. 6 93104 LAK cells PMA/ionomycin and IL-18 12. 9 CNS ca. (glio) U251 17. 3 93578_NK Cells IL-2_resting 17. 4 93109 Mixed Lymphocyte Reaction-Two CNS ca. (glio) SF-295 20. 9 Way MLR 43. 5 93110 Mixed Lymphocyte Reaction-Two Heart 14. 3 Way MLR 19. 3 93111 Mixed Lymphocyte Reaction Two Skeletal muscle 11. 7 Way MLR 12. 6 Bone marrow 21. 9 93112 Mononuclear Cells (PBMCs) _resting 8. 7 Thymus 20. 9 93113_Mononuclear Cells (PBMCs) PWM 28. 5 Spleen 23. 8 93114 Mononuclear Cells (PBMCs) _PHA-L 26. 2 Lymph node 24. 2 93249 Ramos (B cell)_none 0.3 Colon (ascending) 17. 2 93250 Ramos (B cell) ionomycin 1. 2 Stomach 11. 1 93349_B lymphocytes_PWM 25. 7 Small intestine 21. 5 93350 B lymphoytes CD40L and IL-4 13. 0 92665_EOL-1 (Eosinophil)_dbcAMP Colon ca. SW480 12. 2 differentiated 26. 4 Colon ca. * (SW480 93248 EOL-1 met) SW620 8. 6 (Eosinophil)_dbcAMP/PMAionomycin 11. 4 Colon ca. HT29 16. 2 93356 Dendritic Cells none 40. 3 Colon ca.HCT-116 8.1 93355_Dendritic Cells_LPS 100 ng/ml 33. 0 Colon ca. CaCo-2 22. 1 93775 Dendritic Cells anti-CD40 20. 5 Colon ca. HCT-15 18. 6 93774_Monocytes_resting 23. 3 Colon ca. HCC-2998 21. 9 93776MonocytesLPS 50 ng/ml 6. 9 Gastric ca. * (liver met) NCI-N87 42. 9 93581_Macrophages_resting 14. 7 Bladder 95. 3 93582_Macrophages_LPS 100 ng/ml 64. 6 Trachea 18. 3 93098_HUVEC (Endothelial) _none 6. 8 Kidney 25. 7 93099 HUVEC (Endothelial) starved 13. 9 Kidney (fetal) 15. 8 93100_HUVEC (Endothelial)_IL-1b 7.5 Renal ca. 786-0 16. 5 93779 HUVEC (Endothelial) IFN gamma 27. 7 93102 HUVEC (Endothelial) TNF alpha + Renal ca. A498 16. 5 IFN gamma 11. 8 93101 HUVEC (Endothelial) TNF alpha + Renal ca. RXF 393 7. 4 IL4 6. 7 Renal ca. ACHN 11. 9 93781 HUVEC (Endothelial) _IL-11 10. 4 93583_Lung Microvascular Endothelial Renal ca. UO-31 15. 8 Cells none 8. 8 93584 Lung Microvascular Endothelial Cells_TNFa (4 ng/ml) and IL1 b (1 Renal ca. TK-10 28. 7 ng/mi) 8. 6 92662 Microvascular Dermal Liver 100. 0 endothelium none 22. 1 92663 Microsvasular Dermal endothelium_TNFa (4 ng/ml) and IL1 b Liver (fetal) 81. 8 (1 ng/ml) 18. 7 Liver ca. (hepatoblast) 93773_Bronchial epithelium_TNFa (4 ng/ml) HepG2 28. 3 and IL1b (1 ng/ml) ** 35. 4 Lung 10. 7 93347 Small Airway Epithelium none 10. 9 93348 Small Airway Epithelium TNFa (4 Lung (fetal) 10. 9 ng/ml) and IL1b (1 ng/ml) 50. 0 Lung ca. (small cell) LX-1 24. 3 92668 Coronery Artery SMC_resting 27. 9 Lung ca. (small cell) NCI-92669_Coronery Artery SMC TNFa (4 ng/ml) H69 41. 5 and IL1b (1 ng/ml) 25. 4 Lung ca. (s. cell var.) SHP- 77 4. 6 93107astrocytesresting7. 4 Lung ca. (large cell)NCI- 93108_astrocytes_TNFa (4 ng/ml) and IL1b H460 46. 3 (1 ng/ml) 10. 7 Lung ca. (non-sm. cell) A549 45. 4 92666_KU-812 (Basophil)_resting 3.2 Lung ca. (non-s. cell) NCI- H23 54. 3 92667 KU-812 (Basophil) PMA/ionoycin 6. 7 Lung ca (non-s. cell) HOP- 62 50. 7 93579_CCD1106 (Keratinocytes) _none 12. 2 Lung ca. (non-s. cl) NCI- 93580_CCD1106 (Keratinocytes) TNFa and H522 38.4 IFNg ** 100. 0 Lung ca. (squam.) SW 900 30. 8 93791 Liver Cirrhosis 27. 6 Lung ca. (squam.) NCI- H596 15. 5 93792_Lupus Kidney 32. 3 Mammary gland 65. 5 93577 NCI-H292 77. 4 Breast ca. * (pl. effusion) MCF-7 4. 4 93358 NCI-H292 IL-4 70. 2 Breast ca. * (pl.ef) MDA- MB-231 3.5 93360_NCI-H292_IL-9 54. 3 Breast ca. * (pl. effusion) T47D 8. 7 93359 NCI-H292 IL-13 47. 0 Breast ca. BT-549 5.7 93357_NCI-H292_IFN gamma 52. 9 Breast ca.MDA-N 16. 6 93777 HPAEC-23. 8 Ovary 20. 5 93778_HPAEC_IL-1 beta/TNA alpha 21. 5 Ovarian ca. OVCAR-3 21. 6 93254 Normal Human Lung Fibroblast none 49. 3 93253_Normal Human Lung Fibroblast_TNFa Ovarian ca. OVCAR-4 8. 3 (4 ng/ml) and IL-1b (1 ng/ml) 40. 3 Ovarian ca. OVCAR-5 26. 1 93257 Normal Human Lung Fibroblast IL-4 48. 3 Ovarian ca. OVCAR-8 48. 0 93256 Normal Human Lung Fibroblast IL-9 29. 3 Ovarian ca. IGROV-1 9. 3 93255_Normal Human Lung Fibroblast IL-13 73. 7 Ovarian ca. * (ascites) SK- 93258 Normal Human Lung Fibroblast-IFN OV-3 8. 8 gamma 66. 9 Uterus 13. 4 93106 Dermal Fibroblasts CCD1070 resting 20. 2 93361_Dermal Fibroblasts CCD1070_TNF Plancenta 9. 4'alpha 4 ng/ml 35. 1 93105_Dermal Fibroblasts CCD1070_IL-1 Prostate 21. 3 beta 1 ng/ml 15. 0 Prostate ca. * (bone met) PC-3 17. 7 93772 dermal fibroblast IFN gamma 21. 8 Testis 11. 7 93771 dermal fibroblast IL-4 21. 2 Melanoma Hs688 (A). T 9. 0 93259_IBD Colitis 1** 8.8 Melanoma* (met) Hs688 (B). T 12. 9 93260 IBD Colitis 2 3. 5 Melanoma UACC-62 12. 4 93261 IBD Crohns 1. 3 Melanoma M14 9.5 735010_Colon_normal 20. 3 Melanoma LOX IMVI 8. 1 735019 Lung none 40. 3 Melanoma* (met) SK- MEL-5 8.8 64028-1_Thymus_none 33. 5 Melanoma SK-MEL-28 8. 0 64030-1_Kidney_none 21.0 Taqman results in Table 14 show high expression of clone FCTR5 in bladder, liver and adrenal gland suggesting a possible role in the treatment of diseases involving these tissues.

Table 15 : Primer Design for Probe Agl541 (FCTR6) Primer Sequences TM Lengt Start Pos. EQIDNO. Forward 5'-AGAAGAACACCCCAGGGATATA-3'58. 8 22 1076 35 Probe FAM-5'-CCTCGTTGGTGAACTACAACCTCTGG-3'-TAMRA 67. 9 26 1100 36 Reverse 59. 5 22 1129 37 5'-CCTCTAGCTGGGTCACTTTCTC-3'

TABLE 16 : TAQMAN RESULTS FOR FCTR6 (PANEL 1D) Tissue Name Panel 1 D Run 1 Run 2 Liver adenocarcinoma 0. 0 0. 0 Heart (fetal) 0. 0 0. 0 Pancreas 0. 0 0. 0 Pancreatic ca. CAPAN 2 0. 0 0. 0 Adrenal gland 0. 0 0. 0 Thyroid 0. 0 0. 0 Salivary gland 0. 0 0. 0 Pituitary gland 0. 0 0. 0 Brain (fetal) 0. 5 0. 4 Brain (whole) 1. 1 1. 7 Brain (amygdala) 0. 0 1. 8 Brain (cerebellum) 0. 6 1. 9 Brain (hippocampus) 3. 3 3. 4 Brain (thalamus) 1. 0 1. 2 Cerebral Cortex 1. 6 2. 6 Spinal cord 2. 5 0. 4 CNS ca. (glio/astro) U87-MG 0. 0 0. 0 CNS ca. (glio/astro) U-118-MG 0. 0 0. 0 CNS ca. (astro) SW1783 0. 0 0. 0 CNS ca. * (neuro ; met) SK-N-AS 0. 0 0. 0 CNS ca. (astro) SF-539 0. 0 0. 0 CNS ca. (astro) SNB-75 0. 7 0. 0 CNS ca. (glio) SNB-19 0. 0 0. 0 CNS ca. (glio) U251 0. 0 0. 0 CNS ca. (glio) SF-295 0. 0 0. 8 Heart 0. 0 0. 0 Skeletal muscle 0. 0 0. 0 Bone marrow 0. 0 0. 0 Thymus 0. 0 0. 0 Spleen 0. 0 0. 0 Lymph node 0. 0 0. 0 Colorectal 0. 0 0. 6 Stomach 1. 9 0. 0 Small intestine 0. 0 1. 0 Colon ca. SW480 0. 0 0. 0 Colon ca. * (SW480 met) SW620 0. 0 0. 0 Colon ca. HT29 0. 0 0. 0 Colon ca. HCT-116 0. 6 0. 4 Colon ca. CaCo-2 1. 5 0. 0 83219 CC Well to Mod Diff (OD03866) 0. 0 0. 0 Colon ca. HCC-2998 0. 0 0. 0 Gastric ca. * (liver met) NCI-N87 1. 2 0. 0 Bladder 0. 0 0. 0 Trachea 0. 0 0. 4 Kidney 0. 8 1. 2 Kidney (fetal) 0. 5 0. 7 Renal ca. 786-0 0. 0 0. 0 Renal ca. A498 0. 0 0. 0 Renal ca. RXF 393 0. 0 0. 0 Renal ca. ACHN 0. 0 0. 0 Renal ca. UO-31 0. 0 0. 0 Renal ca. TK-10 0. 0. 0. 0 Liver 0. 0 0. 0 Liver (fetal) 0. 2 0. 0 Liver ca. (hepatoblast) HepG2 0. 0 0. 0 Lung 0. 0 0. 0 Lung (fetal) 0. 0 0. 0 Lung ca. (small cell) LX-1 1. 7 2. 3 Lung ca. (small cell) NCI-H69 0. 0 0. 0 Lung ca. (s. cell var.) SHP-77 1. 3 2. 5 Lung ca. (large cell) NCI-H460 0. 0 0. 0 Lung ca. (non-sm. cell) A549 0. 0 0. 0 Lung ca. (non-s. cell) NCI-H23 1. 2 0. 4 Lung ca (non-s. cell) HOP-62 0. 0 0. 0 Lung ca. (non-s. cl) NCI-H522 0. 0 0. 0 Lung ca. (squam.) SW 900 0. 0 0. 7 Lung ca. (squam.) NCI-H596 0 : 0 1. 3 Mammary gland 0. 0 1. 5 Breast ca. * (pl. effusion) MCF-7 0. 0 0. 0 Breast ca. * (pl. ef) MDA-MB-231 5. 8 0. 5 Breast ca. * (pl. effusion) T47D 1. 2 0. 3 Breast ca. BT-549 0. 5 0. 0 Breast ca. MDA-N 0. 0 0. 0 Ovary 0. 0 0. 0 Ovarian ca. OVCAR-3 0. 0 0. 0 Ovarian ca. OVCAR-4 0. 0 0. 0 Ovarian ca. OVCAR-5 3. 6 0. 7 Ovarian ca. OVCAR-8 0. 0 0. 0 Ovarian ca. IGROV-1 0. 0 0. 0 Ovarian ca. * (ascites) SK-OV-3 0. 0 0. 0 Uterus 0. 0 0. 0 Plancenta 0. 0 0. 0 Prostate 0. 0 0. 7 Prostate ca. * (bone met) PC-3 0. 0 0. 0 Testis 100. 0 100. 0 Melanoma Hs688 (A). T 0. 0 0. 0 Melanoma* (met) Hs688 (B). T 0. 0 0. 0 Melanoma UACC-62 0. 0 0. 0 Melanoma M14 0. 0 0. 0 Melanoma LOX IMVI 0. 0 0. 0 Melanoma* (met) SK-MEL-5 0. 0 0. 0 Adipose 0. 5 0. 0 Table 17 : Taqman Results for FCTR6 (Panel 2D) Panel 2D Tissue Name Run 1 Run 2 Normal Colon GENPAK 061003 5. 4 2. 4 83219 CC Well to Mod Diff (OD03866) 7. 3 0. 0 83220 CC NAT (OD03866) 5. 8 1. 5 83221 CC Gr. 2 rectosigmoid (OD03868) 3. 4 0. 0 83222 CC NAT (OD03868) 0. 0 0. 0 83235 CC Mod Diff (OD03920) 11. 0 1. 4 83236 CC NAT (OD03920) 0. 0 0. 0 83237 CC Gr. 2 ascend colon (OD03921) 6. 2 2. 5 83238 CC NAT (OD03921) 10. 2 0. 0 83241 CC from Partial Hepatectomy (OD04309) 3. 6 0. 0 83242 Liver NAT (OD04309) 0. 0 2. 4 87472 Colon mets to lung (OD04451-01) 7. 2 4. 4 87473 Lung NAT (OD04451-02) 0. 0 0. 0 Normal Prostate Clontech A+ 6546-1 4. 8 2. 9 84140 Prostate Cancer (OD04410) 3. 5 0. 0 84141 Prostate NAT (OD04410) 3. 4 0. 0 87073 Prostate Cancer (OD04720-01) 9. 0 8. 5 87074 Prostate NAT (OD04720-02) 0. 0 0. 0 Normal Lung GENPAK 061010 17. 7 6. 5 83239 Lung Met to Muscle (OD04286) 0. 0 2. 3 83240 Muscle NAT (OD04286) 0. 0 0. 0 84136 Lung Malignant Cancer (OD03126) 6. 5 5. 7 84137 Lung NAT (OD03126) 0. 0 0. 0 84871 Lung Cancer (OD04404) 0. 0 0. 0 84872 Lung NAT (OD04404) 0. 0 0. 0 84875 Lung Cancer (OD04565) 0. 0 0. 0 85950 Lung Cancer (OD04237-01) 0. 0 0. 0 85970 Lung NAT (OD04237-02) 0. 0 0. 0 83255 OcularMelMettoLiver (OD04310) 4. 3 0. 0 83256 Liver NAT (OD04310) 0. 0 0. 0 84139 Melanoma Mets to Lung (OD04321) 0. 0 0. 0 84138 Lung NAT (OD04321) 0. 0 0. 0 Normal Kidney GENPAK 061008 28. 1 39. 2 83786 Kidney Ca, Nuclear grade 2 (OD04338) 0. 0 3. 0 83787 Kidney NAT (OD04338) 22. 7 31. 6 83788 Kidney Ca Nuclear grade 1/2 (OD04339) 0. 0 3. 1 83789 Kidney NAT (OD04339) 97. 3 100. 0 83790 Kidney Ca, Clear cell type (OD04340) 0. 0 0. 0 83791 Kidney NAT (OD04340) 100. 0 34. 4 83792 Kidney Ca, Nuclear grade 3 (OD04348) 2. 0 4. 9 83793 Kidney NAT (OD04348) 30. 2 19. 9 87474 Kidney Cancer (OD04622-01) 0. 0 2. 4 87475 Kidney NAT (OD04622-03) 8. 4 7. 2 85973 Kidney Cancer (OD04450-01) 0. 0 0. 0 85974 Kidney NAT (OD04450-03) 47. 3 12. 9 Kidney Cancer Clontech 8120607 0. 0 0. 0 Kidney NAT Clontech 8120608 0. 0 0. 0 Kidney Cancer Clontech 8120613 0. 0 0. 0 Kidney NAT Clontech 8120614 20. 6 22. 9 Kidney Cancer Clontech 9010320 0. 0 0. 0 Kidney NAT Clontech 9010321 3. 4 26. 4 Normal Uterus GENPAK 061018 0. 0 0. 0 Uterus Cancer GENPAK 064011 14. 9 0. 0 Normal Thyroid Clontech A+ 6570-1 0. 0 0. 0 Thyroid Cancer GENPAK 064010 0. 0 0. 0 Thyroid Cancer INVITROGEN A302152 0. 0 0. 0 Thyroid NAT INVITROGEN A302153 0. 0 0. 0 Normal Breast GENPAK 061019 5. 2 3. 5 84877 Breast Cancer (OD04566) 0. 0 0. 0 85975 Breast Cancer (OD04590-01) 0. 0 0. 0 85976 Breast Cancer Mets (OD04590-03) 0. 0 0. 0 87070 Breast Cancer Metastasis (OD04655-05) 0. 0 0. 0 GENPAK Breast Cancer 064006 0. 0 2. 5 Breast Cancer Clontech 9100266 6. 2 0. 0 Breast NAT Clontech 9100265 0. 0 0. 0 Breast Cancer INVITROGEN A209073 1. 5 2. 5 Breast NAT INVITROGEN A2090734 24. 3 26. 2 Normal Liver GENPAK 061009 10. 5 2. 7 Liver Cancer GENPAK 064003 5. 9 1. 7 Liver Cancer Research Genetics RNA 1025 21. 6 11. 0 Liver Cancer Research Genetics RNA 1026 0. 0 0. 0 Paired Liver Cancer Tissue Research Genetics RNA 6004-T 3. 3 13. 5 Paired Liver Tissue Research Genetics RNA 6004-N 3. 2 1. 4 Paired Liver Cancer Tissue Research Genetics RNA 6005-T 0. 0 0. 0 Paired Liver Tissue Research Genetics RNA 6005-N 0. 0 0. 0 Normal Bladder GENPAK 061001 0. 0 0. 0 Bladder Cancer Research Genetics RNA 1023 0. 0 0. 0 Bladder Cancer INVITROGEN A302173 4. 6 2. 3 87071 Bladder Cancer (OD04718-01) 17. 9 11. 4 87072 Bladder Normal Adjacent (OD04718-03) 0. 0 0. 0 Normal Ovary Res. Gen. 0. 0 0. 0 Ovarian Cancer GENPAK 064008 1. 7 4. 8 87492 Ovary Cancer (OD04768-07) 0. 0 2. 1 87493 Ovary NAT (OD04768-08) 0. 0 0. 0 Normal Stomach GENPAK 061017 3. 3 2. 9 NAT Stomach Clontech 9060359 0. 0 0. 0 Gastric Cancer Clontech 9060395 0. 0 0. 0 NAT Stomach Clontech 9060394 0. 0 0. 0 Gastric Cancer Clontech 9060397 0. 0 0. 0 NAT Stomach Clontech 9060396 0. 0 0. 0 Gastric Cancer GENPAK 064005 6. 3 3. 8 Table 18 : Taqman Results for clone 27455183. 0. 19 (Panel 4D) Panel 4D Tissue_Name Run 1 Run 2 93768 Secondary Th1 anti-CD28/anti-CD3 0. 0 0. 0 93769 Secondary Th2 anti-CD28/anti-CD3 0. 0 0. 0 93770 Secondary Tr1 anti-CD28/anti-CD3 13. 5 17. 1 93573_Secondary Th1_resting day 4-6 in IL-2 0. 0 0. 0 93572 Secondary Th2 resting day 4-6 in IL-2 0. 0 0. 0 93571_Secondary Tr1_resting day 4-6 in IL-2 0. 0 0. 0 93568_primary Th1 anti-CD28/anti-CD3 0. 0 0. 0 93569_primary Th2_anti-CD28/anti-CD3 0.0 0. 0 93570_primary Tr1 anti-CD28/anti-CD3 0. 0 0. 0 93565 primary Th1 resting dy 4-6 in IL-2 0. 0 0. 0 93566_primary Th2_resting dy 4-6 in IL-2 0.0 0. 0 93567 primary Tr1_resting dy 4-6 in IL-2 0. 0 0. 0 93351 CD45RA CD4 lymphocyte anti-CD28/anti-CD3 0. 0 0. 0 93352 CD45RO CD4 lymphocyte anti-CD28/anti-CD3 0. 0 0. 0 93251_CD8 Lymphocytes anti-CD28/anti-CD3 0. 0 0. 0 93353 chronic CDS Lymphocytes 2resting dy 4-6 in IL-2 0. 0 0. 0 93574_chronic CD8 Lymphocytes 2ry_activated CD3/CD28 0.0 0. 0 93354_CD4_none 5.8 0. 0 93252_Secondary Th1/Th2/Tr1_anti-CD95 CH11 0.0 0. 0 93103 LAK cells resting 0. 0 0. 0 93788 LAK cells IL-2 0. 0 0. 0 93787_LAK cells_IL-2+IL-12 0.0 0. 0 93789_LAK cells_IL-2+IFN gamma 0.0 0. 0 93790_LAK cells_IL-2+IL-18 0.0 0. 0 93104-LAK cells-PMA/lonomycin and IL-18 0.0 0. 0 93578 NK Cells IL-2 resting 0. 0 0. 0 93109 Mixed Lymphocyte Reaction Two Way MLR 0. 0 0. 0 93110_Mixed Lymphocyte Reaction Two Way MLR 0. 0 0. 0 93111_Mixed Lymphocyte Reaction Two Way MLR 0. 0 0. 0 93112_Mononuclear Cells (PBMCs)_resting 0.0 0. 0 93113 Mononuclear Cells (PBMCs) PWM 0.0 0. 0 93114 Mononuclear Cells (PBMCs) PHA-L 0.0 0. 0 93249 Ramos (B cell) none 0.0 38. 2 93520_Ramos (B cell)_ionomycin 0.0 0. 0 93349 B lymphocytes PWM 0. 0 68. 8 93350 B lymphoytes CD40L and IL-4 31. 0 0. 0 92665 EOL-1 (Eosinophil) dbcAMP differentiated 0. 0 0. 0 93248 EOL-1 (Eosinophil) dbcAMP/PMAionomycin 0. 0 0. 0 93356 Dendritic Cells none 0. 0 0. 0 93355 Dendritic Cells LPS 100 ng/ml 0. 0 0. 0 93775 Dendritic Cells anti-CD40 32. 5 0. 0 93774_Monocytes_resting 0.0 0. 0 93776_Monocytes_LPS 50 ng/ml 0. 0 0. 0 93581 Macrophages resting 0. 0 0. 0 93582 Macrophages LPS 100 ng/ml 0. 0 0. 0 93098_HUVEC (Endothelial)_none 0.0 0. 0 93099_HUVEC (Endothelial)_starved 11.3 0. 0 93100_HUVEC (Endothelial)_IL-1b 0.0 14. 6 93779_HUVEC (Endothelial)_IFN gamma 0.0 0. 0 93102_HUVEC (Endothelial)_TNF alpha + IFN gamma 0. 0 0. 0 93101_HUVEC (Endothelial)_TNF alpha + IL4 0.0 0. 0 93781_HUVEC (Endothelial)_IL-11 0.0 0. 0 93583 Lung Microvascular Endothelial Cells none 0. 0 0. 0 93584_Lung Microvascular Endothelial Cells_TNFa (4 ng/ml) and IL1 b (1 ng/ml) 0. 0 0. 0 92662 Microvascular Dermal endothelium none 0. 0 0. 0 92663 MIcrosvasular Dermal endothelium TNFa (4 ng/ml) and IL1 b (1 ng/ml) 0. 0 0. 0 93773_Bronchial epithelium_TNFa (4 ng/ml) and IL1 b (1 ng/ml) ** 0.0 0. 0 93347 Small Airway Epithelium_none 0. 0 0. 0 93348_Small Airway Epithelium_TNFa (4 ng/ml) and IL1b (1 ng/ml) 0. 0 0. 0 92668 Coronery Artery resting 0. 0 0. 0 92669 Coronery Artery SMC TNFa (4 ng/ml) and IL1 b (1 ng/ml) 0. 0 0. 0 93107_astrocytes_resting 0.0 0. 0 93108astrocytesTNFa (4 ng/ml) and IL1b (1 ng/ml) 0. 0 0. 0 92666_KU-812 (Basophil)_resting 0.0 40. 3 92667_KU-812 (Basophil)_PMA/ionoycin 0.0 0. 0 93579 CCD1106 (Keratinocytes) _none 0. 0 0. 0 93580 CCD1106 (Keratinocytes) _TNFa and IFNg ** 0.0 0. 0 93791_Liver Cirrhosis 100.0 99. 3 93792Lupus Kidney0. 00. 0 93577 NCI-H292 0. 0 0. 0 93358_NCI-H292_IL-4 0.0 0. 0 93360_NCI-H292_IL-9 10.6 0. 0 93359_NCI-H292_IL-13 0.0 65. 5 93357 NCI-H292 IFN gamma 0. 0 24. 8 93777_HPAEC_- 0.0 0.0 93778_HPAEC_IL-1 beta/TNA alpha 0.0 0.0 93254_Normal Human Lung Fibroblast_none 0.0 0.0 93253 Normal Human Lung Fibroblast TNFa (4 ng/ml) and IL-1b (1 ng/ml) 0. 0 0. 0 93257 Normal Human Lung Fibroblast_lL-4 0. 0 0. 0 93256 Normal Human Lung Fibroblast IL-9 0. 0 0. 0 93255 Normal Human Lung Fibroblast IL-13 0. 0 0. 0 93258 Normal Human Lung Fibroblast IFN gamma 0. 0 0. 0 93106 Dermal Fibroblasts CCD1070 resting 0. 0 0. 0 93361 Dermal Fibroblasts CCD1070 TNF alpha 4 ng/ml 0. 0 43. 8 93105_Dermal Fibroblasts CCD1070_IL-1 beta 1 ng/ml 0. 0 0. 0 93772 dermal fibroblast IFN gamma 42. 0 27. 7 93771_dermal fibroblast_IL-4 10.7 90. 1 93259 IBD Colitis 1** 0. 0 0. 0 93260 IBD Colitis 2 13. 8 0. 0 93261 IBD Crohns 0. 0 46. 7 735010 Colon normal 15. 6 0. 0 735019_Lung_none 12.9 16. 8 64028-1Thymusnone69. 3100. 0 64030-1_Kidney_none 0. 0 0. 0

Taqman results in Table 18 demonstrate that clone FCTR6 is differentially expressed in clear cell Renal cell carcinoma tissues versus the normal adjacent kidney tissues and thus could have a potential role in the treatment of renal cell carcinoma.

EQUIVALENTS Although particular embodiments have been disclosed herein in detail, this has been done by way of example for purposes of illustration only, and is not intended to be limiting with respect to the scope of the appended claims which follow. In particular, it is contemplated by the inventors that various substitutions, alterations, and modifications may be made to the invention without departing from the spirit and scope of the invention as defined by the claims. The choice of nucleic acid starting material, clone of interest, or library type is believed to be a matter of routine for a person of ordinary skill in the art with knowledge of the embodiments described herein. Other aspects, advantages, and modifications considered to be within the scope of the following claims.