HIGHLY ENGRAFTABLE HEMATOPOIETIC STEM CELLS

CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Application Serial No.

62/413,821, filed October 27, 2016 and U.S. Provisional Application No. 62/300,694, filed February 26, 2016, the contents of which are incorporated herein by reference in their entireties. BACKGROUND OF THE INVENTION

Hematopoietic stem cell (HSC) transplantation is currently the only curative treatment modality for a number of stem cell disorders, including both malignant and non-malignant hematologic conditions. Yet, despite the fact that hematopoietic transplant is the only curative option for patients having such stem cell disorders, transplant-related morbidity and mortality remains high, and only a fraction of the patients that could benefit from an HSC transplant actually receive one.

Sources of HSCs for transplantation include the bone marrow itself, umbilical cord blood, and mobilized peripheral blood. Under steady state conditions, HSCs and hematopoietic progenitor cells (HPCs) normally reside within the bone marrow niches, while the mature cells produced by these populations of HSCs and HPCs ultimately exit the bone marrow and enter the peripheral blood. Considerable evidence over the last several decades, however, clearly demonstrates that HSCs and HPCs (collectively referred to as "HSPCs") also exit the bone marrow niche and traffic to the peripheral blood and we now know that this natural egress into the periphery can be enhanced, allowing for "mobilization" of these cells from the bone marrow to the peripheral blood. Mobilized adult HSCs and HPCs are widely used for autologous and allogeneic transplantation and have improved patient outcomes when compared to bone marrow grafts.

The hematopoietic growth factor, granulocyte-colony stimulating factor (G- CSF) is widely used clinically to mobilize HSC and HPC for transplantation. G-CSF- mobilized peripheral blood stem cells (PBSCs) are associated with more rapid engraftment, shorter hospital stays, and in some circumstances, superior overall survival compared to bone marrow grafts, though the use of G-CSF-mobilized grafts over bone marrow in some allogeneic settings is under scrutiny.

While successful, G-CSF mobilization regimens involve repeated

subcutaneous injections and are often associated with morbidity from bone pain (an often severe and debilitating complication), nausea, headache, and fatigue. These can be lifestyle disruptive in normal volunteers and particularly distressing for patients who are enduring the rigors of cancer chemotherapy. In a small population of normal donors, G-CSF has also been associated with serious toxicity, including enlargement of the spleen and splenic rupture, and the pro-coagulant effects of G-CSF can increase the risk of myocardial infarction and cerebral ischemia in high-risk individuals.

Despite its success for most patients and donors, poor mobilization in response to G- CSF occurs in 15% of normal, healthy donors, and often those who do achieve sufficient numbers of CD34+ cells require more than one apheresis procedure.

Repeated, prolonged sessions of apheresis are particularly common among autologous donors, which is particularly troubling for them given their ongoing ordeals associated with their underlying cancer and its treatment. Up to 60% of patients that fail to mobilize an optimal CD34+ cell dose for autologous transplantation often requiring tandem cycles of high dose chemotherapy. This is particularly an issue for patients with lymphoma and multiple myeloma, who often require extended aphereses and comprise the largest group of transplant recipients.

The availability of alternative methods for mobilizing HSPC could have high impact on the foregoing obstacles associated with HSC transplantation. Needed are novel therapeutics and methods that are capable of enhancing graft acquisition and hematopoietic recovery and engraftment. Also needed are highly engraftable cells that may be used to treat stem cell and/or progenitor cell disorders, such as malignant and non-malignant hematologic diseases.

SUMMARY OF THE INVENTION

There remains a need for novel compositions, methods and therapies that are capable of reducing hematopoietic stem cell (HSC) transplant-related morbidity and mortality and enhancing engraftment of transplanted HSCs in subjects in need of a stem cell transplant. The present inventions are directed toward further solutions to address these unmet needs, in addition to having other desirable characteristics.

Accordingly, disclosed herein is an isolated, highly engraftable hematopoietic stem cell (heHSC), as well as related methods of preparing such heHSCs and related methods of using such heHSCs for the treatment of stem cell and/or progenitor cell disorders and other diseases for which a stem cell transplant may be indicated.

In certain aspects, the present inventions are directed to an isolated, heHSC, wherein the heHSC is Sca-1+ and c-kit+ and is negative for Lineage markers (e.g., B220-, CD3-, Gr-1-, Mac-1-, TER119-) (e.g., a Sca-1+, c-kit+ and Lin- (SKL) cell). In certain aspects, the isolated heHSC is CD48-. In certain aspects the heHSC is not naturally occurring, i.e., differs from a naturally occurring HSC in one or more ways including but not limited to functionality (e.g., engraftability) and gene expression. In certain aspects, the isolated heHSC is CD150+. In certain aspects, the isolated heHSC is a Signaling lymphocytic activation molecule (SLAM) SKL cell, which is CD150+, CD48-, Sca-1+, c-kit+ and lineage negative. In certain aspects, the isolated heHSC does not express an immunophenotypic means of identifying human hematopoietic stem cells (e.g., the isolated heHSC does not express antigens, markers or other characteristics that may be useful for distinguishing such heHSC from other cell types). In some embodiments, the isolated heHSC comprises a unique transcriptome relative to hematopoietic stem cells contacted with granulocyte colony-stimulating factor (G-CSF), a chemotherapeutic agent, or any combination thereof. For example, in some aspects, the isolated heHSCs disclosed herein are characterized based on their differential expression of one or more of the genes selected from the group consisting of Fos, CD93, Fosb, Duspl, Jun, Dusp6, Cdkl, Fignll, Plk2, Rsad2, Sgkl, Sdcl, Serpine2, Sppl, Cdca8, Nrpl, Mcam, Pbk, Akrlcl and Cypl lal (e.g., relative to the expression of one or more genes by hematopoietic stem cells mobilized using G- CSF). In some embodiments, the isolated heHSC expresses osteopontin (e.g., the heHSC is OPN+). In some embodiments, the isolated heHSC expresses CD93 (e.g., the heHSC is CD93+) than an HSC obtained from a subject subjected to a

conventional mobilization regimen. In some embodiments, the isolated heHSC does not express CD34 or is CD34-. In some embodiments, the isolated heHSC is CD93+ and CD34-. In some embodiments, the heHSC is a non-native or non-naturally occurring cell, i.e., possesses one or more genotypic or phenotypic characteristics not present in native or naturally occurring HSC. In some embodiments, the isolated heHSC is from in a population of cells not present in a non-treated host and/or a host treated with a conventional mobilization regimen (e.g., a cell population with a different gene expression profile or a different phenotype profile). In some embodiments, the heHSC is from in a population of heHSC with a higher proportion of CD93+ cells than a HSC population obtained from a host treated with a

conventional mobilization regimen.

Conventional procedures using G-CSF are known in the art. See Schmitt, M et a!. "Mobilization of PBSC for Allogeneic Transplantation by the Use of the G-CSF Biosimilar XM02 in Healthy Donors." Bone Marrow Transplantation 48.7 (2013): 922-925, PMC. Web. 24 Feb. 2017, incorporated herein by reference.

As used herein, "differentially expresses", when used in reference to a cell population means an expression that is at least 10% higher than or lower than a reference value (e.g., an heHSC population differentially expresses CD93 from an HSC population obtained by a conventional immobilization technique if the heHSC population expresses at least 10% more or less CD93). As used herein, "differentially expresses," when used in reference to a cell, means that the cell has a different expression pattern of one or more phenotypes than a reference cell.

In certain aspects of the present inventions, the isolated heHSCs disclosed herein may be transformed to express a polynucleotide (e.g., an exogenous polynucleotide). For example, in certain embodiments, an isolated heHSC is transformed with an expression vector to express a polynucleotide (e.g., an exogenous polynucleotide). In some embodiments, the expression vector comprises a viral vector selected from the group consisting of a retrovirus, a herpes simplex, an adenovirus,a lentivirus, and an adeno-associated virus. In some embodiments, the isolated heHSC is transfected with an expression vector that comprises the polynucleotide. In some embodiments, the polynucleotide comprises an exogenous polynucleotide.

Also disclosed herein is the use of isolated heHSCs to deliver an exogenous polynucleotide to a subject in need thereof. For example, the isolated heHSCs disclosed herein may be transformed to express an exogenous polynucleotide and, upon engraftment in the subject's tissues (e.g., bone marrow tissues), the engrafted heHSC expresses the exogenous polynucleotide, thereby delivering the expression product (e.g., a protein, enzyme or amino acid) to the subject.

Also disclosed herein are methods of transforming an isolated heHSC, wherein such methods comprise a step of contacting the heHSC with an expression vector under conditions sufficient for the vector to integrate into the heHSC genome. In yet other embodiments, the isolated heHSC of the present inventions are genetically modified to shut off expression of an endogenous polynucleotide.

In certain embodiments, the isolated heHSC is substantially pure (e.g., at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 97.5%, 98%, 99% or more pure). In certain aspects, the isolated heHSC is non-quiescent.

Also disclosed herein are methods of preparing an isolated, heHSC. For example, in some embodiments, the isolated heHSC disclosed herein is prepared by contacting a hematopoietic stem cell and/or a progenitor cell with at least one CXCR2 agonist and at least one CXCR4 antagonist, VLA-4 antagonist, α ₉ βι antagonist, α ₉ βι

integrin/VLA-4 antagonist or combination thereof. In some embodiments, the isolated heHSC disclosed herein is prepared by contacting a hematopoietic stem cell and/or a progenitor cell with at least one CXCR2 agonist and at least one CXCR4 antagonist. In some embodiments, such contacting is performed in vivo, for example by administering GROP or an analog or derivative thereof and plerixafor or an analog or derivative thereof to a human subject. In some embodiments, such contacting is performed in vitro. In some in vivo embodiments, such contacting mobilizes an amount of circulating peripheral blood stem cells in the subject sufficient to harvest a cell dose of between about 1 x 10 ⁶ /kg body weight and 10 x 10 ⁶ /kg body weight in a single apheresis session. In some in vivo embodiments, such contacting mobilizes an amount of circulating peripheral blood stem cells in the subject sufficient to harvest a cell dose of between about 2 x 10 ⁶ /kg body weight and 8 x 10 ⁶ /kg body weight in a single apheresis session. In some in vivo embodiments, such contacting mobilizes an amount of circulating peripheral blood stem cells in the subject sufficient to harvest a cell dose of between about 3 x 10 ⁶ /kg body weight and 6 x 10 ⁶ /kg body weight in a single apheresis session. In some in vitro embodiments, isolated HSC are contacted with sufficient amount of at least one CXCR2 agonist and at least one CXCR4 antagonist, VLA-4 antagonist, α ₉ βι antagonist, α ₉ βι integrin/VLA-4 antagonist or combination thereof to obtain between 1 x 10 ⁶ and 1.2 x 10 ⁹ heHSC cells.

In some embodiments, the at least one CXCR2 agonist comprises GROP or an analog or derivative thereof. In some embodiments the at least one CXCR2 agonist comprises GROP-A4 or an analog or derivative thereof. In some embodiments, the at least one CXCR4 antagonist comprises plerixafor (AMD-3100) or an analog or derivative thereof. In some embodiments, the at least one CXCR4 antagonist comprises ALT1188, ALT! 187, ALT1128, ALT1228, or TG-0054 or an analog or derivative thereof. In some embodiments, the CXCR4 antagonist comprises at least one inhibitor described in Debnath B, et al., "Small Molecule Inhibitors of

X£RA "Theranostics 2013; 3(l):47-75, incorporated herein by reference. In some embodiments, the α ₉ βι integrin/VLA-4 antagonist is N-(benzenesulfonyl)-L-prolyl-L- 0-(l-pyrrolidinylcarbonyl)tyrosine (BOP) or an analog or derivative thereof (e.g., R- BC154). In some embodiments, the VLA-4 antagonist is BIO 5192, Natalizumab, firategrast, or an analog or derivative thereof. In still other embodiments, the at least one CXCR2 agonist is GROP or an analog or derivative thereof and the at least one CXCR4 antagonist is plerixafor or an analog or derivative thereof. In some embodiments, a Gro-beta analog or derivative is the desamino Gro-beta protein (also known as MIP-2alpha), which comprises the amino acid sequence of mature gro-S protein truncated at its N terminus between amino acid positions 2 and 8, as described in PCT International Application Publication WO/1994/029341, incorporated herein by reference in its entirety. In other embodiments, the Gro-beta analog or derivative is the dimeric modified Gro-beta protein described in U.S. Pat. No. 6,413,510, incorporated herein by reference in its entirety. In some embodiments, the Gro-beta analog or derivative is SB-251353, a Gro-beta analog involved in directing movement of stem cells and other leukocytes, as described by Bensinger et al. (Bone Marrow Transplantation (2009), 43, 181-195, incorporated by reference herein).

The isolated heHSCs disclosed herein are characterized by their enhanced ability to engraft in a target tissue of a subject (e.g., the bone marrow tissue of a subject). Accordingly, in some embodiments upon administration or transplant of the heHSC in a subject such heHSC demonstrates increased engrafting ability, for example, relative to engraftment of the same quantity of hematopoietic stem cells that are contacted or mobilized with granulocyte colony-stimulating factor (G-CSF), chemotherapeutic agents (e.g., mobilizing chemotherapeutic agents), or any combinations thereof. In certain embodiments, such engrafting ability is increased by at least about two-fold, three-fold, four-fold, five-fold, six-fold, or more.

In some embodiments, the heHSC is a non-native cell, i.e., possesses one or more genotypic or phenotypic characteristics not present in native HSC. In some embodiments, the isolated heHSC is from in a population of cells not present in a non- treated host and/or a host treated with a conventional mobilization regimen (e.g., a cell population with a different gene expression profile or a different phenotype profile). In some embodiments, the heHSC is from in a population of heHSC with a higher proportion of CD93+ cells than a HSC population obtained from a host treated with a conventional mobilization regimen.

The isolated heHSCs disclosed herein are also characterized by their ability to produce or cause improved or increased donor chimerism following their engraftment. In some embodiments, upon engraftment of the heHSCs in a subject the heHSCs demonstrate increased donor chimerism, for example, relative to the donor chimerism observed following engraftment of the same quantity of hematopoietic stem cells contacted or mobilized with G-CSF, chemotherapeutic agents (e.g., mobilizing chemotherapeutic agents), or any combinations thereof. In certain embodiments, such donor chimerism is increased by at least about two fold, three-fold, four-fold, fivefold, six-fold, or more. In some embodiments, such donor chimerism is at least about 10%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 99%, or more.

In certain aspects, the present inventions are directed to methods of treating a stem cell or progenitor cell disorder. Such methods comprise a step of administering an isolated heHSC (e.g., a SLAM SKL heHSC) to a subject in need thereof, wherein the administered heHSC engrafts in the subject's tissues (e.g., the subject's bone marrow compartment), thereby treating the stem cell or progenitor cell disorder. In some embodiments, the methods described herein comprise administering a population of cells comprising at least about 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% heHSC cells.

In certain aspects, upon engraftment in a subject, the engrafted heHSCs demonstrate enhanced hematopoietic function relative to engraftment of the same quantity of hematopoietic stem cells contacted or mobilized with G-CSF,

chemotherapeutic agents (e.g., mobilizing chemotherapeutic agents), or any combinations thereof. In some embodiments, upon engraftment in a subject the engrafted heHSCs demonstrate an enhanced CD34+ number relative to engraftment of the same quantity of hematopoietic stem cells contacted or mobilized with G-CSF, chemotherapeutic agents, or any combinations thereof. In certain embodiments, upon engraftment in a subject the engrafted heHSCs demonstrate enhanced hematopoietic function relative to engraftment of the same quantity of hematopoietic stem cells contacted or mobilized with granulocyte colony-stimulating factor (G-CSF), chemotherapeutic agents, or any combinations thereof.

In some embodiments, the subject (e.g., a human subject) is conditioned for engraftment prior to administering the isolated heHSCs disclosed herein. In some embodiments, the subject (e.g., a human subject) exhibits poor mobilization in response to a conventional mobilization regimen, such as G-CSF.

Also disclosed herein are methods of treating a stem cell and/or progenitor cell disorder in a subject, the method comprising: (a) depleting an endogenous

hematopoietic stem cell or progenitor cell population in a bone marrow compartment of the subject; and (b) administering an isolated, non-native heHSC to the subject, wherein the heHSC is Sca-1+, c-kit+ and Lin- (SKL), and where the administered heHSC engrafts in the bone marrow compartment of the subject. In certain embodiments, the heHSC is a SLAM SKL heHSC.

The heHSCs disclosed herein may be used for the treatment of stem cell and/or progenitor cell disorders or any diseases for which a stem cell transplant may be indicted. In some embodiments, such a stem cell or progenitor cell disorder is a malignant hematologic disease. For example, in some embodiments, the malignant hematologic disease may be selected from the group consisting of acute lymphoid leukemia, acute myeloid leukemia, chronic lymphoid leukemia, chronic myeloid leukemia, diffuse large B-cell non-Hodgkin's lymphoma, mantle cell lymphoma, lymphoblastic lymphoma, Burkitt's lymphoma, follicular B-cell non-Hodgkin's lymphoma, lymphocyte predominant nodular Hodgkin's lymphoma, multiple myeloma, and juvenile myelomonocytic leukemia. In some embodiments, the stem cell or progenitor cell disorder is a non-malignant disease. For example, in some embodiments the non-malignant disease may be selected from the group consisting of myelofibrosis, myelodysplastic syndrome, amyloidosis, severe aplastic anemia, paroxysmal nocturnal hemoglobinuria, immune cytopenias, systemic sclerosis, rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, Crohn's disorder, chronic inflammatory demyelinating polyradiculoneuropathy, human immunodeficiency virus (HIV), Fanconi anemia, sickle cell disorder, beta thalassemia major, Hurler's syndrome (MPS-IH), adrenoleukodystrophy, metachromatic leukodystrophy, familial erythrophagocytic lymphohistiocytosis and other histiocytic disorders, severe combined immunodeficiency (SCID), and Wiskott-Aldrich syndrome.

Also disclosed herein is an isolated, non-native heHSC, wherein the heHSC is Sca-1+, c-kit+ and Lin- (SKL); wherein the heHSC is prepared by mobilizing hematopoietic stem cells and/or progenitor cells from a bone marrow compartment of a subject to a peripheral compartment of the subject by administering at least one CXCR2 agonist and at least one CXCR4 antagonist, VLA-4 antagonist, α ι antagonist, α ι integrin/VLA-4 antagonist or combination thereof to the subject, and isolating the mobilized hematopoietic stem cells and/or progenitor cells from the peripheral compartment of the subject. In some embodiments, the isolated heHSC does not express CD48 or is CD48-. In some embodiments, the isolated heHSC expresses CD 150 or is CD150+. In some embodiments, the isolated heHSC expresses CD93 or is CD93+. In certain aspects, the isolated heHSC does not express an immunophenotypic means of identifying human hematopoietic stem cells. In some embodiments the heHSC is a SLAM SKL heHSC. In some embodiments, the at least one CXCR2 agonist comprises GROP or an analog or derivative thereof. In some embodiments the at least one CXCR2 agonist comprises GROP-A4 or an analog or derivative thereof. In some embodiments, the at least one CXCR4 antagonist comprises plerixafor (AMD-3100) or an analog or derivative thereof. In still other embodiments, the at least one CXCR2 agonist is GROP or an analog or derivative thereof and the at least one CXCR4 antagonist is plerixafor or an analog or derivative thereof. In some embodiments, the at least one CXCR4 antagonist comprises ALT! 188, ALT! 187, ALT! 128, ALT1228, or TG-0054. In some embodiments, the (*9βι integrin/VLA-4 antagonist is N-(benzenesulfonyl)-L-prolyl-L-0-(l- pyrrolidinylcarbonyl)tyrosine (BOP) or an analog or derivative thereof (e.g., R- BC154). In some embodiments, the VLA-4 antagonist is BIO 5192 or Natalizumab, or an analog or derivative thereof. In some embodiments, the isolated heHSC comprises a unique transcriptome relative to hematopoietic stem cells contacted with granulocyte colony-stimulating factor (G-CSF), a chemotherapeutic agent, or any combination thereof. For example, in some aspects, the isolated heHSCs disclosed herein are characterized based on their differential expression of one or more of the genes selected from the group consisting of Fos, CD93, Fosb, Duspl, Jun, Dusp6, Cdkl, Fignll, Plk2, Rsad2, Sgkl, Sdcl, Serpine2, Sppl, Cdca8, Nrpl, Mcam, Pbk, Akrlcl and Cypl lal, relative to, for example the expression of one or more genes in HSCs mobilized using G-CSF. In certain aspects, the isolated heHSC is non-quiescent. In some embodiments, the isolated heHSC is OPN+ (e.g., the isolated heHSC express osteopontin). In some embodiments, the isolated heHSC differentially expresses CD93 (e.g., the heHSC is CD93+). In some embodiments, the isolated heHSC does not express CD34 or is CD34-. In some embodiments, the isolated heHSC is CD93+ and CD34-.

In certain aspects of the present inventions, the isolated heHSCs disclosed herein are transformed to express a polynucleotide (e.g., an isolated heHSC may be transformed with an expression vector to express an exogenous polynucleotide). In some embodiments, the expression vector comprises a viral vector selected from the group consisting of a retrovirus, a herpes simplex, a lentivirus, an adenovirus, and an adeno-associated virus. In some embodiments, the isolated heHSC is transfected with an expression vector that comprises the polynucleotide. In some embodiments, the polynucleotide comprises an exogenous polynucleotide.

Also disclosed herein is the use of the isolated heHSC to effect or otherwise facilitate the delivery of an exogenous polynucleotide to a subject in need thereof. For example, the isolated heHSC disclosed herein may be transformed to express an exogenous polynucleotide and, upon engraftment in the subject's tissues (e.g., bone marrow tissues), the engrafted heHSC expresses the exogenous polynucleotide, thereby delivering the expression product of the exogenous polynucleotide (e.g., a protein or amino acid) to the subject.

In some embodiments, also disclosed herein are methods of transforming an isolated heHSC, wherein such methods comprise a step of contacting the heHSC with an expression vector under conditions sufficient for the vector to integrate into the heHSC genome. In yet other embodiments, the isolated heHSC of the present inventions are genetically modified to shut off expression of an endogenous polynucleotide. In certain embodiments, the isolated heHSC is substantially pure.

The above discussed, and many other features and attendant advantages of the present inventions will become better understood by reference to the following detailed description of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawings will be provided by the Office upon request and payment of the necessary fee.

FIG. 1 illustrates that relative to G-CSF, the combination of the CXCR2 agonist GROP and the CXCR4 antagonist plerixafor (AMD-3100) mobilized a highly engraftable hematopoietic stem cell (heHSC). As shown in FIG. 1, relative to G-CSF mobilized cells, an increase in donor chimerism was observed following engraftment with the heHSCs that were mobilized with GROP and AMD-3100. In this demonstration, 195 CD150+, CD48-, SKL cells were transplanted per mouse.

FIG. 2 illustrates that relative to G-CSF, the combination of the CXCR2 agonist GROP and the CXCR4 antagonist plerixafor (AMD-3100) mobilized a highly engraftable hematopoietic stem cell (heHSC), in a separate, independent

demonstration from that shown in FIG. 1. As shown in FIG. 2, relative to G-CSF mobilized cells, an increase in donor chimerism was observed following engraftment of the heHSCs that were mobilized with GROp and AMD-3100. In this

demonstration, 50 CD150+CD48-SKL cells were transplanted per mouse.

FIG. 3 illustrates that certain genes showed higher expression in the heHSCs that were mobilized using the combination of the CXCR2 agonist GROP and the CXCR4 antagonist plerixafor (AMD-3100), relative to the cells mobilized using G- CSF.

FIG. 4 illustrates a heat map showing the top twenty discriminating genes between hematopoietic stem cells (HSCs) that were mobilized using G-CSF mobilized (the two Tube B replicates), relative to the heHSCs (Tube C) mobilized using the combination of the CXCR2 agonist GROP and the CXCR4 antagonist plerixafor (AMD-3100). Sppl corresponds to osteopontin marker I.

DETAILED DESCRIPTION OF THE INVENTION The present disclosure relates to a non-native, highly engraftable

hematopoietic stem cell (heHSC) that is useful in connection with stem cell transplantation and the treatment of stem cell and/or progenitor cell disorders.

Disclosed herein are isolated, non-native heHSCs, methods of their use and manufacture, and kits that comprise such heHSCs for use in connection with stem cell transplantation or the treatment of stem cell and/or progenitor cell disorders. The heHSCs disclosed herein are useful, for example, for transplantation and/or engraftment in a subject in connection with the treatment of any disease requiring stem cell transplantation.

The work described herein relates to the surprising discovery that heHSCs that are prepared by contacting or mobilizing with a combination of a CXCR2 agonist (e.g., GROP) and a CXCR4 antagonist (e.g., plerixafor) exhibit superior engrafting ability, for example, superior engrafting ability relative to HSCs or peripheral blood stem cells (PBSCs) that are mobilized using traditional mobilizing regimens (e.g., granulocyte-colony stimulating factor (G-CSF) or chemotherapeutic agents).

Accordingly, certain aspects of the present inventions relate to non-native, isolated heHSCs that are prepared by contacting or mobilizing hematopoietic stem cells and/or progenitor cells using a combination of one or more CXCR2 agonists (e.g., GROP) and one or more CXCR4 antagonists (e.g., plerixafor). An exemplary method of mobilizing hematopoietic stem cells and/or progenitor cells in a subject comprises administering to the subject a combination of at least one CXCR2 agonist and at least one CXCR4 antagonist in amounts sufficient to mobilize such hematopoietic stem cells and/or progenitor cells into the subject's peripheral blood. The isolated heHSCs disclosed herein and the related methods of their preparation by mobilizing hematopoietic stem cells and/or progenitor cells have a variety of useful applications, for example for the treatment of stem cell and/or progenitor cell disorders.

In some embodiments, aspects of the present inventions relate to non-native, isolated heHSCs that are prepared by contacting or mobilizing hematopoietic stem cells and/or progenitor cells using a combination of at least one CXCR2 agonist (e.g., GROP) and at least one CXCR4 antagonist, VLA-4 antagonist, α ₉ βι antagonist, α ₉ βι integrin/VLA-4 antagonist or combination thereof.

As used herein, the term "mobilizing" refers to the act of inducing the migration of hematopoietic stem cells and/or progenitor cells (e.g., heHSCs) from a first location (e.g., the stem cell niche or bone marrow tissues of a subject) to a second location (e.g., the peripheral blood or an organ, such as the spleen, of a subject). For example, in certain embodiments, the non-native, isolated heHSCs disclosed herein may be prepared by mobilizing hematopoietic stem cells and/or progenitor cells from the stem cell niche of a human subject into the subject's peripheral tissue by administering to the subject a combination of one or more CXCR2 agonists (e.g., GROP) and one or more CXCR4 antagonists (e.g., plerixafor), following which the mobilized heHSCs may be harvested or isolated (e.g., by apheresis), as further described herein. With regard to the heHSCs disclosed herein, the term "isolated" means that the heHSC is substantially free of other cell types or cellular materials with which may be present when the heHSC is isolated from a treated subject. In some embodiments, an isolated heHSC or an isolated population of heHSCs is a substantially pure population of heHSCs, for example, as compared to the

heterogeneous population from which the cells were isolated or enriched from (e.g., substantially pure as compared to the population of mobilized cells). In some embodiments, the heHSCs are enriched from a biological sample that is obtained from a subject following treatment with a combination of a CXCR2 agonist (e.g., GROP) and a CXCR4 antagonist (e.g., plerixafor). In one embodiment, the mobilized and harvested heHSCs disclosed herein may be used in connection with an allogeneic or an autologous transplant. The terms "enriching" or "enriched" are used

interchangeably herein and mean that the yield (fraction) of heHSCs is increased by at least about 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99% or more over the fraction of mobilized cells.

As used herein with respect to a population of heHSCs, term "substantially pure", refers to a population of heHSCs that is at least about 75%, preferably at least about 85%), more preferably at least about 90%, and most preferably at least about 95% pure, and still more preferably at least about 99% pure with respect to the cells making up a total population of mobilized cells. Recast, the terms "substantially pure" or "essentially purified", with regard to a population of heHSCs, refers to a population of cells that contain fewer than about 20%, more preferably fewer than about 15%, 12%, 10%, 8%, 7%, most preferably fewer than about 5%, 4%, 3%, 2%, 1%), or less than 1%, of cells that are not heHSCs as defined by the terms herein. In some embodiments, the present invention encompasses methods to expand a population of heHSCs, wherein the expanded population of heHSCs is a substantially pure population.

While certain embodiments disclosed herein contemplate the in vivo preparation of the heHSCs by mobilizing hematopoietic stem cells and/or progenitor cells, it should be understood that the present inventions are not limited to such in vivo methods. Rather, also contemplated are in vitro methods of preparing heHSCs, for example by contacting hematopoietic stem cells and/or progenitor cells with a combination of a CXCR2 agonist (e.g., GROP) and a CXCR4 antagonist (e.g., plerixafor) , VLA-4 antagonist, 019P1 antagonist, 019P1 integrin/VLA-4 antagonist or combination thereof. As used herein, the term "contacting" means bringing two or more moieties together, or within close proximity of one another such that the moieties may interact with each other. For example, in one embodiment of the present invention, a hematopoietic stem cell and/or a progenitor cell is contacted with a CXCR2 agonist and/or a CXCR4 antagonist to produce and/or mobilize a heHSC.

Contemplated CXCR2 agonists include any compounds or agents that are capable of activating the CXCR2 receptor (e.g., the human CXCR2 receptor).

Exemplary CXCR2 agonists include chemokines, cytokines, biologic agents, antibodies and small organic molecules. For example, contemplated chemokines acting via the CXCR2 receptor include without limitation GROP, GROa, GROy, GCP-2 (granulocyte chemo-attractant protein 2), IL-8, NAP -2 (neutrophil activating peptide 2), ENA-78 (epithelial-cell derived neutrophil activating protein 78), and modified forms of any of the foregoing. In some embodiments, the CXCR2 agonist is selected from the group of compounds or agents consisting of small organic or inorganic molecules; oligosaccharides; polysaccharides; biological macromolecules selected from the group consisting of peptides, proteins, peptide analogs and derivatives; peptidomimetics; nucleic acids selected from the group consisting of siRNAs, shRNAs, antisense RNAs, ribozymes, and aptamers; and any combination thereof.

In certain aspects, the CXCR2 agonist comprises GROp.

In some embodiments, the at least one CXCR2 agonist is the chemokine

GROP or an analog or derivative thereof. An exemplary form of GROP is the human GROp polypeptide (GenBank Accession: AAP13104; SEQ ID NO: 1). In certain aspects, an exemplary form of GROP is the human GROP (UniProt ID No. P19875; SEQ ID NO: 2). An exemplary GROP analog or derivative is the desamino GROP protein (also known as MIP-2alpha), which comprises the amino acid sequence of mature gro-S protein truncated at its N terminus between amino acid positions 2 and 8, as described in PCT International Application Publication WO/1994/029341, the contents of which are incorporated herein by reference in their entirety. Another GROP analog or derivative is the dimeric modified GROP protein described in U.S. Patent No.

6,413,510, the contents of which are incorporated herein by reference in their entirety. Still another exemplary GROp analog or derivative is SB-251353, a GROp analog involved in directing movement of stem cells and other leukocytes, as described by Bensinger, et al., Bone Marrow Transplantation (2009), 43, 181-195, the entire contents of which are incorporated by reference herein.

In some embodiments of the present inventions, the at least one CXCR2 agonist is or comprises GROP-A4 (e.g., SEQ ID NO: 3) or an analog or derivative thereof. In some embodiments, the at least one CXCR2 agonist is selected from the group consisting of GROP or an analog or derivative thereof and GROP-A4 or an analog or derivative thereof.

Contemplated CXCR4 antagonists include any compounds or agents that are capable of blocking the CXCR4 receptor or preventing its activation. For example, contemplated are compounds and agents that block or otherwise interfere with the binding or interaction of the CXCR4 receptor with such receptor's ligand. Also contemplated are compounds or agents that block the downstream effects of the activated CXCR4 receptor. In some embodiments, the CXCR4 antagonist is selected from the group of compounds or agents consisting of small organic or inorganic molecules; oligosaccharides; polysaccharides; biological macromolecules selected from the group consisting of peptides, proteins, peptide analogs and derivatives;

peptidomimetics; nucleic acids selected from the group consisting of siRNAs, shRNAs, antisense RNAs, ribozymes, and aptamers; and any combination thereof.

In some embodiments of the present inventions, the at least one CXCR4 antagonist is plerixafor (formerly known as AMD-3100), the structure of which is depicted below (I), or an analog or derivative thereof.

In some embodiments, the at least one CXCR4 antagonist is MOZOBIL® or an analog or derivative thereof. Exemplary analogs of plerixafor include, but are not limited to, AMD11070, AMD3465, KRH-3955, T-140, and 4F-benzoyl-TN14003, as depicted below (II- VI, respectively) and described by De Clercq, Pharmacol Ther. (2010) 128(3):509-18, the contents of which are incorporated by reference herein in their entiret .

KRH-3955 (IV)

(VI)

In some embodiments, the at least one CXCR4 antagonist comprises

ALTl 188, ALTl 187, ALTl 128, ALT1228, or TG-0054 or an analog or derivative thereof. In some embodiments, the CXCR4 antagonist comprises at least one inhibitor described in Debnath B, et al., "Small Molecule Inhibitors of

X RA "Theranostics 2013; 3(l):47-75, incorporated herein by reference.

In some embodiments, non-native, isolated heHSCs are prepared by contacting or mobilizing hematopoietic stem cells and/or progenitor cells using a combination of at least one CXCR2 agonist (e.g., GROP) and at least one 019P1 integrin/VLA-4 antagonist. In some embodiments, the 019P1 integrin/VLA-4 antagonist is N-(benzenesulfonyl)-L-prolyl-L-0-(l-pyrrolidinylcarbonyl)tyr osine (BOP) or an analog or derivative thereof (e.g., R-BC154). In some embodiments, non-native, isolated heHSCs are prepared by contacting or mobilizing hematopoietic stem cells and/or progenitor cells using a combination of at least one CXCR2 agonist (e.g., GROP) and at least one VLA-4 antagonist. In some embodiments, the VLA-4 antagonist is BIO 5192, Natalizumab, or an analog or derivative thereof.

In some embodiments, the at least one CXCR2 agonist is or comprises GROP or an analog or derivative thereof, and the at least one CXCR4 antagonist is or comprises plerixafor (AMD-3100) or an analog or derivative thereof. In some embodiments, the at least one CXCR2 agonist is selected from the group consisting of GROP-A4 or an analog or derivative thereof and the at least one CXCR4 antagonist is selected from the group consisting of plerixafor or an analog or derivative thereof.

The combination of at least one CXCR2 agonist and at least one CXCR4 antagonist, VLA-4 antagonist, α ₉ βι antagonist, α ₉ βι integrin/VLA-4 antagonist or combination thereof may be administered directly to a subject in combination or, in certain aspects, may be administered independently. For example, the at least one CXCR2 agonist and the at least one CXCR4 antagonist, VLA-4 antagonist, α ₉ βι antagonist, α ₉ βι integrin/VLA-4 antagonist or combination thereof can be, but need not be, administered (e.g., administered intravenously) to a subject at the same time. In one embodiment, the at least one CXCR2 agonist is administered in one or more doses, followed by the administration of the at least one CXCR4 antagonist in one or more doses.

In addition to inducing a faster mobilization (e.g., about two-fold, three-fold , four-fold, five-fold, six-fold, seven-fold, eight-fold, nine-fold, ten-fold, twelve-fold, fifteen-fold, twenty -fold or more faster relative to traditional mobilization regimens that are performed using, for example, G-CSF or, alternatively, within one hour, within 45 minutes, within 30 minutes, within 15 minutes within 10 minutes, within 5 minutes or faster) and producing a greater quantity of mobilized stem cells (e.g., heHSCs), the combination of at least one CXCR2 agonist (e.g., GROB-A4 or an analog or derivative thereof) and at least one CXCR4 antagonist (e.g., plerixafor or an analog or derivative thereof) , VLA-4 antagonist, α ₉ βι antagonist, α ₉ βι integrin/VLA-4 antagonist or combination thereof mobilizes a non-native stem cell that is

characterized by its enhanced engrafting ability and its unique genetic signatures, as illustrated in FIG. 3. As used herein to describe the stem cells that are mobilized using the combination of at least one CXCR2 agonist and at least one CXCR4 antagonist, VLA-4 antagonist, α ₉ βι antagonist, α ₉ βι integrin/VLA-4 antagonist or combination thereof the term "unique" refers to one or more distinguishing characteristics of such mobilized stem cells relative to those cells that are mobilized using traditional mobilization regiments using, for example, G-CSF alone. For example, stem cells that are mobilized using the combination of at least one CXCR2 agonist and at least one CXCR4 antagonist, VLA-4 antagonist, α ₉ βι antagonist, α ₉ βι integrin/VLA-4 antagonist or combination thereof may be characterized by their expression of one or more unique markers or antigens (e.g., CD93+) or by their unique transcriptome.

One such marker, CD93, is expressed in hematopoietic cells at the apex of hematopoiesis. These early hematopoietic CD93 expressing cells in humans may also be negative for CD34. heHSC populations generated upon treatment with

combination of at least one CXCR2 agonist and at least one CXCR4 antagonist which also exhibit CD93 expression are indicative of early lineage stem cells and may serve to support improved transplantation and/or engraftment.

Similarly, in certain embodiments, stem cells that are mobilized using the combination of at least one CXCR2 agonist and at least one CXCR4 antagonist, VLA- 4 antagonist, α ₉ βι antagonist, α ₉ βι integrin/VLA-4 antagonist or combination thereof may be characterized by improved function. In particular, the engrafting ability of the heHSCs mobilized using the combination of at least one CXCR2 agonist and at least one CXCR4 antagonist, VLA-4 antagonist, α ₉ βι antagonist, α ₉ βι integrin/VLA-4 antagonist or combination thereof is surprisingly increased or enhanced relative to the engrafting ability of stem cells or PBSCs that are mobilized following the contacting of hematopoietic stem cells and/or progenitor cells with traditional mobilizing agents, such as G-CSF.

In certain aspects, the heHSCs are characterized by their increased or enhanced engrafting ability relative to stem cells or PBSCs that are mobilized following the contacting of hematopoietic stem cells and/or progenitor cells with one or more chemotherapeutic agents (e.g., chemotherapeutic mobilization agents).

Exemplary chemotherapeutic agents include paclitaxel, etoposide, vinblastine, doxorubicin, bleomycin, methotrexate, 5-fluorouracil, 6-thioguanine, cytarabine, cyclophosphamide, cisplatinum and combinations thereof. In certain aspects, such chemotherapeutic agents mobilize hematopoietic stem cells and/or progenitor cells. For example, such a chemotherapeutic mobilization agent may comprise EPO. In some embodiments, such a chemotherapeutic mobilization agent is or comprises stem cell factor. In some embodiments, such a chemotherapeutic mobilization agent is or comprises TPO. In still other embodiments, such a chemotherapeutic mobilization agent is or comprises parathyroid hormone.

As used herein, the term "hematopoietic stem cells" or "HSC" refers to stem cells that can differentiate into the hematopoietic lineage and give rise to all blood cell types such as white blood cells and red blood cells, including myeloid (e.g., monocytes and macrophages, neutrophils, basophils, eosinophils, erythrocytes, megakaryocytes/platelets, dendritic cells), and lymphoid lineages (e.g., T-cells, B- cells, K-cells). Stem cells are defined by their ability to form multiple cell types (multipotency) and their ability to self-renew. Hematopoietic stem cells can be identified, for example by cell surface markers such as CD34-, CD133+, CD48-, CD150+, CD244-, cKit+, Scal+, and lack of lineage markers (negative for B220, CD3, CD4, CD8, Macl, Grl, and Terl l9, among others).

As used herein, the term "hematopoietic progenitor cells" encompasses pluripotent cells which are committed to the hematopoietic cell lineage, generally do not self-renew, and are capable of differentiating into several cell types of the hematopoietic system, such as granulocytes, monocytes, erythrocytes,

megakaryocytes, B-cells and T-cells, including, but not limited to, short term hematopoietic stem cells (ST-HSCs), multi-potent progenitor cells (MPPs), common myeloid progenitor cells (CMPs), granulocyte-monocyte progenitor cells (GMPs), megakaryocyte-erythrocyte progenitor cells (MEPs), and committed lymphoid progenitor cells (CLPs). The presence of hematopoietic progenitor cells can be determined functionally as colony forming unit cells (CFU-Cs) in complete methylcellulose assays, or phenotypically through the detection of cell surface markers (e.g., CD45-, CD34+, Terl l9-, CD16/32, CD127, cKit, Seal) using assays known to those of skill in the art.

In some embodiments, the mobilized hematopoietic stem cells and/or progenitor cells comprise SKL cells. In certain aspects, the mobilized hematopoietic stem cells and/or progenitor cells comprise SKL SLAM cells. In certain aspects, the mobilized hematopoietic stem cells and/or progenitor cells exhibit a SLAM (Signaling lymphocyte activation molecule) expression pattern which is CD150+, CD48-. A SLAM expression pattern (SLAM code) is an expression pattern of specific markers (SLAM markers) that are used to identify subpopulations of hematopoietic stem cells and multipotent progenitors. See Oguro, et al. (2013) "SLAM family markers resolve functionally distinct subpopulations of hematopoietic stem cells and multipotent progenitors," Cell Stem Cell, 13(1), 102-116, and references cited therein.

In some embodiments, the mobilized hematopoietic stem cells and/or progenitor cells comprise CD34-, CD133+ cells. In some embodiments, the mobilized hematopoietic stem cells and/or progenitor cells comprise common myeloid progenitor cells. In some embodiments, the mobilized hematopoietic stem cells and/or progenitor cells comprise granulocyte/monocyte progenitor cells. In some embodiments, the mobilized hematopoietic stem cells and/or progenitor cells comprise megakaryocyte/erythroid progenitor cells. In some embodiments, the mobilized hematopoietic stem cells and/or progenitor cells comprise committed lymphoid progenitor cells. In some embodiments, the mobilized hematopoietic stem cells and/or progenitor cells comprise a combination of common myeloid progenitor cells, granulocyte/monocyte progenitor cells, megakaryocyte/erythroid progenitor cells. In some embodiments, the mobilized hematopoietic stem cells and/or progenitor cells comprise CD150-, CD48-, CD244+ cells. In some embodiments, the mobilized hematopoietic stem cells and/or progenitor cells comprise CD150-, CD48+, CD244+ cells. In some embodiments, the mobilized hematopoietic stem cells and/or progenitor cells comprise Sca-1-, c-kit+, Lin-, CD34+, CD16/32 ^mid cells. In some embodiments, the mobilized hematopoietic stem cells and/or progenitor cells comprise Sca-1-, c-kit+, Lin-, CD34-, CD16/32 ^low cells. In some embodiments, the isolated heHSC does not express an immunophenotypic means of identifying human hematopoietic stem cells.

In some embodiments, the isolated heHSCs disclosed herein comprise a unique transcriptome relative to hematopoietic stem cells contacted with G-CSF, a chemotherapeutic agent, or a combination thereof. For example, in certain aspects, the isolated heHSCs disclosed herein are characterized based on their differential expression of one or more of the genes identified in FIG. 4, relative to, for example the expression of one or more genes in hematopoietic stem cells (HSCs) that were mobilized using G-CSF. In some aspects, the isolated heHSCs disclosed herein are characterized based on their differential expression of one or more of the genes selected from the group consisting of Fos (e.g., SEQ ID NO: 4), CD93 (e.g., SEQ ID NO: 5), Fosb (e.g., SEQ ID NO: 6), Duspl (e.g., SEQ ID NO: 7), Jun (e.g., SEQ ID NO: 8), Dusp6 (e.g., SEQ ID NO: 9), Cdkl (e.g., SEQ ID NO: 10), Fignll (e.g., SEQ ID NO: 11), Plk2 (e.g., SEQ ID NO: 12), Rsad2 (e.g., SEQ ID NO: 13), Sgkl (e.g., SEQ ID NO: 14), Sdcl (e.g., SEQ ID NO: 15), Serpine2 (e.g., SEQ ID NO: 16), Sppl (e.g., SEQ ID NO: 17), Cdca8 (e.g., SEQ ID NO: 18), Nrpl (e.g., SEQ ID NO: 19), Mcam (e.g., SEQ ID NO: 20), Pbk (e.g., SEQ ID NO: 21), Akrlcl (e.g., SEQ ID NO: 22) and Cypl lal (e.g., SEQ ID NO: 23), relative to, for example the expression of one or more genes by hematopoietic stem cells (HSCs) that were mobilized using G- CSF. In some embodiments, the isolated heHSC is OPN+ (e.g., the isolated heHSC express osteopontin). In some embodiments, the isolated heHSC differentially expresses CD93 (e.g., the heHSC is CD93+). In certain aspects, the isolated heHSC disclosed herein is non-quiescent. In some embodiments, the heHSC is CD34-.

The heHSCs disclosed herein are prepared by mobilizing or contacting hematopoietic stem cells and/or progenitor cells with a combination of a CXCR2 agonist and a CXCR4 antagonist, VLA-4 antagonist, α ι antagonist, α ι

integrin/VLA-4 antagonist or combination thereof. As used herein, the terms "highly engraftable hematopoietic stem cell" and "heHSC" refer to the isolated population or fraction of stem cells or PBSCs that are, for example, mobilized from the stem cell niche or bone marrow of a subject into the peripheral blood or organs of the subject following the administration of one or more CXCR2 agonists (e.g., GROP or an analog or derivative thereof) and one or more CXCR4 antagonists (e.g., plerixafor or an analog or derivative thereof), VLA-4 antagonist, α ι antagonist, α ι

integrin/VLA-4 antagonist or combination thereof. In certain aspects, such heHSCs are substantially pure.

In some embodiments, the isolated heHSCs disclosed herein are

immunophenotypically unique relative to cells or stem cells mobilized using traditional mobilization regimens (e.g., stem cells mobilized using G-CSF). For example, as illustrated in FIG. 3, certain genes showed higher expression in the heHSCs that were mobilized using the combination of the CXCR2 agonist GROP and the CXCR4 antagonist plerixafor (AMD-3100), relative to the cells mobilized using G-CSF. In certain aspects, the heHSCs disclosed herein express osteopontin or are osteopontin positive (OPN+). In some embodiments, the isolated heHSC differentially expresses CD93 (e.g., the heHSC is CD93+). In some embodiments, the isolated heHSC does not express CD34 or is CD34-. In some embodiments, the isolated heHSC is CD93+ and CD34-. In some embodiments, the isolated heHSC

differentially expresses one or more genes shown in FIG. 3 or FIG. 4 as compared to an isolated HSC mobilized using traditional mobilization regimens (e.g., stem cells mobilized using G-CSF).

In some embodiments, a population of cells (i.e., a cell population comprising or consisting of heHSC) isolated by the methods disclosed herein (e.g., by contacting cells with a combination of at least one CXCR2 agonist (e.g., GROP) and at least one CXCR4 antagonist, VLA-4 antagonist, α ι antagonist, α ι integrin/VLA-4 antagonist or combination thereof) has an increased or decreased proportion of cells exhibiting one or more cell surface markers or one or more expression profiles disclosed herein as compared to cells isolated by conventional methods. The one or more cell surface markers or cell expression profiles may be increased or decreased by about 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or more. In some embodiments, the one or more cell surface marker is CD93. In some embodiments, after performing the methods disclosed herein, an obtained cell population may be assayed to determine whether the prevalence of one or more cell surface markers or cell expression profiles has increased or decreased to determine whether the obtained cell population is suitable as heHSC for transplantation. In some embodiments, the obtained cell population is assayed to determine if at least about 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or more of the cells are CD93+. Any suitable assay (e.g., FACS analysis) may be used for the determination.

In some embodiments, the obtained cell population may be further enriched for a desired cell surface marker or gene expression pattern to obtain a desired heHSC population for transplantation. In some embodiments, the obtained cell population may be enriched for CD93+ cells or CD93+ and CD34- cells. In some embodiments, the cell population may be enriched by about 1.5-fold, 2-fold, 2.5-fold, 3-fold, 4-fold, 5-fold or more. In some embodiments, the cell population may be enriched to contain at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or more of cells containing a desired cell surface marker or cell expression pattern (e.g., enriched for CD93+ cells or CD93+/CD34- cells). Any suitable procedure (e.g., FACS sorting) may be used for the enrichment.In some embodiments, the isolated heHSCs disclosed herein are not immunophenotypically unique relative to cells or stem cells mobilized using traditional mobilization regimens (e.g., stem cells mobilized using G-CSF). Such isolated heHSC may be functionally unique relative to cells or stem cells mobilized using traditional mobilization regimens.

Upon mobilization, which in certain instances may occur within 15-30 minutes of having administered a CXCR2 agonist and a CXCR4 antagonist, VLA-4 antagonist, α ι antagonist, α ι integrin/VLA-4 antagonist or combination thereof, the mobilized heHSCs can be harvested or isolated (e.g., via apheresis) as disclosed herein and are useful for subsequent transplantation in a subject in need thereof. For example, such mobilized heHSCs may be harvested or isolated for autologous transplantation into a subject or for allogeneic transplantation into a recipient subject. In some instances, the harvesting or isolation of the mobilized hematopoietic stem cells and/or progenitor cells can be initiated within as little as 15 minutes following the administration of the at least one CXCR2 agonist and the at least one CXCR4 antagonist, VLA-4 antagonist, α ₉ βι antagonist, α ₉ βι integrin/VLA-4 antagonist or combination thereof. In some embodiments, the harvesting or isolating procedure can begin in as little as 10 minutes, 12 minutes, 15 minutes, 18 minutes, 20 minutes, 22 minutes, 25 minutes, 30 minutes, 35 minutes, 40 minutes, 47 minutes, 52 minutes, 58 minutes, or an hour after administration of the at least one CXCR2 agonist and the at least one CXCR4 antagonist, VLA-4 antagonist, α ₉ βι antagonist, α ₉ βι integrin/VLA-4 antagonist or combination thereof.

The disclosure contemplates the use of any suitable method of harvesting and/or collecting mobilized hematopoietic stem cells and/or progenitor cells to prepare the isolated heHSCs disclosed herein. In some embodiments harvesting the mobilized hematopoietic stem cells and/or progenitor cells comprises apheresis. In some embodiments, the combination of at least one CXCR2 agonist (e.g., GRC^ or GRC^-A4) and at least one CXCR4 antagonist (e.g., plerixafor), VLA-4 antagonist, α ₉ βι antagonist, α ₉ βι integrin/VLA-4 antagonist or combination thereof rapidly and efficiently mobilizes mobilized hematopoietic stem cells and/or progenitor cells, and exhibits increased efficiencies compared to traditional mobilizing regimens. As a result, in some embodiments an apheresis procedure may be performed on the same day that the at least one CXCR2 agonist and the at least one CXCR4 antagonist, VLA-4 antagonist, α ₉ βι antagonist, α ₉ βι integrin/VLA-4 antagonist or combination thereof are administered to the subject. In other words, harvesting mobilized heHSCs from a subject (e.g., a donor) via apheresis can be performed on the same day that the mobilization agents are administered to the subject (e.g., during a single visit to a healthcare facility). In some embodiments, an apheresis procedure may be performed on the same day that at least one CXCR2 agonist (e.g., GRC^ or GRC^-A4) and at least one CXCR4 antagonist, VLA-4 antagonist, α ₉ βι antagonist, α ₉ βι integrin/VLA-4 antagonist or combination thereof is administered to the subject.

In some embodiments, administration of the at least one CXCR2 agonist (e.g.,

GRC^ or GRC^-A4) and the at least one CXCR4 antagonist, VLA-4 antagonist, α ₉ βι antagonist, α ₉ βι integrin/VLA-4 antagonist or combination thereof mobilizes an amount of hematopoietic stem cells and/or progenitor cells in the subject to harvest a heHSC cell dose of between about 1 x 10 ⁶ /kg body weight and 10 x 10 ⁶ /kg body weight in a single apheresis session. In some embodiments, a single session of apheresis collects enough heHSCs for a cell dose of between about 1 x 10 ⁶ /kg and 10 x 10 ⁶ /kg of the recipient's body weight. In some embodiments, administration of the at least one CXCR2 agonist (e.g., GRC-β or GROp-A4) and the at least one CXCR4 antagonist, VLA-4 antagonist, α ι antagonist, α ι integrin/VLA-4 antagonist or combination thereof mobilizes an amount of hematopoietic stem cells and/or progenitor cells in the subject to harvest enough heHSCs for a cell dose of between about 2 x 10 ⁶ /kg body weight and 8 x 10 ⁶ /kg body weight in a single apheresis session. In some embodiments, a single session of apheresis collects enough heHSCs for a cell dose of between about 2 x 10 ⁶ /kg and 8 x 10 ⁶ /kg of the recipient's body weight. In some embodiments, administration of the at least one CXCR2 agonist (e.g., GROP or GROP-A4) and the at least one CXCR4 antagonist, VLA-4 antagonist, (*9βι antagonist, α ι integrin/VLA-4 antagonist or combination thereof mobilizes an amount of hematopoietic stem cells and/or progenitor cells in the subject to harvest a heHSC cell dose of between about 3 x 10 ⁶ /kg body weight and 6 x 10 ⁶ /kg body weight in a single apheresis session. In some embodiments, a single session of apheresis collects enough heHSCs for a cell dose of between about 1 x 10 ⁶ /kg and 10 x 10 ⁶ /kg of the recipient's body weight.

Following harvesting, the isolated heHSCs disclosed herein may be administered to or transplanted in the donor subject (e.g., an autologous transplant), or alternatively may be donated to a different subject in need thereof (e.g., allogeneic transplant). In certain aspects, the administration or transplant of the isolated heHsCs occurs following or in combination with radiation or chemotherapy.

The mobilized heHSC disclosed herein are characterized by their increased engrafting ability (e.g., a two-fold increased engrafting ability), which makes such heHSCs suitable for use in connection with gene therapy. For example, where genetic manipulation of cells is associated with a corresponding reduction in their engrafting ability and, due to the improved or enhanced engrafting ability of the heHSCs disclosed herein, such heHSCs are rendered more tolerant to genetic manipulation, following which only limited reductions in their engrafting ability may be observed.

Gene therapy can be used to transform a heHSC, modify a heHSC to replace a gene product, to treat disease, or to improve engraftment of the heHSC following implantation into a subject. For example, in certain embodiments, the heHSCs disclosed herein may be transformed with an expression vector (e.g., a viral vector selected from the group consisting of a retrovirus, a herpes simplex, a lentivirus, an adenovirus, and an adeno-associated virus). In some embodiments, the isolated heHSC is transformed or transfected with an expression vector that comprises a polynucleotide. In some embodiments, the polynucleotide comprises an exogenous polynucleotide. In some embodiments, the expression product of a polynucleotide is a protein that is not endogenously expressed or is under expressed by the subject's cells.

As used herein, the term "transform" means to introduce into a heHSC an exogenous polynucleotide (e.g., a nucleic acid or nucleic acid analog) which replicates within that heHSC, that encodes a gene product (e.g., an amino acid, polypeptide sequence, protein or enzyme) which is expressed in that heHSC, and/or that is integrated into the genome of that heHSC so as to affect the expression of a genetic locus within the genome. The term "transform" is used to embrace all of the various methods of introducing such polynucleotides (e.g., nucleic acids or nucleic acid analogs), including, but not limited to the methods referred to in the art as transformation, transfection, transduction, or gene transfer, and including techniques such as microinjection, DEAE-dextran-mediated endocytosis, calcium phosphate coprecipitation, electroporation, liposome-mediated transfection, ballistic injection, viral-mediated transfection, and the like.

In some embodiments, also disclosed herein are methods of transforming an isolated heHSC, wherein such methods comprise a step of contacting the heHSC with an expression vector under conditions sufficient for the vector to integrate into the heHSC genome. In yet other embodiments, the isolated heHSC of the present inventions are genetically modified to shut off expression of an endogenous polynucleotide.

As used herein, the term "vector" means any genetic construct, such as for example, a plasmid, phage, transposon, cosmid, chromosome, virus and/or virion, which is capable transferring nucleic acids between cells. Vectors may be capable of one or more of replication, expression, and insertion or integration, but need not possess each of these capabilities. Thus, the term includes cloning, expression, homologous recombination, and knock-out vectors.

In certain aspects, prior to engraftment, a mobilized hematopoietic stem cell and/or progenitor cell can be manipulated to express one or more desired

polynucleotides or gene products (e.g., one or more of a polypeptide, amino acid sequence protein and/or enzyme). Gene therapy can be used to either modify a mobilized hematopoietic stem cell and/or progenitor cell to replace a polynucleotide or gene product or to add or knockdown a gene product. In some embodiments the genetic engineering is done, for example, to treat disease, following which the genetically engineered heHSC would be transplanted and engraft into a subject. For example, a mobilized heHSC may be manipulated to express one or more

polynucleotides or genes that would enhance the engrafting ability of the transplanted heHSC.

Techniques for transfecting cells are known in the art. In an exemplary embodiment, gene therapy can be used to insert a polynucleotide (e.g., DNA) into a mobilized hematopoietic stem cell from a patient or subject with a genetic defect to correct such genetic defect, following which the corrected or genetically engineered mobilized hematopoietic stem cell may be transplanted into a subject.

In some other embodiments, the heHSCs disclosed herein can be used as carriers for gene therapy.

In some embodiments, the isolated heHSCs and the related methods of mobilizing such heHSCs are useful for treating subjects that have demonstrated poor mobilization in response to a conventional hematopoietic stem cell and/or progenitor cell mobilization regimen (e.g., subjects that have failed to mobilize a sufficient numbers of stem cells following a mobilization regimen comprising or consisting of G-CSF). For example, such heHSCs and the related methods disclosed herein may be used to enhance hematopoietic stem cell and/or progenitor cell mobilization in individuals exhibiting stem cell and/or progenitor cell mobilopathy. Accordingly, in certain embodiments, any of the methods and compositions disclosed herein may be suitable for use in mobilizing hematopoietic stem cell and/or progenitor stem cells in a subject having an underlying disease that impairs egress of such hematopoietic stem cells and/or progenitor stem cells from bone marrow and into the peripheral circulation, including, for example, subjects that have or are at risk of developing diabetic stem cell mobilopathy. In certain aspects, subjects that have failed to mobilize a sufficient number of hematopoietic stem cells and/or progenitor cells in response to a mobilization regimen comprising G-CSF (e.g., subjects that have failed to mobilize a sufficient number of stem cells about five days after receiving a G-CSF mobilization regimen) are candidates for mobilization using the methods and compositions disclosed herein. In certain embodiments, the isolated heHSCs may be administered to a subject exhibiting mobilopathy for the treatment of a stem cell or progenitor cell disorder.

As used herein to describe a mobilization regimen, the term "conventional" generally refers to those mobilization regimens that have traditionally been used to mobilize stem cells. For example, conventional mobilization regimens include those comprising or consisting of G-CSF and that have historically been used to mobilize stem cells from the bone marrow compartment. Such convention mobilization regimens are frequently associated with poor mobilization results, which may often occur over an extended period of time (e.g., over about 5 days), and subjecting the patient to repeated and prolonged apheresis procedures.

In addition to being phenotypically unique relative to stem cells mobilized using traditional mobilization regimens, the heHSCs disclosed herein are

characterized by their improved functional properties. For example, in certain embodiments, the heHSCs disclosed herein are characterized by their improved engrafting ability. Accordingly, certain aspects of the methods disclosed herein comprise administering or otherwise transplanting the isolated, non-native heHSCs to a subject in need, such that the administered heHSCs engraft in the tissues (e.g., the bone marrow tissue) of the recipient subject. As used herein, the terms "engrafting" and "engraftment" refer to placing or administration of the heHSCs into an animal (e.g., by injection), wherein following such placement or administration, the heHSCs persist in vivo. Engraftment may be readily measured by the ability of the

transplanted heHSCs to, for example, contribute to the ongoing blood cell formation or by assessing donor chimerism following the transplant of such heHSCs.

Successful stem cell transplantation depends on the ability to engraft sufficient quantities of transplanted stem cells in the tissues of the subject (e.g., the bone marrow tissues of the subject). The heHSCs disclosed herein are characterized by their improved engrafting ability and accordingly, certain aspects of the present invention relate to methods of treating stem cell and/or progenitor cell disorders or other diseases requiring transplantation of hematopoietic stem cells and/or progenitor cells by administering to a subject the non-native, isolated heHSCs disclosed herein.

The heHSCs disclosed herein are also characterized by their ability to achieve enhanced or improved donor chimerism following their engraftment in the tissues of a subject. For example, as illustrated in FIG. 1, relative to G-CSF-mobilized stem cells, in certain embodiments, an increase in donor chimerism is observed following engraftment of heHSCs that were mobilized with the combination of one or more CXCR2 agonists (e.g., GROP and analogs or derivatives thereof) and one or more CXCR4 antagonist (e.g., AMD-3100 and analogs or derivatives thereof). As used herein, the term "donor chimerism" refers to the fraction or percentage of bone marrow cells that originate from the donor heHSCs following engraftment of such heHSCs in a subject. In certain embodiments, donor chimerism following

engraftment of the heHSCs is increased relative to, for example, donor chimerism observed following engraftment of the same or a similar quantity of stem cells that are mobilized using conventional mobilization regimens (e.g., conventional mobilization regimens comprising or consisting of G-CSF or other chemotherapeutic agents). In certain embodiments, donor chimerism following engraftment of the heHSCs is increased by at least about two fold, three-fold, four-fold, five-fold, six-fold, or more. In some embodiments, such donor chimerism is at least about 10%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 99%, or more.

In certain aspects, the heHSCs disclosed herein are also characterized by their ability to achieve an enhanced or improved CD34+ number upon engraftment in a subject. For example, such engrafted heHSCs demonstrate an enhanced or improved CD34+ number relative to an engraftment of the same quantity of hematopoietic stem cells contacted with G-CSF or one or more chemotherapeutic agents described herein. In some embodiments, such CD34+ number is increased by at least about 10%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 99%, 100%, 150%), 200%), 300%), or more relative to, for example, the CD34+ number observed following engraftment of a G-CSF-mobilized stem cell. In some embodiments, such CD34+ number is increased by at least about 1.2-fold, 1.3-fold, 1.4-fold, 1.5-fold, 1.6- fold, 1.7-fold, 1.8-fold, 1.9-fold, 2-fold, 2.5-fold, 3-fold, 3.5-fold, 4-fold, or more relative to, for example, the CD34+ number observed following engraftment of a G- CSF-mobilized stem cell.

In some embodiments, also disclosed herein are methods of treating a stem cell or progenitor cell disorder or a disease requiring transplantation of stem cells, the methods comprising administering the isolated, non-native heHSCs to a subject, wherein the administered heHSCs engrafts in the subject's tissues (e.g., the subject's bone marrow compartment), thereby treating the stem cell or progenitor cell disorder.

As used herein, the terms "treat," "treatment," "treating," or "amelioration" when used in reference to a stem cell disorder, progenitor cell disorder or any disease requiring stem cell transplantation, generally refer to therapeutic treatments for a condition, wherein the object is to reverse, alleviate, ameliorate, inhibit, slow down or stop the progression or severity of a symptom or condition. The term "treating" also includes reducing or alleviating at least one adverse effect or symptom of a condition, disease or disorder. Treatment is generally effective if one or more symptoms or clinical markers of the condition or disease are reduced. Alternatively, treatment is effective if the progression of a condition is reduced or halted. That is, treatment includes not just the improvement of symptoms or markers, but also a cessation or at least slowing of progress or worsening of symptoms that would be expected in the absence of treatment. Beneficial or desired clinical results include, but are not limited to, alleviation of one or more symptom(s), diminishment of extent of the deficit, stabilized state of, for example, a condition, disease, or disorder described herein, or delaying or slowing onset of a condition, disease, or disorder described herein, and an increased lifespan as compared to that expected in the absence of treatment.

As used herein, the term "administering," generally refers to the placement of the heHSCs described herein into a subject (e.g., the parenteral placement of heHSCs into a subject) by a method or route which results in delivery of such heHSCs to an intended target tissue or site of action (e.g., the bone marrow tissue of a subject). In certain aspects, the term "administering" refers to the placement of at least one CXCR2 agonist and at least one CXCR4 antagonist, VLA-4 antagonist, α ₉ βι antagonist, α ι integrin/VLA-4 antagonist or combination thereof to a subject to mobilize hematopoietic stem cells and/or progenitor cells from, for example, the subject's bone marrow tissues and into the subject's peripheral tissues (e.g., mobilizing such hematopoietic stem cells and/or progenitor cells out of the bone marrow compartment and into one or more of the peripheral compartments, such as the peripheral blood compartment).

The isolated, non-native heHSCs disclosed herein are useful for the treatment of any disease, disorder, condition, or complication associated with a disease, disorder, or condition, in which transplantation of hematopoietic stem cells and/or progenitor cells is desirable. In some embodiments, the present inventions relate to methods of treating diseases that require peripheral blood stem cell transplantation. In some embodiments, the disclosure provides method of treating stem cell disorders and progenitor cell disorders in a subject in need of such treatment. Examples of such stem cell and progenitor disorders include hematological malignancies and non- malignant hematological diseases.

In some embodiments, the disease, stem cell disorder or progenitor cell disorder is a hematological malignancy. Exemplary hematological malignancies which can be treated with the heHSCs and methods described herein include, but are not limited to, acute lymphoid leukemia, acute myeloid leukemia, chronic lymphoid leukemia, chronic myeloid leukemia, diffuse large B-cell non-Hodgkin's lymphoma, mantle cell lymphoma, lymphoblastic lymphoma, Burkitt's lymphoma, follicular B- cell non-Hodgkin's lymphoma, T-cell non-Hodgkin's lymphoma, lymphocyte predominant nodular Hodgkin's lymphoma, multiple myeloma, and juvenile myelomonocytic leukemia.

In some embodiments, the disease, stem cell disorder or progenitor cell disorder is a non-malignant disorder. Exemplary non-malignant diseases which can be treated with the methods and heHSCs described herein include, but are not limited to, myelofibrosis, myelodysplastic syndrome, amyloidosis, severe aplastic anemia, paroxysmal nocturnal hemoglobinuria, immune cytopenias, systemic sclerosis, rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, Crohn's disease, chronic inflammatory demyelinating polyradiculoneuropathy, human immunodeficiency virus (HIV), Fanconi anemia, sickle cell disease, beta thalassemia major, Hurler's syndrome (MPS-IH), adrenoleukodystrophy, metachromatic leukodystrophy, familial erythrophagocytic lymphohistiocytosis and other histiocytic disorders, severe combined immunodeficiency (SCID), and Wiskott-Aldrich syndrome.

As used herein, the term "subject" means any human or animal. In certain aspects, the animal is a vertebrate such as a primate, rodent, domestic animal or game animal. Primates include chimpanzees, cynomologous monkeys, spider monkeys, and macaques, e.g., Rhesus. Rodents include mice, rats, woodchucks, ferrets, rabbits and hamsters. Domestic and game animals include cows, horses, pigs, deer, bison, buffalo, feline species, e.g., domestic cat, canine species, e.g., dog, fox, wolf, avian species, e.g., chicken, emu, ostrich, and fish, e.g., trout, catfish and salmon. Patient or subject includes any subset of the foregoing (e.g., all of the above), but excluding one or more groups or species such as humans, primates or rodents. In certain embodiments, the subject is a mammal (e.g., a primate or human). In some embodiments, the subject is a mammal. In some embodiments, the mammal is a human, a non-human primate, a mouse, a rat, a dog, a cat, a horse, or a cow, and is not limited to these examples. Mammals other than humans can be advantageously used, for example, as subjects that represent animal models of, for example, a hematological malignancy. In addition, the methods described herein can be used to treat domesticated animals and/or pets. A subject can be male or female.

In certain embodiments, a subject can be one who has been previously diagnosed with or otherwise identified as suffering from or having a condition, disease, stem cell disorder or progenitor cell disorder described herein in need of treatment (e.g., of a hematological malignancy or non-malignant disease described herein) or one or more complications related to such a condition, and optionally, but need not have already undergone treatment for a condition or the one or more complications related to the condition. Alternatively, a subject can also be one who has not been previously diagnosed as having a condition in need of treatment or one or more complications related to such a condition. Rather, a subject can include one who exhibits one or more risk factors for a condition or one or more complications related to a condition.

A "subject in need" of treatment for a particular condition (e.g., a stem cell or progenitor cell disorder) can be a subject having that condition, diagnosed as having that condition, or at increased risk of developing that condition relative to a given reference population. In some embodiments, the methods of treatment described herein comprise selecting a subject diagnosed with, suspected of having, or at risk of developing a hematological malignancy, for example a hematological malignancy described herein. In some embodiments, the methods described herein comprise selecting a subject diagnosed with, suspected of having, or at risk of developing a non-malignant disease, for example a non-malignant disease described herein.

In other aspects of the invention, heHSC described herein may be produced by obtaining a HSC cell population by any conventional method disclosed in the art and enriching the HSC cell population for one or more cell surface markers or gene expression profiles for heHSC disclosed herein. In some embodiments, the obtained HSC cell population is enriched for CD93+ cells. In some embodiments, the HSC cell population is enriched for CD93+/CD34- cells. In some embodiments, the HSC cell population is enriched by about 1.5-fold, 2-fold, 2.5-fold, 3-fold, 4-fold, 5-fold or more. In some embodiments, the cell population may be enriched to contain at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or more of cells containing a desired cell surface marker or cell expression pattern (e.g., enriched for CD93+ cells or CD93+/CD34- cells). Any suitable procedure (e.g., FACS sorting) may be used for the enrichment.

Some aspects of the invention are directed towards a method of making an HSC product comprising: i) contacting hematopoietic stem cells and/or progenitor cells with at least one CXCR2 agonist and at least one CXCR4 antagonist, VLA-4 antagonist, α9β1 antagonist, α9β1 integrin/VLA-4 antagonist or combination thereof to produce a candidate product; ii) providing a target expression profile for an heHSC product; iii) determining whether the candidate product meets the target expression profile of an heHSC product; and iv) releasing the candidate product as an heHSC product if the candidate product meets the target expression profile of an heHSC product.

In some embodiments, the target expression profile comprises Sca-1+, c-kit+ and Lin- (SKL) cells. In some embodiments, the the target expression profile comprises CD48- cells. . In some embodiments, the target expression profile comprises CD 150+ cells. In some embodiments, the target expression profile comprises CD93+ cells. In some embodiments, the target expression profile comprises CD34- cells. In some embodiments, the target expression profile comprises OPN+ cells.

"The target expression profile" refers to a transcriptome and/or cell surface marker profile indicating the presence of heHSC cells or a certain percentage of heHSC cells in a cell population. In some embodiments, the target expression profile comprises at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%), or more of cells in the candidate product or enriched candidate product having one or more cell surface markers. In some embodiments, the target expression profile can be a transcriptome profile of the candidate product or enriched candidate product indicating an heHSC product. In some embodiments, the transcriptome profile can be similar or substantially similar to the profiles shown in FIG. 3 or FIG. 4.

In some embodiments, the contacting of the hematopoietic stem cells and/or progenitor cells with at least one CXCR2 agonist and at least one CXCR4 antagonist, VLA-4 antagonist, α9β1 antagonist, α9β1 integrin/VLA-4 antagonist or combination thereof is performed in vivo. In some embodiments, the contacting is performed in vitro. In some embodiments, the at least one CXCR2 agonist comprises GROP or an analog or derivative thereof. In some embodiments, the at least one CXCR2 agonist comprises GROP-A4 or an analog or derivative thereof. In some embodiments, the at least one CXCR4 antagonist comprises plerixafor or an analog or derivative thereof. In some embodiments, the at least one CXCR2 agonist is GROP or an analog or derivative thereof, and wherein the at least one CXCR4 antagonist is plerixafor or an analog or derivative thereof.

In some embodiments of the invention, the heHSC product, upon transplant into a subject, demonstrates increased engrafting ability relative to engraftment of the same quantity of hematopoietic stem cells contacted with granulocyte colony- stimulating factor (G-CSF), a chemotherapeutic agent, or a combination thereof. In some embodiments, the engrafting ability is increased by at least about two-fold. In certain embodiments, such engrafting ability is increased by at least about two-fold, three-fold, four-fold, five-fold, six-fold, or more.

In some embodiments of the invention, upon engraftment in a subject the heHSC product demonstrates increased donor chimerism relative to engraftment of the same quantity of hematopoietic stem cells contacted with G-CSF, a

chemotherapeutic agent, or a combination thereof. In some embodiments, the donor chimerism is increased by at least about two fold. . In certain embodiments, such donor chimerism is increased by at least about two-fold, three-fold, four-fold, fivefold, six-fold, or more. In some embodiments, donor chimerism is increased by at least about 50%.

In some embodiments, the heHSC product is non-quiescent.

In some embodiments, the method of making an HSC product additionally comprises a step of enriching the candidate product for one or more cell surface markers and/or one or more gene expression profiles. Any suitable method of enrichment may be employed. In some embodiments, the method is FACS.

In some embodiments, the heHSC product comprises a unique transcriptome relative to hematopoietic stem cells contacted with granulocyte colony-stimulating factor (G-CSF), a chemotherapeutic agent, or a combination thereof. In some embodiments, the heHSC product differentially express one or more of genes selected from the group consisting of Fos, CD93, Fosb, Duspl, Jun, Dusp6, Cdkl, Fignll, Plk2, Rsad2, Sgkl, Sdcl, Serpine2, Sppl, Cdca8, Nrpl, Mcam, Pbk, Akrlcl and Cypl lal, relative to one or more genes expressed by hematopoietic stem cells mobilized using G-CSF. In some embodiments, the heHSC product comprises at least a unique transcriptome or a unique phenotype as compared to a naturally occurring HSC.

In some aspects of the invention, the heHSC product is transformed to express a polynucleotide. In some embodiments, the heHSC product is transformed with an expression vector to express a polynucleotide. In some embodiments, the expression vector comprises a viral vector selected from the group consisting of a retrovirus, a herpes simplex, a lentivirus, an adenovirus, and an adeno-associated virus. In some embodiments, the heHSC product is transfected with an expression vector that comprises the polynucleotide. In some embodiments, polynucleotide comprises an exogenous polynucleotide.

In some embodiments, the heHSC product comprises at least 40% CD93+ cells. In some embodiments, the heHSC product comprises at least about 2 x 106 cells. In some embodiments, the hematopoietic stem cells and/or progenitor cells are human or mouse cells.

Another aspect of the invention is directed to a method of treating a stem cell or progenitor cell disorder comprising: i) contacting hematopoietic stem cells and/or progenitor cells with at least one CXCR2 agonist and at least one CXCR4 antagonist, VLA-4 antagonist, α9β1 antagonist, α9β1 integrin/VLA-4 antagonist or combination thereof to produce a candidate product; ii) providing a target expression profile for an heHSC product; iii) determining whether the candidate product meets the target expression profile of an heHSC product; and iv) administering the candidate product to a subject in need thereof if the candidate product meets the target expression profile of an heHSC product.

In some embodiments, the target expression profile comprises Sca-1+, c-kit+ and Lin- (SKL) cells. In some embodiments, the target expression profile comprises CD48- cells. In some embodiments, the target expression profile comprises CD 150+ cells. In some embodiments, the target expression profile comprises CD93+ cells. In some embodiments, the target expression profile comprises CD34- cells. In some embodiments, the target expression profile comprises OPN+ cells.

"The target expression profile" refers to a transcriptome and/or cell surface marker profile indicating the presence of heHSC cells or a certain percentage of heHSC cells in a cell population. In some embodiments, the target expression profile comprises at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or more of cells in the candidate product or enriched candidate product having one or more cell surface markers. In some embodiments, the target expression profile can be a transcriptome profile of the candidate product or enriched candidate product indicating an heHSC product. In some embodiments, the transcriptome profile can be similar or substantially similar to the profiles shown in FIG. 3 or FIG. 4.

In some embodiments, the contacting of the hematopoietic stem cells and/or progenitor cells with at least one CXCR2 agonist and at least one CXCR4 antagonist, VLA-4 antagonist, α9β1 antagonist, α9β1 integrin/VLA-4 antagonist or combination thereof is performed in vivo. In some embodiments, the contacting is performed in vitro.

In some embodiments, the at least one CXCR2 agonist comprises GROP or an analog or derivative thereof. In some embodiments, the at least one CXCR2 agonist comprises GROP-A4 or an analog or derivative thereof. In some embodiments, the at least one CXCR4 antagonist comprises plerixafor or an analog or derivative thereof. In some embodiments, the at least one CXCR2 agonist is GROP or an analog or derivative thereof, and wherein the at least one CXCR4 antagonist is plerixafor or an analog or derivative thereof.

In some embodiments of the invention, the heHSC product, upon transplant into a subject, demonstrates increased engrafting ability relative to engraftment of the same quantity of hematopoietic stem cells contacted with granulocyte colony- stimulating factor (G-CSF), a chemotherapeutic agent, or a combination thereof. In some embodiments, the engrafting ability is increased by at least about two-fold. In certain embodiments, such engrafting ability is increased by at least about two-fold, three-fold, four-fold, five-fold, six-fold, or more.

In some embodiments of the invention, upon engraftment in a subject the heHSC product demonstrates increased donor chimerism relative to engraftment of the same quantity of hematopoietic stem cells contacted with G-CSF, a

chemotherapeutic agent, or a combination thereof. In some embodiments, the donor chimerism is increased by at least about two fold. . In certain embodiments, such donor chimerism is increased by at least about two-fold, three-fold, four-fold, fivefold, six-fold, or more. In some embodiments, donor chimerism is increased by at least about 50%.

In some embodiments, the heHSC product is non-quiescent. In some embodiments, the method of making an HSC product additionally comprises a step of enriching the candidate product for one or more cell surface markers and/or one or more gene expression profiles. Any suitable method of enrichment may be employed. In some embodiments, the method is FACS.

In some embodiments, the heHSC product comprises a unique transcriptome relative to hematopoietic stem cells contacted with granulocyte colony-stimulating factor (G-CSF), a chemotherapeutic agent, or a combination thereof. In some embodiments, the heHSC product differentially express one or more of genes selected from the group consisting of Fos, CD93, Fosb, Duspl, Jun, Dusp6, Cdkl, Fignll, Plk2, Rsad2, Sgkl, Sdcl, Serpine2, Sppl, Cdca8, Nrpl, Mcam, Pbk, Akrlcl and Cypl lal, relative to one or more genes expressed by hematopoietic stem cells mobilized using G-CSF. In some embodiments, the heHSC product comprises at least a unique transcriptome or a unique phenotype as compared to a naturally occurring HSC.

In some aspects of the invention, the heHSC product is transformed to express a polynucleotide. In some embodiments, the heHSC product is transformed with an expression vector to express a polynucleotide. In some embodiments, the expression vector comprises a viral vector selected from the group consisting of a retrovirus, a herpes simplex, a lentivirus, an adenovirus, and an adeno-associated virus. In some embodiments, the heHSC product is transfected with an expression vector that comprises the polynucleotide. In some embodiments, polynucleotide comprises an exogenous polynucleotide.

In some embodiments, the heHSC product comprises at least 40% CD93+ cells. In some embodiments, the heHSC product comprises at least about 2 x 106 cells. In some embodiments, the hematopoietic stem cells and/or progenitor cells are human or mouse cells.

In some embodiments, the stem cell or progenitor cell disorder is a malignant hematologic disease. In some embodiments, the malignant hematologic disease is selected from the group consisting of acute lymphoid leukemia, acute myeloid leukemia, chronic lymphoid leukemia, chronic myeloid leukemia, diffuse large B-cell non-Hodgkin's lymphoma, mantle cell lymphoma, lymphoblastic lymphoma, Burkitt's lymphoma, follicular B-cell non-Hodgkin's lymphoma, lymphocyte predominant nodular Hodgkin's lymphoma, multiple myeloma, and juvenile myelomonocytic leukemia. In some embodiments, the stem cell or progenitor cell disorder is a non-malignant disease. In some embodiments, the non-malignant disease is selected from the group consisting of myelofibrosis, myelodysplastic syndrome, amyloidosis, severe aplastic anemia, paroxysmal nocturnal hemoglobinuria, immune cytopenias, systemic sclerosis, rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, Crohn's disorder, chronic inflammatory demyelinating

polyradiculoneuropathy, human immunodeficiency virus (HIV), Fanconi anemia, sickle cell disorder, beta thalassemia major, Hurler's syndrome (MPS-IH), adrenoleukodystrophy, metachromatic leukodystrophy, familial erythrophagocytic lymphohistiocytosis and other histiocytic disorders, severe combined

immunodeficiency (SCID), and Wiskott-Aldrich syndrome.

In certain aspects, the heHSCs described herein can be provided in the form of a kit. For example, the kit may comprise one or more isolated, non-native heHSCs and informational or instructional materials relating to the use or administration of such heHSCs to a subject in need. In some embodiments, such kits may comprise at least one CXCR2 agonist, at least one CXCR4 antagonist and instructions for their administration to a subject to mobilize and/or harvest the hematopoietic stem cells and/or progenitor cells, thereby preparing the isolated heHSCs disclosed herein.

It is to be understood that the invention is not limited in its application to the details set forth in the description or as exemplified. The invention encompasses other embodiments and is capable of being practiced or carried out in various ways. Also, it is to be understood that the phraseology and terminology employed herein is for the purpose of description and should not be regarded as limiting.

While certain agents, compounds, compositions and methods of the present invention have been described with specificity in accordance with certain

embodiments, the following examples serve only to illustrate the methods and compositions of the invention and are not intended to limit the same.

The articles "a" and "an" as used herein in the specification and in the claims, unless clearly indicated to the contrary, should be understood to include the plural referents. Claims or descriptions that include "or" between one or more members of a group are considered satisfied if one, more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process unless indicated to the contrary or otherwise evident from the context. The invention includes embodiments in which exactly one member of the group is present in, employed in, or otherwise relevant to a given product or process. The invention also includes embodiments in which more than one, or the entire group members are present in, employed in, or otherwise relevant to a given product or process.

Furthermore, it is to be understood that the invention encompasses all variations, combinations, and permutations in which one or more limitations, elements, clauses, descriptive terms, etc., from one or more of the listed claims is introduced into another claim dependent on the same base claim (or, as relevant, any other claim) unless otherwise indicated or unless it would be evident to one of ordinary skill in the art that a contradiction or inconsistency would arise. Where elements are presented as lists, (e.g., in Markush group or similar format) it is to be understood that each subgroup of the elements is also disclosed, and any element(s) can be removed from the group. It should be understood that, in general, where the invention, or aspects of the invention, is/are referred to as comprising particular elements, features, etc., certain embodiments of the invention or aspects of the invention consist, or consist essentially of, such elements, features, etc. For purposes of simplicity those embodiments have not in every case been specifically set forth in so many words herein. It should also be understood that any embodiment or aspect of the invention can be explicitly excluded from the claims, regardless of whether the specific exclusion is recited in the specification. The publications and other reference materials referenced herein to describe the background of the invention and to provide additional detail regarding its practice are hereby incorporated by reference.

EXAMPLES

Example 1 Rapid regimen

To address the still remaining deficiencies in hematopoietic mobilization, the present inventors believe an effective alternative method is the use of rapid mobilizing agents that do not require multiple injections, that are more predictable in their peak mobilization kinetics, and that result in an enhanced CD34+ number and

hematopoietic function upon transplant. One agent with potential is the CXCR2 agonist, GROp. GROp and GROp-A4 (collectively referred to herein as "GROp") rapidly mobilize hematopoietic stem cells (HSC), including all classes of short-term progenitor cells as well as long-term repopulating cells. In mice, peak GROP-induced mobilization occurs within 15-30 minutes of administration. Moreover, not only was the observed mobilization faster following GROP administration, the present inventors believe that the stem cell quality was also greater, at least in view of the improved engrafting ability of the mobilized stem cells (e.g., the two-fold greater engrafting ability of the stem cells mobilized from the bone marrow compartment, relative to stem cells mobilized using, for example, a mobilization regimen comprising C-GSF) and the donor chimerism observed following engraftment of such mobilized stem cells.

To assess this, the present inventors mobilized large cohorts of mice (15-20 per group) with either G-CSF (125ug/kg/day, five days) or with a combination of GROp (2.5mg/kg) and plerixafor (AMD-3100) (5mg/kg), and then sorted the peripheral blood for highly purified SLAM SKL cells (CD150+, CD48-, Sca-1+, c- kit+, lineage negative)

In two separate experiments, the present inventors then competitively transplanted either (a) 190 SLAM SKL cells against 300,000 whole bone marrow competitors, or (b) 50 SLAM SKL cells against 300,000 whole bone marrow competitors. This experimental design allowed for a direct assessment of the engrafting ability of the mobilized SLAM SKL cells, independent of accessory cell populations (e.g., non- CD150+, CD48-, Sca-1+, c-kit+, lineage negative cells) that may have been mobilized, as well as normalized the HSC content so that the same number of HSCs from either the G-CSF-mobilized donors, or the GROP plus plerixafor-mobilized donors, went into the irradiated recipients. As illustrated in

FIGS. 1 and 2 in both sets of experiments, the SLAM SKL cells that were mobilized by the combination of GROP plus plerixafor demonstrated superior engrafting ability (2 fold greater) relative to the cells that were mobilized by G-CSF. This was evident even when the exact same numbers of phenotypically defined (SLAM SKL) HSCs were transplanted.

Example 2 Transcriptome signatures

Over the last decade, there has been increasing evidence that the

hematopoietic stem cell (HSC) pool is heterogeneous in function, with identification of HSCs with differing lineage outputs, kinetics of repopulation, length of life-span, and perhaps differences amongst HSCs contributing to homeostatic blood production from those that are the engraftable units in transplantation. To date, however, there are no reliable methods for prospectively isolating differing HSC populations to study heterogeneity. Rather, much of the available data has been acquired based on clonal tracking, single cell transplantation, etc.

Much like panning for gold, the present inventors can now use the differential mobilization properties of the mobilization regimen using GROP and plerixafor and the regimen using G-CSF as a "biologic sieve" to isolate the heterogeneous HSC populations from the blood. These differential mobilization properties enabled the present inventors, and without destroying the cell, to prospectively isolate what is referred to herein as a highly engraftable HSC (heHSC) population for further functional analysis, and to prospectively isolate a differing HSC population with known, predictable function (the heHSCs) for further molecular characterization.

As a preliminary proof of concept and to demonstrate the feasibility of the approach described herein, SLAM SKL cells were sorted from large cohorts of mice that were treated or mobilized with either G-CSF, or with the combination of GROP and plerixafor (AMD-3100), as described in Example 1.

In the present study, 200 cells were directly sorted into 5 uL TCL lysis buffer

(Qiagen, #1031576). Library preparation was performed by the Smart-Seq2 protocol (Picelli et al., 2013) with subsequent RNA sequencing by Illumina NextSeq500. In addition to SLAM SKL cells from the G-CSF mobilized blood and the GROp plus plerixafor mobilized blood, additional control samples were sequenced, including steady state bone marrow, bone marrow from the G-CSF -treated mice group, bone marrow from the GROP plus plerixafor-treated mice, and a "drug spike" control, which consisted of G-CSF mobilized blood spiked with GROP (350ng/ml) plus AMD-3100 (lOug/ml), concentrations based on prior PK data, for 15 minutes, with subsequent downstream processing for FACS sorting. This enabled the present inventors to directly compare the heHSCs from those that were isolated from G-CSF mobilized HSCs, HSCs from the bone marrow of treated and untreated mice, and a drug control to account for any direct effects the GROP plus plerixafor may have had on the gene signatures that are not due to specific, differential mobilization effects. The RNASeq data was subsequently analyzed, as illustrated in FIG. 3.

Surprisingly, as illustrated in FIG. 4, the highly purified SLAM SKL cells from the GROP plus plerixafor-mobilized peripheral blood demonstrated a unique transcriptomic signature, including, for example, the expression of CD93 a marker of early lineage stem cells, relative to those HSCs mobilized by G-CSF, as well as from the treated or untreated bone marrow and from the drug spike control. The present inventors believe that the foregoing studies represent the first demonstration of predictable, differential HSC mobilization and provide a novel method to isolate the heHSC cells which have superior clinical utility. Example 3 Generation of unique stem cell populations

Hematopoietic stem cells (HSCs) are at the apex of lifelong blood cell production. Recent clonal analysis studies suggest that HSCs are heterogeneous in function and those that contribute to homeostatic production may be distinct from those that engraft during transplant. The present inventors developed a rapid mobilization regimen utilizing a unique CXCR2 agonist (an N-terminal truncated

MTP-2a) and the CXCR4 antagonist AMD-3100. A single subcutaneous injection of both agents together resulted in rapid mobilization in mice with a peak progenitor cell content in blood reached within 15 minutes.

The observed mobilization was equivalent to a 5-day regimen of G-CSF and is the result of synergistic signaling, and was blocked in CXCR4 or CXCR2 knockout mice, confirming receptor and mechanism specificity and is caused by synergistic release of MMP-9 from neutrophils that was blocked in MMP-9 knockout mice, mice treated with an anti -MMP-9 antibody, TEVIP-l transgenic mice, or mice where neutrophils were depleted in vivo using anti-GR-1 antibody. In vivo confocal imaging of mice demonstrated that the mobilization regimen caused a rapid and transient increase in bone marrow vascular permeability, "opening the doorway" for hematopoietic egress to the peripheral blood.

Transplantation of 2xl0 ⁶ peripheral blood mononuclear cells (PBMCs) from the rapid regimen resulted in a 4 or 6 day quicker recovery of neutrophils and platelets, respectively, compared to a G-CSF mobilized graft (n=12 mice per group, P<0.01). In limiting dilution competitive transplants, the rapid regimen demonstrated a greater than 2-fold enhancement in competitiveness (n=30 mice/treatment group, 2 individual experiments, PO.001). Additionally, in secondarily transplanted mice, competitiveness of the rapidly mobilized graft increased as measured by contribution to chimerism, while G-CSF mobilized grafts remained static (n=16 mice/group, P<0.01). Surprisingly, despite robust enhancement in both short and long-term engraftment by the rapidly mobilized graft, phenotypic analysis of the blood of mobilized mice for CD 150+ CD48- Sca-1+ c-kit+ Lineage neg (SLAM SKL) cells, a highly purified HSC population, showed lower numbers of phenotypically defined HSCs than in the G-CSF group.

The foregoing data suggest that a unique subset of "highly engraftable" HSCs (heHSCs) are mobilized by the rapid regimen comprising an N-terminal truncated MTP-2a and AMD-3100, compared to G-CSF. However, as our earlier studies were performed using grafts that contained the total PBMC fraction (similar to the clinical apheresis product) the present inventors could not rule out the potential contribution of accessory cells to the enhanced engrafting ability of the heHSCs. Example 4 Long term effects

Following the conclusions set out in Example 3, in 3 independent experiments, the present inventors mobilized large cohorts of mice with the rapid regimen comprising an N-terminal truncated MIP-2a (2.5mg/kg) and AMD-3100 (5mg/kg), or G-CSF (125ug/kg/day, fice days) and sorted SLAM SKL cells from the PBMC fraction and competitively transplanted equal numbers of SLAM SKL cells (190, or 50) from either the rapid regimen or G-CSF and tracked contribution to chimerism over 36 weeks. Remarkably, the heHSCs from the rapid regimen demonstrated a 2- fold enhancement in competitiveness compared to SLAM SKL cells from the G-CSF group (n=l l mice/group, PO.0004). See Figure 1.

Example 5 Molecular cell sorting and signature determination

While appreciation for HSC heterogeneity has grown, methods are lacking for prospectively isolating differing HSC populations with known biologic function, to study molecular heterogeneity. The present inventors sought to use the differential mobilization properties of our rapid regimen and G-CSF to isolate the heterogeneous HSC populations from the blood. The present inventors again flow sorted SLAM SKL cells from mice mobilized with the rapid regimen or G-CSF and performed RNASeq analysis of the purified populations. The heHSCs mobilized by the rapid regimen had a unique transcriptomic signature compared to G-CSF mobilized or random HSCs acquired from bone marrow (P<0.000001). Strikingly, gene set enrichment analysis (GSEA) demonstrated that the heHSCs had a gene signature highly significantly clustered to that of fetal liver HSCs, further demonstrating the selective harvesting of a subset of highly engraftable stem cells.

Our results mechanistically define a new mobilization strategy, that in a single day can mobilize a graft with superior engraftment properties compared to G-CSF, and selectively mobilize a novel population of heHSCs with an immature molecular phenotype capable of robust long-term engraftment.

SEQUENCE LISTING

<120> HIGHLY ENGRAFTABLE HEMATOPOIETIC STEM CELLS

<130> HRVY-078-WO1 <150> 62/300,694

<151> 2016-02-26

<150> 62/413,821

<151> 2016-10-27

<160> 23

<210> 1

<211> 73

<212> PRT

<213> Homo sapiens

<220>

<221> MISC FEATURE

<223> Human Gro-beta

<400> 1 Ala Pro Leu Ala Thr Glu Leu Arg Cys Gin Cys Leu Gin Thr Leu Gin

1 5 10 15

Gly He His Leu Lys Asn He Gin Ser Val Lys Val Lys Ser Pro Gly

20 25 30

Pro His Cys Ala Gin Thr Glu Val lie Ala Thr Leu Lys Asn Gly Gin

35 40 45

Lys Ala Cys Leu Asn Pro Ala Ser Pro Met Val Lys Lys He He Glu

50 55 60

Lys Met Leu Lys Asn Gly Lys Ser Asn

65 70 <210> 2

<211> 107

<212> PRT

<213> Homo sapiens <220>

<221> MISC FEATURE

<223> UniProt ID No. PI 9875- human GRO-beta

<400> 2

Met Ala Arg Ala Thr Leu Ser Ala Ala Pro Ser Asn Pro Arg Leu Leu 1 5 10 15

Arg Val Ala Leu Leu Leu Leu Leu Leu Val Ala Ala Ser Arg Arg Ala 20 25 30

Ala Gly Ala Pro Leu Ala Thr Glu Leu Arg Cys Gin Cys Leu Gin Thr 35 40 45

Leu Gin Gly He His Leu Lys Asn He Gin Ser Val Lys Val Lys Ser 50 55 60

Pro Gly Pro His Cys Ala Gin Thr Glu Val He Ala Thr Leu Lys Asn 65 70 75 80

Gly Gin Lys Ala Cys Leu Asn Pro Ala Ser Pro Met Val Lys Lys He

85 90 95

He Glu Lys Met Leu Lys Asn Gly Lys Ser Asn

100 105

<210> 3

<2\ \> 69

<212> PRT

<213> Homo sapiens

<220>

<221> MISC FEATURE

<223> GRO-beta-delta-4

<400> 3 Thr Glu Leu Arg Cys Gin Cys Leu Gin Thr Leu Gin Gly He His Leu 1 5 10 15

Lys Asn He Gin Ser Val Lys Val Lys Ser Pro Gly Pro His Cys Ala 20 25 30

Gin Thr Glu Val He Ala Thr Leu Lys Asn Gly Gin Lys Ala Cys Leu 35 40 45

Asn Pro Ala Ser Pro Met Val Lys Lys He He Glu Lys Met Leu Lys 50 55 60 Asn Gly Lys Ser Asn

65

<210> 4

<2\ \> 380

<212> PRT

<213> Homo sapiens

<220>

<221> MISC FEATURE

<223> FOS

<400> 4

Met Met Phe Ser Gly Phe Asn Ala Asp Tyr Glu Ala Ser Ser Ser Arg 1 5 10 15

Cys Ser Ser Ala Ser Pro Ala Gly Asp Ser Leu Ser Tyr Tyr His Ser 20 25 30

Pro Ala Asp Ser Phe Ser Ser Met Gly Ser Pro Val Asn Ala Gin Asp 35 40 45

Phe Cys Thr Asp Leu Ala Val Ser Ser Ala Asn Phe lie Pro Thr Val 50 55 60

Thr Ala He Ser Thr Ser Pro Asp Leu Gin Trp Leu Val Gin Pro Ala 65 70 75 80

Leu Val Ser Ser Val Ala Pro Ser Gin Thr Arg Ala Pro His Pro Phe

85 90 95

Gly Val Pro Ala Pro Ser Ala Gly Ala Tyr Ser Arg Ala Gly Val Val 100 105 110

Lys Thr Met Thr Gly Gly Arg Ala Gin Ser lie Gly Arg Arg Gly Lys 115 120 125 Val Glu Gin Leu Ser Pro Glu Glu Glu Glu Lys Arg Arg lie Arg Arg 130 135 140

Glu Arg Asn Lys Met Ala Ala Ala Lys Cys Arg Asn Arg Arg Arg Glu 145 150 155 160

Leu Thr Asp Thr Leu Gin Ala Glu Thr Asp Gin Leu Glu Asp Glu Lys

165 170 175

Ser Ala Leu Gin Thr Glu He Ala Asn Leu Leu Lys Glu Lys Glu Lys 180 185 190 Leu Glu Phe He Leu Ala Ala His Arg Pro Ala Cys Lys He Pro Asp 195 200 205 Asp Leu Gly Phe Pro Glu Glu Met Ser Val Ala Ser Leu Asp Leu Thr 210 215 220

Gly Gly Leu Pro Glu Val Ala Thr Pro Glu Ser Glu Glu Ala Phe Thr 225 230 235 240

Leu Pro Leu Leu Asn Asp Pro Glu Pro Lys Pro Ser Val Glu Pro Val

245 250 255

Lys Ser lie Ser Ser Met Glu Leu Lys Thr Glu Pro Phe Asp Asp Phe 260 265 270

Leu Phe Pro Ala Ser Ser Arg Pro Ser Gly Ser Glu Thr Ala Arg Ser 275 280 285 Val Pro Asp Met Asp Leu Ser Gly Ser Phe Tyr Ala Ala Asp Tip Glu 290 295 300

Pro Leu His Ser Gly Ser Leu Gly Met Gly Pro Met Ala Thr Glu Leu 305 310 315 320

Glu Pro Leu Cys Thr Pro Val Val Thr Cys Thr Pro Ser Cys Thr Ala

325 330 335

Tyr Thr Ser Ser Phe Val Phe Thr Tyr Pro Glu Ala Asp Ser Phe Pro 340 345 350

Ser Cys Ala Ala Ala His Arg Lys Gly Ser Ser Ser Asn Glu Pro Ser 355 360 365 Ser Asp Ser Leu Ser Ser Pro Thr Leu Leu Ala Leu

370 375 380

<210> 5

<211> 652

<212> PRT

<213> Homo sapiens

<220>

<221> MISC FEATURE

<223> CD93

<400> 5

Met Ala Thr Ser Met Gly Leu Leu Leu Leu Leu Leu Leu Leu Leu Thr 1 5 10 15 Gin Pro Gly Ala Gly Thr Gly Ala Asp Thr Glu Ala Val Val Cys Val 20 25 30 Gly Thr Ala Cys Tyr Thr Ala His Ser Gly Lys Leu Ser Ala Ala Glu 35 40 45

Ala Gin Asn His Cys Asn Gin Asn Gly Gly Asn Leu Ala Thr Val Lys 50 55 60

Ser Lys Glu Glu Ala Gin His Val Gin Arg Val Leu Ala Gin Leu Leu 65 70 75 80

Arg Arg Glu Ala Ala Leu Thr Ala Arg Met Ser Lys Phe Trp lie Gly

85 90 95

Leu Gin Arg Glu Lys Gly Lys Cys Leu Asp Pro Ser Leu Pro Leu Lys 100 105 110 Gly Phe Ser Trp Val Gly Gly Gly Glu Asp Thr Pro Tyr Ser Asn Trp 115 120 125

His Lys Glu Leu Arg Asn Ser Cys He Ser Lys Arg Cys Val Ser Leu 130 135 140

Leu Leu Asp Leu Ser Gin Pro Leu Leu Pro Ser Arg Leu Pro Lys Trp 145 150 155 160

Ser Glu Gly Pro Cys Gly Ser Pro Gly Ser Pro Gly Ser Asn lie Glu

165 170 175

Gly Phe Val Cys Lys Phe Ser Phe Lys Gly Met Cys Arg Pro Leu Ala 180 185 190

Leu Gly Gly Pro Gly Gin Val Thr Tyr Thr Thr Pro Phe Gin Thr Thr 195 200 205

Ser Ser Ser Leu Glu Ala Val Pro Phe Ala Ser Ala Ala Asn Val Ala 210 215 220

Cys Gly Glu Gly Asp Lys Asp Glu Thr Gin Ser His Tyr Phe Leu Cys 225 230 235 240 Lys Glu Lys Ala Pro Asp Val Phe Asp Trp Gly Ser Ser Gly Pro Leu

245 250 255

Cys Val Ser Pro Lys Tyr Gly Cys Asn Phe Asn Asn Gly Gly Cys His 260 265 270 Gin Asp Cys Phe Glu Gly Gly Asp Gly Ser Phe Leu Cys Gly Cys Arg 275 280 285

Pro Gly Phe Arg Leu Leu Asp Asp Leu Val Thr Cys Ala Ser Arg Asn 290 295 300

Pro Cys Ser Ser Ser Pro Cys Arg Gly Gly Ala Thr Cys Val Leu Gly 305 310 315 320 Pro His Gly Lys Asn Tyr Thr Cys Arg Cys Pro Gin Gly Tyr Gin Leu

325 330 335

Asp Ser Ser Gin Leu Asp Cys Val Asp Val Asp Glu Cys Gin Asp Ser 340 345 350

Pro Cys Ala Gin Glu Cys Val Asn Thr Pro Gly Gly Phe Arg Cys Glu 355 360 365

Cys Tip Val Gly Tyr Glu Pro Gly Gly Pro Gly Glu Gly Ala Cys Gin 370 375 380

Asp Val Asp Glu Cys Ala Leu Gly Arg Ser Pro Cys Ala Gin Gly Cys 385 390 395 400 Thr Asn Thr Asp Gly Ser Phe His Cys Ser Cys Glu Glu Gly Tyr Val

405 410 415

Leu Ala Gly Glu Asp Gly Thr Gin Cys Gin Asp Val Asp Glu Cys Val 420 425 430

Gly Pro Gly Gly Pro Leu Cys Asp Ser Leu Cys Phe Asn Thr Gin Gly 435 440 445 Ser Phe His Cys Gly Cys Leu Pro Gly Trp Val Leu Ala Pro Asn Gly 450 455 460

Val Ser Cys Thr Met Gly Pro Val Ser Leu Gly Pro Pro Ser Gly Pro 465 470 475 480

Pro Asp Glu Glu Asp Lys Gly Glu Lys Glu Gly Ser Thr Val Pro Arg

485 490 495

Ala Ala Thr Ala Ser Pro Thr Arg Gly Pro Glu Gly Thr Pro Lys Ala 500 505 510

Thr Pro Thr Thr Ser Arg Pro Ser Leu Ser Ser Asp Ala Pro He Thr 515 520 525 Ser Ala Pro Leu Lys Met Leu Ala Pro Ser Gly Ser Pro Gly Val Trp 530 535 540

Arg Glu Pro Ser lie His His Ala Thr Ala Ala Ser Gly Pro Gin Glu 545 550 555 560

Pro Ala Gly Gly Asp Ser Ser Val Ala Thr Gin Asn Asn Asp Gly Thr

565 570 575 Asp Gly Gin Lys Leu Leu Leu Phe Tyr He Leu Gly Thr Val Val Ala 580 585 590

He Leu Leu Leu Leu Ala Leu Ala Leu Gly Leu Leu Val Tyr Arg Lys 595 600 605

Arg Arg Ala Lys Arg Glu Glu Lys Lys Glu Lys Lys Pro Gin Asn Ala 610 615 620

Ala Asp Ser Tyr Ser Trp Val Pro Glu Arg Ala Glu Ser Arg Ala Met 625 630 635 640

Glu Asn Gin Tyr Ser Pro Thr Pro Gly Thr Asp Cys

645 650 <210> 6

<2\ \> 338

<212> PRT

<213> Homo sapiens <220>

<221> MISC FEATURE

<223> FOSB

<400> 6

Met Phe Gin Ala Phe Pro Gly Asp Tyr Asp Ser Gly Ser Arg Cys Ser 1 5 10 15

Ser Ser Pro Ser Ala Glu Ser Gin Tyr Leu Ser Ser Val Asp Ser Phe 20 25 30

Gly Ser Pro Pro Thr Ala Ala Ala Ser Gin Glu Cys Ala Gly Leu Gly 35 40 45 Glu Met Pro Gly Ser Phe Val Pro Thr Val Thr Ala lie Thr Thr Ser 50 55 60

Gin Asp Leu Gin Trp Leu Val Gin Pro Thr Leu lie Ser Ser Met Ala 65 70 75 80 Gin Ser Gin Gly Gin Pro Leu Ala Ser Gin Pro Pro Val Val Asp Pro 85 90 95

Tyr Asp Met Pro Gly Thr Ser Tyr Ser Thr Pro Gly Met Ser Gly Tyr 100 105 110

Ser Ser Gly Gly Ala Ser Gly Ser Gly Gly Pro Ser Thr Ser Gly Thr 115 120 125 Thr Ser Gly Pro Gly Pro Ala Arg Pro Ala Arg Ala Arg Pro Arg Arg 130 135 140

Pro Arg Glu Glu Thr Leu Thr Pro Glu Glu Glu Glu Lys Arg Arg Val 145 150 155 160

Arg Arg Glu Arg Asn Lys Leu Ala Ala Ala Lys Cys Arg Asn Arg Arg

165 170 175

Arg Glu Leu Thr Asp Arg Leu Gin Ala Glu Thr Asp Gin Leu Glu Glu 180 185 190

Glu Lys Ala Glu Leu Glu Ser Glu He Ala Glu Leu Gin Lys Glu Lys 195 200 205 Glu Arg Leu Glu Phe Val Leu Val Ala His Lys Pro Gly Cys Lys lie 210 215 220

Pro Tyr Glu Glu Gly Pro Gly Pro Gly Pro Leu Ala Glu Val Arg Asp 225 230 235 240

Leu Pro Gly Ser Ala Pro Ala Lys Glu Asp Gly Phe Ser Trp Leu Leu

245 250 255

Pro Pro Pro Pro Pro Pro Pro Leu Pro Phe Gin Thr Ser Gin Asp Ala 260 265 270

Pro Pro Asn Leu Thr Ala Ser Leu Phe Thr His Ser Glu Val Gin Val 275 280 285 Leu Gly Asp Pro Phe Pro Val Val Asn Pro Ser Tyr Thr Ser Ser Phe 290 295 300

Val Leu Thr Cys Pro Glu Val Ser Ala Phe Ala Gly Ala Gin Arg Thr 305 310 315 320

Ser Gly Ser Asp Gin Pro Ser Asp Pro Leu Asn Ser Pro Ser Leu Leu

325 330 335

Ala Leu <210> 7

<211> 367

<212> PRT

<213> Homo sapiens

<220>

<221> MISC FEATURE

<223> Duspl

<400> 7

Met Val Met Glu Val Gly Thr Leu Asp Ala Gly Gly Leu Arg Ala Leu 1 5 10 15

Leu Gly Glu Arg Ala Ala Gin Cys Leu Leu Leu Asp Cys Arg Ser Phe 20 25 30

Phe Ala Phe Asn Ala Gly His lie Ala Gly Ser Val Asn Val Arg Phe 35 40 45

Ser Thr lie Val Arg Arg Arg Ala Lys Gly Ala Met Gly Leu Glu His 50 55 60 lie Val Pro Asn Ala Glu Leu Arg Gly Arg Leu Leu Ala Gly Ala Tyr 65 70 75 80

His Ala Val Val Leu Leu Asp Glu Arg Ser Ala Ala Leu Asp Gly Ala

85 90 95

Lys Arg Asp Gly Thr Leu Ala Leu Ala Ala Gly Ala Leu Cys Arg Glu 100 105 110

Ala Arg Ala Ala Gin Val Phe Phe Leu Lys Gly Gly Tyr Glu Ala Phe 115 120 125

Ser Ala Ser Cys Pro Glu Leu Cys Ser Lys Gin Ser Thr Pro Met Gly 130 135 140 Leu Ser Leu Pro Leu Ser Thr Ser Val Pro Asp Ser Ala Glu Ser Gly 145 150 155 160

Cys Ser Ser Cys Ser Thr Pro Leu Tyr Asp Gin Gly Gly Pro Val Glu

165 170 175

He Leu Pro Phe Leu Tyr Leu Gly Ser Ala Tyr His Ala Ser Arg Lys 180 185 190

Asp Met Leu Asp Ala Leu Gly He Thr Ala Leu He Asn Val Ser Ala 195 200 205 Asn Cys Pro Asn His Phe Glu Gly His Tyr Gin Tyr Lys Ser He Pro 210 215 220 Val Glu Asp Asn His Lys Ala Asp He Ser Ser Trp Phe Asn Glu Ala 225 230 235 240 lie Asp Phe lie Asp Ser He Lys Asn Ala Gly Gly Arg Val Phe Val

245 250 255

His Cys Gin Ala Gly He Ser Arg Ser Ala Thr He Cys Leu Ala Tyr 260 265 270

Leu Met Arg Thr Asn Arg Val Lys Leu Asp Glu Ala Phe Glu Phe Val 275 280 285

Lys Gin Arg Arg Ser He He Ser Pro Asn Phe Ser Phe Met Gly Gin 290 295 300 Leu Leu Gin Phe Glu Ser Gin Val Leu Ala Pro His Cys Ser Ala Glu 305 310 315 320

Ala Gly Ser Pro Ala Met Ala Val Leu Asp Arg Gly Thr Ser Thr Thr

325 330 335

Thr Val Phe Asn Phe Pro Val Ser He Pro Val His Ser Thr Asn Ser 340 345 350

Ala Leu Ser Tyr Leu Gin Ser Pro He Thr Thr Ser Pro Ser Cys

355 360 365

<210> 8

<211> 331

<212> PRT

<213> Homo sapiens

<220>

<221> MISC FEATURE

<223> Jun

<400> 8

Met Thr Ala Lys Met Glu Thr Thr Phe Tyr Asp Asp Ala Leu Asn Ala 1 5 10 15

Ser Phe Leu Pro Ser Glu Ser Gly Pro Tyr Gly Tyr Ser Asn Pro Lys 20 25 30

He Leu Lys Gin Ser Met Thr Leu Asn Leu Ala Asp Pro Val Gly Ser Leu Lys Pro His Leu Arg Ala Lys Asn Ser Asp Leu Leu Thr Ser Pro 50 55 60 Asp Val Gly Leu Leu Lys Leu Ala Ser Pro Glu Leu Glu Arg Leu He 65 70 75 80 lie Gin Ser Ser Asn Gly His lie Thr Thr Thr Pro Thr Pro Thr Gin

85 90 95

Phe Leu Cys Pro Lys Asn Val Thr Asp Glu Gin Glu Gly Phe Ala Glu 100 105 110

Gly Phe Val Arg Ala Leu Ala Glu Leu His Ser Gin Asn Thr Leu Pro 115 120 125

Ser Val Thr Ser Ala Ala Gin Pro Val Asn Gly Ala Gly Met Val Ala 130 135 140 Pro Ala Val Ala Ser Val Ala Gly Gly Ser Gly Ser Gly Gly Phe Ser 145 150 155 160

Ala Ser Leu His Ser Glu Pro Pro Val Tyr Ala Asn Leu Ser Asn Phe

165 170 175

Asn Pro Gly Ala Leu Ser Ser Gly Gly Gly Ala Pro Ser Tyr Gly Ala 180 185 190

Ala Gly Leu Ala Phe Pro Ala Gin Pro Gin Gin Gin Gin Gin Pro Pro 195 200 205

His His Leu Pro Gin Gin Met Pro Val Gin His Pro Arg Leu Gin Ala 210 215 220 Leu Lys Glu Glu Pro Gin Thr Val Pro Glu Met Pro Gly Glu Thr Pro 225 230 235 240

Pro Leu Ser Pro lie Asp Met Glu Ser Gin Glu Arg lie Lys Ala Glu

245 250 255

Arg Lys Arg Met Arg Asn Arg He Ala Ala Ser Lys Cys Arg Lys Arg 260 265 270

Lys Leu Glu Arg He Ala Arg Leu Glu Glu Lys Val Lys Thr Leu Lys 275 280 285

Ala Gin Asn Ser Glu Leu Ala Ser Thr Ala Asn Met Leu Arg Glu Gin 290 295 300 Val Ala Gin Leu Lys Gin Lys Val Met Asn His Val Asn Ser Gly Cys 305 310 315 320

Gin Leu Met Leu Thr Gin Gin Leu Gin Thr Phe

325 330

<210> 9

<2\ \> 381

<212> PRT

<213> Homo sapiens

<220>

<221> MISC FEATURE

<223> DUSP6

<400> 9

Met lie Asp Thr Leu Arg Pro Val Pro Phe Ala Ser Glu Met Ala lie 1 5 10 15

Ser Lys Thr Val Ala Tip Leu Asn Glu Gin Leu Glu Leu Gly Asn Glu 20 25 30

Arg Leu Leu Leu Met Asp Cys Arg Pro Gin Glu Leu Tyr Glu Ser Ser 35 40 45

His lie Glu Ser Ala lie Asn Val Ala lie Pro Gly lie Met Leu Arg

50 55 60

Arg Leu Gin Lys Gly Asn Leu Pro Val Arg Ala Leu Phe Thr Arg Gly 65 70 75 80

Glu Asp Arg Asp Arg Phe Thr Arg Arg Cys Gly Thr Asp Thr Val Val

85 90 95

Leu Tyr Asp Glu Ser Ser Ser Asp Tip Asn Glu Asn Thr Gly Gly Glu 100 105 110

Ser Val Leu Gly Leu Leu Leu Lys Lys Leu Lys Asp Glu Gly Cys Arg 115 120 125

Ala Phe Tyr Leu Glu Gly Gly Phe Ser Lys Phe Gin Ala Glu Phe Ser 130 135 140 Leu His Cys Glu Thr Asn Leu Asp Gly Ser Cys Ser Ser Ser Ser Pro 145 150 155 160

Pro Leu Pro Val Leu Gly Leu Gly Gly Leu Arg He Ser Ser Asp Ser

165 170 175 Ser Ser Asp He Glu Ser Asp Leu Asp Arg Asp Pro Asn Ser Ala Thr 180 185 190

Asp Ser Asp Gly Ser Pro Leu Ser Asn Ser Gin Pro Ser Phe Pro Val 195 200 205

Glu He Leu Pro Phe Leu Tyr Leu Gly Cys Ala Lys Asp Ser Thr Asn 210 215 220 Leu Asp Val Leu Glu Glu Phe Gly lie Lys Tyr lie Leu Asn Val Thr 225 230 235 240

Pro Asn Leu Pro Asn Leu Phe Glu Asn Ala Gly Glu Phe Lys Tyr Lys

245 250 255

Gin He Pro He Ser Asp His Tip Ser Gin Asn Leu Ser Gin Phe Phe 260 265 270

Pro Glu Ala lie Ser Phe He Asp Glu Ala Arg Gly Lys Asn Cys Gly 275 280 285

Val Leu Val His Cys Leu Ala Gly He Ser Arg Ser Val Thr Val Thr 290 295 300 Val Ala Tyr Leu Met Gin Lys Leu Asn Leu Ser Met Asn Asp Ala Tyr 305 310 315 320

Asp He Val Lys Met Lys Lys Ser Asn He Ser Pro Asn Phe Asn Phe

325 330 335

Met Gly Gin Leu Leu Asp Phe Glu Arg Thr Leu Gly Leu Ser Ser Pro 340 345 350

Cys Asp Asn Arg Val Pro Ala Gin Gin Leu Tyr Phe Thr Thr Pro Ser 355 360 365

Asn Gin Asn Val Tyr Gin Val Asp Ser Leu Gin Ser Thr

370 375 380

<210> 10

<211> 297

<212> PRT

<213> Homo sapiens

<220>

<221> MISC FEATURE

<223> CDK1

<400> 10 Met Glu Asp Tyr Thr Lys lie Glu Lys lie Gly Glu Gly Thr Tyr Gly 1 5 10 15

Val Val Tyr Lys Gly Arg His Lys Thr Thr Gly Gin Val Val Ala Met 20 25 30

Lys Lys lie Arg Leu Glu Ser Glu Glu Glu Gly Val Pro Ser Thr Ala 35 40 45 He Arg Glu He Ser Leu Leu Lys Glu Leu Arg His Pro Asn He Val 50 55 60

Ser Leu Gin Asp Val Leu Met Gin Asp Ser Arg Leu Tyr Leu He Phe 65 70 75 80

Glu Phe Leu Ser Met Asp Leu Lys Lys Tyr Leu Asp Ser He Pro Pro

85 90 95

Gly Gin Tyr Met Asp Ser Ser Leu Val Lys Ser Tyr Leu Tyr Gin He 100 105 110

Leu Gin Gly He Val Phe Cys His Ser Arg Arg Val Leu His Arg Asp 115 120 125 Leu Lys Pro Gin Asn Leu Leu He Asp Asp Lys Gly Thr He Lys Leu 130 135 140

Ala Asp Phe Gly Leu Ala Arg Ala Phe Gly He Pro He Arg Val Tyr 145 150 155 160

Thr His Glu Val Val Thr Leu Trp Tyr Arg Ser Pro Glu Val Leu Leu

165 170 175

Gly Ser Ala Arg Tyr Ser Thr Pro Val Asp He Trp Ser He Gly Thr 180 185 190

He Phe Ala Glu Leu Ala Thr Lys Lys Pro Leu Phe His Gly Asp Ser 195 200 205 Glu He Asp Gin Leu Phe Arg He Phe Arg Ala Leu Gly Thr Pro Asn 210 215 220

Asn Glu Val Trp Pro Glu Val Glu Ser Leu Gin Asp Tyr Lys Asn Thr 225 230 235 240

Phe Pro Lys Trp Lys Pro Gly Ser Leu Ala Ser His Val Lys Asn Leu

245 250 255

Asp Glu Asn Gly Leu Asp Leu Leu Ser Lys Met Leu He Tyr Asp Pro 260 265 270 Ala Lys Arg He Ser Gly Lys Met Ala Leu Asn His Pro Tyr Phe Asn 275 280 285 Asp Leu Asp Asn Gin He Lys Lys Met

290 295

<210> 11

<211> 674

<212> PRT

<213> Homo sapiens

<220>

<221> MISC FEATURE

<223> Fignll

<400> 11

Met Gin Thr Ser Ser Ser Arg Ser Val His Leu Ser Glu Tip Gin Lys 1 5 10 15

Asn Tyr Phe Ala He Thr Ser Gly He Cys Thr Gly Pro Lys Ala Asp 20 25 30 Ala Tyr Arg Ala Gin He Leu Arg He Gin Tyr Ala Trp Ala Asn Ser 35 40 45

Glu He Ser Gin Val Cys Ala Thr Lys Leu Phe Lys Lys Tyr Ala Glu 50 55 60

Lys Tyr Ser Ala He He Asp Ser Asp Asn Val Glu Ser Gly Leu Asn 65 70 75 80

Asn Tyr Ala Glu Asn He Leu Thr Leu Ala Gly Ser Gin Gin Thr Asp

85 90 95

Ser Asp Lys Trp Gin Ser Gly Leu Ser He Asn Asn Val Phe Lys Met 100 105 110 Ser Ser Val Gin Lys Met Met Gin Ala Gly Lys Lys Phe Lys Asp Ser 115 120 125

Leu Leu Glu Pro Ala Leu Ala Ser Val Val He His Lys Glu Ala Thr 130 135 140

Val Phe Asp Leu Pro Lys Phe Ser Val Cys Gly Ser Ser Gin Glu Ser 145 150 155 160

Asp Ser Leu Pro Asn Ser Ala His Asp Arg Asp Arg Thr Gin Asp Phe

165 170 175 Pro Glu Ser Asn Arg Leu Lys Leu Leu Gin Asn Ala Gin Pro Pro Met 180 185 190 Val Thr Asn Thr Ala Arg Thr Cys Pro Thr Phe Ser Ala Pro Val Gly 195 200 205

Glu Ser Ala Thr Ala Lys Phe His Val Thr Pro Leu Phe Gly Asn Val 210 215 220

Lys Lys Glu Asn His Ser Ser Ala Lys Glu Asn He Gly Leu Asn Val 225 230 235 240

Phe Leu Ser Asn Gin Ser Cys Phe Pro Ala Ala Cys Glu Asn Pro Gin

245 250 255

Arg Lys Ser Phe Tyr Gly Ser Gly Thr He Asp Ala Leu Ser Asn Pro 260 265 270 He Leu Asn Lys Ala Cys Ser Lys Thr Glu Asp Asn Gly Pro Lys Glu 275 280 285

Asp Ser Ser Leu Pro Thr Phe Lys Thr Ala Lys Glu Gin Leu Tip Val 290 295 300

Asp Gin Gin Lys Lys Tyr His Gin Pro Gin Arg Ala Ser Gly Ser Ser 305 310 315 320

Tyr Gly Gly Val Lys Lys Ser Leu Gly Ala Ser Arg Ser Arg Gly He

325 330 335

Leu Gly Lys Phe Val Pro Pro He Pro Lys Gin Asp Gly Gly Glu Gin 340 345 350 Asn Gly Gly Met Gin Cys Lys Pro Tyr Gly Ala Gly Pro Thr Glu Pro 355 360 365

Ala His Pro Val Asp Glu Arg Leu Lys Asn Leu Glu Pro Lys Met He 370 375 380

Glu Leu He Met Asn Glu He Met Asp His Gly Pro Pro Val Asn Tip 385 390 395 400

Glu Asp He Ala Gly Val Glu Phe Ala Lys Ala Thr He Lys Glu He

405 410 415

Val Val Tip Pro Met Leu Arg Pro Asp He Phe Thr Gly Leu Arg Gly 420 425 430 Pro Pro Lys Gly He Leu Leu Phe Gly Pro Pro Gly Thr Gly Lys Thr 435 440 445

Leu lie Gly Lys Cys lie Ala Ser Gin Ser Gly Ala Thr Phe Phe Ser 450 455 460

He Ser Ala Ser Ser Leu Thr Ser Lys Tip Val Gly Glu Gly Glu Lys 465 470 475 480 Met Val Arg Ala Leu Phe Ala Val Ala Arg Cys Gin Gin Pro Ala Val

485 490 495

He Phe He Asp Glu He Asp Ser Leu Leu Ser Gin Arg Gly Asp Gly 500 505 510

Glu His Glu Ser Ser Arg Arg He Lys Thr Glu Phe Leu Val Gin Leu 515 520 525

Asp Gly Ala Thr Thr Ser Ser Glu Asp Arg He Leu Val Val Gly Ala 530 535 540

Thr Asn Arg Pro Gin Glu He Asp Glu Ala Ala Arg Arg Arg Leu Val 545 550 555 560 Lys Arg Leu Tyr He Pro Leu Pro Glu Ala Ser Ala Arg Lys Gin He

565 570 575

Val He Asn Leu Met Ser Lys Glu Gin Cys Cys Leu Ser Glu Glu Glu 580 585 590

He Glu Gin He Val Gin Gin Ser Asp Ala Phe Ser Gly Ala Asp Met 595 600 605

Thr Gin Leu Cys Arg Glu Ala Ser Leu Gly Pro He Arg Ser Leu Gin 610 615 620

Thr Ala Asp He Ala Thr He Thr Pro Asp Gin Val Arg Pro He Ala 625 630 635 640

Tyr He Asp Phe Glu Asn Ala Phe Arg Thr Val Arg Pro Ser Val Ser

645 650 655

Pro Lys Asp Leu Glu Leu Tyr Glu Asn Tip Asn Lys Thr Phe Gly Cys 660 665 670

Gly Lys <210> 12

<2\ \> 685

<212> PRT

<213> Homo sapiens

<220>

<221> MISC FEATURE

<223> Plk2

<400> 12

Met Glu Leu Leu Arg Thr lie Thr Tyr Gin Pro Ala Ala Ser Thr Lys 1 5 10 15 Met Cys Glu Gin Ala Leu Gly Lys Gly Cys Gly Ala Asp Ser Lys Lys 20 25 30

Lys Arg Pro Pro Gin Pro Pro Glu Glu Ser Gin Pro Pro Gin Ser Gin 35 40 45

Ala Gin Val Pro Pro Ala Ala Pro His His His His His His Ser His 50 55 60

Ser Gly Pro Glu lie Ser Arg lie lie Val Asp Pro Thr Thr Gly Lys 65 70 75 80

Arg Tyr Cys Arg Gly Lys Val Leu Gly Lys Gly Gly Phe Ala Lys Cys

85 90 95 Tyr Glu Met Thr Asp Leu Thr Asn Asn Lys Val Tyr Ala Ala Lys lie 100 105 110

He Pro His Ser Arg Val Ala Lys Pro His Gin Arg Glu Lys He Asp 115 120 125

Lys Glu He Glu Leu His Arg He Leu His His Lys His Val Val Gin 130 135 140 Phe Tyr His Tyr Phe Glu Asp Lys Glu Asn He Tyr He Leu Leu Glu 145 150 155 160

Tyr Cys Ser Arg Arg Ser Met Ala His He Leu Lys Ala Arg Lys Val

165 170 175

Leu Thr Glu Pro Glu Val Arg Tyr Tyr Leu Arg Gin He Val Ser Gly 180 185 190

Leu Lys Tyr Leu His Glu Gin Glu He Leu His Arg Asp Leu Lys Leu 195 200 205 Gly Asn Phe Phe lie Asn Glu Ala Met Glu Leu Lys Val Gly Asp Phe 210 215 220 Gly Leu Ala Ala Arg Leu Glu Pro Leu Glu His Arg Arg Arg Thr He 225 230 235 240

Cys Gly Thr Pro Asn Tyr Leu Ser Pro Glu Val Leu Asn Lys Gin Gly

245 250 255

Gly Cys Glu Ser Asp lie Trp Ala Leu Gly Cys Val Met Tyr Thr 260 265 270

Met Leu Leu Gly Arg Pro Pro Phe Glu Thr Thr Asn Leu Lys Glu Thr 275 280 285

Tyr Arg Cys He Arg Glu Ala Arg Tyr Thr Met Pro Ser Ser Leu Leu 290 295 300 Ala Pro Ala Lys His Leu He Ala Ser Met Leu Ser Lys Asn Pro Glu 305 310 315 320

Asp Arg Pro Ser Leu Asp Asp He He Arg His Asp Phe Phe Leu Gin

325 330 335

Gly Phe Thr Pro Asp Arg Leu Ser Ser Ser Cys Cys His Thr Val Pro 340 345 350 Asp Phe His Leu Ser Ser Pro Ala Lys Asn Phe Phe Lys Lys Ala Ala 355 360 365

Ala Ala Leu Phe Gly Gly Lys Lys Asp Lys Ala Arg Tyr He Asp Thr 370 375 380

His Asn Arg Val Ser Lys Glu Asp Glu Asp He Tyr Lys Leu Arg His 385 390 395 400

Asp Leu Lys Lys Thr Ser He Thr Gin Gin Pro Ser Lys His Arg Thr

405 410 415

Asp Glu Glu Leu Gin Pro Pro Thr Thr Thr Val Ala Arg Ser Gly Thr 420 425 430 Pro Ala Val Glu Asn Lys Gin Gin He Gly Asp Ala He Arg Met He 435 440 445

Val Arg Gly Thr Leu Gly Ser Cys Ser Ser Ser Ser Glu Cys Leu Glu 450 455 460 Asp Ser Thr Met Gly Ser Val Ala Asp Thr Val Ala Arg Val Leu Arg 465 470 475 480

Gly Cys Leu Glu Asn Met Pro Glu Ala Asp Cys He Pro Lys Glu Gin

485 490 495

Leu Ser Thr Ser Phe Gin Tip Val Thr Lys Trp Val Asp Tyr Ser Asn 500 505 510 Lys Tyr Gly Phe Gly Tyr Gin Leu Ser Asp His Thr Val Gly Val Leu 515 520 525

Phe Asn Asn Gly Ala His Met Ser Leu Leu Pro Asp Lys Lys Thr Val 530 535 540

His Tyr Tyr Ala Glu Leu Gly Gin Cys Ser Val Phe Pro Ala Thr Asp 545 550 555 560

Ala Pro Glu Gin Phe lie Ser Gin Val Thr Val Leu Lys Tyr Phe Ser

565 570 575

His Tyr Met Glu Glu Asn Leu Met Asp Gly Gly Asp Leu Pro Ser Val 580 585 590 Thr Asp He Arg Arg Pro Arg Leu Tyr Leu Leu Gin Trp Leu Lys Ser 595 600 605

Asp Lys Ala Leu Met Met Leu Phe Asn Asp Gly Thr Phe Gin Val Asn 610 615 620

Phe Tyr His Asp His Thr Lys He He He Cys Ser Gin Asn Glu Glu 625 630 635 640

Tyr Leu Leu Thr Tyr He Asn Glu Asp Arg He Ser Thr Thr Phe Arg

645 650 655

Leu Thr Thr Leu Leu Met Ser Gly Cys Ser Ser Glu Leu Lys Asn Arg 660 665 670 Met Glu Tyr Ala Leu Asn Met Leu Leu Gin Arg Cys Asn

675 680 685

<210> 13

<2\ \> 361

<212> PRT

<213> Homo sapiens

<220>

<221> MISC FEATURE

<223> RSAD2 <400> 13

Met Trp Val Leu Thr Pro Ala Ala Phe Ala Gly Lys Leu Leu Ser Val 1 5 10 15

Phe Arg Gin Pro Leu Ser Ser Leu Trp Arg Ser Leu Val Pro Leu Phe 20 25 30 Cys Trp Leu Arg Ala Thr Phe Trp Leu Leu Ala Thr Lys Arg Arg Lys 35 40 45

Gin Gin Leu Val Leu Arg Gly Pro Asp Glu Thr Lys Glu Glu Glu Glu 50 55 60

Asp Pro Pro Leu Pro Thr Thr Pro Thr Ser Val Asn Tyr His Phe Thr 65 70 75 80 Arg Gin Cys Asn Tyr Lys Cys Gly Phe Cys Phe His Thr Ala Lys Thr

85 90 95

Ser Phe Val Leu Pro Leu Glu Glu Ala Lys Arg Gly Leu Leu Leu Leu 100 105 110

Lys Glu Ala Gly Met Glu Lys lie Asn Phe Ser Gly Gly Glu Pro Phe 115 120 125

Leu Gin Asp Arg Gly Glu Tyr Leu Gly Lys Leu Val Arg Phe Cys Lys 130 135 140

Val Glu Leu Arg Leu Pro Ser Val Ser He Val Ser Asn Gly Ser Leu 145 150 155 160 He Arg Glu Arg Trp Phe Gin Asn Tyr Gly Glu Tyr Leu Asp He Leu

165 170 175

Ala lie Ser Cys Asp Ser Phe Asp Glu Glu Val Asn Val Leu He Gly 180 185 190

Arg Gly Gin Gly Lys Lys Asn His Val Glu Asn Leu Gin Lys Leu Arg 195 200 205

Arg Trp Cys Arg Asp Tyr Arg Val Ala Phe Lys He Asn Ser Val He 210 215 220

Asn Arg Phe Asn Val Glu Glu Asp Met Thr Glu Gin He Lys Ala Leu 225 230 235 240 Asn Pro Val Arg Tip Lys Val Phe Gin Cys Leu Leu He Glu Gly Glu 245 250 255

Asn Cys Gly Glu Asp Ala Leu Arg Glu Ala Glu Arg Phe Val lie Gly 260 265 270

Asp Glu Glu Phe Glu Arg Phe Leu Glu Arg His Lys Glu Val Ser Cys 275 280 285 Leu Val Pro Glu Ser Asn Gin Lys Met Lys Asp Ser Tyr Leu He Leu 290 295 300

Asp Glu Tyr Met Arg Phe Leu Asn Cys Arg Lys Gly Arg Lys Asp Pro 305 310 315 320

Ser Lys Ser lie Leu Asp Val Gly Val Glu Glu Ala lie Lys Phe Ser

325 330 335

Gly Phe Asp Glu Lys Met Phe Leu Lys Arg Gly Gly Lys Tyr He Tip 340 345 350

Ser Lys Ala Asp Leu Lys Leu Asp Trp

355 360

<210> 14

<2\ \> 431

<212> PRT

<213> Homo sapiens

<220>

<221> MISC FEATURE

<223> SGK1

<400> 14

Met Thr Val Lys Thr Glu Ala Ala Lys Gly Thr Leu Thr Tyr Ser Arg 1 5 10 15

Met Arg Gly Met Val Ala He Leu He Ala Phe Met Lys Gin Arg Arg 20 25 30

Met Gly Leu Asn Asp Phe He Gin Lys He Ala Asn Asn Ser Tyr Ala 35 40 45 Cys Lys His Pro Glu Val Gin Ser He Leu Lys He Ser Gin Pro Gin 50 55 60

Glu Pro Glu Leu Met Asn Ala Asn Pro Ser Pro Pro Pro Ser Pro Ser 65 70 75 80 Gin Gin He Asn Leu Gly Pro Ser Ser Asn Pro His Ala Lys Pro Ser 85 90 95

Asp Phe His Phe Leu Lys Val lie Gly Lys Gly Ser Phe Gly Lys Val 100 105 110

Leu Leu Ala Arg His Lys Ala Glu Glu Val Phe Tyr Ala Val Lys Val 115 120 125 Leu Gin Lys Lys Ala He Leu Lys Lys Lys Glu Glu Lys His He Met 130 135 140

Ser Glu Arg Asn Val Leu Leu Lys Asn Val Lys His Pro Phe Leu Val 145 150 155 160

Gly Leu His Phe Ser Phe Gin Thr Ala Asp Lys Leu Tyr Phe Val Leu

165 170 175

Asp Tyr He Asn Gly Gly Glu Leu Phe Tyr His Leu Gin Arg Glu Arg 180 185 190

Cys Phe Leu Glu Pro Arg Ala Arg Phe Tyr Ala Ala Glu He Ala Ser 195 200 205 Ala Leu Gly Tyr Leu His Ser Leu Asn He Val Tyr Arg Asp Leu Lys 210 215 220

Pro Glu Asn He Leu Leu Asp Ser Gin Gly His He Val Leu Thr Asp 225 230 235 240

Phe Gly Leu Cys Lys Glu Asn He Glu His Asn Ser Thr Thr Ser Thr

245 250 255

Phe Cys Gly Thr Pro Glu Tyr Leu Ala Pro Glu Val Leu His Lys Gin 260 265 270

Pro Tyr Asp Arg Thr Val Asp Tip Trp Cys Leu Gly Ala Val Leu Tyr 275 280 285

Glu Met Leu Tyr Gly Leu Pro Pro Phe Tyr Ser Arg Asn Thr Ala Glu 290 295 300 Met Tyr Asp Asn He Leu Asn Lys Pro Leu Gin Leu Lys Pro Asn He 305 310 315 320

Thr Asn Ser Ala Arg His Leu Leu Glu Gly Leu Leu Gin Lys Asp Arg

325 330 335 Thr Lys Arg Leu Gly Ala Lys Asp Asp Phe Met Glu He Lys Ser His 340 345 350

Val Phe Phe Ser Leu He Asn Trp Asp Asp Leu He Asn Lys Lys He 355 360 365

Thr Pro Pro Phe Asn Pro Asn Val Ser Gly Pro Asn Asp Leu Arg His 370 375 380

Phe Asp Pro Glu Phe Thr Glu Glu Pro Val Pro Asn Ser He Gly Lys 385 390 395 400

Ser Pro Asp Ser Val Leu Val Thr Ala Ser Val Lys Glu Ala Ala Glu

405 410 415

Ala Phe Leu Gly Phe Ser Tyr Ala Pro Pro Thr Asp Ser Phe Leu

420 425 430 <210> 15

<211> 310

<212> PRT

<213> Homo sapiens <220>

<221> MISC FEATURE

<223> Sdcl

<400> 15

Met Arg Arg Ala Ala Leu Trp Leu Trp Leu Cys Ala Leu Ala Leu Ser 1 5 10 15

Leu Gin Pro Ala Leu Pro Gin He Val Ala Thr Asn Leu Pro Pro Glu 20 25 30

Asp Gin Asp Gly Ser Gly Asp Asp Ser Asp Asn Phe Ser Gly Ser Gly 35 40 45 Ala Gly Ala Leu Gin Asp He Thr Leu Ser Gin Gin Thr Pro Ser Thr 50 55 60

Trp Lys Asp Thr Gin Leu Leu Thr Ala He Pro Thr Ser Pro Glu Pro 65 70 75 80

Thr Gly Leu Glu Ala Thr Ala Ala Ser Thr Ser Thr Leu Pro Ala Gly

85 90 95

Glu Gly Pro Lys Glu Gly Glu Ala Val Val Leu Pro Glu Val Glu Pro 100 105 110 Gly Leu Thr Ala Arg Glu Gin Glu Ala Thr Pro Arg Pro Arg Glu Thr 115 120 125 Thr Gin Leu Pro Thr Thr His Leu Ala Ser Thr Thr Thr Ala Thr Thr 130 135 140

Ala Gin Glu Pro Ala Thr Ser His Pro His Arg Asp Met Gin Pro Gly 145 150 155 160

His His Glu Thr Ser Thr Pro Ala Gly Pro Ser Gin Ala Asp Leu His

165 170 175

Thr Pro His Thr Glu Asp Gly Gly Pro Ser Ala Thr Glu Arg Ala Ala 180 185 190

Glu Asp Gly Ala Ser Ser Gin Leu Pro Ala Ala Glu Gly Ser Gly Glu 195 200 205 Gin Asp Phe Thr Phe Glu Thr Ser Gly Glu Asn Thr Ala Val Val Ala 210 215 220

Val Glu Pro Asp Arg Arg Asn Gin Ser Pro Val Asp Gin Gly Ala Thr 225 230 235 240

Gly Ala Ser Gin Gly Leu Leu Asp Arg Lys Glu Val Leu Gly Gly Val

245 250 255 lie Ala Gly Gly Leu Val Gly Leu lie Phe Ala Val Cys Leu Val Gly 260 265 270

Phe Met Leu Tyr Arg Met Lys Lys Lys Asp Glu Gly Ser Tyr Ser Leu 275 280 285 Glu Glu Pro Lys Gin Ala Asn Gly Gly Ala Tyr Gin Lys Pro Thr Lys 290 295 300

Gin Glu Glu Phe Tyr Ala

305 310

<210> 16

<2\ \> 398

<212> PRT

<213> Homo sapiens

<220>

<221> MISC FEATURE

<223> Serpine2 <400> 16 Met Asn Trp His Leu Pro Leu Phe Leu Leu Ala Ser Val Thr Leu Pro 1 5 10 15 Ser He Cys Ser His Phe Asn Pro Leu Ser Leu Glu Glu Leu Gly Ser 20 25 30

Asn Thr Gly lie Gin Val Phe Asn Gin lie Val Lys Ser Arg Pro His 35 40 45

Asp Asn lie Val lie Ser Pro His Gly lie Ala Ser Val Leu Gly Met 50 55 60

Leu Gin Leu Gly Ala Asp Gly Arg Thr Lys Lys Gin Leu Ala Met Val 65 70 75 80

Met Arg Tyr Gly Val Asn Gly Val Gly Lys He Leu Lys Lys He Asn

85 90 95 Lys Ala He Val Ser Lys Lys Asn Lys Asp He Val Thr Val Ala Asn 100 105 110

Ala Val Phe Val Lys Asn Ala Ser Glu He Glu Val Pro Phe Val Thr 115 120 125

Arg Asn Lys Asp Val Phe Gin Cys Glu Val Arg Asn Val Asn Phe Glu 130 135 140

Asp Pro Ala Ser Ala Cys Asp Ser He Asn Ala Trp Val Lys Asn Glu 145 150 155 160

Thr Arg Asp Met He Asp Asn Leu Leu Ser Pro Asp Leu He Asp Gly

165 170 175 Val Leu Thr Arg Leu Val Leu Val Asn Ala Val Tyr Phe Lys Gly Leu 180 185 190

Trp Lys Ser Arg Phe Gin Pro Glu Asn Thr Lys Lys Arg Thr Phe Val 195 200 205

Ala Ala Asp Gly Lys Ser Tyr Gin Val Pro Met Leu Ala Gin Leu Ser 210 215 220

Val Phe Arg Cys Gly Ser Thr Ser Ala Pro Asn Asp Leu Trp Tyr Asn 225 230 235 240

Phe He Glu Leu Pro Tyr His Gly Glu Ser He Ser Met Leu He Ala

245 250 255 Leu Pro Thr Glu Ser Ser Thr Pro Leu Ser Ala He He Pro His He 260 265 270

Ser Thr Lys Thr He Asp Ser Trp Met Ser He Met Val Pro Lys Arg 275 280 285

Val Gin Val He Leu Pro Lys Phe Thr Ala Val Ala Gin Thr Asp Leu 290 295 300 Lys Glu Pro Leu Lys Val Leu Gly He Thr Asp Met Phe Asp Ser Ser 305 310 315 320

Lys Ala Asn Phe Ala Lys He Thr Thr Gly Ser Glu Asn Leu His Val

325 330 335

Ser His He Leu Gin Lys Ala Lys He Glu Val Ser Glu Asp Gly Thr 340 345 350

Lys Ala Ser Ala Ala Thr Thr Ala He Leu He Ala Arg Ser Ser Pro 355 360 365

Pro Trp Phe He Val Asp Arg Pro Phe Leu Phe Phe He Arg His Asn 370 375 380 Pro Thr Gly Ala Val Leu Phe Met Gly Gin He Asn Lys Pro

385 390 395

<210> 17

<211> 314

<212> PRT

<213> Homo sapiens

<220>

<221> MISC FEATURE

<223> Sppl

<400> 17 Met Arg He Ala Val He Cys Phe Cys Leu Leu Gly He Thr Cys Ala 1 5 10 15

He Pro Val Lys Gin Ala Asp Ser Gly Ser Ser Glu Glu Lys Gin Leu 20 25 30

Tyr Asn Lys Tyr Pro Asp Ala Val Ala Thr Trp Leu Asn Pro Asp Pro 35 40 45

Ser Gin Lys Gin Asn Leu Leu Ala Pro Gin Asn Ala Val Ser Ser Glu 50 55 60 Glu Thr Asn Asp Phe Lys Gin Glu Thr Leu Pro Ser Lys Ser Asn Glu 65 70 75 80 Ser His Asp His Met Asp Asp Met Asp Asp Glu Asp Asp Asp Asp His

85 90 95

Val Asp Ser Gin Asp Ser He Asp Ser Asn Asp Ser Asp Asp Val Asp 100 105 110

Asp Thr Asp Asp Ser His Gin Ser Asp Glu Ser His His Ser Asp Glu 115 120 125

Ser Asp Glu Leu Val Thr Asp Phe Pro Thr Asp Leu Pro Ala Thr Glu 130 135 140

Val Phe Thr Pro Val Val Pro Thr Val Asp Thr Tyr Asp Gly Arg Gly 145 150 155 160 Asp Ser Val Val Tyr Gly Leu Arg Ser Lys Ser Lys Lys Phe Arg Arg

165 170 175

Pro Asp He Gin Tyr Pro Asp Ala Thr Asp Glu Asp He Thr Ser His 180 185 190

Met Glu Ser Glu Glu Leu Asn Gly Ala Tyr Lys Ala lie Pro Val Ala 195 200 205

Gin Asp Leu Asn Ala Pro Ser Asp Trp Asp Ser Arg Gly Lys Asp Ser 210 215 220

Tyr Glu Thr Ser Gin Leu Asp Asp Gin Ser Ala Glu Thr His Ser His 225 230 235 240 Lys Gin Ser Arg Leu Tyr Lys Arg Lys Ala Asn Asp Glu Ser Asn Glu

245 250 255

His Ser Asp Val lie Asp Ser Gin Glu Leu Ser Lys Val Ser Arg Glu 260 265 270

Phe His Ser His Glu Phe His Ser His Glu Asp Met Leu Val Val Asp 275 280 285 Pro Lys Ser Lys Glu Glu Asp Lys His Leu Lys Phe Arg He Ser His 290 295 300

Glu Leu Asp Ser Ala Ser Ser Glu Val Asn

305 310 <210> 18

<2\ \> 280

<212> PRT

<213> Homo sapiens

<220>

<221> MISC FEATURE

<223> Cdca8

<400> 18

Met Ala Pro Arg Lys Gly Ser Ser Arg Val Ala Lys Thr Asn Ser Leu 1 5 10 15 Arg Arg Arg Lys Leu Ala Ser Phe Leu Lys Asp Phe Asp Arg Glu Val 20 25 30

Glu He Arg He Lys Gin He Glu Ser Asp Arg Gin Asn Leu Leu Lys 35 40 45

Glu Val Asp Asn Leu Tyr Asn He Glu He Leu Arg Leu Pro Lys Ala 50 55 60

Leu Arg Glu Met Asn Trp Leu Asp Tyr Phe Ala Leu Gly Gly Asn Lys 65 70 75 80

Gin Ala Leu Glu Glu Ala Ala Thr Ala Asp Leu Asp He Thr Glu He

85 90 95 Asn Lys Leu Thr Ala Glu Ala He Gin Thr Pro Leu Lys Ser Ala Lys 100 105 110

Thr Arg Lys Val He Gin Val Asp Glu Met He Val Glu Glu Glu Glu 115 120 125

Glu Glu Glu Asn Glu Arg Lys Asn Leu Gin Thr Ala Arg Val Lys Arg 130 135 140

Cys Pro Pro Ser Lys Lys Arg Thr Gin Ser He Gin Gly Lys Gly Lys 145 150 155 160

Gly Lys Arg Ser Ser Arg Ala Asn Thr Val Thr Pro Ala Val Gly Arg

165 170 175 Leu Glu Val Ser Met Val Lys Pro Thr Pro Gly Leu Thr Pro Arg Phe 180 185 190

Asp Ser Arg Val Phe Lys Thr Pro Gly Leu Arg Thr Pro Ala Ala Gly 195 200 205 Glu Arg He Tyr Asn He Ser Gly Asn Gly Ser Pro Leu Ala Asp Ser 210 215 220

Lys Glu He Phe Leu Thr Val Pro Val Gly Gly Gly Glu Ser Leu Arg 225 230 235 240

Leu Leu Ala Ser Asp Leu Gin Arg His Ser He Ala Gin Leu Asp Pro

245 250 255 Glu Ala Leu Gly Asn He Lys Lys Leu Ser Asn Arg Leu Ala Gin He 260 265 270

Cys Ser Ser He Arg Thr His Lys

275 280

<210> 19

<211> 923

<212> PRT

<213> Homo sapiens

<220>

<221> MISC FEATURE

<223> Nrpl

<400> 19

Met Glu Arg Gly Leu Pro Leu Leu Cys Ala Val Leu Ala Leu Val Leu 1 5 10 15

Ala Pro Ala Gly Ala Phe Arg Asn Asp Lys Cys Gly Asp Thr He Lys 20 25 30

He Glu Ser Pro Gly Tyr Leu Thr Ser Pro Gly Tyr Pro His Ser Tyr 35 40 45

His Pro Ser Glu Lys Cys Glu Trp Leu He Gin Ala Pro Asp Pro Tyr 50 55 60 Gin Arg He Met He Asn Phe Asn Pro His Phe Asp Leu Glu Asp Arg 65 70 75 80

Asp Cys Lys Tyr Asp Tyr Val Glu Val Phe Asp Gly Glu Asn Glu Asn

85 90 95

Gly His Phe Arg Gly Lys Phe Cys Gly Lys He Ala Pro Pro Pro Val 100 105 110

Val Ser Ser Gly Pro Phe Leu Phe He Lys Phe Val Ser Asp Tyr Glu 115 120 125 Thr His Gly Ala Gly Phe Ser lie Arg Tyr Glu lie Phe Lys Arg Gly 130 135 140 Pro Glu Cys Ser Gin Asn Tyr Thr Thr Pro Ser Gly Val He Lys Ser 145 150 155 160

Pro Gly Phe Pro Glu Lys Tyr Pro Asn Ser Leu Glu Cys Thr Tyr He

165 170 175

Val Phe Val Pro Lys Met Ser Glu He He Leu Glu Phe Glu Ser Phe 180 185 190

Asp Leu Glu Pro Asp Ser Asn Pro Pro Gly Gly Met Phe Cys Arg Tyr 195 200 205

Asp Arg Leu Glu He Trp Asp Gly Phe Pro Asp Val Gly Pro His He 210 215 220 Gly Arg Tyr Cys Gly Gin Lys Thr Pro Gly Arg He Arg Ser Ser Ser 225 230 235 240

Gly He Leu Ser Met Val Phe Tyr Thr Asp Ser Ala He Ala Lys Glu

245 250 255

Gly Phe Ser Ala Asn Tyr Ser Val Leu Gin Ser Ser Val Ser Glu Asp 260 265 270 Phe Lys Cys Met Glu Ala Leu Gly Met Glu Ser Gly Glu He His Ser 275 280 285

Asp Gin He Thr Ala Ser Ser Gin Tyr Ser Thr Asn Trp Ser Ala Glu 290 295 300

Arg Ser Arg Leu Asn Tyr Pro Glu Asn Gly Trp Thr Pro Gly Glu Asp 305 310 315 320

Ser Tyr Arg Glu Trp He Gin Val Asp Leu Gly Leu Leu Arg Phe Val

325 330 335

Thr Ala Val Gly Thr Gin Gly Ala He Ser Lys Glu Thr Lys Lys Lys 340 345 350 Tyr Tyr Val Lys Thr Tyr Lys He Asp Val Ser Ser Asn Gly Glu Asp 355 360 365

Trp He Thr He Lys Glu Gly Asn Lys Pro Val Leu Phe Gin Gly Asn 370 375 380 Thr Asn Pro Thr Asp Val Val Val Ala Val Phe Pro Lys Pro Leu lie 385 390 395 400

Thr Arg Phe Val Arg lie Lys Pro Ala Thr Tip Glu Thr Gly lie Ser

405 410 415

Met Arg Phe Glu Val Tyr Gly Cys Lys lie Thr Asp Tyr Pro Cys Ser 420 425 430 Gly Met Leu Gly Met Val Ser Gly Leu lie Ser Asp Ser Gin lie Thr 435 440 445

Ser Ser Asn Gin Gly Asp Arg Asn Trp Met Pro Glu Asn He Arg Leu 450 455 460

Val Thr Ser Arg Ser Gly Trp Ala Leu Pro Pro Ala Pro His Ser Tyr 465 470 475 480

He Asn Glu Trp Leu Gin He Asp Leu Gly Glu Glu Lys He Val Arg

485 490 495

Gly He He He Gin Gly Gly Lys His Arg Glu Asn Lys Val Phe Met 500 505 510 Arg Lys Phe Lys He Gly Tyr Ser Asn Asn Gly Ser Asp Trp Lys Met 515 520 525

He Met Asp Asp Ser Lys Arg Lys Ala Lys Ser Phe Glu Gly Asn Asn 530 535 540

Asn Tyr Asp Thr Pro Glu Leu Arg Thr Phe Pro Ala Leu Ser Thr Arg 545 550 555 560

Phe He Arg He Tyr Pro Glu Arg Ala Thr His Gly Gly Leu Gly Leu

565 570 575

Arg Met Glu Leu Leu Gly Cys Glu Val Glu Ala Pro Thr Ala Gly Pro 580 585 590 Thr Thr Pro Asn Gly Asn Leu Val Asp Glu Cys Asp Asp Asp Gin Ala 595 600 605

Asn Cys His Ser Gly Thr Gly Asp Asp Phe Gin Leu Thr Gly Gly Thr 610 615 620

Thr Val Leu Ala Thr Glu Lys Pro Thr Val He Asp Ser Thr He Gin 625 630 635 640

Ser Glu Phe Pro Thr Tyr Gly Phe Asn Cys Glu Phe Gly Trp Gly Ser

645 650 655 His Lys Thr Phe Cys His Tip Glu His Asp Asn His Val Gin Leu Lys 660 665 670 Trp Ser Val Leu Thr Ser Lys Thr Gly Pro He Gin Asp His Thr Gly 675 680 685

Asp Gly Asn Phe He Tyr Ser Gin Ala Asp Glu Asn Gin Lys Gly Lys 690 695 700

Val Ala Arg Leu Val Ser Pro Val Val Tyr Ser Gin Asn Ser Ala His 705 710 715 720

Cys Met Thr Phe Trp Tyr His Met Ser Gly Ser His Val Gly Thr Leu

725 730 735

Arg Val Lys Leu Arg Tyr Gin Lys Pro Glu Glu Tyr Asp Gin Leu Val 740 745 750

Trp Met Ala lie Gly His Gin Gly Asp His Trp Lys Glu Gly Arg Val 755 760 765

Leu Leu His Lys Ser Leu Lys Leu Tyr Gin Val He Phe Glu Gly Glu 770 775 780 lie Gly Lys Gly Asn Leu Gly Gly lie Ala Val Asp Asp lie Ser lie 785 790 795 800 Asn Asn His He Ser Gin Glu Asp Cys Ala Lys Pro Ala Asp Leu Asp

805 810 815

Lys Lys Asn Pro Glu He Lys He Asp Glu Thr Gly Ser Thr Pro Gly 820 825 830

Tyr Glu Gly Glu Gly Glu Gly Asp Lys Asn He Ser Arg Lys Pro Gly 835 840 845

Asn Val Leu Lys Thr Leu Asp Pro He Leu He Thr He He Ala Met 850 855 860

Ser Ala Leu Gly Val Leu Leu Gly Ala Val Cys Gly Val Val Leu Tyr 865 870 875 880 Cys Ala Cys Trp His Asn Gly Met Ser Glu Arg Asn Leu Ser Ala Leu

885 890 895

Glu Asn Tyr Asn Phe Glu Leu Val Asp Gly Val Lys Leu Lys Lys Asp 900 905 910 Lys Leu Asn Thr Gin Ser Thr Tyr Ser Glu Ala

915 920

<210> 20

<211> 646

<212> PRT

<213> Homo sapiens

<220>

<221> MISC FEATURE

<223> Mcam

<400> 20 Met Gly Leu Pro Arg Leu Val Cys Ala Phe Leu Leu Ala Ala Cys Cys 1 5 10 15

Cys Cys Pro Arg Val Ala Gly Val Pro Gly Glu Ala Glu Gin Pro Ala 20 25 30

Pro Glu Leu Val Glu Val Glu Val Gly Ser Thr Ala Leu Leu Lys Cys 35 40 45

Gly Leu Ser Gin Ser Gin Gly Asn Leu Ser His Val Asp Trp Phe Ser 50 55 60

Val His Lys Glu Lys Arg Thr Leu lie Phe Arg Val Arg Gin Gly Gin 65 70 75 80 Gly Gin Ser Glu Pro Gly Glu Tyr Glu Gin Arg Leu Ser Leu Gin Asp

85 90 95

Arg Gly Ala Thr Leu Ala Leu Thr Gin Val Thr Pro Gin Asp Glu Arg 100 105 110

He Phe Leu Cys Gin Gly Lys Arg Pro Arg Ser Gin Glu Tyr Arg He 115 120 125

Gin Leu Arg Val Tyr Lys Ala Pro Glu Glu Pro Asn He Gin Val Asn 130 135 140

Pro Leu Gly lie Pro Val Asn Ser Lys Glu Pro Glu Glu Val Ala Thr 145 150 155 160 Cys Val Gly Arg Asn Gly Tyr Pro lie Pro Gin Val lie Trp Tyr Lys

165 170 175

Asn Gly Arg Pro Leu Lys Glu Glu Lys Asn Arg Val His He Gin Ser 180 185 190 Ser Gin Thr Val Glu Ser Ser Gly Leu Tyr Thr Leu Gin Ser He Leu 195 200 205

Lys Ala Gin Leu Val Lys Glu Asp Lys Asp Ala Gin Phe Tyr Cys Glu 210 215 220

Leu Asn Tyr Arg Leu Pro Ser Gly Asn His Met Lys Glu Ser Arg Glu 225 230 235 240 Val Thr Val Pro Val Phe Tyr Pro Thr Glu Lys Val Tip Leu Glu Val

245 250 255

Glu Pro Val Gly Met Leu Lys Glu Gly Asp Arg Val Glu lie Arg Cys 260 265 270

Leu Ala Asp Gly Asn Pro Pro Pro His Phe Ser He Ser Lys Gin Asn 275 280 285 Pro Ser Thr Arg Glu Ala Glu Glu Glu Thr Thr Asn Asp Asn Gly Val 290 295 300

Leu Val Leu Glu Pro Ala Arg Lys Glu His Ser Gly Arg Tyr Glu Cys 305 310 315 320

Gin Gly Leu Asp Leu Asp Thr Met He Ser Leu Leu Ser Glu Pro Gin

325 330 335

Glu Leu Leu Val Asn Tyr Val Ser Asp Val Arg Val Ser Pro Ala Ala 340 345 350

Pro Glu Arg Gin Glu Gly Ser Ser Leu Thr Leu Thr Cys Glu Ala Glu 355 360 365 Ser Ser Gin Asp Leu Glu Phe Gin Tip Leu Arg Glu Glu Thr Gly Gin 370 375 380

Val Leu Glu Arg Gly Pro Val Leu Gin Leu His Asp Leu Lys Arg Glu 385 390 395 400

Ala Gly Gly Gly Tyr Arg Cys Val Ala Ser Val Pro Ser lie Pro Gly

405 410 415

Leu Asn Arg Thr Gin Leu Val Asn Val Ala He Phe Gly Pro Pro Trp 420 425 430

Met Ala Phe Lys Glu Arg Lys Val Tip Val Lys Glu Asn Met Val Leu 435 440 445 Asn Leu Ser Cys Glu Ala Ser Gly His Pro Arg Pro Thr He Ser Trp 450 455 460

Asn Val Asn Gly Thr Ala Ser Glu Gin Asp Gin Asp Pro Gin Arg Val 465 470 475 480

Leu Ser Thr Leu Asn Val Leu Val Thr Pro Glu Leu Leu Glu Thr Gly

485 490 495

Val Glu Cys Thr Ala Ser Asn Asp Leu Gly Lys Asn Thr Ser He Leu 500 505 510

Phe Leu Glu Leu Val Asn Leu Thr Thr Leu Thr Pro Asp Ser Asn Thr 515 520 525

Thr Thr Gly Leu Ser Thr Ser Thr Ala Ser Pro His Thr Arg Ala Asn 530 535 540 Ser Thr Ser Thr Glu Arg Lys Leu Pro Glu Pro Glu Ser Arg Gly Val 545 550 555 560

Val lie Val Ala Val lie Val Cys lie Leu Val Leu Ala Val Leu Gly

565 570 575

Ala Val Leu Tyr Phe Leu Tyr Lys Lys Gly Lys Leu Pro Cys Arg Arg 580 585 590

Ser Gly Lys Gin Glu He Thr Leu Pro Pro Ser Arg Lys Ser Glu Leu 595 600 605

Val Val Glu Val Lys Ser Asp Lys Leu Pro Glu Glu Met Gly Leu Leu 610 615 620 Gin Gly Ser Ser Gly Asp Lys Arg Ala Pro Gly Asp Gin Gly Glu Lys 625 630 635 640

Tyr He Asp Leu Arg His

645

<210> 21

<2\ \> 322

<212> PRT

<213> Homo sapiens

<220>

<221> MISC FEATURE

<223> Pbk <400> 21

Met Glu Gly He Ser Asn Phe Lys Thr Pro Ser Lys Leu Ser Glu Lys 1 5 10 15

Lys Lys Ser Val Leu Cys Ser Thr Pro Thr He Asn He Pro Ala Ser 20 25 30

Pro Phe Met Gin Lys Leu Gly Phe Gly Thr Gly Val Asn Val Tyr Leu 35 40 45

Met Lys Arg Ser Pro Arg Gly Leu Ser His Ser Pro Trp Ala Val Lys 50 55 60 Lys He Asn Pro He Cys Asn Asp His Tyr Arg Ser Val Tyr Gin Lys 65 70 75 80

Arg Leu Met Asp Glu Ala Lys He Leu Lys Ser Leu His His Pro Asn

85 90 95

He Val Gly Tyr Arg Ala Phe Thr Glu Ala Asn Asp Gly Ser Leu Cys 100 105 110

Leu Ala Met Glu Tyr Gly Gly Glu Lys Ser Leu Asn Asp Leu He Glu 115 120 125

Glu Arg Tyr Lys Ala Ser Gin Asp Pro Phe Pro Ala Ala He He Leu 130 135 140 Lys Val Ala Leu Asn Met Ala Arg Gly Leu Lys Tyr Leu His Gin Glu 145 150 155 160

Lys Lys Leu Leu His Gly Asp He Lys Ser Ser Asn Val Val He Lys

165 170 175

Gly Asp Phe Glu Thr He Lys He Cys Asp Val Gly Val Ser Leu Pro 180 185 190

Leu Asp Glu Asn Met Thr Val Thr Asp Pro Glu Ala Cys Tyr He Gly 195 200 205

Thr Glu Pro Trp Lys Pro Lys Glu Ala Val Glu Glu Asn Gly Val He 210 215 220 Thr Asp Lys Ala Asp He Phe Ala Phe Gly Leu Thr Leu Trp Glu Met 225 230 235 240

Met Thr Leu Ser He Pro His He Asn Leu Ser Asn Asp Asp Asp Asp

245 250 255 Glu Asp Lys Thr Phe Asp Glu Ser Asp Phe Asp Asp Glu Ala Tyr Tyr 260 265 270

Ala Ala Leu Gly Thr Arg Pro Pro lie Asn Met Glu Glu Leu Asp Glu 275 280 285

Ser Tyr Gin Lys Val lie Glu Leu Phe Ser Val Cys Thr Asn Glu Asp 290 295 300 Pro Lys Asp Arg Pro Ser Ala Ala His lie Val Glu Ala Leu Glu Thr 305 310 315 320

Asp Val

<210> 22

<211> 262

<212> PRT

<213> Mus musculus

<220>

<221> MISC FEATURE

<223> Akrlcl

<400> 22

Gly Leu Ala lie Arg Ser Lys Val Ala Asp Gly Thr Val Arg Arg Glu 1 5 10 15 Asp He Phe Tyr Thr Ser Lys Leu Pro Cys Thr Cys His Arg Pro Glu 20 25 30

Leu Val Gin Pro Cys Leu Glu Gin Ser Leu Arg Lys Leu Gin Leu Asp 35 40 45

Tyr Val Asp Leu Tyr Leu He His Cys Pro Val Ser Met Lys Pro Gly 50 55 60

Asn Asp Leu He Pro Thr Asp Glu Asn Gly Lys Leu Leu Phe Asp Thr 65 70 75 80

Val Asp Leu Cys Asp Thr Tip Glu Ala Met Glu Lys Cys Lys Asp Ser

85 90 95 Gly Leu Ala Lys Ser He Gly Val Ser Asn Phe Asn Arg Arg Gin Leu 100 105 110

Glu Met He Leu Asn Lys Pro Gly Leu Arg Tyr Lys Pro Val Cys Asn 115 120 125 Gin Val Glu Cys His Pro Tyr Leu Asn Gin Ser Lys Leu Leu Asp Tyr 130 135 140 Cys Lys Ser Lys Asp He Val Leu Val Ala Tyr Gly Ala Leu Gly Ser 145 150 155 160

Gin Arg Cys Lys Asn Trp He Glu Glu Asn Ala Pro Tyr Leu Leu Glu

165 170 175

Asp Pro Thr Leu Cys Ala Met Ala Glu Lys His Lys Gin Thr Pro Ala 180 185 190

Leu He Ser Leu Arg Tyr Leu Leu Gin Arg Gly He Val He Val Thr 195 200 205

Lys Ser Phe Asn Glu Lys Arg He Lys Glu Asn Leu Lys Val Phe Glu 210 215 220 Phe His Leu Pro Ala Glu Asp Met Ala Val He Asp Arg Leu Asn Arg 225 230 235 240

Asn Tyr Arg Tyr Ala Thr Ala Arg He He Ser Ala His Pro Asn Tyr

245 250 255

Pro Phe Leu Asp Glu Tyr

260

<210> 23

<211> 521

<212> PRT

<213> Homo sapiens

<220>

<221> MISC FEATURE

<223> Cypl lal <400> 23

Met Leu Ala Lys Gly Leu Pro Pro Arg Ser Val Leu Val Lys Gly Cys 1 5 10 15

Gin Thr Phe Leu Ser Ala Pro Arg Glu Gly Leu Gly Arg Leu Arg Val 20 25 30

Pro Thr Gly Glu Gly Ala Gly He Ser Thr Arg Ser Pro Arg Pro Phe 35 40 45 Asn Glu He Pro Ser Pro Gly Asp Asn Gly Trp Leu Asn Leu Tyr His 50 55 60

Phe Trp Arg Glu Thr Gly Thr His Lys Val His Leu His His Val Gin 65 70 75 80

Asn Phe Gin Lys Tyr Gly Pro He Tyr Arg Glu Lys Leu Gly Asn Val

85 90 95 Glu Ser Val Tyr Val He Asp Pro Glu Asp Val Ala Leu Leu Phe Lys 100 105 110

Ser Glu Gly Pro Asn Pro Glu Arg Phe Leu He Pro Pro Trp Val Ala 115 120 125

Tyr His Gin Tyr Tyr Gin Arg Pro He Gly Val Leu Leu Lys Lys Ser 130 135 140

Ala Ala Trp Lys Lys Asp Arg Val Ala Leu Asn Gin Glu Val Met Ala 145 150 155 160

Pro Glu Ala Thr Lys Asn Phe Leu Pro Leu Leu Asp Ala Val Ser Arg

165 170 175 Asp Phe Val Ser Val Leu His Arg Arg He Lys Lys Ala Gly Ser Gly 180 185 190

Asn Tyr Ser Gly Asp He Ser Asp Asp Leu Phe Arg Phe Ala Phe Glu 195 200 205

Ser He Thr Asn Val He Phe Gly Glu Arg Gin Gly Met Leu Glu Glu 210 215 220

Val Val Asn Pro Glu Ala Gin Arg Phe He Asp Ala He Tyr Gin Met 225 230 235 240

Phe His Thr Ser Val Pro Met Leu Asn Leu Pro Pro Asp Leu Phe Arg

245 250 255

Leu Phe Arg Thr Lys Thr Trp Lys Asp His Val Ala Ala Trp Asp Val 260 265 270

He Phe Ser Lys Ala Asp He Tyr Thr Gin Asn Phe Tyr Trp Glu Leu 275 280 285

Arg Gin Lys Gly Ser Val His His Asp Tyr Arg Gly He Leu Tyr Arg 290 295 300 Leu Leu Gly Asp Ser Lys Met Ser Phe Glu Asp He Lys Ala Asn Val 305 310 315 320

Thr Glu Met Leu Ala Gly Gly Val Asp Thr Thr Ser Met Thr Leu Gin

325 330 335

Trp His Leu Tyr Glu Met Ala Arg Asn Leu Lys Val Gin Asp Met Leu 340 345 350 Arg Ala Glu Val Leu Ala Ala Arg His Gin Ala Gin Gly Asp Met Ala 355 360 365

Thr Met Leu Gin Leu Val Pro Leu Leu Lys Ala Ser He Lys Glu Thr

370 375 380

Leu Arg Leu His Pro He Ser Val Thr Leu Gin Arg Tyr Leu Val Asn 385 390 395 400

Asp Leu Val Leu Arg Asp Tyr Met He Pro Ala Lys Thr Leu Val Gin

405 410 415

Val Ala He Tyr Ala Leu Gly Arg Glu Pro Thr Phe Phe Phe Asp Pro

420 425 430 Glu Asn Phe Asp Pro Thr Arg Trp Leu Ser Lys Asp Lys Asn He Thr

435 440 445

Tyr Phe Arg Asn Leu Gly Phe Gly Trp Gly Val Arg Gin Cys Leu Gly 450 455 460

Arg Arg He Ala Glu Leu Glu Met Thr He Phe Leu He Asn Met Leu 465 470 475 480

Glu Asn Phe Arg Val Glu He Gin His Leu Ser Asp Val Gly Thr Thr

485 490 495

Phe Asn Leu He Leu Met Pro Glu Lys Pro He Ser Phe Thr Phe Trp

500 505 510 Pro Phe Asn Gin Glu Ala Thr Gin Gin

515 520

The following "DNA" are from mRNA

FOS Human DNA

AACCGCATCTGCAGCGAGCAACTGAGAAGCCAAGACTGAGCCGGCGGCCGCGGCGCA GCG AACGAGCAGTGACCGTGCTCCTACCCAGCTCTGCTTCACAGCGCCCACCTGTCTCCGCCC CTCGGCCCCTCGCCCGGCTTTGCCTAACCGCCACGATGATGTTCTCGGGCTTCAACGCAG ACTACGAGGCGTCATCCTCCCGCTGCAGCAGCGCGTCCCCGGCCGGGGATAGCCTCTCTT ACTACCACTCACCCTTTCGGAGTCCCCGCCCCCTCCGCTGGGGCTTACTCCAGGGCTGGC GT T GT GAAGAC CAT GAC AG GAG G C C GAG C G C AGAG CAT T G G C AG GAG G G G C AAG GT G GAA C AGT TAT C T C C T GAAGAAGAAGAGAAAAG GAGAAT C C GAAG G GAAAG GAAT AAGAT G G C T G C AG C C AAAT G C C G C AAC C G GAG GAGG GAG C T GAC T GAT AC AC T C C AAG C G GAGAC AGAC

C AAC T AGAAGAT GAGAAGT CTGCTTTG C AGAC C GAGAT T G C C AAC C T G C T GAAG GAGAAG GAAAAACTAGAGTTCATCCTGGCAGCTCACCGACCTGCCTGCAAGATCCCTGATGACCTG GGCTTCCCAGAAGAGATGTCTGTGGCTTCCCTTGATCTGACTGGGGGCCTGCCAGAGGTT GCCACCCCGGAGTCTGAGGAGGCCTTCACCCTGCCTCTCCTCAATGACCCTGAGCCCAAG CCCTCAGTGGAACCTGTCAAGAGCATCAGCAGCATGGAGCTGAAGACCGAGCCCTTTGAT GACTTCCTGTTCCCAGCATCATCCAGGCCCAGTGGCTCTGAGACAGCCCGCTCCGTGCCA GACATGGACCTATCTGGGTCCTTCTATGCAGCAGACTGGGAGCCTCTGCACAGTGGCTCC CTGGGGATGGGGCCCATGGCCACAGAGCTGGAGCCCCTGTGCACTCCGGTGGTCACCTGT ACTCCCAGCTGCACTGCTTACACGTCTTCCTTCGTCTTCACCTACCCCGAGGCTGACTCC TTCCCCAGCTGTGCAGCTGCCCACCGCAAGGGCAGCAGCAGCAATGAGCCTTCCTCTGAC TCGCTCAGCTCACCCACGCTGCTGGCCCTGTGAGGGGGCAGGGAAGGGGAGGCAGCCGGC AC C C AC AAGT G C C AC T G C C C GAG C T GGT G CAT T AC AGAGAG GAGAAAC AC AT CTTCCCTA GAGGGTTCCTGTAGACCTAGGGAGGACCTTATCTGTGCGTGAAACACACCAGGCTGTGGG CCTCAAGGACTTGAAAGCATCCATGTGTGGACTCAAGTCCTTACCTCTTCCGGAGATGTA GCAAAACGCATGGAGTGTGTATTGTTCCCAGTGACACTTCAGAGAGCTGGTAGTTAGTAG CATGTTGAGCCAGGCCTGGGTCTGTGTCTCTTTTCTCTTTCTCCTTAGTCTTCTCATAGC ATTAACTAATCTATTGGGTTCATTATTGGAATTAACCTGGTGCTGGATATTTTCAAATTG TATCTAGTGCAGCTGATTTTAACAATAACTACTGTGTTCCTGGCAATAGTGTGTTCTGAT TAGAAAT GAC C AAT AT TAT AC T AAGAAAAGAT AC GACTTTATTTTCT G GT AGAT AGAAAT AAATAGCTATATCCATGTACTGTAGTTTTTCTTCAACATCAATGTTCATTGTAATGTTAC TGATCATGCATTGTTGAGGTGGTCTGAATGTTCTGACATTAACAGTTTTCCATGAAAACG TTTTATTGTGTTTTTAATTTATTTATTAAGATGGATTCTCAGATATTTATATTTTTATTT TATTTTTTTCTACCTTGAGGTCTTTTGACATGTGGAAAGTGAATTTGAATGAAAAATTTA

AGCATTGTTTGCTTATTGTTCCAAGACATTGTCAATAAAAGCATTTAAGTT

GAATGCG

FOS Mouse Protein

MMFSGFNADYEAS S SRCS SAS PAGDSLSYYHS PADS FS SMGS P TQDFCADLSVS SANF I PTVTAI STS PDLQWLVQPTLVS SVAPSQTRAPHPYGLPTQSAGAYARAGMVKTVSGGRA QS I GRRGKVEQLS PEEEEKRRI RRERNKMAAAKCRNRRRELTDTLQAETDQLEDEKSALQ TEIANLLKEKEKLEFI LAAHRPACKI PDDLGFPEEMSVASLDLTGGLPEASTPESEEAFT LPLLNDPEPKPSLEPVKS I SNVELKAEPFDDFLFPAS SRPSGSETSRSVPDVDLSGS FYA ADWEPLHSNSLGMGPMVTELEPLCTPWTCTPGCTTYTS S FVFTYPEADS FPSCAAAHRK

GSSS EPSSDSLSSPTLLAL FOS Mouse DNA

CAGCGAGCAACTGAGAAGACTGGATAGAGCCGGCGGTTCCGCGAACGAGCAGTGACCGCG CTCCCACCCAGCTCTGCTCTGCAGCTCCCACCAGTGTCTACCCCTGGACCCCTTGCCGGG CTTTCCCCAAACTTCGACCATGATGTTCTCGGGTTTCAACGCCGACTACGAGGCGTCATC CTCCCGCTGCAGTAGCGCCTCCCCGGCCGGGGACAGCCTTTCCTACTACCATTCCCCAGC CGACTCCTTCTCCAGCATGGGCTCTCCTGTCAACACACAGGACTTTTGCGCAGATCTGTC CGTCTCTAGTGCCAACTTTATCCCCACGGTGACAGCCATCTCCACCAGCCCAGACCTGCA GTGGCTGGTGCAGCCCACTCTGGTCTCCTCCGTGGCCCCATCGCAGACCAGAGCGCCCCA TCCTTACGGACTCCCCACCCAGTCTGCTGGGGCTTACGCCAGAGCGGGAATGGTGAAGAC C GT GT C AG GAG G C AGAG C G C AGAG CAT C G G C AGAAG G G G C AAAGT AGAG C AG C TAT C T C C T GAAGAG GAAGAGAAAC G GAGAAT C C GAAG G GAAC G GAAT AAGAT G G C T G C AG C C AAGT G C C G GAAT C G GAG GAG G GAG C T GAC AGAT AC AC T C C AAG C G GAGAC AGAT C AAC T T GAAGA T GAGAAGT CTGCGTTG C AGAC T GAGAT T G C C AAT C T G C T GAAAGAGAAG GAAAAAC T G GA GTTTATTTTGGCAGCCCACCGACCTGCCTGCAAGATCCCCGATGACCTTGGCTTCCCAGA GGAGATGTCTGTGGCCTCCCTGGATTTGACTGGAGGTCTGCCTGAGGCTTCCACCCCAGA GTCTGAGGAGGCCTTCACCCTGCCCCTTCTCAACGACCCTGAGCCCAAGCCATCCTTGGA GCCAGTCAAGAGCATCAGCAACGTGGAGCTGAAGGCAGAACCCTTTGATGACTTCTTGTT TCCGGCATCATCTAGGCCCAGTGGCTCAGAGACCTCCCGCTCTGTGCCAGATGTGGACCT GTCCGGTTCCTTCTATGCAGCAGACTGGGAGCCTCTGCACAGCAATTCCTTGGGGATGGG GCCCATGGTCACAGAGCTGGAGCCCCTGTGTACTCCCGTGGTCACCTGTACTCCGGGCTG CACTACTTACACGTCTTCCTTTGTCTTCACCTACCCTGAAGCTGACTCCTTCCCAAGCTG TGCCGCTGCCCACCGAAAGGGCAGCAGCAGCAACGAGCCCTCCTCCGACTCCCTGAGCTC ACCCACGCTGCTGGCCCTGTGAGCAGTCAGAGAAGGCAAGGCAGCCGGCATCCAGACGTG CCACTGCCCGAGCTGGTGCATTACAGAGAGGAGAAACACGTCTTCCCTCGAAGGTTCCCG TCGACCTAGGGAGGACCTTACCTGTTCGTGAAACACACCAGGCTGTGGGCCTCAAGGACT TGCAAGCATCCACATCTGGCCTCCAGTCCTCACCTCTTCCAGAGATGTAGCAAAAACAAA ACAAAACAAAACAAAAAACCGCATGGAGTGTGTTGTTCCTAGTGACACCTGAGAGCTGGT

AGTTAGTAGAGCATGTGAGTCAAGGCCTGGTCTGTGTCTCTTTTCTCTTTCTCCTTA GTT TTCTCATAGCACTAACTAATCTGTTGGGTTCATTATTGGAATTAACCTGGTGCTGGATTG TATCTAGTGCAGCTGATTTTAACAATACCTACTGTGTTCCTGGCAATAGCGTGTTCCAAT TAGAAACGACCAATATTAAACTAAGAAAAGATAGGACTTTATTTTCCAGTAGATAGAAAT CAATAGCTATATCCATGTACTGTAGTCCTTCAGCGTCAATGTTCATTGTCATGTTACTGA TCATGCATTGTCGAGGTGGTCTGAATGTTCTGACATTAACAGTTTTCCATGAAAACGTTT TTATTGTGTTTTCAATTTATTTATTAAGATGGATTCTCAGATATTTATATTTTTATTTTA TTTTTTTCTACCCTGAGGTCTTTCGACATGTGGAAAGTGAATTTGAATGAAAAATTTTAA GCATTGTTTGCTTATTGTTCCAAGACATTGTCAATAAAAGCATTTAAGTTGAAAAAAAAA

AAAAAAA CD93 Human DNA

CTTCTCTGCGCCGGAGTGGCTGCAGCTCACCCCTCAGCTCCCCTTGGGGCCCAGCTGGGA GCCGAGATAGAAGCTCCTGTCGCCGCTGGGCTTCTCGCCTCCCGCAGAGGGCCACACAGA GACCGGGATGGCCACCTCCATGGGCCTGCTGCTGCTGCTGCTGCTGCTCCTGACCCAGCC CGGGGCGGGGACGGGAGCTGACACGGAGGCGGTGGTCTGCGTGGGGACCGCCTGCTACAC GGCCCACTCGGGCAAGCTGAGCGCTGCCGAGGCCCAGAACCACTGCAACCAGAACGGGGG CAACCTGGCCACTGTGAAGAGCAAGGAGGAGGCCCAGCACGTCCAGCGAGTACTGGCCCA GCTCCTGAGGCGGGAGGCAGCCCTGACGGCGAGGATGAGCAAGTTCTGGATTGGGCTCCA GCGAGAGAAGGGCAAGTGCCTGGACCCTAGTCTGCCGCTGAAGGGCTTCAGCTGGGTGGG CGGGGGGGAGGACACGCCTTACTCTAACTGGCACAAGGAGCTCCGGAACTCGTGCATCTC CAAGCGCTGTGTGTCTCTGCTGCTGGACCTGTCCCAGCCGCTCCTTCCCAGCCGCCTCCC CAAGTGGTCTGAGGGCCCCTGTGGGAGCCCAGGCTCCCCCGGAAGTAACATTGAGGGCTT CGTGTGCAAGTTCAGCTTCAAAGGCATGTGCCGGCCTCTGGCCCTGGGGGGCCCAGGTCA GGTGACCTACACCACCCCCTTCCAGACCACCAGTTCCTCCTTGGAGGCTGTGCCCTTTGC CTCTGCGGCCAATGTAGCCTGTGGGGAAGGTGACAAGGACGAGACTCAGAGTCATTATTT CCTGTGCAAGGAGAAGGCCCCCGATGTGTTCGACTGGGGCAGCTCGGGCCCCCTCTGTGT CAGCCCCAAGTATGGCTGCAACTTCAACAATGGGGGCTGCCACCAGGACTGCTTTGAAGG GGGGGATGGCTCCTTCCTCTGCGGCTGCCGACCAGGATTCCGGCTGCTGGATGACCTGGT GACCTGTGCCTCTCGAAACCCTTGCAGCTCCAGCCCATGTCGTGGGGGGGCCACGTGCGT CCTGGGACCCCATGGGAAAAACTACACGTGCCGCTGCCCCCAAGGGTACCAGCTGGACTC GAGTCAGCTGGACTGTGTGGACGTGGATGAATGCCAGGACTCCCCCTGTGCCCAGGAGTG TGTCAACACCCCTGGGGGCTTCCGCTGCGAATGCTGGGTTGGCTATGAGCCGGGCGGTCC TGGAGAGGGGGCCTGTCAGGATGTGGATGAGTGTGCTCTGGGTCGCTCGCCTTGCGCCCA GGGCTGCACCAACACAGATGGCTCATTTCACTGCTCCTGTGAGGAGGGCTACGTCCTGGC CGGGGAGGACGGGACTCAGTGCCAGGACGTGGATGAGTGTGTGGGCCCGGGGGGCCCCCT CTGCGACAGCTTGTGCTTCAACACACAAGGGTCCTTCCACTGTGGCTGCCTGCCAGGCTG GGTGCTGGCCCCAAATGGGGTCTCTTGCACCATGGGGCCTGTGTCTCTGGGACCACCATC TGGGCCCCCCGATGAGGAGGACAAAGGAGAGAAAGAAGGGAGCACCGTGCCCCGTGCTGC AACAGCCAGTCCCACAAGGGGCCCCGAGGGCACCCCCAAGGCTACACCCACCACAAGTAG ACCTTCGCTGTCATCTGACGCCCCCATCACATCTGCCCCACTCAAGATGCTGGCCCCCAG TGGGTCCCCAGGCGTCTGGAGGGAGCCCAGCATCCATCACGCCACAGCTGCCTCTGGCCC CCAGGAGCCTGCAGGTGGGGACTCCTCCGTGGCCACACAAAACAACGATGGCACTGACGG GCAAAAGCTGCTTTTATTCTACATCCTAGGCACCGTGGTGGCCATCCTACTCCTGCTGGC CCTGGCTCTGGGGCTACTGGTCTATCGCAAGCGGAGAGCGAAGAGGGAGGAGAAGAAGGA GAAGAAGCCCCAGAATGCGGCAGACAGTTACTCCTGGGTTCCAGAGCGAGCTGAGAGCAG GGCCATGGAGAACCAGTACAGTCCGACACCTGGGACAGACTGCTGAAAGTGAGGTGGCCC TAGAGACACTAGAGTCACCAGCCACCATCCTCAGAGCTTTGAACTCCCCATTCCAAAGGG GCACCCACATTTTTTTGAAAGACTGGACTGGAATCTTAGCAAACAATTGTAAGTCTCCTC CTTAAAGGCCCCTTGGAACATGCAGGTATTTTCTACGGGTGTTTGATGTTCCTGAAGTGG AAGCTGTGTGTTGGCGTGCCACGGTGGGGATTTCGTGACTCTATAATGATTGTTACTCCC CCTCCCTTTTCAAATTCCAATGTGACCAATTCCGGATCAGGGTGTGAGGAGGCCGGGGCT AAGGGGCTCCCCTGAATATCTTCTCTGCTCACTTCCACCATCTAAGAGGAAAAGGTGAGT TGCTCATGCTGATTAGGATTGAAATGATTTGTTTCTCTTCCTAGGATGAAAACTAAATCA

ATTAATTATTCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA

AAAAAAAAA

CD93 Mouse Protein

MAISTGLFLLLGLLGQPWAGAAADSQAWCEGTACYTAHWGKLSAAEAQHRCNENGGNLA TVKSEEEARHVQQALTQLLKTKAPLEAKMGKFWIGLQREKGNCTYHDLPMRGFSWVGGGE DTAYSNWYKASKSSCIFKRCVSLILDLSLTPHPSHLPKWHESPCGTPEAPGNSIEGFLCK FNFKGMCRPLALGGPGRVTYTTPFQATTS SLEAVPFASVANVACGDEAKSETHYFLCNEK TPGI FHWGS SGPLCVS PKFGCS FNNGGCQQDCFEGGDGS FRCGCRPGFRLLDDLVTCASR NPCS SNPCTGGGMCHSVPLSENYTCRCPSGYQLDS SQVHCVDI DECQDS PCAQDC TLG S FHCECWVGYQPSGPKEEACEDVDECAAANS PCAQGCINTDGS FYCSCKEGYIVSGEDST QCEDI DECSDARGNPCDSLCFNTDGSFRCGCPPGWELAPNGVFCSRGTVFSELPARPPQK EDNDDRKESTMPPTEMPS S PSGSKDVSNRAQTTGLFVQSDI PTASVPLEI EI PSEVSDVW FELGTYLPTTSGHSKPTHEDSVSAHSDTDGQNLLLFYI LGTWAI SLLLVLALGI LIYHK

RRAKKEEIKEKKPQNAADSYSWVPERAESQAPENQYSPTPGTDC CD93 Mouse DNA

GAAAGCAGCAGTGCGCCTCTGCTCCCTTCAGAGCACAGCCTGGTGTCAAGGTCCAGGTTC CACCGGCTGCTGCTGTCACCGCAGGGGAGTCTAGCCCCTCCCAGAAGGAGACACAGAAGA ATGGCCATCTCAACTGGTTTGTTCCTGCTGCTGGGGCTCCTTGGCCAGCCCTGGGCAGGG GCTGCTGCTGATTCACAGGCTGTGGTGTGCGAGGGGACTGCCTGCTATACAGCCCATTGG GGCAAGCTGAGTGCCGCTGAAGCCCAGCATCGCTGCAATGAGAATGGAGGCAATCTTGCC ACCGTGAAGAGTGAGGAGGAGGCCCGGCATGTTCAGCAAGCCCTGACTCAGCTCCTGAAG ACCAAGGCACCCTTGGAAGCAAAGATGGGCAAATTCTGGATCGGGCTCCAGCGAGAGAAG GGCAACTGTACGTACCATGATTTGCCAATGAGGGGCTTCAGCTGGGTGGGTGGTGGAGAG GAC AC AG C T TAT T C AAAC T G GT AC AAAG C C AG C AAGAG C T C C T GT AT C T T T AAAC G C T GT GTGTCCCTCATACTGGACCTGTCCTTGACACCTCACCCCAGCCATCTGCCCAAGTGGCAT GAGAGTCCCTGTGGGACCCCCGAAGCTCCAGGTAACAGCATTGAAGGTTTCCTGTGCAAG TTCAACTTCAAAGGCATGTGTAGGCCACTGGCGCTGGGTGGTCCAGGGCGGGTGACCTAT ACCACCCCTTTCCAGGCCACTACCTCCTCTCTGGAGGCTGTGCCTTTTGCCTCTGTAGCC AATGTAGCTTGTGGGGATGAAGCTAAGAGTGAAACCCACTATTTCCTATGCAATGAAAAG ACTCCAGGAATATTTCACTGGGGCAGCTCAGGCCCACTCTGTGTCAGCCCCAAGTTTGGT TGCAGTTTCAACAACGGGGGCTGCCAGCAGGATTGCTTCGAAGGTGGCGATGGCTCCTTC CGCTGCGGCTGCCGGCCTGGATTTCGACTGCTGGATGATCTAGTAACTTGTGCCTCCAGG AACCCCTGCAGCTCAAACCCATGCACAGGAGGTGGCATGTGCCATTCTGTACCACTCAGT GAAAACTACACTTGCCGTTGTCCCAGCGGCTACCAGCTGGACTCTAGCCAAGTGCACTGT GTGGATATAGATGAGTGCCAGGACTCCCCCTGTGCCCAGGATTGTGTCAACACTCTAGGG AGCTTCCACTGTGAATGTTGGGTTGGTTACCAACCCAGTGGCCCCAAGGAAGAGGCCTGT GAAGATGTGGATGAGTGTGCAGCTGCCAACTCGCCCTGTGCCCAAGGCTGCATCAACACT GATGGCTCTTTCTACTGCTCCTGTAAAGAGGGCTATATTGTGTCTGGGGAAGACAGTACC CAGTGTGAGGATATAGATGAGTGTTCGGACGCAAGGGGCAATCCATGTGATTCCCTGTGC TTCAACACAGATGGTTCCTTCAGGTGTGGCTGCCCGCCAGGCTGGGAGCTGGCTCCCAAT GGGGTCTTTTGTAGCAGGGGCACTGTGTTTTCTGAACTACCAGCCAGGCCTCCCCAAAAG GAAGAC AAC GAT GAC AGAAAG GAGAGT AC TAT GCCTCCTACT GAAAT G C C C AGT T C T C C T AGTGGCTC T AAG GAT GT C T C C AAC AGAG C AC AGAC AAC AG GT CTCTTCGTC C AAT C AGAT ATTCCCACTGCCTCTGTTCCACTAGAAATAGAAATCCCTAGTGAAGTATCTGATGTCTGG T T C GAGT T G G G C AC AT AC C T C C C C AC GAC C T C C G G C C AC AG C AAG C C GAC AC AT GAAGAT TCTGTGTCTGCACACAGTGACACCGATGGGCAGAACCTGCTTCTGTTTTACATCCTGGGG ACGGTGGTGGCCATCTCACTCTTGCTGGTGCTGGCCCTAGGGATTCTCATTTATCATAAA C G GAGAG C C AAGAAG GAG GAGAT AAAAGAGAAGAAG C C T C AGAAT G C AG C C GAC AG C TAT TCCTGGGTTC C AGAG C GAG C AGAGAGC C AAG C C C C G GAGAAT C AGT AC AG C C C AAC AC C A G G GAC AGAC T G C T GAAGAC TAT GT G GC C T T AGAGAC AG C T G C C AC T AC C T T C AGAG C T AC CTTCTTAGATGAGGGGGAAGCCACATCATTCTGAATGACTTGACTGGACTCTCAGCAAAA AAATTGTGCACCTTCCACTTAAGAACCTGGTGGCTTGGGATAGGCAGGTATTTTCTTGGT GCCTTTGATATGTCTGGGGGTGAAAGCTGTGTGTTGGTTTGTCATTGTGGGGAGTTTTGT GGATATTGACAGACCTCACTCAAACACCCTTTTCAAATCCAATAGCAACTGGTTCCTCTG GTTCCTAATTAGGGGGAAAGGAGTCAGAGGGGTGGGACAGGGTGGGGGGATGGGGCTTCA AAGTTTTTTCTTATCACTTGATTTATCATCGAAGGAGTTACTGGTGCTAATTACAATGGA AAC AGT T C C T T T C CAT C AC AG GAC AGAC AC AC C T C AAT C C T C CAT G G G GT C AAC AAC TAT ATACCCCCAGTGACCCCTTAGGCAAGGACTTGTTGAGAACTGCATCACATTTTGACCTGT TCTCAACAGTACCCATCTATTTCAGGTGGGATCTCTGGACCTTTCCTCCTTCCCATCTTG TCTGCAATGTGGCAAATGGCTTCTTTTTGCATTTTTACTCCGCCCCCACCCCAAGCTGAA GTTCATTTGCAGATCAGCGATTAAGTCTGAATTGTGTGGTGGTCAGTCTTGTTTCCTTTT GTCAGGGGTTATTGTAAATGTTAGTAATTTCGCCTCAAGCCCTCAGTAAGAACATAAATA TTTTAAAATATGTGCGTTTGAAATCTGTTTCATGCATCCTGGAACTGTGGGATGCTCAGG CAAGAGTGACTTTAGTCTTTCAGTGAATGTTGCCCAGAATGTGGGTAGGGAAGGCTCACA GGTTACTCTCCTCCTTAGAGCTACAACATAACATTCTGAGGGGAGTCACAGGGTTGCCTT TAAAAAGTGGGAGCTATGTCATGCTTTGAGCTTTCTGTTAAGCACCTCTCCTAATAAACT C TGA A A A A AT

FOSB Human DNA

CAT T C AT AAGAC T C AGAG C T AC G G C CAC G G C AG G GAC AC G C G GAAC C AAGAC T T G GAAAC TTGATTGTTGTGGTTCTTCTTGGGGGTTATGAAATTTCATTAATCTTTTTTTTTTCCGGG GAGAAAGTTTTTGGAAAGATTCTTCCAGATATTTCTTCATTTTCTTTTGGAGGACCGACT TACTTTTTTTGGTCTTCTTTATTACTCCCCTCCCCCCGTGGGACCCGCCGGACGCGTGGA GGAGACCGTAGCTGAAGCTGATTCTGTACAGCGGGACAGCGCTTTCTGCCCCTGGGGGAG CAACCCCTCCCTCGCCCCTGGGTCCTACGGAGCCTGCACTTTCAAGAGGTACAGCGGCAT CCTGTGGGGGCCTGGGCACCGCAGGAAGACTGCACAGAAACTTTGCCATTGTTGGAACGG GACGTTGCTCCTTCCCCGAGCTTCCCCGGACAGCGTACTTTGAGGACTCGCTCAGCTCAC CGGGGACTCCCACGGCTCACCCCGGACTTGCACCTTACTTCCCCAACCCGGCCATAGCCT TGGCTTCCCGGCGACCTCAGCGTGGTCACAGGGGCCCCCCTGTGCCCAGGGAAATGTTTC AGGCTTTCCCCGGAGACTACGACTCCGGCTCCCGGTGCAGCTCCTCACCCTCTGCCGAGT CTCAATATCTGTCTTCGGTGGACTCCTTCGGCAGTCCACCCACCGCCGCGGCCTCCCAGG AGTGCGCCGGTCTCGGGGAAATGCCCGGTTCCTTCGTGCCCACGGTCACCGCGATCACAA CCAGCCAGGACCTCCAGTGGCTTGTGCAACCCACCCTCATCTCTTCCATGGCCCAGTCCC AGGGGCAGCCACTGGCCTCCCAGCCCCCGGTCGTCGACCCCTACGACATGCCGGGAACCA GCTACTCCACACCAGGCATGAGTGGCTACAGCAGTGGCGGAGCGAGTGGCAGTGGTGGGC CTTCCACCAGCGGAACTACCAGTGGGCCTGGGCCTGCCCGCCCAGCCCGAGCCCGGCCTA G GAGAC C C C GAGAG GAGAC G C T CAC C C C AGAG GAAGAG GAGAAG C GAAG GGTGCGCCGGG AAC GAAAT AAAC TAG C AG C AG C T AAAT G C AG GAAC C G G C G GAG G GAG C T GAC C GAC C GAC T C C AG G C G GAGAC AGAT C AGT T G GAGGAAGAAAAAG C AGAG C T G GAGT C G GAGAT C G C C G AGCTCCAAAAGGAGAAGGAACGTCTGGAGTTTGTGCTGGTGGCCCACAAACCGGGCTGCA AGATCCCCTACGAAGAGGGGCCCGGGCCGGGCCCGCTGGCGGAGGTGAGAGATTTGCCGG GCTCAGCACCGGCTAAGGAAGATGGCTTCAGCTGGCTGCTGCCGCCCCCGCCACCACCGC CCCTGCCCTTCCAGACCAGCCAAGACGCACCCCCCAACCTGACGGCTTCTCTCTTTACAC ACAGTGAAGTTCAAGTCCTCGGCGACCCCTTCCCCGTTGTTAACCCTTCGTACACTTCTT CGTTTGTCCTCACCTGCCCGGAGGTCTCCGCGTTCGCCGGCGCCCAACGCACCAGCGGCA GTGACCAGCCTTCCGATCCCCTGAACTCGCCCTCCCTCCTCGCTCGGTGAACTCTTTAGA CAC AC AAAAC AAAC AAAC AC AT G G G GGAGAGAGAC T T G GAAGAG GAG GAG GAG GAG GAGA AGGAGGAGAGAGAGGGGAAGAGACAAAGTGGGTGTGTGGCCTCCCTGGCTCCTCCGTCTG ACCCTCTGCGGCCACTGCGCCACTGCCATCGGACAGGAGGATTCCTTGTGTTTTGTCCTG CCTCTTGTTTCTGTGCCCCGGCGAGGCCGGAGAGCTGGTGACTTTGGGGACAGGGGGTGG GAAGGGGATGGACACCCCCAGCTGACTGTTGGCTCTCTGACGTCAACCCAAGCTCTGGGG ATGGGTGGGGAGGGGGGCGGGTGACGCCCACCTTCGGGCAGTCCTGTGTGAGGATGAAGG GACGGGGGTGGGAGGTAGGCTGTGGGGTGGGCTGGAGTCCTCTCCAGAGAGGCTCAACAA GGAAAAATGCCACTCCCTACCCAATGTCTCCCACACCCACCCTTTTTTTGGGGTGCCCAG GTTGGTTTCCCCTGCACTCCCGACCTTAGCTTATTGATCCCACATTTCCATGGTGTGAGA TCCTCTTTACTCTGGGCAGAAGTGAGCCCCCCCTTAAAGGGAATTCGATGCCCCCCTAGA ATAATCTCATCCCCCCACCCGACTTCTTTTGAAATGTGAACGTCCTTCCTTGACTGTCTA GCCACTCCCTCCCAGAAAAACTGGCTCTGATTGGAATTTCTGGCCTCCTAAGGCTCCCCA CCCCGAAATCAGCCCCCAGCCTTGTTTCTGATGACAGTGTTATCCCAAGACCCTGCCCCC TGCCAGCCGACCCTCCTGGCCTTCCTCGTTGGGCCGCTCTGATTTCAGGCAGCAGGGGCT GCTGTGATGCCGTCCTGCTGGAGTGATTTATACTGTGAAATGAGTTGGCCAGATTGTGGG GTGCAGCTGGGTGGGGCAGCACACCTCTGGGGGGATAATGTCCCCACTCCCGAAAGCCTT TCCTCGGTCTCCCTTCCGTCCATCCCCCTTCTTCCTCCCCTCAACAGTGAGTTAGACTCA AGGGGGTGACAGAACCGAGAAGGGGGTGACAGTCCTCCATCCACGTGGCCTCTCTCTCTC TCCTCAGGACCCTCAGCCCTGGCCTTTTTCTTTAAGGTCCCCCGACCAATCCCCAGCCTA GGACGCCAACTTCTCCCACCCCTTGGCCCCTCACATCCTCTCCAGGAAGGCAGTGAGGGG CTGTGACATTTTTCCGGAGAAGATTTCAGAGCTGAGGCTTTGGTACCCCCAAACCCCCAA TATTTTTGGACTGGCAGACTCAAGGGGCTGGAATCTCATGATTCCATGCCCGAGTCCGCC CATCCCTGACCATGGTTTTGGCTCTCCCACCCCGCCGTTCCCTGCGCTTCATCTCATGAG GATTTCTTTATGAGGCAAATTTATATTTTTTAATATCGGGGGGTGGACCACGCCGCCCTC CATCCGTGCTGCATGAAAAACATTCCACGTGCCCCTTGTCGCGCGTCTCCCATCCTGATC CCAGACCCATTCCTTAGCTATTTATCCCTTTCCTGGTTTCCGAAAGGCAATTATATCTAT TAT GT AT AAGT AAAT AT AT T AT AT AT GGAT GTGTGTGTGTGCGTGCGCGT GAGT GT GT GA GCGCTTCTGCAGCCTCGGCCTAGGTCACGTTGGCCCTCAAAGCGAGCCGTTGAATTGGAA ACTGCTTCTAGAAACTCTGGCTCAGCCTGTCTCGGGCTGACCCTTTTCTGATCGTCTCGG CCCCTCTGATTGTTCCCGATGGTCTCTCTCCCTCTGTCTTTTCTCCTCCGCCTGTGTCCA TCTGACCGTTTTCACTTGTCTCCTTTCTGACTGTCCCTGCCAATGCTCCAGCTGTCGTCT GACTCTGGGTTCGTTGGGGACATGAGATTTTATTTTTTGTGAGTGAGACTGAGGGATCGT AGATTTTTACAATCTGTATCTTTGACAATTCTGGGTGCGAGTGTGAGAGTGTGAGCAGGG

CTTGCTCCTGCCAACCACAATTCAATGAATCCCCGACCCCCCTACCCCATGCTGTAC TTG TGGTTCTCTTTTTGTATTTTGCATCTGACCCCGGGGGGCTGGGACAGATTGGCAATGGGC

CGTCCCCTCTCCCCTTGGTTCTGCACTGTTGCCAATAAAAAGCTCTTAAAA ACGC

FOSB Mouse DNA

ATAAATTCTTATTTTGACACTCACCAAAATAGTCACCTGGAAAACCCGCTTTTTGTGACA AAGTACAGAAGGCTT GGT C AC AT T T AAAT CACT GAGAACTAGAGAGAAATACTAT CGCAA ACT GT AAT AGACAT T ACAT C CAT AAAAGT T T C C C CAGT C CT T AT T GT AAT AT T GCACAGT G C AAT T G C T AC AT G G C AAAC T AGT GT AG C AT AGAAGT C AAAG C AAAAAC AAAC C AAAGAA AG GAG C C AC AAGAGT AAAAC T GT T C AAC AGT T AAT AGT T C AAAC T AAG C CAT T GAAT C T A TCATTGGGATCGTTAAAATGAATCTTCCTACACCTTGCAGTGTATGATTTAACTTTTACA GAAC AC AAG C C AAGT T T AAAAT C AG CAGT AGAGAT AT T AAAAT GAAAAG GT T T G C T AAT A GAGT AAC AT T AAAT AC C C T GAAG GAAAAAAAAC C T AAAT AT C AAAAT AAC T GAT T AAAAT T C AC T T G C AAAT TAG C AC AC GAAT AT G C AAC T T G GAAAT CAT G CAGT GT T T TAT T T AAGA AAAC AT AAAAC AAAAC TAT T AAAAT AGT T T T AGAG G G G GT AAAAT C C AG GT C C T C T G C C A GGATGCTAAAATTAGACTTCAGGGGAATTTTGAAGTCTTCAATTTTGAAACCTATTAAAA AG C C CAT GAT T AC AGT T AAT T AAGAGC AGT G C AC G C AAC AGT GAC AC G C C T T T AGAGAG C ATTACTGTGTATGAACATGTTGGCTGCTACCAGCCACAGTCAATTTAACAAGGCTGCTCA GT CAT GAAC T T AAT AC AGAGAGAG C AC G C C T AG G C AG C AAG C AC AG CTTGCTGGGC C AC T TTCCTCCCTGTCGTGACACAATCAATCCGTGTACTTGGTGTATCTGAAGCGCACGCTGCA CCGCGGCACTGCCCGGCGGGTTTCTGGGCGGGGAGCGATCCCCGCGTCGCCCCCCGTGAA ACCGACAGAGCCTGGACTTTCAGGAGGTACAGCGGCGGTCTGAAGGGGATCTGGGATCTT GCAGAGGGAACTTGCATCGAAACTTGGGCAGTTCTCCGAACCGGAGACTAAGCTTCCCCG AGCAGCGCACTTTGGAGACGTGTCCGGTCTACTCCGGACTCGCATCTCATTCCACTCGGC CATAGCCTTGGCTTCCCGGCGACCTCAGCGTGGTCACAGGGGCCCCCCTGTGCCCAGGGA AATGTTTCAAGCTTTTCCCGGAGACTACGACTCCGGCTCCCGGTGTAGCTCATCACCCTC CGCCGAGTCTCAGTACCTGTCTTCGGTGGACTCCTTCGGCAGTCCACCCACCGCCGCCGC CTCCCAGGAGTGCGCCGGTCTCGGGGAAATGCCCGGCTCCTTCGTGCCAACGGTCACCGC AATCACAACCAGCCAGGATCTTCAGTGGCTCGTGCAACCCACCCTCATCTCTTCCATGGC CCAGTCCCAGGGGCAGCCACTGGCCTCCCAGCCTCCAGCTGTTGACCCTTATGACATGCC AGGAACCAGCTACTCAACCCCAGGCCTGAGTGCCTACAGCACTGGCGGGGCAAGCGGAAG TGGTGGGCCTTCAACCAGCACAACCACCAGTGGACCTGTGTCTGCCCGTCCAGCCAGAGC C AG G C C T AGAAGAC C C C GAGAAGAGAC AC T T AC C C C AGAAGAAGAAGAAAAG C GAAG GGT TCGCAGAGAGCGGAACAAGCTGGCTGCAGCTAAGTGCAGGAACCGTCGGAGGGAGCTGAC AGAT C GAC T T C AG G C G GAAAC T GAT CAG C T T GAAGAG GAAAAG G C AGAG C T G GAGT C G GA GATCGCCGAGCTGCAAAAAGAGAAGGAACGCCTGGAGTTTGTCCTGGTGGCCCACAAACC GGGCTGCAAGATCCCCTACGAAGAGGGGCCGGGGCCAGGCCCGCTGGCCGAGGTGAGAGA TTTGCCAGGGTCAACATCCGCTAAGGAAGACGGCTTCGGCTGGCTGCTGCCGCCCCCTCC ACCACCCCCCCTGCCCTTCCAGAGCAGCCGAGACGCACCCCCCAACCTGACGGCTTCTCT CTTTACACACAGTGAAGTTCAAGTCCTCGGCGACCCCTTCCCCGTTGTTAGCCCTTCGTA CACTTCCTCGTTTGTCCTCACCTGCCCGGAGGTCTCCGCGTTCGCCGGCGCCCAACGCAC CAGCGGCAGCGAGCAGCCGTCCGACCCGCTGAACTCGCCCTCCCTTCTTGCTCTGTAAAC T C T T TAGAC AAAC AAAAC AAAC AAAC C C G C AAG GAAC AAG GAG GAG GAAGAT GAG GAG GA GAGGGGAGGAAGCAGTCCGGGGGTGTGTGTGTGGACCCTTTGACTCTTCTGTCTGACCAC CTGCCGCCTCTGCCATCGGACATGACGGAAGGACCTCCTTTGTGTTTTGTGCTCCGTCTC TGGTTTTCTGTGCCCCGGCGAGACCGGAGAGCTGGTGACTTTGGGGACAGGGGGTGGGGC GGGGATGGACACCCCTCCTGCATATCTTTGTCCTGTTACTTCAACCCAACTTCTGGGGAT AGATGGCTGGCTGGGTGGGTAGGGTGGGGTGCAACGCCCACCTTTGGCGTCTTGCGTGAG GCTGGAGGGGAAAGGGTGCTGAGTGTGGGGTGCAGGGTGGGTTGAGGTCGAGCTGGCATG CACCTCCAGAGAGACCCAACGAGGAAATGACAGCACCGTCCTGTCCTTCTTTTCCCCCAC CCACCCATCCACCCTCAAGGGTGCAGGGTGACCAAGATAGCTCTGTTTTGCTCCCTCGGG CCTTAGCTGATTAACTTAACATTTCCAAGAGGTTACAACCTCCTCCTGGACGAATTGAGC CCCCGACTGAGGGAAGTCGATGCCCCCTTTGGGAGTCTGCTAACCCCACTTCCCGCTGAT TCCAAAATGTGAACCCCTATCTGACTGCTCAGTCTTTCCCTCCTGGGAAAACTGGCTCAG GTTGGATTTTTTTCCTCGTCTGCTACAGAGCCCCCTCCCAACTCAGGCCCGCTCCCACCC CTGTGCAGTATTATGCTATGTCCCTCTCACCCTCACCCCCACCCCAGGCGCCCTTGGCCG TCCTCGTTGGGCCTTACTGGTTTTGGGCAGCAGGGGGCGCTGCGACGCCCATCTTGCTGG AGCGCTTTATACTGTGAATGAGTGGTCGGATTGCTGGGTGCGCCGGATGGGATTGACCCC CAGCCCTCCAAAACTTTCCCTGGGCCTCCCCTTCTTCCACTTGCTTCCTCCCTCCCCTTG ACAGGGAGTTAGACTCGAAAGGATGACCACGACGCATCCCGGTGGCCTTCTTGCTCAGGC CCCAGACTTTTTCTCTTTAAGTCCTTCGCCTTCCCCAGCCTAGGACGCCAACTTCTCCCC ACCCTGGGAGCCCCGCATCCTCTCACAGAGGTCGAGGCAATTTTCAGAGAAGTTTTCAGG GCTGAGGCTTTGGCTCCCCTATCCTCGATATTTGAATCCCCAAATATTTTTGGACTAGCA TACTTAAGAGGGGGCTGAGTTCCCACTATCCCACTCCATCCAATTCCTTCAGTCCCAAAG ACGAGTTCTGTCCCTTCCCTCCAGCTTTCACCTCGTGAGAATCCCACGAGTCAGATTTCT ATTTTTTAATATTGGGGAGATGGGCCCTACCGCCCGTCCCCCGTGCTGCATGGAACATTC CATACCCTGTCCTGGGCCCTAGGTTCCAAACCTAATCCCAAACCCCACCCCCAGCTATTT AT CCCTTTCCTGGTTCC C AAAAAG C AC T TAT AT C TAT TAT GT AT AAAT AAAT AT AT TATA TATGAGTGTGCGTGTGTGTGCGTGTGCGTGCGTGCGTGCGTGCGTGCGAGCTTCCTTGTT TTCAAGTGTGCTGTGGAGTTCAAAATCGCTTCTGGGGATTTGAGTCAGACTTTCTGGCTG TCCCTTTTTGTCACCTTTTTGTTGTTGTCTCGGCTCCTCTGGCTGTTGGAGACAGTCCCG GCCTCTCCCTTTATCCTTTCTCAAGTCTGTCTCGCTCAGACCACTTCCAACATGTCTCCA CTCTCAATGACTCTGATCTCCGGTNTGTCTGTTAATTCTGGATTTGTCGGGGACATGCAA TTTTACTTCTGTAAGTAAGTGTGACTGGGTGGTAGATTTTTTACAATCTATATCGTTGAG

AATTC

FOSB Mouse Protein

MFQAFPGDYDSGSRCS S S PSAESQYLS SVDS FGS PPTAAASQECAGLGEMPGS FVPTVTA ITTSQDLQWLVQPTLI S SMAQSQGQPLASQPPAVDPYDMPGTSYSTPGLSAYSTGGASGS GGPSTSTTTSGPVSARPARARPRRPREETLTPEEEEKRRVRRERNKLAAAKCRNRRRELT DRLQAETDQLEEEKAELESEIAELQKEKERLEFVLVAHKPGCKI PYEEGPGPGPLAEVRD LPGSTSAKEDGFGWLLPPPPPPPLPFQS SRDAPPNLTASLFTHSEVQVLGDPFPWS PSY

TS SF VLTCPEVS AF AGAQRT SGSEQP SDPLNSP SLL AL

Duspl Human DNA

TTTGGGCTGTGTGTGCGACGCGGGTCGGAGGGGCAGTCGGGGGAACCGCGAAGAAGCCGA GGAGCCCGGAGCCCCGCGTGACGCTCCTCTCTCAGTCCAAAAGCGGCTTTTGGTTCGGCG CAGAGAGACCCGGGGGTCTAGCTTTTCCTCGAAAAGCGCCGCCCTGCCCTTGGCCCCGAG AACAGACAAAGAGCACCGCAGGGCCGATCACGCTGGGGGCGCTGAGGCCGGCCATGGTCA TGGAAGTGGGCACCCTGGACGCTGGAGGCCTGCGGGCGCTGCTGGGGGAGCGAGCGGCGC AATGCCTGCTGCTGGACTGCCGCTCCTTCTTCGCTTTCAACGCCGGCCACATCGCCGGCT CTGTCAACGTGCGCTTCAGCACCATCGTGCGGCGCCGGGCCAAGGGCGCCATGGGCCTGG AGCACATCGTGCCCAACGCCGAGCTCCGCGGCCGCCTGCTGGCCGGCGCCTACCACGCCG TGGTGTTGCTGGACGAGCGCAGCGCCGCCCTGGACGGCGCCAAGCGCGACGGCACCCTGG CCCTGGCGGCCGGCGCGCTCTGCCGCGAGGCGCGCGCCGCGCAAGTCTTCTTCCTCAAAG GAGGATACGAAGCGTTTTCGGCTTCCTGCCCGGAGCTGTGCAGCAAACAGTCGACCCCCA TGGGGCTCAGCCTTCCCCTGAGTACTAGCGTCCCTGACAGCGCGGAATCTGGGTGCAGTT CCTGCAGTACCCCACTCTACGATCAGGGTGGCCCGGTGGAAATCCTGCCCTTTCTGTACC TGGGCAGTGCGTATCACGCTTCCCGCAAGGACATGCTGGATGCCTTGGGCATAACTGCCT T GAT C AAC GT C T C AG C C AAT T GT C C CAAC CAT T T T GAG G GT C AC T AC C AGT AC AAGAG C A TCCCTGTGGAGGACAACCACAAGGCAGACATCAGCTCCTGGTTCAACGAGGCCATTGACT TCATAGACTCCATCAAGAATGCTGGAGGAAGGGTGTTTGTCCACTGCCAGGCAGGCATTT CCCGGTCAGCCACCATCTGCCTTGCTTACCTTATGAGGACTAATCGAGTCAAGCTGGACG AGGCCTTTGAGTTTGTGAAGCAGAGGCGAAGCATCATCTCTCCCAACTTCAGCTTCATGG GCCAGCTGCTGCAGTTTGAGTCCCAGGTGCTGGCTCCGCACTGTTCGGCAGAGGCTGGGA GCCCCGCCATGGCTGTGCTCGACCGAGGCACCTCCACCACCACCGTGTTCAACTTCCCCG TCTCCATCCCTGTCCACTCCACGAACAGTGCGCTGAGCTACCTTCAGAGCCCCATTACGA CCTCTCCCAGCTGCTGAAAGGCCACGGGAGGTGAGGCTCTTCACATCCCATTGGGACTCC ATGCTCCTTGAGAGGAGAAATGCAATAACTCTGGGAGGGGCTCGAGAGGGCTGGTCCTTA TTTATTTAACTTCACCCGAGTTCCTCTGGGTTTCTAAGCAGTTATGGTGATGACTTAGCG T C AAGAC AT T T G C T GAAC T C AG C AC AT T C G G GAC C AAT AT AT AGT G G GT AC AT C AAGT C C ATCTGACAAAATGGGGCAGAAGAGAAAGGACTCAGTGTGTGATCCGGTTTCTTTTTGCTC GCCCCTGTTTTTTGTAGAATCTCTTCATGCTTGACATACCTACCAGTATTATTCCCGACG AC AC AT AT AC AT AT GAGAAT AT AC C T TAT T TAT TTTTGTGTAGGTGTCTGCCTT C AC AAA TGTCATTGTCTACTCCTAGAAGAACCAAATACCTCAATTTTTGTTTTTGAGTACTGTACT ATCCTGTAAATATATCTTAAGCAGGTTTGTTTTCAGCACTGATGGAAAATACCAGTGTTG GGTTTTTTTTTAGTTGCCAACAGTTGTATGTTTGCTGATTATTTATGACCTGAAATAATA TAT TTCTTCTTC T AAGAAGAC AT T T T GT T AC AT AAG GAT GAC τ T T T T TAT AC AAT G GAAT

AAATTATGGCATTTCTATTG

Duspl Mouse DNA

CGGCGGGAGGAAAGCGCGGTGAAGCCAGATTAGGAGCAGCGAGCACTTGGGGACTTAGGG C C AC AG GAC AC C G C AC AAGAT C GAC C GAC TTTTTCTG GAGAAC C G C AGAAC G G G C AC G C T GGGGTCGCTGGGGCTGGCCATGGTGATGGAGGTGGGCATCCTGGACGCCGGGGGGCTGCG CGCGCTGCTGCGAGAGGGCGCCGCGCAGTGCCTGTTGTTGGATTGTCGCTCCTTCTTCGC TTTCAACGCCGGCCACATCGCGGGCTCAGTGAACGTGCGCTTCAGCACCATCGTGCGGCG CCGCGCCAAGGGCGCCATGGGCCTGGAGCATATCGTGCCCAACGCTGAACTGCGTGGCCG CCTGCTGGCCGGAGCCTACCACGCCGTGGTGCTGCTGGACGAGCGCAGCGCCTCCCTGGA CGGCGCCAAGCGCGACGGCACCCTGGCCCTGGCCGCGGGCGCGCTCTGCCGAGAGGCGCG CTCCACTCAAGTCTTCTTTCTCCAAGGAGGATATGAAGCGTTTTCGGCTTCCTGCCCTGA GCTGTGCAGCAAACAGTCCACCCCCACGGGGCTCAGCCTCCCCCTGAGTACTAGTGTGCC TGACAGTGCAGAATCCGGATGCAGCTCCTGTAGTACCCCTCTCTACGATCAGGGGGGCCC AGTGGAGATCCTGTCCTTCCTGTACCTGGGCAGTGCCTATCACGCTTCTCGGAAGGATAT GCTTGACGCCTTGGGCATCACCGCCTTGATCAACGTCTCAGCCAATTGTCCTAACCACTT T GAGGGT C AC T AC C AGT AC AAGAG CAT C C C T GT G GAG GAC AAC C AC AAG G C AGAC AT CAG CTCCTGGTTCAACGAGGCTATTGACTTCATAGACTCCATCAAGGATGCTGGAGGGAGAGT GTTTGTTCATTGCCAGGCCGGCATCTCCCGGTCAGCCACCATCTGCCTTGCTTACCTCAT GAGGACTAACCGGGTAAAGCTGGACGAGGCCTTTGAGTTTGTGAAGCAGAGGCGGAGTAT CATCTCCCCGAACTTCAGCTTCATGGGCCAGCTGCTGCAGTTTGAGTCCCAAGTGCTAGC CCCTCACTGCTCTGCTGAAGCTGGGAGCCCTGCCATGGCTGTCCTTGACCGGGGCACCTC TACTACCACAGTCTTCAACTTCCCTGTTTCCATCCCCGTCCACCCCACGAACAGTGCCCT GAACTACCTTAAAAGCCCCATCACCACCTCTCCAAGCTGCTGAAGGGCAAGGGGAGGTGT GGAGTTTCACTTGCCACCGGGTCGCCACTCCTCCTGTGGGAGGAGCAATGCAATAACTCT GGGAGAGGCTCATGGGAGCTGGTCCTTATTTATTTAACACCCCCCTCACCCCCCAACTCC T C C T GAGT T C C AC T GAGT T C C T AAG CAGT C AC AAC AAT GAC T T GAC C G C AAGAC AT T T G C T GAAC T C G G C AC AT T C G G GAC C AAT AT AT T GT G G GT AC AT C AAGT C C C T C T GAC AAAAC A GGGCAGAAGAGAAAGGACTCTGTTTGAGGCAGTTTCTTCGCTTGCCTGTTTTTTTTTTCT AGAAAC T T CAT G C T T GAC AC AC C C AC CAGT AT T AAC CAT T C C C GAT GAC AT G C G C GT AT G AGAGTTTTTACCTTTATTTATTTTTGTGTAGGTCGGTGGTTTCTGCCTTCACAAATGTCA TTGTCTACTCATAGAAGAACCAAATACCTCAATTTTGTGTTTGCGTACTGTACTATCTTG TAAATAGACCCAGAGCAGGTTTGCTTTCGGCACTGACAGACAAAGCCAGTGTAGGTTTGT AGCTTT CAGT TAT C GACAGT T GT AT GT T T GT T TAT T TAT GAT CT GAAGT AAT AT AT T T CT TCTTCTGT GAAGAC AT TTTGTTACT GG GAT GAC τ T T T T T T AT AC AAC AGAAT AAAT TAT G

ACGTTTCTATTGA

Duspl Mouse Protein

MVMEVGI LDAGGLRALLREGAAQCLLLDCRS FFAFNAGHIAGS VRFSTIVRRRAKGAM GLEHIVPNAELRGRLLAGAYHAWLLDERSASLDGAKRDGTLALAAGALCREARSTQVFF LQGGYEAFSASCPELCSKQSTPTGLSLPLSTSVPDSAESGCS SCSTPLYDQGGPVEI LS F LYLGSAYHASRKDMLDALGITALINVSANCPNHFEGHYQYKS I PVEDNHKADI S SWFNEA I DFI DS I KDAGGRVFVHCQAGI S RSAT I CLAYLMRTNRVKLDEAFEFVKQRRS I I S PNFS FMGQLLQFESQVLAPHCSAEAGS PAMAVLDRGTSTTTVFNFPVS I PVHPTNSALNYLKS P

ITTSPSC

Jun Human DNA

ATGACTGCAAAGATGGAAACGACCTTCTATGACGATGCCCTCAACGCCTCGTTCCTCCCG T C C GAGAG C G GAC C T TAT G G C T AC AGT AAC C C C AAGAT C C T GAAAC AGAG CAT GAC C C T G AACCTGGCCGACCCAGTGGGGAGCCTGAAGCCGCACCTCCGCGCCAAGAACTCGGACCTC CTCACCTCGCCCGACGTGGGGCTGCTCAAGCTGGCGTCGCCCGAGCTGGAGCGCCTGATA ATCCAGTCCAGCAACGGGCACATCACCACCACGCCGACCCCCACCCAGTTCCTGTGCCCC AAGAACGTGACAGATGAGCAGGAGGGCTTCGCCGAGGGCTTCGTGCGCGCCCTGGCCGAA CTGCACAGCCAGAACACGCTGCCCAGCGTCACGTCGGCGGCGCAGCCGGTCAACGGGGCA GGCATGGTGGCTCCCGCGGTAGCCTCGGTGTCAGGGGGCAGCGGCAGCGGCGGCTTCAGC GCCAGCCTGCACAGCGAGCCGCCGGTCTACGCAAACCTCAGCAACTTCAACCCAGGCGCG CTGAGCAGCGGCGGCGGGGCGCCCTCCTACGGCGCGGCCGGCCTGGCCTTTCCCGCGCAA CCCCAGCAGCAGCAGCAGCCGCCGCACCACCTGCCCCAGCAGATGCCCGTGCAGCACCCG CGGCTGCAGGCCCTGAAGGAGGAGCCTCAGACAGTGCCCGAGATGCCCGGCGAGACACCG CCCCTGTCCCCCATCGACATGGAGTCCCAGGAGCGGATCAAGGCGGAGAGGAAGCGCATG AGGAACCGCATCGCTGCCTCCAAGTGCCGAAAAAGGAAGCTGGAGAGAATCGCCCGGCTG GAGGAAAAAGTGAAAACCTTGAAAGCTCAGAACTCGGAGCTGGCGTCCACGGCCAACATG CT CAGGGAACAGGT GGCACAGCTTAAACAGAAAGT CAT GAAC CACGTTAACAGT GGGT GC

CAACTCATGCTAACGCAGCAGTTGCAAACATTTTGA

Jun Mouse DNA

GTGACGACTGGTCAGCACCGCCGGAGAGCCGCTGTTGCTGGGACTGGTCTGCGGGCTCCA AGGAACCGCTGCTCCCCGAGAGCGCTCCGTGAGTGACCGCGACTTTTCAAAGCTCGGCAT CGCGCGGGAGCCTACCAACGTGAGTGCTAGCGGAGTCTTAACCCTGCGCTCCCTGGAGCA ACTGGGGAGGAGGGCTCAGGGGGAAGCACTGCCGTCTGGAGCGCACGCTCTAAACAAACT TTGTTACAGAAGCGGGGACGCGCGGGTATCCCCCCGCTTCCCGGCGCGCTGTTGCGGCCC CGAAACTTCTGCGCACAGCCCAGGCTAACCCCGCGTGAAGTGACGGACCGTTCTATGACT GCAAAGATGGAAACGACCTTCTACGACGATGCCCTCAACGCCTCGTTCCTCCAGTCCGAG AGCGGTGCCTACGGCTACAGTAACCCTAAGATCCTAAAACAGAGCATGACCTTGAACCTG GCCGACCCGGTGGGCAGTCTGAAGCCGCACCTCCGCGCCAAGAACTCGGACCTTCTCACG TCGCCCGACGTCGGGCTGCTCAAGCTGGCGTCGCCGGAGCTGGAGCGCCTGATCATCCAG TCCAGCAATGGGCACATCACCACTACACCGACCCCCACCCAGTTCTTGTGCCCCAAGAAC GTGACCGACGAGCAGGAGGGCTTCGCCGAGGGCTTCGTGCGCGCCCTGGCTGAACTGCAT AGCCAGAACACGCTTCCCAGTGTCACCTCCGCGGCACAGCCGGTCAGCGGGGCGGGCATG GTGGCTCCCGCGGTGGCCTCAGTAGCAGGCGCTGGCGGCGGTGGTGGCTACAGCGCCAGC CTGCACAGTGAGCCTCCGGTCTACGCCAACCTCAGCAACTTCAACCCGGGTGCGCTGAGC TGCGGCGGTGGGGCGCCCTCCTATGGCGCGGCCGGGCTGGCCTTTCCCTCGCAGCCGCAG CAGCAGCAGCAGCCGCCTCAGCCGCCGCACCACTTGCCCCAACAGATCCCGGTGCAGCAC CCGCGGCTGCAAGCCCTGAAGGAAGAGCCGCAGACCGTGCCGGAGATGCCGGGAGAGACG CCGCCCCTGTCCCCTATCGACATGGAGTCTCAGGAGCGGATCAAGGCAGAGAGGAAGCGC ATGAGGAACCGCATTGCCGCCTCCAAGTGCCGGAAAAGGAAGCTGGAGCGGATCGCTCGG CTAGAGGAAAAAGTGAAAACCTTGAAAGCGCAAAACTCCGAGCTGGCATCCACGGCCAAC ATGCTCAGGGAACAGGTGGCACAGCTTAAGCAGAAAGTCATGAACCACGTTAACAGTGGG TGCCAACTCATGCTAACGCAGCAGTTGCAAACGTTTTGAGAACAGACTGTCAGGGCTGAG GGGCAATGGAAGAAAAAAAATAACAGAGACAAACTTGAGAACTTGACTGGAAGCGACAGA GAAAAAAAAAGTGTCCGAGTACTGAAGCCAAGGGTACACAAGATGGACTGGGTTGCGACC TGACGGCGCCCCCAGTGTGCTGGAGTGGGAAGGACGTGGCGCGCCTGGCTTTGGCGTGGA GCCAGAGAGCAGAGGCCTATTGGCCGGCAGACTTTGCGGACGGGCTGTGCCCGCGCGACC AGAACGATGGACTTTTCGTTAACATTGACCAAGAACTGCATGGACCTAACATTCGATCTC ATTCAGTATTAAAGGGGGGTGGGAGGGGTTACAAACTGCAATAGAGACTGTAGATTGCTT CTGTAGTGCTCCTTAACACAAAGCAGGGAGGGCTGGGAAGGGGGGGGAGGCTTGTAAGTG CCAGGCTAGACTGCAGATGAACTCCCCTGGCCTGCCTCTCTCAACTGTGTATGTACATAT ATTTTTTTTTTTAATTTGATGAAAGCTGATTACTGTCAATAAACAGCTTCCGCCTTTGTA AGTTATTCCATGTTTGTTTGGGTGTCCTGCCCAGTGTTTGTAAATAAGAGATTTGAAGCA TTCTGAGTTTACCATTTGTAATAAAGTATATAATTTTTTTATGTTTTGTTTCTGAAAATT TCCAGAAAGGATATTTAAGAAAAATACAATAAACTATTGAAAAGTAGCCCCCAACCTCTT TGCTGCATTATCCATAGATAATGATAGCTAGATGAAGTGACAGCTGAGTGCCCAATATAC TAGGGTGAAAGCTGTGTCCCCTGTCTGATTGTAGGAATAGATACCCTGCATGCTATCATT GGCTCATACTCTCTCCCCCGGCAACACACAAGTCCAGACTGTACACCAGAAGATGGTGTG GTGTTTCTTAAGGCTGGAAGAAGGGCTGTTGCAAGGGGAGAGGGTCAGCCCGCTGGAAAG CAGACACTTTGGTTGAAAGCTGTATGAAGTGGCATGTGCTGTGATCATTTATAATCATAG GAAAGATTTAGTAATTAGCTGTTGATTCTCAAAGCAGGGACCCATGGAAGTTTTTAACAA AAGGTGTCTCCTTCCAACTTTGAATCTGACAACTCCTAGAAAAAGATGACCTTTGCTTGT

GCATATTTATAATAGCGTTCGTTATCACAATAAATGTATTCAAAT

Jun Mouse Protein

MTAKMETTFYDDALNASFLQSESGAYGYSNPKILKQSMTLNLADPVGSLKPHLRAKNSDL LTSPDVGLLKLASPELERLIIQSSNGHITTTPTPTQFLCPKNVTDEQEGFAEGFVRALAE LHSQNTLPSVTSAAQPVSGAGMVAPAVASVAGAGGGGGYSASLHSEPPVYANLSNFNPGA LSSGGGAPSYGAAGLAFPSQPQQQQQPPQPPHHLPQQIPVQHPRLQALKEEPQTVPEMPG ETPPLSPIDMESQERIKAERKRMRNRIAASKCRKRKLERIARLEEKVKTLKAQNSELAST

A MLREQVAQLKQKVMNHVNSGCQLMLTQQLQTF

Dusp6 Human DNA

CCAGCCTCGGAGGGAGGGATTAGAAGCCGCTAGACTTTTTTTCCTCCCCTCTCAGTAGCA CGGAGTCCGAATTAATTGGATTTCATTCACTGGGGAGGAACAAAAACTATCTGGGCAGCT TCATTGAGAGAGATTCATTGACACTAAGAGCCAGCGCTGCAGCTGGTGCAGAGAGAACCT CCGGCTTTGACTTCTGTCTCGTCTGCCCCAAGGCCGCTAGCCTCGGCTTGGGAAGGCGAG GCGGAATTAAACCCCGCTCCGAGAGCGCACGTTCGCGCGCGGTGCGTCGGCCATTGCCTG CCCCGAGGGGCGTCTGGTAGGCACCCCGCCCTCTCCCGCAGCTCGACCCCCATGATAGAT ACGCTCAGACCCGTGCCCTTCGCGTCGGAAATGGCGATCAGCAAGACGGTGGCGTGGCTC AACGAGCAGCTGGAGCTGGGCAACGAGCGGCTGCTGCTGATGGACTGCCGGCCGCAGGAG CTATACGAGTCGTCGCACATCGAGTCGGCCATCAACGTGGCCATCCCGGGCATCATGCTG CGGCGCCTGCAGAAGGGTAACCTGCCGGTGCGCGCGCTCTTCACGCGCGGCGAGGACCGG GACCGCTTCACCCGGCGCTGTGGCACCGACACAGTGGTGCTCTACGACGAGAGCAGCAGC GACTGGAACGAGAATACGGGCGGCGAGTCGTTGCTCGGGCTGCTGCTCAAGAAGCTCAAG GACGAGGGCTGCCGGGCGTTCTACCTGGAAGGTGGCTTCAGTAAGTTCCAAGCCGAGTTC TCCCTGCATTGCGAGACCAATCTAGACGGCTCGTGTAGCAGCAGCTCGCCGCCGTTGCCA GTGCTGGGGCTCGGGGGCCTGCGGATCAGCTCTGACTCTTCCTCGGACATCGAGTCTGAC C T T GAC C GAGAC C C C AAT AGT G C AACAGAC T C G GAT GGTAGTCCGCTGTC C AAC AG C C AG CCTTCCTTCCCAGTGGAGATCTTGCCCTTCCTCTACTTGGGCTGTGCCAAAGACTCCACC AACTTGGACGTGTTGGAGGAATTCGGCATCAAGTACATCTTGAACGTCACCCCCAATTTG C C GAAT C T C T T T GAGAAC G C AG GAGAGT T T AAAT AC AAG C AAAT C C C CAT C T C G GAT C AC TGGAGCCAAAACCTGTCCCAGTTTTTCCCTGAGGCCATTTCTTTCATAGATGAAGCCCGG GGCAAGAACTGTGGTGTCTTGGTACATTGCTTGGCTGGCATTAGCCGCTCAGTCACTGTG ACTGTGGCTTACCTTATGCAGAAGCTCAATCTGTCGATGAACGATGCCTATGACATTGTC AAAATGAAAAAATCCAACATATCCCCTAACTTCAACTTCATGGGTCAGCTGCTGGACTTC GAGAG GAC G C T G G GAC T C AG C AG C C CAT GT GAC AAC AG G GT T C C AG C AC AG C AG C T GT AT TTTACCACCCCTTCCAACCAGAATGTATACCAGGTGGACTCTCTGCAATCTACGTGAAAG ACCCCACACCCCTCCTTGCTGGAATGTGTCTGGCCCTTCAGCAGTTTCTCTTGGCAGCAT CAGCTGGGCTGCTTTCTTTGTGTGTGGCCCCAGGTGTCAAAATGACACCAGCTGTCTGTA C T AGAC AAG GT T AC C AAGT G C G GAAT T G GT T AAT AC T AAC AGAGAGAT T T G C T C CAT T C T CTTTGGAATAACAGGACATGCTGTATAGATACAGGCAGTAGGTTTGCTCTGTACCCATGT GT AC AG C C T AC C CAT G C AG G GAC T G GGAT T C GAG GAC T T C C AG G C G CAT AG G GT AGAAC C AAATGATAGGGTAGGAGCATGTGTTCTTTAGGGCCTTGTAAGGCTGTTTCCTTTTGCATC T G GAAC T GAC TAT AT AAT T GT C T T C AAT GAAGAC T AAT T C AAT T T T G C AT AT AGAG GAG C CAAAGAGAGATTTCAGCTCTGTATTTGTGGTATCAGTTTGGAAAAAAAAATCTGATACTC CAT T T GAT TAT T GT AAAT AT T T GAT CT T GAAT CACT T GACAGT GTTTGTTT GAAT T GT GT TTGTTTTTTCCTTTGATGGGCTTAAAAGAAATTATCCAAAGGGAGAAAGAGCAGTATGCC ACTTCTTAA

Dusp6 Mouse DNA

GATCCATTGAGGAGCTGCCTCGCACAGGGGGTGTGCTCTCGCGGAGTCCTAGGGACTGTG AGCAAACCCAGTCTTGAATAATCCGGCGAGAAACACCGGGTTGGATCCGAGGTGCAGCCT CAGAGGGAAGGATTAAGAGCCGCTAGACTTTTTTTCTTTTCCCTTTTTCTCCTCTCAGTG GCACGGAGTCCGAATTAATTGGATTTCATTCACTGGGTAGGAACAAAACTGGGCACCTTC AT T C AGAGAGAGAGAT T CAT T GAC T C G GAGAGT GAT C T G GT G C AGAG G GAC C AC C GAC T T GACTTCTGTGTCGCTTTCCCTAACCGCTAGCCTCGGCTTGGGAAAGGCGAGGCGGAATCA AACCCCGCTCCGAGAGCGGGAGCTTCGCGCAGCGTGCTCGGCCTATGCCTGCCTCGAGGG GCGTCTGCTAGGCACCCCGCCTTCTCCTGCAGCTCGACCCCCATGATAGATACGCTCAGA CCCGTGCCCTTCGCGTCGGAAATGGCGATCTGCAAGACGGTGTCGTGGCTCAACGAGCAG CTGGAGCTGGGCAACGAACGGCTTCTGCTGATGGACTGCCGACCACAGGAGCTGTACGAG TCGTCACACATCGAATCTGCCATTAATGTGGCCATCCCCGGCATCATGCTGCGGCGTCTG CAGAAGGGCAACCTGCCCGTGCGTGCGCTCTTCACGCGCTGCGAGGACCGGGACCGCTTT ACCAGGCGCTGCGGCACCGACACCGTGGTGCTGTACGACGAGAATAGCAGCGACTGGAAT GAGAACACTGGTGGAGAGTCGGTCCTCGGGCTGCTGCTCAAGAAACTCAAAGACGAGGGC TGCCGGGCGTTCTACCTGGAAGGTGGCTTCAGTAAGTTCCAGGCCGAGTTCGCCCTGCAC TGCGAGACCAATCTAGACGGCTCGTGCAGCAGCAGTTCCCCGCCTTTGCCAGTGCTGGGG CTCGGGGGCCTGCGGATCAGCTCGGACTCTTCCTCGGACATTGAGTCTGACCTTGACCGA GACCCCAATAGTGCAACGGACTCTGATGGCAGCCCGCTGTCCAACAGCCAGCCTTCCTTC CCGGTGGAGATTTTGCCCTTCCTTTACCTGGGCTGTGCCAAGGACTCGACCAACTTGGAC GTGTTGGAAGAGTTTGGCATCAAGTACATCTTGAATGTCACCCCCAATTTGCCCAATCTG TTTGAGAATGCGGGCGAGTTCAAATACAAGCAAATTCCTATCTCGGATCACTGGAGCCAA AACCTGTCCCAGTTTTTCCCTGAGGCCATTTCTTTCATAGATGAAGCCCGAGGCAAAAAC TGTGGTGTCCTGGTGCATTGCTTGGCAGGTATCAGCCGCTCTGTCACCGTGACAGTGGCG T AC C T CAT G C AGAAG C T C AAC C T GT C CAT GAAC GAT G C T T AC GAC AT T GT T AAGAT GAAG AAGTCCAACATCTCCCCCAACTTCAACTTCATGGGCCAGCTGCTTGACTTCGAAAGGACC CTGGGACTGAGCAGCCCTTGTGACAACCGTGTCCCCACTCCGCAGCTGTACTTCACCACG CCCTCCAACCAGAACGTCTACCAGGTGGACTCCCTGCAGTCTACGTGAAAGGCACCCACC TCTCCTAGCCGGGAGTTGTCCCCATTCCTTCAGTTCCTCTTGAGCAGCATCGACCAGGCT GCTTTCTTTCTGTGTGTGGCCCCGGGTGTCAAAAGTGTCACCAGCTGTCTGTGTTAGACA AGGTTGCCAAGTGCAAAATTGGTTATTACGGAGGGAGAGATTTGCTCCATTCATTGTTTT TTTGGAAGGACAGGACATGCTGTCTCTAGATCCAGCAATAGGTTTGCTTCTGTACCCCAG C C T AC C C AAG C AG G GAC T G GAC AT C CAT C C AGAT AGAG G GT AG CAT AG GAAT AG G GAC AG GAGCATCTGTTCTTTAAGGCCTTGTATGGCTGTTTCCTGTTGCATCTGGAACTAACTATA TATATTGTCTTCAGTGAAGACTGATTCAACTTTGGGTATAGTGGAGCCAAAGAGATTTTT AGCTCTGTATTTGCGGTATCGGTTTAGAAGACAAAAAAAATTAAAACCTGATACTTTTAT CTGATTATTGTAAATATTTGATCTTCAATCACTTGACAGTGTTTGTTTGGCTTGTATTTG TTTTTTATCTTTGGGCTTAAAAGAGATCCAAAGAGAGAAAGAGCAGTATGCCACTTCTTA GAACAAAAGTATAAGGAAAAAAATGTTCTTTTTAATCCAAAGGGTATATTTGCAGCATGC TTGACCTTGATGTACCAATTCTGACGGCATTTTCGTGGATATTATTATCACTAAGACTTT GTTATGATGAGGTCTTCAGTCTCTTTCATATATCTTCCTTGTAACTTTTTTTTTCCTCTT AATGTAGTTTTGACTCTGCCTTACCTTTGTAAATATTTGGCTTACAGTGTCTCAAGGGGT ATTTTGGAAAGACACCAAAATTGTGGGTTCACTTTTTTTTTTTTTTTAAATAACTTCAGC TGTGCTAAACAGCATATTACCTCTGTACAAAATTCTTCAGGGAGTGTCACCTCAAATGCA ATACTTTGGGTTGGTTTCTTTCCTTTTAAAAAAAAAATACGAAACTGGAAGTGTGTGTAT GTGTGCGAGTATGAGCGCCCATTTGGTGGATGCAACAGGTTGAGAGGAAGGGAGAATTAA CTTGCTCCATGATGTTCGTGGTGTAAAGTTTTGAGCTGGAATTTATTATAAGAATGTAAA

ACCTTAAATTATTAATAAATAACTATTTTGGCT

Dusp6 Mouse Protein

MIDTLRPVPFASEMAICKTVSWLNEQLELGNERLLLMDCRPQELYESSHIESAINVAIPG IMLRRLQKGNLPVRALFTRCEDRDRFTRRCGTDTWLYDENSSDWNENTGGESVLGLLLK KLKDEGCRAFYLEGGFSKFQAEFALHCETNLDGSCSSSSPPLPVLGLGGLRISSDSSSDI ESDLDRDPNSATDSDGSPLSNSQPSFPVEILPFLYLGCAKDSTNLDVLEEFGIKYILNVT PNLPNLFENAGEFKYKQIPISDHWSQNLSQFFPEAISFIDEARGKNCGVLVHCLAGISRS VTVTVAYLMQKLNLSMNDAYDIVKMKKSNISPNFNFMGQLLDFERTLGLSSPCDNRVPTP

QL YFTTP SNQN V YQ VD SLQ S T

Cdkl Human DNA

GGGGGGGGGGGGCACTTGGCTTCAAAGCTGGCTCTTGGAAATTGAGCGGAGACGAGCGGC TTGTTGTAGCTGCCGTGCGGCCGCCGCGGAATAATAAGCCGGGATCTACCATACCATTGA CTAACTATGGAAGATTATACCAAAATAGAGAAAATTGGAGAAGGTACCTATGGAGTTGTG TATAAGGGTAGACACAAAACTACAGGTCAAGTGGTAGCCATGAAAAAAATCAGACTAGAA AGTGAAGAGGAAGGGGTTCCTAGTACTGCAATTCGGGAAATTTCTCTATTAAAGGAACTT CGTCATCCAAATATAGTCAGTCTTCAGGATGTGCTTATGCAGGATTCCAGGTTATATCTC ATCTTTGAGTTTCTTTCCATGGATCTGAAGAAATACTTGGATTCTATCCCTCCTGGTCAG TACATGGATTCTTCACTTGTTAAGAGTTATTTATACCAAATCCTACAGGGGATTGTGTTT TGTCACTCTAGAAGAGTTCTTCACAGAGACTTAAAACCTCAAAATCTCTTGATTGATGAC AAAGGAACAATTAAACTGGCTGATTTTGGCCTTGCCAGAGCTTTTGGAATACCTATCAGA GTATATACACATGAGGTAGTAACACTCTGGTACAGATCTCCAGAAGTATTGCTGGGGTCA GCTCGTTACTCAACTCCAGTTGACATTTGGAGTATAGGCACCATATTTGCTGAACTAGCA ACTAAGAAACCACTTTTCCATGGGGATTCAGAAATTGATCAACTCTTCAGGATTTTCAGA GCTTTGGGCACTCCCAATAATGAAGTGTGGCCAGAAGTGGAATCTTTACAGGACTATAAG AATACATTTCCCAAATGGAAACCAGGAAGCCTAGCATCCCATGTCAAAAACTTGGATGAA AATGGCTTGGATTTGCTCTCGAAAATGTTAATCTATGATCCAGCCAAACGAATTTCTGGC AAAATGGCACTGAATCATCCATATTTTAATGATTTGGACAATCAGATTAAGAAGATGTAG

CTTTCTGACAAAAAGTTTCCATATGTTATG

Cdkl Mouse DNA

TCCGTCGTAACCTGTTGAGTAACTATGGAAGACTATATCAAAATAGAGAAAATTGGAGAA GGTACTTACGGTGTGGTGTATAAGGGTAGACACAGAGTCACTGGCCAGATAGTGGCCATG AAGAAGATCAGACTTGAAAGCGAGGAAGAAGGAGTGCCCAGTACTGCAATTCGGGAAATC TCTCTATTAAAAGAACTTCGACATCCAAATATAGTCAGCCTGCAGGATGTGCTCATGCAG GACTCCAGGCTGTATCTCATCTTTGAGTTCCTGTCCATGGACCTCAAGAAGTACCTGGAC TCCATCCCTCCTGGGCAGTTCATGGATTCTTCACTCGTTAAGAGTTACTTACACCAAATC CTCCAGGGAATTGTGTTTTGCCACTCCCGGCGAGTTCTTCACAGAGACTTGAAACCTCAA AATCTATTGATTGATGACAAAGGAACAATCAAACTGGCTGATTTCGGCCTTGCCAGAGCG TTTGGAATACCGATACGAGTGTACACACACGAGGTAGTGACGCTGTGGTACCGATCTCCA GAAGTGTTGCTGGGCTCGGCTCGTTACTCCACTCCGGTTGACATCTGGAGTATAGGGACC ATATTTGCAGAACTGGCCACCAAGAAGCCGCTTTTCCACGGCGACTCAGAGATTGACCAG CTCTTCAGGATCTTCAGAGCTCTGGGCACTCCTAACAACGAAGTGTGGCCAGAAGTCGAG TCCCTGCAGGACTACAAGAACACCTTTCCCAAGTGGAAGCCGGGGAGCCTCGCATCCCAC GTCAAGAACCTGGACGAGAACGGCTTGGATTTGCTCTCAAAAATGCTAGTCTATGATCCT GCCAAACGAATCTCTGGCAAAATGGCCCTGAAGCACCCGTACTTTGATGACTTGGACAAT CAGATTAAGAAGATGTAGCCCTCTGGATGGATGTCCCTGTCTGCTGGTCGTAGGGGAAGA

TCG Cdkl Mouse Protein

MEDYI KI EKI GEGTYGWYKGRHRVTGQIVAMKKI RLESEEEGVPSTAI REI SLLKELRH PNIVSLQDVLMQDSRLYLI FEFLSMDLKKYLDS I PPGQFMDS SLVKSYLHQI LQGIVFCH S RRVLHRDLKPQNLLI DDKGT I KLADFGLARAFGI P I RVYTHEWTLWYRS PEVLLGSAR YSTPVDIWS I GTI FAELATKKPLFHGDSEI DQLFRI FRALGTPNNEVWPEVESLQDYKNT

FPKWKPGSLASHVK LDENGLDLLSKMLVYDPAKRISGKMALKHPYFDDLD

NQIKKM

Fignll Human DNA

GTCAGTCCCCGCGCTTTTCGGAGGCTGCCAGCGTCCCACACCAGCCGCAGGTGAAAACCG G C AGAAAGAC AT T AAGAGAT T T T C C T G C AGT C AC T G C T G G C AGAT GAT AGAG C C AG GAT T TGAAAGCAGGCAGCCTGGCTCCAGACCCTGTGCTCTTAACTCCCGTTTTGCATCAAGAAC AGAAT C C TAT GAAAG G C T T GT AC AGT G C T T G GAT AG C AG CAT C AAG GAG CAT T GT GT AC A TGCAGAAGTGCACAGTACCTGGAGTGAAACTGCTTGTGTTCGATTTCTGATACCATTCAT AACTGGCTGTGTGATCTCAAAACCTCTAAAATGCAGACCTCCAGCTCTAGATCTGTGCAC C T GAGT GAAT G G C AGAAGAAT T AC T T C G C AAT T AC AT C T G G CAT AT GT AC C G GAC C GAAG G C AGAT G CAT AC C GT G C AC AGAT AT T AC G CAT T C AGT AT G CAT G G G C AAAC T C T GAGAT T T C C C AG GT CTGTGCTAC C AAAC T GT T C AAAAAAT AT G C AGAGAAAT AT T C T G C AAT TAT T GATTCTGACAATGTTGAATCTGGGTTGAATAATTATGCAGAAAACATTTTAACTTTGGCA GGAT CT CAACAAACAGATAGT GACAAGT GGCAGT CT GGATT GT CAATAAATAAT GTTTTC AAAAT GAGT AGT GT AC AGAAGAT GAT G C AAG C T G G C AAAAAAT T C AAAGAC TCTCTGTTG GAACCTGCTCTTGCATCAGTGGTAATCCATAAGGAGGCCACTGTCTTTGATCTTCCTAAA TTTAGTGTTTGTGGTAGTTCTCAAGAGAGTGACTCATTACCTAACTCAGCTCATGATCGA GACCGGACCCAAGACTTCCCGGAGAGCAATCGTTTGAAACTCCTTCAGAATGCCCAGCCA CCTATGGTGACTAACACTGCTAGGACTTGTCCTACATTCTCAGCACCTGTAGGTGAGTCA G C T AC T G C AAAAT T C CAT GT C AC AC CAT T GT T T G GAAAT GT C AAAAAG GAAAAT C AC AG C TCTGCAAAAGAAAACATAGGACTTAATGTGTTCTTATCTAACCAGTCTTGTTTTCCTGCT GCCTGTGAAAATCCACAGAGGAAGTCTTTTTATGGTTCTGGCACCATTGATGCACTTTCC AAT C C AAT AC T GAAT AAG G C T T GT AGT AAAAC AGAAGAT AAT G G C C C AAAG GAG GAT AG C AGCCTGCC T AC AT T T AAAAC T G C AAAAGAAC AAT TAT G G GT AGAT C AG C AAAAAAAGT AC CACCAACCTCAGCGTGCATCAGGGTCTTCATATGGTGGTGTAAAAAAGTCTCTAGGAGCT AGTAGATCCCGAGGGATACTTGGAAAGTTTGTTCCTCCTATACCCAAGCAAGATGGGGGA GAG C AGAAT G GAG GAAT G C AAT GT AAG C C T TAT G G G G C AG GAC C T AC AGAAC C AG C AC AT C C AGT T GAT GAG C GT C T GAAGAAC T T G GAG C C AAAGAT GAT T GAAC T TAT TAT GAAT GAG AT TAT G GAT CAT G GAC C T C C AGT AAAT T G G GAAGAT AT T G C AG GAGT AGAAT T T G C T AAA GCCACCATAAAGGAAATAGTTGTGTGGCCCATGTTGAGGCCAGACATCTTTACTGGTTTA AGGGGACCCCCTAAAGGAATTTTGCTCTTTGGTCCTCCTGGGACTGGTAAAACTCTAATT GGCAAGTGCATTGCTAGTCAGTCTGGGGCAACATTCTTTAGCATCTCTGCTTCATCCTTA ACTTCTAAATGGGTAGGTGAGGGGGAGAAAATGGTCCGTGCATTGTTTGCTGTTGCAAGG TGTCAGCAACCAGCTGTGATATTTATTGACGAAATTGATTCCTTGTTATCTCAACGGGGA GAT G GT GAG CAT GAAT C T T C TAGAAGGATAAAAAC AGAAT TTTTAGTT C AAT T AGAT G GA G C AAC AAC AT C T T C T GAAGAT C GT AT CCTAGTGGTGG GAG C AAC AAAT C G G C C AC AAGAA ATTGATGAGGCTGCCCGGAGAAGATTGGTGAAAAGGCTTTATATTCCCCTCCCAGAAGCT TCAGCCAGGAAACAGATAGTAATTAATCTAATGTCCAAAGAGCAGTGTTGCCTCAGTGAA GAAGAAAT T GAAC AGAT T GT AC AG C AGT C T GAT G C GT T T T C AG GAG C AGAC AT GAC AC AG CTTTGCAGGGGGGCTTCTCTTGGTCCTATTCGCAGTTTACAAACTGCTGACATTGCTACC AT AAC AC C G GAT C AAGT T C GAC C CAT AG C T T AC AT T GAT T T T GAAAAT G C T T T T AGAAC T GTGCGACCTAGTGTTTCTCCAAAAGATTTAGAGCTTTATGAAAACTGGAACAAAACTTTT GGTTGTGGAAAGTAAGTGGGATACTTGGAATCAAGGCATCTCTGTATTACAGTCTTCTTT AT T T T T T AG C AT AGAAAGT T G G G GAT GT GT T AAT T GT AT T T T T AAGAAT AT AT T C T AAAT

TCTGTACTTCAAATAATAGCACAGATTTTACATCTG

Fignll Mouse DNA

CATCGAGAAGTGTTCAGTGCCTGGTAAAGTACATAGACCTTGCTTCACTTGGAACTCGGC CTTGATTTCTGCCGTTGGTCATAATCAGCAGAGTTCTCTCTAAACCTTTGACATGGAGAC GTCCAGCTCCATGTCTGTGGAGACGACTAGGTCTGTGCAGGTGGACGAATGGCAGAAGAA TTACTGTGTGGTTACATCCAGCATATGTACACCAAAGCAGAAGGCCGATGCATACCGTGC ACTACTACTG CAT AT T C AGT AT G CAT AT G C C AAC T C C GAGAT C T C T C AG GT CTTTGCTAC C AAC C T GT T C AAAAG GT AT AC AGAAAAAT AC T C T G C AAT TAT T GAT T C T GAC AAT GT T GT AACTGGCTTGAATAACTATGCAGAGAGCATTTTTGCTTTGGCAGGATCTCGACAGGCTGA CAGT AACAAGT GGCAGT CT GGAT T GT CAAT AGAT AAT GT T T T C AAAAT GAGT T GT GT ACA GGAGAT GAT GCAGGCT GGCAAGAAATTT GAAGAGT CT CT GTT GGAACCT GCT GAT GCAT C AGTAGTCCTGTGTAAAGAGCCCACCGCCTTTGAGGTTCCTCAGCTTAGTGTTTGTGGAGG

T T C T GAAGAC G C T GAC AT AT TAT C CAGT T C AG GT CAT GAC AC AGAT AAGAC C C AAG C CAT TCCAGGGAGCAGTCTGAGATGTTCCCCTTTTCAGAGTGCTCGGCTGCCTAAGGAAACTAA T AC C AC T AAGAC AT G C C T C AC C T C C T C AAC AT CTTTAGGT GAGT C AG C C AC T G C AG CAT T T C AC AT GAC AC CAT TAT T T G GAAAC AC C GAAAAG GAC AC T C AAAG C T T T C C T AAAAC C AG CACAGGACTAAATATGTTCTTATCTAATCTGTCTTGTGTTCCTTCTGGCTGTGAAAACCC T C AAGAAAG GAAG G C T T T T AAT GAC T C T GAC AT CAT T GAC AT AC T T T C C AAT C C AAC AC T GAAC AAG G C T C C TAGT AAAAC AGAAGACAGAG G C C GAAG G GAAGAT AAT AG CCTGCCTAC C T T T AAAAC T G C AAAAGAAC AAT TAT G G GT AGAT C AAAAGAAAAAG G G C CAT C AAT C C C A GCATACATCTAAATCTTCTAATGGTGTTATGAAAAAGTCTCTGGGAGCTGGGAGGTCGAG AGGGATATTTGGCAAGTTTGTTCCTCCTGTATCTAATAAGCAAGACGGAAGTGAGCAGCA T G C C AAGAAG C AC AAGT C TAGT AG G GC AG G GT C T G C AGAAC C AG C AC AC C T C AC T GAT GA TTGTCTGAAGAACGTGGAGCCAAGGATGGTTGAACTTGTTATGAATGAAATTATGGACCA TGGGCCTCCAGTACATTGGGACGATATTGCTGGAGTAGAATTTGCCAAAGCCACAATAAA GGAAATCGTTGTGTGGCCCATGATGAGGCCAGATATCTTTACTGGATTGCGAGGGCCCCC TAAAGGAATTCTACTCTTTGGCCCTCCAGGGACTGGTAAAACTCTGATTGGCAAGTGCAT TGCTAGCCAGTCTGGAGCAACATTCTTCAGCATCTCTGCTTCATCGCTGACTTCTAAGTG GGTAGGTGAGGGAGAAAAAATGGTCCGTGCACTGTTTGCTGTTGCCAGGTGTCAGCAGCC AG C T GT CAT AT T TAT T GAT GAAAT T GAT T C T T TAT T GT C T C AAC GAG GAGAT G GT GAAC A T GAAT C T T C AAGAAG GAT AAAAAC G GAAT TTTTAGTT CAGT T AGAT G GAG C AAC C AC AT C TTCTGAAGACCGGATTCTTGTGGTGGGAGCTACAAATCGGCCCCAAGAGATTGATGAAGC TGCCCGGAGAAGATTGGTGAAAAGACTTTATATTCCCCTCCCAGAAGCTTCAGCCAGGAA ACAGATAGTAGGTAAT CTAAT GT CTAAGGAGCAAT GTT GT CT CAGT GAT GAAGAAACT GA TCTGGTAGTGCAGCAGTCTGATGGGTTTTCTGGCGCAGATATGACACAGCTTTGCAGAGA GGCTTCTCTTGGTCCTATTCGCAGTTTGCACGCTGCTGACATTGCTACCATAAGTCCAGA TCAAGTTCGACCAATAGCTTATATTGATTTTGAAAATGCTTTTAAAACTGTGCGACCTAC TGTATCTCCAAAAGACTTGGAGCTTTATGAAAACTGGAATGAAACATTTGGTTGTGGAAA GTGAATATAGCGATTGAAAGGAGAAGCTGTTATCTAGTAGTCGTCTTTACCTTTAGCCTC GGAAGCTTGCTGTGCTACTTGTATTGTTTTGGAGTATATCCTGAATTCTGTGCCTCAGAT

TAGAATGATAACAGCTTGACTACTGACTGATATATTAGTATGTTGTATTTG CC

Fignl 1 Mouse Protein

METS S SMSVETTRSVQVDEWQKNYCWTS S I CTPKQKADAYRALLLHIQYAYANSEI SQV FATNLFKRYTEKYSAI I DSDNWTGLNNYAES I FALAGSRQADSNKWQSGLS I DNVFKMS CVQEMMQAGKKFEESLLEPADASWLCKEPTAFEVPQLSVCGGSEDADI LS S SGHDTDKT QAI PGS SLRCS PFQSARLPKETNTTKTCLTS STSLGESATAAFHMTPLFGNTEKDTQS FP KTSTGLNMFLSNLSCVPSGCENPQERKAFNDSDI I DI LSNPTLNKAPSKTEDRGRREDNS LPTFKTAKEQLWVDQKKKGHQSQHTSKS SNGVMKKSLGAGRSRGI FGKFVPPVSNKQDGS EQHAKKHKS SRAGSAEPAHLTDDCLKNVEPRMVELIMNEIMDHGPPVHWDDIAGVEFAKA TI KEIWWPMMRPDI FTGLRGPPKGILLFGPPGTGKTLI GKCIASQSGATFFS I SAS SLT SKWVGEGEKMVRALFAVARCQQPAVI FI DEI DSLLSQRGDGEHES SRRI KTEFLVQLDGA TTS SEDRI LWGATNRPQEI DEAARRRLVKRLYI PLPEASARKQIVGNLMSKEQCCLSDE ETDLWQQSDGFSGADMTQLCREASLGPI RSLHAADIATI S PDQVRPIAYI DFENAFKTV

RPTVSPKDLELYENW ETFGCGK

Plk2 Human DNA

GCGCGCGGCTCCGATGGGAAGCATGACCCGGGTGGCGGGACAAGACTTGCTTCCCGGCCA CGCGCGCTCGGCCGGCCGTGGGGCGGGGCATAGGCGTGACGTGGTGTCGCGTATCGAGTC TCCGCCCCCTTCCCGCCTCCCCGTATATAAGACTTCGCCGAGCACTCTCACTCGCACAAG TGGACCGGGGTGTTGGGTGCTAGTCGGCACCAGAGGCAAGGGTGCGAGGACCACGGCCGG CTCGGACGTGTGACCGCGCCTAGGGGGTGGCAGCGGGCAGTGCGGGGCGGCAAGGCGACC ATGGARCTTTTGCGGACTATCACCTACCAGCCAGCCGCCAGCACCAAAATGTGCGAGCAG GCGCTGGGCAAGGGTTGCGGAGGGGACTCGAAGAAGAAGCGGCCGCCGCAGCCCCCCGAG GAATCGCAGCCACCTCAGTCCCAGGCGCAAGTGCCCCCGGCGGCCCCTCACCACCATCAC CACCATTCGCACTCGGGGCCGGAGATCTCGCGGATTATCGTCGACCCCACGACTGGGAAG CGCTACTGCCGGGGCAAAGTGCTGGGAAAGGGTGGCTTTGCAAAATGTTACGAGATGACA GAT T T GAC AAAT AAC AAAGT CTACGCCG C AAAAAT TAT T C C T C AC AG C AGAGT AG C T AAA C C T CAT C AAAG G GAAAAGAT T GAC AAAGAAAT AGAG C T T C AC AGAAT T C T T CAT CAT AAG CAT GT AGT G CAGT T T T AC C AC T AC T T C GAG GAC AAAGAAAAC AT T T AC AT T C T C T T G GAA T AC T G C AGT AGAAG GT C AAT G G C T CAT AT T T T GAAAG C AAGAAAG GT GTT GAC AGAG C C A GAAGT T C GAT AC T AC C T C AG G C AGAT TGTGTCTG GAC T GAAAT AC C T T CAT GAAC AAGAA AT C T T G C AC AGAGAT C T C AAAC T AG GGAAC τ T TT T TAT T AAT GAAG C CAT G GAAC T AAAA GTTGGGGACTTCGGTCTGGCAGCCAGGCTAGAACCCYTGGAACACAGAAGGAGAACGATA TGTGGTACCCCAAATTATCTCTCTCCTGAAGTCCTCAACAAACAAGGACATGGCTGTGAA TCAGACATTTGGGCCCTGGGCTGTGTAATGTATACAATGTTACTAGGGAGGCCCCCATTT GAAAC T AC AAAT C T C AAAGAAAC T T AT AG GT G C AT AAG G GAAG C AAG GT AT AC AAT G C C G TCCTCATTGCTGGCTCCTGCCAAGCACTTAATTGCTAGTATGTTGTCCAAAAACCCAGAG GATCGTCCCAGTTTGGATGACATCATTCGACATGACTTTTTTTTGCAGGGCTTCACTCCG GACAGACTGTCTTCTAGCTGTTGTCATACAGTTCCAGATTTCCACTTATCAAGCCCAGCT AAGAATTTCTTTAAGAAAGCAGCTGCTGCTCTTTTTGGTGGCAAAAAAGACAAAGCAAGA TAT AT T GACACACAT AAT AGAGT GT CTAAAGAAGAT GAAGAC AT C T AC AAG C T T AG G CAT GAT T T GAAAAAGAC T T C AAT AAC T C AG C AAC C C AG C AAAC AC AG GAC AGAT GAG GAG C T C C AG C C AC C T AC C AC C AC AGT T G C C AGGT C T G GAAC AC C C G C AGT AGAAAAC AAG C AG C AG ATTGGGGATGCTATTCGGATGATAGTCAGAGGGACTCTTGGCAGCTGTAGCAGCAGCAGT GAATGCCTTGAAGACAGTACCATGGGAAGTGTTGCAGACACAGTGGCAAGGGTTCTTCGG GGATGTCTGGAAAACATGCCGGAAGCTGATTGCATTCCCAAAGAGCAGCTGAGCACATCA TTTCAGTGGGTCACCAAATGGGTTGATTACTCTAACAAATATGGCTTTGGGTACCAGCTC TCAGACCACACCGTCGGTGTCCTTTTCAACAATGGTGCTCACATGAGCCTCCTTCCAGAC AAAAAAAC AGT T C AC TAT T AC G C AGAG C T T G G C C AAT G C T C AGT T T T C C C AG C AAC AGAT GCTCCTGAGCAATTTATTAGTCAAGTGACGGTGCTGAAATACTTTTCTCATTACATGGAG GAGAACCTCATGGATGGTGGAGATCTGCCTAGTGTTACTGATATTCGAAGACCTCGGCTC TACCTCCTTCAGTGGCTAAAATCTGATAAGGCCCTAATGATGCTCTTTAATGATGGCACC T T T C AG GT GAAT T T C T AC CAT GAT C AT AC AAAAAT CAT CAT C T GT AG C CAAAAT GAAGAA TACCTTCT C AC C T AC AT C AAT GAG GAT AG GAT AT C T AC AAC T T T C AG G C T GAC AAC T C T G CTGATGTCTGGCTGTTCATCAGAATTAAAAAATCGAATGGAATATGCCCTGAACATGCTC TTACAAAGATGTAACTGAAAGACTTTTCGAATGGACCCTATGGGACTCCTCTTTTCCACT GT GAGAT C T AC AG G GAAG C C AAAAGAAT GAT CTAGAGTAT GTT GAAGAAGAT GGACAT GT GGTGGTACGAAAACAATTCCCCTGTGGCCTGCTGGACTGGGTGGAACCCAGAACCAGGCT AAGGCATACAGTTCTTGACTTTGGACAATCCCAAGAGTGAACCAGAATGCAGTTTTCCTT GAGATACCTGTTTTAAAAGGTTTTTCAGACAATTTTGCAGAAAGGTGCATTGATTCTTAA ATTCTCTCTGTTGAGAGCATTTCAGCCAGAGGACTTTGGAACTGTGAATATACTTCCTGA AGGGGAGGGAGAAGGGAGGAAGCTCCCATGTTGTTTAAAGGCTGTAATTGGAGCAGCTTT TGGCTGCGTAACTGTGAACTATGGCCATATATAATTTTTTTTCATTAATTTTTGAAGATA CTTGTGGCTGGAAAAGTGCATTCCTTGTTAATAAACTTTTTATTTATTACAGCCCAAAGA GCAGTATTTATTATCAAAATGTCTTTTTTTTTATGTTGACCATTTTAAACCGTTGGCAAT

AAAGAGTATGAAAACGCAAAAAAAAAAAAAAA

Plk2 Mouse DNA

CGTAGGGAGAGAGACTGGTGCTCGAGGGACAGGGCTAGCCCGGACGCGTGTCCGCGCCTC GGAGGTGGCAAGTAGGCAGTGTCGGGTGGCGAGGCAACGATGGAGCTCCTGCGGACTATC ACCTACCAGCCGGCCGCCGGCACCAAGATGTGCGAGCAGGCTCTGGGCAAAGCTTGCGGC GGGGACTCAAAGAAGAAGCGACCACAGCAGCCTTCTGAAGATGGGCAGCCCCAAGCCCAG GTGACCCCGGCGGCCCCGCACCACCATCACCACCATTCCCACTCGGGACCCGAGATCTCG CGGATTATAGTCGACCCCACGACGGGGAAGCGCTACTGCCGGGGCAAAGTGCTGGGCAAG G GT G GAT T T G C AAAGT GT T AC GAAAT GAC AGAT C T GAC AAAC AAC AAAGT CTACGCTG C A AAAAT TAT T C C T C AC AG C AGAGT AG CT AAAC C T CAT C AGAG G GAAAAGAT C GAC AAAGAA AT C GAG C T T C AC AGAC T AC T G C AC CAT AAG CAT GT C GT G C AGT T T T AC C AC T AC T T T GAA GAC AAAGAAAAC AT T T AC AT T C T C T T G GAAT AC T G C AGT AGAAG GT C CAT G G C T C AC AT C T T GAAAG C AAGAAAG GT GTT GAC AGAG C C AGAAGT C C GAT AC T AC C T C AG G C AGAT T GT G T CAGGACT CAAGTAT CTT CACGAACAAGAAAT CTT GCACAGGGAT CT CAAGCTAGGGAAC TTTTTTATTAATGAAGCCATGGAGCTGAAGGTGGGAGACTTTGGTTTGGCAGCCAGACTG GAAC C AC T G GAAC AC AGAAG GAGAACAAT AT GT G GAAC C C C AAAT TAT CTCTCCCCC GAA GTCCTCAACAAACAAGGACACGGCTGTGAATCAGACATCTGGGCCTTAGGCTGTGTAATG TAT AC GAT GCTGCTAG GAAGAC C T C CAT T C GAAAC C AC AAAT C T GAAAGAAAC GT AC AG G TGCATAAGGGAAGCAAGGTATACCATGCCGTCCTCATTGCTGGCCCCTGCTAAGCACTTG ATAGCTAGCATGCTGTCCAAAAACCCAGAGGACCGCCCCAGTTTGGATGACATCATTCGG CATGACTTCTTCCTGCAGGGTTTCACTCCGGACAGACTCTCTTCCAGCTGTTGCCACACA GTTCCAGATTTCCACTTGTCAAGCCCAGCCAAGAATTTCTTTAAGAAAGCCGCAGCCGCT CTTTTTGGTGG C AAGAAG GAC AAAG CAAGAT AT AAC GAC AC AC AC AAT AAG GT GT C T AAG GAAGAT GAAGAC AT T T AC AAG C T T C GG C AT GAT T T GAAGAAAGT GT C GAT AAC C C AG C AG C C T AG C AAAC AC AGAG C AGAC GAG GAG C C C C AG CCGCCTCC C AC TACTGTTGC C AGAT C T G GAAC GT C C G C AGT G GAAAAC AAAC AG C AGAT T G G G GAT G C AAT C C G GAT GAT AGT C AG G GGGACTCTCGGCAGCTGCAGCAGCAGCAGCGAATGCCTTGAAGACAGCACCATGGGAAGT GT T G C AGAC AC AGT G G C AAGAGT C C T T C GAG GAT GT C T AGAAAAC AT G C C G GAAG C T GAC TGTATCCCCAAAGAGCAGCTGAGCACGTCCTTTCAGTGGGTCACCAAGTGGGTCGACTAC TCCAACAAATATGGCTTTGGGTACCAGCTCTCGGACCACACTGTTGGCGTCCTTTTCAAC AACGGGGCTCACATGAGCCTCCTTCCGGACAAAAAGACAGTTCACTATTATGCGGAACTT GGCCAATGCTCTGTTTTCCCAGCAACAGATGCCCCTGAACAATTTATTAGTCAAGTGACG GTGCTGAAATACTTTTCTCATTACATGGAGGAGAACCTCATGGATGGTGGTGATCTCCCG AGTGTTACTGACATTCGAAGACCTCGGCTCTACCTCCTGCAGTGGTTAAAGTCTGATAAA G C C T T AAT GAT G C T C T T C AAT GAC G GC AC AT T T C AG GT GAAT T T C T AC C AC GAT CAT AC A AAAAT CAT CAT CT GTAACCAGAGT GAAGAAT AC C T T C T C AC C T AC AT CAAT GAGGACAGG ATCTCTACAACTTTCAGACTGACGACTCTGCTGATGTCTGGCTGTTCGTTAGAATTGAAA AAT C GAAT G GAAT AT G C C C T GAAC AT G C T C T T AC AGAGAT GT AAC T GAAAAC AT TAT TAT TATTATTATTATAATTATTTCGAGCGGACCTCATGGGACTCTTTTCCACTGTGAGATCAA CAGGGAAGCCAGCGGAAAGATACAGAGCATGTTAGAGAAGTCGGACAGGTGGTGGTACGA ATACAATTCCTCTGTGGCCTGCTGGACTGCTGGAACCAGACCAGCCTAAGGTGTAGAGTT GACTTTGGACAATCCTGAGTGTGGAGCCGAGTGCAGTTTTCCCTGAGATACCTGTCGTGA AAAGGTTTATGGGACAGTTTTTCAGAAAGATGCATTGACTCTGAAGTTCTCTCTGTTGAG AGCGTCTTCAGTTGGAAGACTTGGAACTGTGAATACACTTCCTGAAGGGGAGGGAGAAGG GAGGTTGCTCCCTTGCTGTTTAAAGGCTACAATCAGAGCAGCTTTTGGCTGCTTAACTGT GAACTATGGCCATACATTTTTTTTTTTTTTGGTTATTTTTGAATACACTTGTGGTTGGAA AAGT G CAT T C C T T GT T AAT AAAC T T T T TAT T TAT T AC AG C C C C AAGAG C AGT AT T TAT T A TCAAGATGTTCTCTTTTTTTATGTTGACCATTTCAAACTCTTGGCAATAAAGAGTATGAC

ATAGAAAAAAAA

Plk2 Mouse Protein

MELLRTITYQPAAGTKMCEQALGKACGGDSKKKRPQQPSEDGQPQAQVTPAAPHHHHHHS HSGPEI SRI IVDPTTGKRYCRGKVLGKGGFAKCYEMTDLTNNKVYAAKI I PHSRVAKPHQ REKI DKEI ELHRLLHHKHWQFYHYFEDKENIYI LLEYCSRRSMAHI LKARKVLTEPEVR YYLRQIVSGLKYLHEQEI LHRDLKLGNFFINEAMELKVGDFGLAARLEPLEHRRRTI CGT PNYLS PEVLNKQGHGCESDIWALGCVMYTMLLGRPPFETTNLKETYRCI REARYTMPS SL LAPAKHLIASMLSKNPEDRPSLDDI IRHDFFLQGFTPDRLS S SCCHTVPDFHLS S PAKNF FKKAAAALFGGKKDKARYNDTHNKVSKEDEDIYKLRHDLKKVS ITQQPSKHRADEEPQPP PTTVARSGTSAVENKQQI GDAI RMIVRGTLGSCS S S SECLEDSTMGSVADTVARVLRGCL ENMPEADCI PKEQLSTS FQWVTKWVDYSNKYGFGYQLSDHTVGVLFNNGAHMSLLPDKKT VHYYAELGQCSVFPATDAPEQFI SQVTVLKYFSHYMEENLMDGGDLPSVTDI RRPRLYLL QWLKSDKALMMLFNDGTFQ FYHDHTKI I I CNQSEEYLLTYINEDRI STTFRLTTLLMS

GC SLELK RMEYAL MLLQRCN

Rsad2 Human DNA

C AG GAAG G G C CAT GAAGAT T AAT AAAGAT T T G GAC T C AG G G C AAAT AT TTACTTAGTAGC AAT AAC T C AAAGAAT T AC T GT T GAAT AAAT AAG C CAAT T AAG C AG C CAAT C AC GT AC TAT G C G GAT G C AC AC AAAT GAAAC C C T C AC T T C AAC C T GAAGAC AT T C G C AC AT GAGT T AC GT AGAG G GAC C T G C AG GAAG C G GT AGAGAAAAC AT AAG G C T TAT G C GT T T AAT T T C C AC AC C AAT T T C AG GAT C T T T GT C AC T GAC AGC AG C AC T AAGAC T T GT T AAC T T TAT AT AGT T AAG AAGAACAAGGCTGAGCGCGATGACTCACGCCTGTAAGCCTAGAACTTTGGGAGGCCAAAG CAGGCAGACTGCTTGAGCCCAGGAGTTCCAGACCAGCCTGGGCAACATGGCAACACCCCA T CT CTACAAAAAAATACAAGAAT CAGCT GGGCGT GGT GAT GT GTT CCT GTAAT CT CAGCT ACTCGGGAGGCAGAGGCAGGAGGATTGCTTGAACCCGGGAGGCAGAGGTTGTAGTTAGCC GAGAT C T C G C C AC T G C AC T C C AGT C T G GAC GAC AGAGT GAGAC T C AGT C T C AAAT AAAT A AAT AAAT ACAT AAAT AT AAGGAAAAAAATAAAGCTGCTTTCTCCTCTTCCTCCTCTTTGG TCTCATCTGGCTCTGCTCCAGGCATCTGCCACAATGTGGGTGCTTACACCTGCTGCTTTT GCTGGGAAGTTCTTGAGTGTGTTCAGGCAACCTCTGAGCTCTCTGTGGAGGAGCCTGGTC CCGCTGTTCTGCTGGCTGAGGGCAACCTTCTGGCTGCTAGCTACCAAGAGGAGAAAGCAG CAGCTGGTCCTGAGAGGGCCAGATGAGACCAAAGAGGAGGAAGAGGACCCTCCTCTGCCC ACCACCCCAACCAGCGTCAACTATCACTTCACTCGCCAGTGCAACTACAAATGCGGCTTC TGTTTCCACACAGCCAAAACATCCTTTGTGCTGCCCCTTGAGGAAGCAAAGAGAGGATTG CTTTTGCTTAAGGAAGCTGGTATGGAGAAGATCAACTTTTCAGGTGGAGAGCCATTTCTT CAAGACCGGGGAGAATACCTGGGCAAGTTGGTGAGGTTCTGCAAAGTAGAGTTGCGGCTG CCCAGCGTGAGCATCGTGAGCAATGGAAGCCTGATCCGGGAGAGGTGGTTCCAGAATTAT GGTGAGTATTTGGACATTCTCGCTATCTCCTGTGACAGCTTTGACGAGGAAGTCAATGTC CTTATTGGCCGTGGCCAAGGAAAGAAGAACCATGTGGAAAACCTTCAAAAGCTGAGGAGG TGGTGTAGGGATTATAGAATCCCTTTCAAGATAAATTCTGTCATTAATCGTTTCAACGTG GAAGAG GAC AT GAC G GAAC AGAT C AAAG C AC T AAAC CCTGTCCGCTG GAAAGT GT T C C AG TGCCTCTTAATTGAAGGTGAGAATTGTGGAGAAGATGCTCTAAGAGAAGCAGAAAGATTT

GTTATTGGTGATGAAGAATTTGAAAGATTCTTGGAGCGCCACAAAGAAGTGTCCTGC TTG GTGCCTGAATCTAACCAGAAGATGAAAGACTCCTACCTTATTCTGGATGAATATATGCGC TTTCTGAACTGTAGAAAGGGACGGAAGGACCCTTCCAAGTCCATCCTGGATGTTGGTGTA GAAGAAGCTATAAAATTCAGTGGATTTGATGAAAAGATGTTTCTGAAGCGAGGAGGAAAA TACATATGGAGTAAGGCTGATCTGAAGCTGGATTGGTAGAGCGGAAAGTGGAACGAGACT TCAACACACCAGTGGGAAAACTCCTAGAGTAACTGCCATTGTCTGCAATACTATCCCGTT GGTATTTCCCAGTGGCTGAAAACCTGATTTTCTGCTGCACGTGGCATCTGATTACCTGTG GTCACTGAACACACGAATAACTTGGATAGCAAATCCTGAGACAATGGAAAACCATTAACT TTACTTCATTGGCTTATAACCTTGTTGTTATTGAAACAGCACTTCTGTTTTTGAGTTTGT TTTAGCTAAAAAGAAGGAATACACACAGGAATAATGACCCCAAAAATGCTTAGATAAGGC CCCTATACACAGGACCTGACATTTAGCTCAATGATGCGTTTGTAAGAAATAAGCTCTAGT GATATCTGTGGGGGCAATATTTAATTTGGATTTGATTTTTTAAAACAATGTTTACTGCGA TTTCTATATTTCCATTTTGAAACTATTTCTTGTTCCAGGTTTGTTCATTTGACAGAGTCA GTATTTTTTGCCAAATATCCAGATAACCAGTTTTCACATCTGAGACATTACAAAGTATCT GCCTCAATTATTTCTGCTGGTTATAATGCTTTTTTTTTTTTTTGCTTTTATGCCATTGCA GTCTTGTACTTTTTACTGTGATGTACAGAAATAGTCAACAGATGTTTCCAAGAACATATG ATATGATAATCCTACCAATTTTCAAGAAGTCTCTAGAAAGAGATAACACATGGAAAGACG GCGTGGTGCAGCCCAGCCCACGGTGCCTGTTCCATGAATGCTGGCTACCTATGTGTGTGG TACCTGTTGTGTCCCTTTCTCTTCAAAGATCCCTGAGCAAAACAAAGATACGCTTTCCAT TTGATGATGGAGTTGACATGGAGGCAGTGCTTGCATTGCTTTGTTCGCCTATCATCTGGC CACATGAGGCTGTCAAGCAAAAGAATAGGAGTGTAGTTGAGTAGCTGGTTGGCCCTACAT TTCTGAGAAGTGACGTTACACTGGGTTGGCATAAGATATCCTAAAATCACGCTGGAACCT TGGGCAAGGAAGAATGTGAGCAAGAGTAGAGAGAGTGCCTGGATTTCATGTCAGTGAAGC CATGTCACCATATCATATTTTTGAATGAACTCTGAGTCAGTTGAAATAGGGTACCATCTA GGTCAGTTTAAGAAGAGTCAGCTCAGAGAAAGCAAGCATAAGGGAAAATGTCACGTAAAC TAGATCAGGGAACAAAATCCTCTCCTTGTGGAAATATCCCATGCAGTTTGTTGATACAAC TTAGTATCTTATTGCCTAAAAAAAAATTTCTTATCATTGTTTCAAAAAAGCAAAATCATG GAAAATTTTTGTTGTCCAGGCAAATAAAAGGTCATTTTAATTTAAAAAAAAAAAAAAAAA

AAAAAAAAAAAAAAAGGCCA

Rsad2 Mouse DNA

CCTATCACCATGGGGATGCTGGTGCCCACTGCTCTAGCTGCTCGGCTGCTGAGCCTGTTC CAGCAGCAGCTGGGTTCCCTCTGGAGTGGCCTGGCCATCCTGTTCTGCTGGCTGAGAATA GCATTAGGGTGGCTAGATCCCGGGAAGGAACAGCCACAGGTCCGGGGTGAGCTGGAGGAG ACCCAGGAGACCCAGGAAGATGGGAACAGCACTCAGCGCACAACCCCCGTGAGTGTCAAC TACCACTTCACTCGTCAGTGCAACTACAAATGTGGCTTCTGCTTCCACACAGCCAAGACA TCCTTCGTGCTGCCCCTGGAGGAGGCCAAGCGAGGACTGCTTCTGCTCAAACAGGCTGGT TTGGAGAAGATCAACTTTTCTGGAGGAGAACCCTTCCTTCAGGACAGGGGTGAATACTTG GGCAAGCTTGTGAGATTCTGCAAGGAGGAGCTAGCCCTGCCCTCTGTGAGCATAGTGAGC AATGGCAGCCTTATCCAGGAGAGATGGTTCAAGGACTATGGGGAGTATTTGGACATTCTT GCTATCTCCTGCGACAGCTTCGATGAGCAGGTTAATGCTCTGATTGGCCGTGGTCAAGGA AAAAAGAACCACGTGGAAAACCTTCAAAAGCTGAGGAGGTGGTGCAGGGATTACAAGGTG GCTTTCAAGATCAACTCTGTCATTAATCGCTTCAACGTGGACGAAGACATGAATGAACAC ATCAAGGCCCTGAGCCCTGTGCGCTGGAAGGTTTTCCAGTGCCTCCTAATTGAGGGTGAG AACTCAGGAGAAGATGCCCTGAGGGAAGCAGAAAGATTTCTTATAAGCAATGAAGAATTT GAAACATTCTTGGAGCGTCACAAAGAGGTGTCCTGTTTGGTGCCTGAATCTAACCAGAAG ATGAAAGACTCCTACCTTATCCTAGATGAATATATGCGCTTTCTGAACTGTACCGGTGGC CGGAAGGACCCTTCCAAGTCTATTCTGGATGTTGGCGTGGAAGAAGCAATAAAGTTCAGT GGATTTGATGAGAAGATGTTTCTGAAGCGTGGCGGAAAGTATGTGTGGAGTAAAGCTGAC CTGAAGCTGGACTGGTGAGGCTGAGATGGGAAGGAAACTCCGACCAGCTACAGGGACATT

CACGCCCAGCTATCCTTCAACAAGCTACATCTTCTGGCTGTCTACAGACTG TTGTT

Rsad2 Mouse Protein

MGMLVPTALAARLLSLFQQQLGSLWSGLAILFCWLRIALGWLDPGKEQPQVRGEPEDTQE TQEDGNSTQPTTPVS YHFTRQCNYKCGFCFHTAKTSFVLPLEEAKRGLLLLKQAGLEK INFSGGEPFLQDRGEYLGKLVRFCKEELALPSVSIVSNGSLIRERWFKDYGEYLDILAIS CDSFDEQ ALIGRGQGKKNHVENLQKLRRWCRDYKVAFKINSVINRFNVDEDMNEHIKA LSPVRWKVFQCLLIEGENSGEDALREAERFLISNEEFETFLERHKEVSCLVPESNQKMKD SYLILDEYMRFLNCTGGRKDPSKSILDVGVEEAIKFSGFDEKMFLKRGGKYVWSKADLKL

DW Sgkl Human DNA

CACGAGGGAGCGCTAACGTCTTTCTGTCTCCCCGCGGTGGTGATGACGGTGAAAACTGAG GCTGCTAAGGGCACCCTCACTTACTCCAGGATGAGGGGCATGGTGGCAATTCTCATCGCT T T CAT GAAG C AGAG GAG GAT G G GT C T GAAC GAC T T TAT T C AGAAGAT T G C C AAT AAC T C C TATGCATGCAAACACCCTGAAGTTCAGTCCATCTTGAAGATCTCCCAACCTCAGGAGCCT GAGCTTATGAATGCCAACCCTTCTCCTCCACCAAGTCCTTCTCAGCAAATCAACCTTGGC CCGTCGTCCAATCCTCATGCTAAACCATCTGACTTTCACTTCTTGAAAGTGATCGGAAAG GGCAGTTTTGGAAAGGTTCTTCTAGCAAGACACAAGGCAGAAGAAGTGTTCTATGCAGTC AAAGT T T T AC AGAAGAAAG C AAT C C T GAAAAAGAAAGAG GAGAAG CAT AT TAT GT C G GAG CGGAATGTTCTGTTGAAGAATGTGAAGCACCCTTTCCTGGTGGGCCTTCACTTCTCTTTC CAGACTGCTGACAAATTGTACTTTGTCCTAGACTACATTAATGGTGGAGAGTTGTTCTAC CATCTCCAGAGGGAACGCTGCTTCCTGGAACCACGGGCTCGTTTCTATGCTGCTGAAATA GCCAGTGCCTTGGGCTACCTGCATTCACTGAACATCGTTTATAGAGACTTAAAACCAGAG AATATTTTGCTAGATTCACAGGGACACATTGTCCTTACTGATTTCGGACTCTGCAAGGAG AAC AT T GAAC AC AAC AG C AC AAC AT C C AC CTTCTGTGG C AC G C C G GAGT AT C T C G C AC C T GAGGTGCTTCATAAGCAGCCTTATGACAGGACTGTGGACTGGTGGTGCCTGGGAGCTGTC TTGTATGAGATGCTGTATGGCCTGCCGCCTTTTTATAGCCGAAACACAGCTGAAATGTAC GAC AAC AT T C T GAAC AAG C C T C T C C AG C T GAAAC C AAAT AT T AC AAAT T C C G C AAGAC AC CTCCTGGAGGGCCTCCTGCAGAAGGACAGGACAAAGCGGCTCGGGGCCAAGGATGACTTC ATGGAGATTAAGAGTCATGTCTTCTTCTCCTTAATTAACTGGGATGATCTCATTAATAAG AAGATTACTCCCCCTTTTAACCCAAATGTGAGTGGGCCCAACGAGCTACGGCACTTTGAC CCCGAGTTTACCGAAGAGCCTGTCCCCAACTCCATTGGCAAGTCCCCTGACAGCGTCCTC GTCACAGCCAGCGTCAAGGAAGCTGCCGAGGCTTTCCTAGGCTTTTCCTATGCGCCTCCC ACGGACTCTTTCCTCTGAACCCTGTTAGGGCTTGGTTTTAAAGGATTTTATGTGTGTTTC CGAATGTTTTAGTTAGCCTTTTGGTGGAGCCGCCAGCTGACAGGACATCTTACAAGAGAA TTTGCACATCTCTGGAAGCTTAGCAATCTTATTGCACACTGTTCGCTGGAATTTTTTGAA GAGCACATTCTCCTCAGTGAGCTCATGAGGTTTTCATTTTTATTCTTCCTTCCAACGTGG TGCTATCTCTGAAACGAGCGTTAGAGTGCCGCCTTAGACGGAGGCAGGAGTTTCGTTAGA AAGCGGACCTGTTCTAAAAAAGGTCTCCTGCAGATCTGTCTGGGCTGTGATGACGAATAT TATGAAATGTGCCTTTTCTGAAGAGATTGTGTTAGCTCCAAAGCTTTTCCTATCGCAGTG TTTCAGTTCTTTATTTTCCCTTGTGGATATGCTGTGTGAACCGTCGTGTGAGTGTGGTAT G C C T GAT C AC AGAT G GAT T T T GT TAT AAG CAT C AAT GT GAC AC T T G C AG GAC AC T AC AAC GTGGGACATTGTTTGTTTCTTCCATATTTGGAAGATAAATTTATGTGTAGACTTTTTTGT AAGAT AC G GT T AAT AAC T AAAAT T TAT T GAAAT G GT C T T G C AAT GAC T C GT AT T C AGAT G CCTAAAGAAAGCATTGCTGCTACAAATATTTCTATTTTTAGAAAGGGTTTTTATGGACCA ATGCCCCAGTTGTCAGTCAGAGCCGTTGGTGTTTTTCATTGTTTAAAATGTCACCTGTAA AATGGGCATTATTTATGTTTTTTTTTTTGCATTCCTGATAATTGTATGTATTGTATAAAG AACGTCTGTACATTGGGTTATAACACTAGTATATTTAAACTTACAGGCTTATTTGTAATG TAAAC C AC CAT T T T AAT GT AC T GT AAT T AAC AT G GT TAT AAT AC GT AC AAT CCTTCCCTC ATCCCATCACACAACTTTTTTTGTGTGTGATAAACTGATTTTGGTTTGCAATAAAACCTT

GAAAAATAAAAAAAAAAAAAAAAAAAAAAA

Sgkl Mouse DNA

ACCCACGCGTCCGGCCGGTTTCACTGCTCCCCTCAGTCTCTTTTGGGCTCTTTCCGGGCA TCGGGACGATGACCGTCAAAGCCGAGGCTGCTCGAAGCACCCTTACCTACTCCAGAATGA GGGGAATGGTAGCGATTCTCATCGCTTTTATGAAACAGAGAAGGATGGGCCTGAACGATT T TAT T C AGAAGAT T G C C AG C AAC AC CT AT G CAT G C AAAC AC G C T GAAGT T C AGT C CAT T T TGAAAATGTCCCATCCTCAGGAGCCGGAGCTTATGAACGCTAACCCCTCTCCTCCGCCAA GTCCCTCTCAACAAATCAACCTGGGTCCGTCCTCCAACCCTCACGCCAAACCCTCCGACT TTCACTTCTTGAAAGTGATCGGAAAGGGCAGTTTTGGAAAGGTTCTTCTGGCTAGGCACA AG G C AGAAGAAGT AT T C TAT G C AGT CAAAGT T T T AC AGAAGAAAG C CAT C C T GAAGAAGA AAGAGGAGAAGCATATTATGTCAGAGCGGAATGTTCTGTTGAAGAATGTGAAGCACCCTT TCCTGGTGGGCCTTCACTTCTCATTCCAGACCGCTGACAAACTCTACTTTGTCCTGGACT ACATTAATGGTGGAGAGCTGTTCTACCATCTCCAGAGGGAGCGCTGCTTCCTGGAACCAC GGGCTCGATTCTACGCAGCTGAAATAGCCAGTGCCTTGGGCTATCTGCACTCCCTAAACA TCGTTTATAGAGACTTAAAACCTGAGAATATTCTCCTAGACTCCCAGGGGCACATCGTCC TCACTGACTTTGGGCTCTGCAAAGAGAATATTGAGCATAACGGGACAACATCTACCTTCT GTGGCACGCCTGAGTATCTGGCTCCTGAGGTCCTCCATAAGCAGCCGTATGACCGGACGG TGGACTGGTGGTGTCTTGGGGCTGTCCTGTATGAGATGCTCTACGGCCTGCCCCCGTTTT AT AG C C G GAAC AC G G C T GAGAT GT AC GAC AAT AT T C T GAAC AAG C C T C T C C AGT T GAAAC CAAATATTACAAACTCGGCAAGGCACCTCCTGGAAGGCCTCCTGCAGAAGGACCGGACCA AGAGGCTGGGTGCCAAGGATGACTTTATGGAGATTAAGAGTCATATTTTCTTCTCTTTAA TTAACTGGGATGATCTCATCAATAAGAAGATTACACCCCCATTTAACCCAAATGTGAGTG GGCCCAGTGACCTTCGGCACTTTGATCCCGAGTTTACCGAGGAGCCGGTCCCCAGCTCCA TCGGCAGGTCCCCTGACAGCATCCTTGTCACGGCCAGTGTGAAGGAAGCAGCAGAAGCCT TCCTCGGCTTCTCCTATGCACCTCCTGTGGATTCCTTCCTCTGAGTGCTCCCGGGATGGT TCTGAAGGACTTCCTCAGCGTTTCCTAAAGTGTTTTCCTTACCCTTTGGTGGAGGTTGCC AGCTGACAGAACATTTTAAAAGAATTTGCACACCTGGAAGCTTGGCAGTCTCGCCTGCCC GGCGTGGCGCGACGCAGCGCGCGCTGCTTGATGGGAGCTTTCCGAAGAGCACACCCTCCT CTCAATGAGCTTGTGAGGTCTTCTTTTCTTCTCTTCCTTCCAACGTGGTGCTAGCTCCAG GCGAGCGAGCGTGAGAGTGCCGCCTGAGACAGACACCTTGGTCTCAGTTAGAAGGAAGAT GCAGGTCTAAGAGGAATCCCCGCAGTCTGTCTGAGCTGTGATCAAGAATATTCTGCAATG TGCCTTTTCTGAGATCGTGTTAGCTCCAAAGCTTTTTCCTATCGCAGAGTGTTCAGTTTG TGTTTGTTTGTTTTTGTTTTGTTTTGTTTTTCCCTTGGCGGATTTCCCGTGTGTGCAGTG GCGTGAGTGTGCTATGCCTGATCACAGACGGTTTTGTTGTGAGCATCAATGTGACACTTG CAGGACACTACAATGTGGGACATTGTTTGTTTCTTCCACATTTGGAAGATAAATTTATGT GTAGACTGTTTTGTAAGATATAGTTAATAACTAAAACCTATTGAAACGGTCTTGCAATGA CGAGCATTCAGATGCTTAAGGAAAGCATTGCTGCTACAAATATTTCTATTTTTAGAAAGG GTTTTTATGGACCAATGCCCCAGTTGTCAGTCAAAGCCGTTGGTGTTTTCATTGTTTAAA ATGTCACCTATAAAACGGGCATTATTTATGTTTTTTTTCCCTTTGTTCATATTCTTTTGC ATTCCTGATTATTGTATGTATCGTGTAAAGGAAGTCTGTACATTGGGTTATAACACTAGA TATTTAAACTTACAGGCTTATTTGTAAACCATCATTTTAATGTACTGTAATTAACATGGG TTATAATATGTACAATTCCTCCTCCTTACCACACAACTTTTTTTGTGTGCGATAAACCAA

TTTTGGTTTGCAATAAAATCTTGAAACCT

Sgkl Mouse Protein

MTVKAEAARSTLTYSRMRGMVAILIAFMKQRRMGLNDFIQKIASNTYACKHAEVQSILKM SHPQEPELMNANPSPPPSPSQQINLGPSSNPHAKPSDFHFLKVIGKGSFGKVLLARHKAE EVFYAVKVLQKKAILKKKEEKHIMSERNVLLKNVKHPFLVGLHFSFQTADKLYFVLDYIN GGELFYHLQRERCFLEPRARFYAAEIASALGYLHSLNIVYRDLKPENILLDSQGHIVLTD FGLCKENIEHNGTTSTFCGTPEYLAPEVLHKQPYDRTVDWWCLGAVLYEMLYGLPPFYSR NTAEMYDNILNKPLQLKPNITNSARHLLEGLLQKDRTKRLGAKDDFMEIKSHIFFSLINW DDLINKKITPPFNPNVSGPSDLRHFDPEFTEEPVPSSIGRSPDSILVTASVKEAAEAFLG

FSYAPPVDSFL

Sdcl Human DNA

ATGAGACGCGCGGCGCTCTGGCTCTGGCTCTGCGCGCTGGCGCTGAGCCTGCAGCCGGCC CTGCCGCAAATTGTGGCTACTAATTTGCCCCCTGAAGATCAAGATGGCTCTGGGGATGAC TCTGACAACTTCTCCGGCTCAGGTGCAGGTGCTTTGCAAGATATCACCTTGTCACAGCAG ACCCCCTCCACTTGGAAGGACACGCAGCTCCTGACGGCTATTCCCACGTCTCCAGAACCC ACCGGCCTGGAAGCTACAGCTGCCTCCACCTCCACCCTGCCGGCTGGAGAGGGGCCCAAG GAGGGAGAGGCTGTAGTCCTGCCAGAAGTGGAGCCTGGCCTCACCGCCCGGGAGCAGGAG GCCACCCCCCGACCCAGGGAGACCACACAGCTCCCGACCACTCATCAGGCCTCAACGACC ACAGCCACCACGGCCCAGGAGCCCGCCACCTCCCACCCCCACAGGGACATGCAGCCTGGC CACCATGAGACCTCAACCCCTGCAGGACCCAGCCAAGCTGACCTTCACACTCCCCACACA GAGGATGGAGGTCCTTCTGCCACCGAGAGGGCTGCTGAGGATGGAGCCTCCAGTCAGCTC CCAGCAGCAGAGGGCTCTGGGGAGCAGGACTTCACCTTTGAAACCTCGGGGGAGAATACG GCTGTAGTGGCCGTGGAGCCTGACCGCCGGAACCAGTCCCCAGTGGATCAGGGGGCCACG GGGGCCTCACAGGGCCTCCTGGACAGGAAAGAGGTGCTGGGAGGGGTCATTGCCGGAGGC CTCGTGGGGCTCATCTTTGCTGTGTGCCTGGTGGGTTTCATGCTGTACCGCATGAAGAAG AAGGACGAAGGCAGCTACTCCTTGGAGGAGCCGAAACAAGCCAACGGCGGTGCCTACCAG

AAACCCACCAAGCAGGAGGAGTTCTACGCC

Sdcl Mouse DNA

ACTCCGCGGGAGAGGTGCGGGCCAGAGGAGACAGAGCCTAACGCAGAGGAAGGGACCTGG CAGTCGGGAGCTGACTCCAGCCGGCGAAACCTACAGCCCTCGCTCGAGAGAGCAGCGAGC TGGGCAGGAGCCTGGGACAGCAAAGCGCAGAGCAATCAGCAGAGCCGGCCCGGAGCTCCG TGCAACCGGCAACTCGGATCCACGAAGCCCACCGAGCTCCCGCCGCCGGTCTGGGCAGCA TGAGACGCGCGGCGCTCTGGCTCTGGCTCTGCGCGCTGGCGCTGCGCCTGCAGCCTGCCC TCCCGCAAATTGTGGCTGTAAATGTTCCTCCTGAAGATCAGGATGGCTCTGGGGATGACT CTGACAACTTCTCTGGCTCTGGCACAGGTGCTTTGCCAGATACTTTGTCACGGCAGACAC CTTCCACTTGGAAGGACGTGTGGCTGTTGACAGCCACGCCCACAGCTCCAGAGCCCACCA GCAGCAACACCGAGACTGCTTTTACCTCTGTCCTGCCAGCCGGAGAGAAGCCCGAGGAGG GAGAGCCTGTGCTCCATGTAGAAGCAGAGCCTGGCTTCACTGCTCGGGACAAGGAAAAGG AGGTCACCACCAGGCCCAGGGAGACCGTGCAGCTCCCCATCACCCAACGGGCCTCAACAG

TCAGAGTCACCACAGCCCAGGCAGCTGTCACATCTCATCCGCACGGGGGCATGCAAC CTG GCCTCCATGAGACCTCGGCTCCCACAGCACCTGGTCAACCTGACCATCAGCCTCCACGTG TGGAGGGTGGCGGCACTTCTGTCATCAAAGAGGTTGTCGAGGATGGAACTGCCAATCAGC TTCCCGCAGGAGAGGGCTCTGGAGAACAAGACTTCACCTTTGAAACATCTGGGGAGAACA CAGCTGTGGCTGCCGTAGAGCCCGGCCTGCGGAATCAGCCCCCGGTGGACGAAGGAGCCA CAGGTGCTTCTCAGAGCCTTTTGGACAGGAAGGAAGTGCTGGGAGGTGTCATTGCCGGAG GCCTAGTGGGCCTCATCTTTGCTGTGTGCCTGGTGGCTTTCATGCTGTACCGGATGAAGA AGAAGGACGAAGGCAGCTACTCCTTGGAGGAGCCCAAACAAGCCAATGGCGGTGCCTACC AGAAACCCACCAAGCAGGAGGAGTTCTACGCCTGATGGGGAAATAGTTCTTTCTCCCCCC CACAGCCCCTGCCACTCACTAGGCTCCCACTTGCCTCTTCTGTGAAAAACTTCAAGCCCT GGCCTCCCCACCACTGGGTCATGTCCTCTGCACCCAGGCCCTTCCAGCTGTTCCTGCCCG AGCGGTCCCAGGGTGTGCTGGGAACTGATTCCCCTCCTTTGACTTCTGCCTAGAAGCTTG GGTGCAAAGGGTTTCTTGCATCTGATCTTTCTACCACAACCACACCTGTCGTCCACTCTT CTGACTTGGTTTCTCCAAATGGGAGGAGACCCAGCTCTGGACAGAAAGGGGACCCGACTG CTTTGGACCTAGATGGCCTATTGCGGCTGGAGGATCCTGAGGACAGGAGAGGGGCTTCGG CTGACCAGCCATAGCACTTACCCATAGAGACCGCTAGGGTTGGCCGTGCTGTGGTGGGGG ATGGAGGCCTGAGCTCCTTGGAATCCACTTTTCATTGTGGGGAGGTCTACTTTAGACAAC TTGGTTTTGCACATATTTTCTCTAATTTCTCTGTTCAGAGCCCCAGCAGACCTTATTACT GGGGTAAGGCAAGTCTGTTGACTGGTGTCCCTCACCTCGCTTCCCTAATCTACATTCAGG AGACCGAATCGGGGGTTAATAAGACTTTTTTTGTTTTTTGTTTTTGTTTTTAACCTAGAA GAACCAAATCTGGACGCCAAAACGTAGGCTTAGTTTGTGTGTTGTCTCTGAGTTTGTGCT CATGCGTACAACAGGGTATGGACTATCTGTATGGTGCCCCATTTTTGGCGGCCCGTAAGT AGGCTAGGCTAGTCCAGGATACTGTGGAATAGCCACCTCTTGACCAGTCATGCCTGTGTG CATGGACTCAGGGCCACGGCCTTGGCCTGGGCCACCGTGACATTGGAAGAGCCTGTGTGA GAACTTACTCGAAGTTCACAGTCTAGGAGTGGAGGGGAGGAGACTGTAGAGTTTTGGGGG AGGGGTAGCAAGGGTGCCCAAGCGTCTCCCACCTTTGGTACCATCTCTAGTCATCCTTCC TCCCGGAAGTTGACAAGACACATCTTGAGTATGGCTGGCACTGGTTCCTCCATCAAGAAC CAAGTTCACCTTCAGCTCCTGTGGCCCCGCCCCCAGGCTGGAGTCAGAAATGTTTCCCAA AGAGTGAGTCTTTTGCTTTTGGCAAAACGCTACTTAATCCAATGGGTTCTGTACAGTAGA

TTTTGCAGATGTAATAAACTTTAATATAAAGG

Sdcl Mouse Protein

MRRAALWLWLCALALRLQPALPQIVA VPPEDQDGSGDDSDNFSGSGTGALPDTLSRQT PSTWKDVWLLTATPTAPEPTS SNTETAFTSVLPAGEKPEEGEPVLHVEAEPGFTARDKEK EVTTRPRETVQLPITQRASTVRVTTAQAAVTSHPHGGMQPGLHETSAPTAPGQPDHQPPR VEGGGTSVI KEWEDGTANQLPAGEGSGEQDFTFETSGENTAVAAVEPGLRNQPPVDEGA TGASQSLLDRKEVLGGVIAGGLVGLI FAVCLVAFMLYRMKKKDEGSYSLEEPKQANGGAY

QKPTKQEEFYA

Serpine2 Human DNA

ATGAACTGGCATCTCCCCCTCTTCCTCTTGGCCTCTGTGACGCTGCCTTCCATCTGCTCC CACTTCAATCCTCTGTCTCTCGAGGAACTAGGCTCCAACACGGGGATCCAGGTTTTCAAT CAGATTGTGAAGTCGAGGCCTCATGACAACATCGTGATCTCTCCCCATGGGATTGCGTCG GTCCTGGGGATGCTTCAGCTGGGGGCGGACGGCAGGACCAAGAAGCAGCTCGCCATGGTG AT GAGAT AC G G C GT AAAT G GAGT T G GT AAAAT AT T AAAGAAGAT C AAC AAG G C CAT C GT C TCCAAGAAGAATAAAGACATTGTGACAGTGGCTAACGCCGTGTTTGTTAAGAATGCCTCT GAAAT T GAAGT GC CT T T T GT T ACAAGGAACAAAGAT GT GT T C CAGT GT GAGGT C C GGAAT GTGAACTTTGAGGATCCAGCCTCTGCCTGTGATTCCATCAATGCATGGGTTAAAAACGAA ACCAGGGATATGATTGACAATCTGCTGTCCCCAGATCTTATTGATGGTGTGCTCACCAGA CTGGTCCTCGTCAACGCAGTGTATTTCAAGGGTCTGTGGAAATCACGGTTCCAACCCGAG AACACAAAGAAACGCACTTTCGTGGCAGCCGACGGGAAATCCTATCAAGTGCCAATGCTG GCCCAGCTCTCCGTGTTCCGGTGTGGGTCGACAAGTGCCCCCAATGATTTATGGTACAAC TTCATTGAACTGCCCTACCACGGGGAAAGCATCAGCATGCTGATTGCACTGCCGACTGAG AG C T C C AC TCCGCTGTCTGC CAT CAT C C C AC AC AT C AG C AC C AAGAC C AT AGAC AG C T G G ATGAGCATCATGGTCCCCAAGAGGGTGCAGGTGATCCTGCCCAAGTTCACAGCTGTAGCA CAAACAGATTTGAAGGAGCCGCTGAAAGTTCTTGGCATTACTGACATGTTTGATTCATCA AAG G C AAAT T T T G C AAAAAT AAC AAGGT C AGAAAAC C T C CAT GT T T C T CAT AT C T T G C AA AAAGCAAAAATT GAAGT CAGT GAAGAT G GAAC C AAAG C T T C AG C AG C AAC AAC T G C AAT T CTCATTGCAAGATCATCGCCTCCCTGGTTTATAGTAGACAGACCTTTTCTGTTTTTCATC

CGACATAATCCTACAGGTGCTGTGTTATTCATGGGGCAGATAAACAAACC C Serpine2 Mouse DNA

AGTGCAGTGGTTGCACGGGAGTGCGGGCTGCACGCGTCACCGTCACCGCCGCCTGTCCCC CACCGCCGCGCAGCGCCGATCTCCCTCCCGGTTTCGGCCGCCACCTGGGGATCCAAGCGA GGACGGGCTGTCCTTGTTGGAAGGAACCATGAATTGGCATTTTCCTTTCTTCATCTTGAC CACAGTGACTTTATACTCTGTGCACTCCCAGTTCAACTCTCTGTCACTGGAGGAACTAGG C T C C AAC AC AG G GAT C C AG GT C T T C AAT C AGAT CAT C AAGT C AC G G C C T CAT GAGAAC GT TGTTGTCTCCCCACATGGGATCGCGTCCATCTTGGGCATGCTGCAGCTCGGGGCTGACGG C AAGAC AAAGAAG C AG C T C T C C AC G GT GAT G C GAT AT AAT GT AAAC G GAGT T G GT AAAGT G C T GAAGAAGAT C AAC AAG G C TAT T GT C T C C AAGAAAAAT AAAGAC AT T GT GAC C GT G G C CAATGCTGTGTTTCTCAGGAATGGCTTTAAAATGGAAGTGCCTTTTGCAGTAAGGAACAA AGATGTGTTTCAGTGTGAAGTGCAGAATGTGAACTTCCAGGACCCAGCCTCTGCCTCTGA GTCCATCAATTTTTGGGTCAAAAATGAGACCAGGGGCATGATTGATAATCTGCTTTCCCC AAATCTGATCGATGGTGCCCTTACCAGGCTGGTCCTCGTTAATGCAGTGTATTTCAAGGG TTTGTGGAAGTCTCGGTTTCAACCAGAGAGCACAAAGAAACGGACATTCGTGGCAGGTGA TGGGAAATCCTACCAAGTACCCATGTTGGCTCAGCTCTCTGTGTTCCGCTCAGGGTCTAC CAGGACCCCGAATGGCTTATGGTACAACTTCATTGAGCTGCCCTACCATGGTGAGAGCAT CAGCATGCTGATCGCCCTGCCAACAGAGAGCTCCACCCCACTGTCTGCCATCATCCCTCA CAT C AC T AC C AAGAC CAT T GAT AG C T G GAT GAAC AC CAT G GT AC C C AAGAG GAT G C AG C T GGTCCTACCCAAGTTCACAGCTGTGGCACAAACAGATCTGAAGGAGCCACTGAAAGCCCT T G G CAT TACT GAGAT GT T T GAG C CAT C AAAG G C AAAT T T T AC AAAAAT AAC AAG GT C AGA GAGCCTT CAT GT CT CT CACAT CTT GCAAAAAGC AAAAAT T GAAGT CAGT GAAGAT G GAAC CAAAGCTTCAGCAGCAACAACTGCAATCCTAATTGCAAGGTCATCACCTCCCTGGTTTAT AGTAGACAGGCCTTTCCTGTTTTCCATCCGACACAATCCCACAGGTGCCATCTTGTTCCT G G G C C AG GT GAAC AAG C C C T GAAG GAC AGAC AAAG GAAAG C C AC G C AAAG C C AAGAC GAC TTGGCTCTGAAGAGAGACTCCCTCCCCACATCTTTCATAGTTCTGTTAAATATTTTTATA TACTGCTTTCTTTTTTGAAACTGGTTCATAGCAGCAGTTAAGTGACGCAAGTGTTTCTGG TCGGGGCTGTGTCAGAAGAAAGGGCTGGATGCCTGGGATGCTGGATGCCTGGGATGCTGG ATGCCTGGGATGCTGGATGCCTGGGATGCTGGATGCCTGGGATGCTGGATGCCTGGGATG CTGTAGTGAAGGATGAGCAGGCCGGTTTCACGATGTCTAGAAGATTTCTTTAAACTACTG ATCAGTTATCTAGGTTAACAACCCTCTCGAGTATTTGCTGTCTGTCAAGTTCAGCATCTT TGTTTCATTCCTGTTGATATGTGTGACTTTCCAGGAGAGGATTAATCAGTGTGGCAGGAG AGGT T AAAAAAAAAAAAGACAT T T T AT AGT AGT T T T TAT GT T T T T AT GGAAAACAAT AT C ATTTGCCTTTTTAATTCTTTTTCCTCTCACTTCCACCCAAAGGCTTGAGGGTGGCAAGGG ATGGAGCTAGCAAAAGCCGTAGCCTCTTCGTGTGTTGTTTCTGTTGCTGTTGCTCTTGTT

GTTTTATATACTGCATGTGTTCACTAAAATAAAGTTGGAAAACT

Serpine2 Mouse Protein

MNWHFPFFI LTTVTLYSVHSQFNSLSLEELGSNTGIQVFNQI I KSRPHENVWS PHGIAS I LGMLQLGADGKTKKQLSTVMRYN GVGKVLKKINKAIVSKKNKDIVTVANAVFLRNGF KMEVPFAVRNKDVFQCEVQN FQDPASASES INFWVKNETRGMI DNLLS PNLI DGALTR LVL AVYFKGLWKSRFQPESTKKRTFVAGDGKSYQVPMLAQLSVFRSGSTRTPNGLWYN FI ELPYHGES I SMLIALPTES STPLSAI I PHITTKTI DSWMNTMVPKRMQLVLPKFTAVA QTDLKEPLKALGITEMFEPSKANFTKITRSESLHVSHI LQKAKI EVSEDGTKASAATTAI

LIARS SPPWFIVDRPFLF SIRHNPTGAILFLGQ V KP

Sppl Human DNA

GACCAGACTCGTCTCAGGCCAGTTGCAGCCTTCTCAGCCAAACGCCGACCAAGGAAAACT CACTACCATGAGAATTGCAGTGATTTGCTTTTGCCTCCTAGGCATCACCTGTGCCATACC AGT T AAAC AG G C T GAT T C T G GAAGT T C T GAG GAAAAG C AG CTT T AC AAC AAAT AC C C AGA TGCTGTGGCCACATGGCTAAACCCTGACCCATCTCAGAAGCAGAATCTCCTAGCCCCACA GAATGCTGTGTCCTCTGAAGAAACCAATGACTTTAAACAAGAGACCCTTCCAAGTAAGTC CAAC GAAAGC CAT GAC CACAT GGAT GAT AT GGAT GAT GAAGAT GAT GAT GAC CAT GT GGA C AG C C AG GAC T C CAT T GAC T C GAAC GAC T C T GAT GAT GT AGAT GAC AC T GAT GAT T C T C A CCAGTCTGATGAGTCTCACCATTCTGATGAATCTGATGAACTGGTCACTGATTTTCCCAC G GAC C T G C C AG CAAC C GAAGT T T T C AC T C CAGT T GT C C C C AC AGT AGAC AC AT AT GAT G G CCGAGGTGATAGTGTGGTTTATGGACTGAGGTCAAAATCTAAGAAGTTTCGCAGACCTGA CAT C CAGT AC C C T GAT G C T AC AGAC GAG GAC AT C AC C T C AC AC AT G GAAAG C GAG GAGT T GAATGGTGCATACAAGGCCATCCCCGTTGCCCAGGACCTGAACGCGCCTTCTGATTGGGA C AG C C GT G G GAAG GAC AGT TAT GAAAC GAGT C AG C T G GAT GAC C AGAGT G C T GAAAC C C A C AG C C AC AAG CAGT C C AGAT TAT AT AAG C G GAAAG C C AAT GAT GAGAG C AAT GAG CAT T C C GAT GT GAT T GAT AGT C AG GAAC T T T C C AAAGT C AG C C GT GAAT T C C AC AG C CAT GAAT T T C AC AG C CAT GAAGAT AT G C T G GT T GT AGAC C C C AAAAGT AAG GAAGAAGAT AAAC AC C T GAAATTTCGTATTTCTCATGAATTAGATAGTGCATCTTCTGAGGTCAATTAAAAGGAGAA

AAAATACAATTTCTCACTTTGCATTTAGTCAAAAGAAAAAATGCTTTATAGCAAAAT GAA AGAGAACATGAAATGCTTCTTTCTCAGTTTATTGGTTGAATGTGTATCTATTTGAGTCTG GAAATAACTAATGTGTTTGATAATTAGTTTAGTTTGTGGCTTCATGGAAACTCCCTGTAA ACTAAAAGCTTCAGGGTTATGTCTATGTTCATTCTATAGAAGAAATGCAAACTATCACTG TATTTTAATATTTGTTATTCTCTCATGAATAGAAATTTATGTAGAAGCAAACAAAATACT TTTACCCACTTAAAAAGAGAATATAACATTTTATGTCACTATAATCTTTTGTTTTTTAAG

TTAGTGTATATTTTGTTGTGATTATCTTTTTGTGGTGTGAATAA

Sppl Mouse DNA

CTTGCTTGGGTTTGCAGTCTTCTGCGGCAGGCATTCTCGGAGGAAACCAGCCAAGGACTA ACTACGACCATGAGATTGGCAGTGATTTGCTTTTGCCTGTTTGGCATTGCCTCCTCCCTC CCGGTGAAAGTGACTGATTCTGGCAGCTCAGAGGAGAAGCTTTACAGCCTGCACCCAGAT CCTATAGCCACATGGCTGGTGCCTGACCCATCTCAGAAGCAGAATCTCCTTGCGCCACAG AATGCTGTGTCCTCTGAAGAAAAGGATGACTTTAAGCAAGAAACTCTTCCAAGCAATTCC AATGAAAGCCATGACCACATGGACGACGATGATGACGATGATGATGACGATGGAGACCAT GCAGGGAGCGAGGATTCTGTGGACTCGGATGAATCTGACGAATCTCACCATTCGGATGAG TCTGATGAGACCGTCACTGCTAGTACACAAGCAGACACTTTCACTCCAATCGTCCCTACA GTCGATGTCCCCAACGGCCGAGGTGATAGCTTGGCTTATGGACTGAGGTCAAAGTCTAGG AGTTTCCAGGTTTCTGATGAACAGTATCCTGATGCCACAGATGAGGACCTCACCTCTCAC ATGAAGAGCGGTGAGTCTAAGGAGTCCCTCGATGTCATCCCTGTTGCCCAGCTTCTGAGC ATGCCCTCTGATCAGGACAACAACGGAAAGGGCAGCCATGAGTCAAGTCAGCTGGATGAA CCAAGTCTGGAAACACACAGACTTGAGCATTCCAAAGAGAGCCAGGAGAGTGCCGATCAG TCGGATGTGATCGATAGTCAAGCAAGTTCCAAAGCCAGCCTGGAACATCAGAGCCACAAG TTTCACAGCCACAAGGACAAGCTAGTCCTAGACCCTAAGAGTAAGGAAGATGATAGGTAT CTGAAATTCCGAATTTCTCATGAATTAGAGAGTTCATCTTCTGAGGTCAACTAAAGAAGA GGCAAAAACACAGTTCCTTACTTTGCATTTAGTAAAAACAAGAAAAAGTGTTAGTGAGGA TTAAGCAGGAATACTAACTGCTCATTTCTCAGTTCAGTGGATATATGTATGTAGAGAAAG AGAGGTAATATTTTGGGCTCTTAGCTTAGTCTGTTGTTTCATGCAAACAACCGTTGTAAC CAAAAGCTTCTGCACTTTGCTTCTGTTCTTCCTGTACAAGAAATGCAAACGGCCACTGCA TTTTAATGATTGTTATTCTTTTATGAATAAAATGTATGTAGAAACAAGCAAATTTACTGA AACAAGCAGAATTAAAAGAGAAACTGTAACAGTCTATATCACTATACCCTTTTAGTTTTA TAATTAGCATATATTTTGTTGTGATTATTTTTTTTGTTGGTGTGAATAAATCTTGTAACG

AATGT

Sppl Mouse Protein

MRLAVICFCLFGIASSLPVKVTDSGSSEEKLYSLHPDPIATWLVPDPSQKQNLLAPQNAV SSEEKDDFKQETLPSNSNESHDHMDDDDDDDDDDGDHAESEDSVDSDESDESHHSDESDE TVTASTQADTFTPIVPTVDVPNGRGDSLAYGLRSKSRSFQVSDEQYPDATDEDLTSHMKS GESKESLDVI PVAQLLSMPSDQDNNGKGSHESSQLDEPSLETHRLEHSKESQESADQSDV

IDSQ AS SKASLEHQSHKFHSHKDKLVLDPKSKEDDRYLKFRISHELES S S SEVN

Cdca8 Human DNA

GGTTGACTGTAGAGCCGCTCTCTCTCACTGGCACAGCGAGGTTTTGCTCAGCCCTTGTCT CGGGACCGCAGGTACGTGTCTGGCGACTTCTTCGGGTGGTCCCCGTCCGCCCTCCTCGTC CCTACCCAGTTTCTTGCTTCCCTGCCCCATCTCCGCCGCTCCCCGCAGCCTCCGCCGAGC GCCATGGCTCCTAGGAAGGGCAGTAGTCGGGTGGCCAAGACCAACTCCTTACGGAGGCGG AAGCTCGCCTCCTTTCTGAAAGACTTCGACCGTGAAGTGGAAATACGAATCAAGCAAATT GAGTCAGACAGGCAGAACCTCCTCAAGGAGGTGGATAACCTCTACAACATCGAGATCCTG CGGCTCCCCAAGGCTCTGCGCGAGATGAACTGGCTTGACTACTTCGCCCTTGGAGGAAAC AAACAGGCCCTGGAAGAGGCGGCAACAGCTGACCTGGATATCACCGAAATAAACAAACTA ACAGCAGAAGCTATTCAGACACCCCTGAAATCTGCCAAAACACGAAAGGTAATACAGGTA GATGAAATGATAGTGGAAGAGGGAAGAAGGAGAAGGAAAATTTACGTAAGAATCTTCAAA CTGCAAGAGTCAAAAGGTGTCCTCCATCCAAGAAGAGAACTCAGTCCATACAAGGCAAAG GAAAAGGGAAAAGGTCAAGCCGTGCTAACACTGTTACCCCAGCCGTGGGCCGATTGGAGG TGTCCATGGTCAAACCAACTCCAGGCCTGACACCCAGGTTTGACTCAAGGGTCTTCAAGA CCCTGGCCTGCGTACTCCAGCAGCAGGAGAGCGGATTTACAACATCTCAGGGAATGGCAG CCCTCTTGCTGACAGCAAAGAGATCTTCCTCACTGTGCCAGTGGGCGGCGGAGAGAGCCT GCGATTATTGGCCAGTGACTTGCAGAGGCACAGTATTGCCCAGCTGGATCCAGAGGCCTT GGGAAACATTAAGAAGCTCTCCAACCGTCTCGCCCAAATCTGCAGCAGCATACGGACCCA CAAATGAGACACCAAAGTTGACAGGATGGACTTTTAATGGGCACTTCTGGGACCCTGAAG AGACTTCTTCCCTTCAGGCTTATTGTTTGAGTGTGAAGTTCCAGAGCAAGGAGCCATGTT CCTCTAAGGGAATTCAGGAATTCAGACGTGCTAGTCCCACACCAGTTAGGTAGAGCTGTC TGTTCACCCTCCCATCCCAGCTGATCCCAGTCACTGCTTGCTGGGGCCATGCCATGGAAG

CTTCCCATCAGTCTCCCAGCTGAATCCTCCCTGCTCTCTGAGCTGCTGCCTTTTGCC TCC TGCAACTCAACATCCTCTTCACCCTGCCCTGCCTGCAGTTGAGGGGGCGAAGAAGAACCC TGTGTTCTCAGGAAGACTGCCTCCACCACCGCTACCCAGAGAACCTCTGCATCTGGCATT TCTGCTCTCTATGCTTGAGACCGGGAGGTTTAGGCTCAGATAAGTGAGCTCTGGGCCATG AGAGGGTAGGTCCAGAAGGTGGGGGGAACTGTACAGATCAGCAGAGCAGGACAGTTGGCA GCAGTGACCTCAGTAGGGAACATGTCCGTCTACCCTCTCGCACTCATGACACCTCCCCCT ACCAGCCTCTCTCTCTCTCACCTCCTCTGTGGGAGGTGGTCAGTGGGACTTAGGGATCTT TCACCTGCTGTGCCCAGTAGTTCTGAAGTCTGCTTGTGGAGCAGTGTTTTATGTTTATCC CTGTTTACTGAAGACCAAATACTGGTTTGGAGACAACTTCCATGTCTTGCTCTTCTACCT CCCTAGTTAGTGGAAATTTGGATAAGGGAACTGTAGGGCCCAGATTCTGGAGGTTTTATG TCATTGGCCACAGAATAACTGTCTCTAAGCTATCCATGGTCCAGTGGTCCCTGCCAAGTC TGTAGACTTCAGAGAGCACTTCTCTCTTATGGGGTTCATGGGAACAGGGGCGGGTGTGAC TTGCTTGGTGGCCTCATTCCATGTGTGCCTGTGCCTGGGGCATGGACTTTGTTAAGCAGA GTCAGCAGTGAGGTCCTCATTCTCCAGCCAGCCTCTCTGCCCTGGAGAATCATGTGCTAT GTTCTAAGAATTTGAGAACTAGAGTCCTCATCCCCAGGCTTGAAGGCACATGGCTTTCTC ATGTAGGGCTCTCTGTGGTATTTGTTATTATTTTGCAACAAGACCATTTTAGTAAAACAG TCCTGTTCAAGTTGTATTCTTTTAAGTTCTTTTATTCTCCTTTCCCTGAGATTTTTGTAT ATATTGTTCTGAGTAATGGTATCTTTGAGCTGATTGTTCTAATCAGAGCTGGTACCTACT

TTCAATAAATTCTGGTTTTGTGTTTTCTTTTGT

Cdca8 Mouse DNA

GGAATTGAATTGGGTGGCGGTTAACCGAGGAGCCGCCCGTCCCTTAGTTGGAGCTGTGAG GGTTCCTCAGACTGTGTTTTGGGACCTGCAGGTAGGTTTCGGCAGAGTTCTGGAAACCTA GACTCCAACGACTGAACTTTCTCAGCTCTCCGACCGCTCACACCCTCTCCCCGTCTCAGT CGCGGAGCCGGCTGCTTGGCCCCTCGCTCGACGCAGCCAGGCGCCATGGCTCCCAAGAAA CGCAGCAGCCGCGGAACCAGGACCAACACGCTGCGGAGCCGGAAGCTCGCCTCCTTCCTG AAGGACTTCGACCGCGAGGTGCAAGTTCGAACCAAGCAAATTGAGTCCGACAGACAGACC CTCCTCAAGGAGGTGGAAAATCTGTACAACATCGAGATCCTTCGGCTCCCCAAGGCGCTG CAAGGGATGAAGTGGCTTGACTACTTCGCCCTAGGAGGAAACAAGCAGGCCCTGGAAGAG GCAGCAAAAGCTGATCGAGACATCACAGAAATAAACAATTTAACAGCTGAAGCTATTCAG ACACCTTTGAAATCTGTTAAAAAGCGAAAGGTAATCGAGGTGGAGGAATCGATAAAGGAA GAAGAAGAAGAGGAAGAAGAAGGAGGAGGAGAAGGAGGAAGAACAAAAAAGAGCCATAAG AATCTTCGATCTGCAAAAGTCAAAAGATGCCTTCCATCCAAGAAGAGAACCCAGTCCATA CAAGGAAGAGGCAGAAGTAAAAGGTTAAGCCATGACTTTGTGACGCCAGCTATGAGCAGG CTGGAGCCGTCTCTGGTGAAACCAACCCCAGGCATGACACCTAGGTTTGACTCCCGGGTC TTCAAGACTCCAGGGCTACGCACTCCAGCAGCCAAAGAGCAAGTTTACAACATCTCCATC AACGGCAGCCCTCTCGCAGACAGCAAAGAGATCTCCCTCAGTGTGCCCATAGGTGGCGGT GCGAGCTTGCGGTTATTGGCCAGTGACTTGCAAAGGATTGATATTGCTCAGCTGAATCCA GAGGCCCTGGGAAACATTAGAAAGCTCTCGAGCCGCCTCGCCCAGATCTGCAGCAGCATA CGGACGGGCCGATGAGAGGACAACAGGACACACAGTGGCAGCAGGGACTGTGGTAGCAGA GTGCACACATCTGTCCTTCTTCTGTGGGGTCCTTCACTGCCAACACCTGCAACGGTGCTT TGTCTCTCTGACAGCTATGGTGTCTTGCTGCACACTTCTAGTTAGTGGGAATTTTAGACG GGGAACACAGGGCTAGTCAGGGCCTTTGTGTGCTTGGTGTGGAGTGACTGAGAACCGTCT ATGGTTCAAGGTCCCACTGGGGATAAACTGCTTAGAGCACTGTCCTAGAGGGCAAGTGTA GCCTTCGCCTCCGGGCCCAGGCAGGCTATGCAGTCAGCAGTAGGGTCTGTGCTCCATGCG GGTCCAGGCGCACGGCTCTCCTATTCTGTTGTCATTTGTGCCCTCTATGGGCAGGTGTGT TTCAAGTTGGTTTTCTGTTGCTGAGGCTTTCATACACATCAGTTACCATCTCAGCTGATT

TGTCTACTGAAAGCTTGCTGTTTTCAATAAATCTTAGTTTGCCATGGTTTTA AGTC

Cdca8 Mouse Protein

MAPKKRSSRGTRTNTLRSRKLASFLKDFDREVQVRTKQIESDRQTLLKEVENLYNIEILR LPKALQGMKWLDYFALGGNKQALEEAAKADRDITEINNLTAEAIQTPLKSVKKRKVIEVE ESIKEEEEEEEEGGGGGGRTKKSHKNLRSAKVKRCLPSKKRTQSIQGRGRSKRLSHDFVT PAMSRLEPSLVKPTPGMTPRFDSRVFKTPGLRTPAAKEQVYNISINGSPLADSKEISLSV

PIGGGASLRLLASDLQRIDIAQL PEALGNIRKLSSRLAQICSSIRTGR

Nrpl Human DNA

ATGGAGAGGGGGCTGCCGCTCCTCTGCGCCGTGCTCGCCCTCGTCCTCGCCCCGGCCGGC GCTTTTCGCAACGATGAATGTGGCGATACTATAAAAATTGAAAGCCCCGGGTACCTTACA TCTCCTGGTTATCCTCATTCTTATCACCCAAGTGAAAAATGCGAATGGCTGATTCAGGCT CCGGACCCATACCAGAGAATTATGATCAACTTCAACCCTCACTTCGATTTGGAGGACAGA GAC T G C AAGT AT GAC T AC GT G GAAGT C T T C GAT G GAGAAAAT GAAAAT G GAC AT T T T AG G GGAAAGTTCTGTGGAAAGATAGCCCCTCCTCCTGTTGTGTCTTCAGGGCCATTTCTTTTT AT C AAAT TTGTCTCT GAC T AC GAAACAC AT G GT G C AG GAT T T T C CAT AC GT TAT GAAAT T TTCAAGAGAGGTCCTGAATGTTCCCAGAACTACACAACACCTAGTGGAGTGATAAAGTCC CCCGGATTCCCTGAAAAATATCCCAACAGCCTTGAATGCACTTATATTGTCTTTGCGCCA AAGATGTCAGAGATTATCCTGGAATTTGAAAGCTTTGACCTGGAGCCTGACTCAAATCCT CCAGGGGGGATGTTCTGTCGCTACGACCGGCTAGAAATCTGGGATGGATTCCCTGATGTT GGCCCTCACATTGGGCGTTACTGTGGACAGAAAACACCAGGTCGAATCCGATCCTCATCG GGCATTCTCTCCATGGTTTTTTACACCGACAGCGCGATAGCAAAAGAAGGTTTCTCAGCA AACTACAGTGTCTTGCAGAGCAGTGTCTCAGAAGATTTCAAATGTATGGAAGCTCTGGGC AT G GAAT C AG GAGAAAT T CAT T C T GAC C AGAT C AC AG CTTCTTCC C AGT AT AG C AC C AAC TGGTCTGCAGAGCGCTCCCGCCTGAACTACCCTGAGAATGGGTGGACTCCCGGAGAGGAT TCCTACCGAGAGTGGATACAGGTAGACTTGGGCCTTCTGCGCTTTGTCACGGCTGTCGGG AC AC AG G G C G C CAT T T C AAAAGAAAC C AAGAAGAAAT AT TAT GT C AAGAC T T AC AAGAT C GAC GTTAGCTC C AAC G G G GAAGAC T GGAT C AC C AT AAAAGAAG GAAAC AAAC CTGTTCTC T T T C AG G GAAACAC C AAC C C C AC AGAT GTTGTGGTTG C AGT AT T C C C C AAAC C AC T GAT A ACTCGATTTGTCCGAATCAAGCCTGCAACTTGGGAAACTGGCATATCTATGAGATTTGAA GTATACGGTTGCAAGATAACAGATTATCCTTGCTCTGGAATGTTGGGTATGGTGTCTGGA C T TAT T T C T GAC T C C C AGAT C AC AT CAT C C AAC C AAG GAGAC AGAAAC T G GAT G C C T GAA AACATCCGCCTGGTAACCAGTCGCTCTGGCTGGGCACTTCCACCCGCACCTCATTCCTAC AT C AAT GAGT G G C T C C AAAT AGAC C T G G G G GAG GAGAAGAT C GT GAG G G G CAT CAT CAT T CAGGGTGGGAAGCACCGAGAGAACAAGGTGTTCATGAGGAAGTTCAAGATCGGGTACAGC AACAACGGCTCGGACTGGAAGATGATCATGGATGACAGCAAACGCAAGGCGAAGTCTTTT GAGGGCAACAACAACTATGATACACCTGAGCTGCGGACTTTTCCAGCTCTCTCCACGCGA TTCATCAGGATCTACCCCGAGAGAGCCACTCATGGCGGACTGGGGCTCAGAATGGAGCTG CTGGGCTGTGAAGTGGAAGCCCCTACAGCTGGACCGACCACTCCCAACGGGAACTTGGTG GAT GAAT GT GAT GAC GAC C AG G C C AAC T G C C AC AGT G GAAC AG GT GAT GAC T T C C AG C T C AC AG GT G G C AC C AC TGTGCTGGC C ACAGAAAAG C C C AC G GT CAT AGAC AG C AC C AT AC AA TCAGAGTTTCCAACATATGGTTTTAACTGTGAATTTGGCTGGGGCTCTCACAAGACCTTC TGCCACTGGGAACATGACAATCACGTGCAGCTCAAGTGGAGTGTGTTGACCAGCAAGACG G GAC C CAT T C AG GAT C AC AC AG GAGAT G G C AAC T T CAT C TAT T C C C AAG C T GAC GAAAAT CAGAAGGGCAAAGTGGCTCGCCTGGTGAGCCCTGTGGTTTATTCCCAGAACTCTGCCCAC TGCATGACCTTCTGGTATCACATGTCTGGGTCCCACGTCGGCACACTCAGGGTCAAACTG C G C T AC C AGAAG C C AGAG GAGT AC GAT C AG CTGGTCTG GAT G G C CAT T G GAC AC C AAG GT GACCACTGGAAGGAAGGGCGTGTCTTGCTCCACAAGTCTCTGAAACTTTATCAGGTGATT TTCGAGGGCGAAATCGGAAAAGGAAACCTTGGTGGGATTGCTGTGGATGACATTAGTATT AAT AAC C AC AT T T C AC AAGAAGAT T GT G C AAAAC C AG C AGAC C T G GAT AAAAAGAAC C C A GAAAT T AAAAT T GAT GAAAC AG G GAGC AC G C C AG GAT AC GAAG GT GAAG GAGAAG GT GAC AAGAAC AT C T C C AG GAAG C C AG G C AAT GT GT T GAAGAC C T T AGAAC C CAT C C T CAT C AC C ATCATAGCCATGAGCGCCCTGGGGGTCCTCCTGGGGGCTGTCTGTGGGGTCGTGCTGTAC TGTGCCTGTTGGCATAATGGGATGTCAGAAAGAAACTTGTCTGCCCTGGAGAACTATAAC TTTGAACTTGTGGATGGTGTGAAGTTGAAAAAAGACAAACTGAATACACAGAGTACTTAT

TCGGAGGCATGA

Nrpl Mouse DNA

TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTCCTCCTTCTTCTTCTTCCTGAGACA TGGCCCGGGCAGTGGCTCCTGGAAGAGGAACAAGTGTGGGAAAAGGGAGAGGAAATCGGA G C T AAAT GAC AG GAT G C AG G C GAC T T GAGAC AC AAAAAGAGAAG CGCTTCTCGC GAAT T C AGGCATTGCCTCGCCGCTAGCCTTCCCCGCCAAGACCCGCTGAGGATTTTATGGTTCTTA GGCGGACTTAAGAGCGTTTCGGATTGTTAAGATTATCGTTTGCTGGTTTTTCGTCCGCGC AATCGTGTTCTCCTGCGGCTGCCTGGGGACTGGCTTGGCGAAGGAGGATGGAGAGGGGGC TGCCGTTGCTGTGCGCCACGCTCGCCCTTGCCCTCGCCCTGGCGGGCGCTTTCCGCAGCG ACAAATGTGGCGGGACCATAAAAATCGAAAACCCAGGGTACCTCACATCTCCCGGTTACC CTCATTCTTACCATCCAAGTGAGAAGTGTGAATGGCTAATCCAAGCTCCGGAACCCTACC AGAGAAT CAT AAT C AAC T T C AAC C C AC AT T T C GAT T T G GAG GAC AGAGAC T G C AAGT AT G ACTACGTGGAAGTAATTGATGGGGAGAATGAAGGCGGCCGCCTGTGGGGGAAGTTCTGTG GGAAGATTGCACCTTCTCCTGTGGTGTCTTCAGGGCCCTTTCTCTTCATCAAATTTGTCT CTGACTATGAGACACATGGGGCAGGGTTTTCCATCCGCTAT GAAAT CTTCAAGAGAGGGC CCGAATGTTCTCAGAACTATACAGCACCTACTGGAGTGATAAAGTCCCCTGGGTTCCCTG AAAAATACCCCAACTGCTTGGAGTGCACCTACATCATCTTTGCACCAAAGATGTCTGAGA TAATCCTGGAGTTTGAAAGTTTTGACCTGGAGCAAGACTCGAATCCTCCCGGAGGAATGT TCTGTCGCTATGACCGGCTGGAGATCTGGGATGGATTCCCTGAAGTTGGCCCTCACATTG GGCGTTATTGTGGGCAGAAAACTCCTGGCCGGATCCGCTCCTCTTCAGGCGTTCTATCCA

TGGTCTTTTACACTGACAGCGCAATAGCAAAAGAAGGTTTCTCAGCCAACTACAGTG TGC TACAGAGCAGCATCTCTGAAGATTTTAAGTGTATGGAGGCTCTGGGCATGGAATCTGGAG AGATCCATTCTGATCAGATCACTGCATCTTCACAGTATGGTACCAACTGGTCTGTAGAGC GCTCCCGCCTGAACTACCCTGAAAATGGGTGGACTCCAGGAGAAGACTCCTACAAGGAGT GGATCCAGGTGGACTTGGGCCTCCTGCGATTCGTTACTGCTGTAGGGACACAGGGTGCCA TTTCCAAGGAAACCAAGAAGAAATATTATGTCAAGACTTACAGAGTAGACATCAGCTCCA ACGGAGAGGACTGGATCTCCCTGAAAGAGGGAAATAAAGCCATTATCTTTCAGGGAAACA CCAACCCCACAGATGTTGTCTTAGGAGTTTTCTCCAAACCACTGATAACTCGATTTGTCC GAATCAAACCTGTATCCTGGGAAACTGGTATATCTATGAGATTTGAAGTTTATGGCTGCA AGATAACAGATTATCCTTGCTCTGGAATGTTGGGCATGGTGTCTGGACTTATTTCAGACT CCCAGATTACAGCATCCAATCAAGCCGACAGGAATTGGATGCCAGAAAACATCCGTCTGG TGACCAGTCGTACCGGCTGGGCACTGCCACCCTCACCCCACCCATACACCAATGAATGGC TCCAAGTGGACCTGGGAGATGAGAAGATAGTAAGAGGTGTCATCATTCAGGGTGGGAAGC ACCGAGAAAACAAGGTGTTCATGAGGAAGTTCAAGATCGCCTATAGTAACAATGGCTCTG ACTGGAAAACTATCATGGATGACAGCAAGCGCAAGGCTAAGTCGTTCGAAGGCAACAACA ACTATGACACACCTGAGCTTCGGACGTTTTCACCTCTCTCCACAAGGTTCATCAGGATCT ACCCTGAGAGAGCCACACACAGTGGGCTTGGGCTGAGGATGGAGCTACTGGGCTGTGAAG TGGAAGCACCTACAGCTGGACCAACCACACCCAATGGGAACCCAGTGCATGAGTGTGACG ACGACCAGGCCAACTGCCACAGTGGCACAGGTGATGACTTCCAGCTCACAGGAGGCACCA CTGTCCTGGCCACAGAGAAGCCAACCATTATAGACAGCACCATCCAATCAGAGTTCCCGA CATACGGTTTTAACTGCGAGTTTGGCTGGGGCTCTCACAAGACATTCTGCCACTGGGAGC ATGACAGCCATGCACAGCTCAGGTGGAGTGTGCTGACCAGCAAGACAGGGCCGATTCAGG ACCATACAGGAGATGGCAACTTCATCTATTCCCAAGCTGATGAAAATCAGAAAGGCAAAG TAGCCCGCCTGGTGAGCCCTGTGGTCTATTCCCAGAGCTCTGCCCACTGTATGACCTTCT GGTATCACATGTCCGGCTCTCATGTGGGTACACTGAGGGTCAAACTACGCTACCAGAAGC CAGAGGAATATGATCAACTGGTCTGGATGGTGGTTGGGCACCAAGGAGACCACTGGAAAG AAGGACGTGTCTTGCTGCACAAATCTCTGAAACTATATCAGGTTATTTTTGAAGGTGAAA TCGGAAAAGGAAACCTTGGTGGAATTGCTGTGGATGATATCAGTATTAACAACCATATTT CTCAGGAAGACTGTGCAAAACCAACAGACCTAGATAAAAAGAACACAGAAATTAAAATTG ATGAAACAGGGAGCACTCCAGGATATGAAGGAGAAGGGGAAGGTGACAAGAACATCTCCA GGAAGCCAGGCAATGTGCTTAAGACCCTGGATCCCATCCTGATCACCATCATAGCCATGA GTGCCCTGGGAGTACTCCTGGGTGCAGTCTGTGGAGTTGTGCTGTACTGTGCCTGTTGGC ACAATGGGATGTCAGAAAGGAACCTATCTGCCCTGGAGAACTATAACTTTGAACTTGTGG ATGGTGTAAAGTTGAAAAAAGATAAACTGAACCCACAGAGTAATTACTCAGAGGCGTGAA GGCACGGAGCTGGAGGGAACAAGGGAGGAGCACGGCAGGAGAACAGGTGGAGGCATGGGG ACTCTGTTACTCTGCTTTCACTGTAAGCTGGGAAGGGCGGGGACTCTGTTACTCCGCTTT CACTGTAAGCTCGGAAGGGCATCCACGATGCCATGCCAGGCTTTTCTCAGGAGCTTCAAT GAGCGTCACCTACAGACACAAGCAGGTGACTGCGGTAACAACAGGAATCATGTACAAGCC TGCTTTCTTCTCTTGGTTTCATTTGGGTAATCAGAAGCCATTTGAGACCAAGTGTGACTG ACTTCATGGTTCATCCTACTAGCCCCCTTTTTTCCTCTCTTTCTCCTTACCCTGTGGTGG ATTCTTCTCGGAAACTGCAAAATCCAAGATGCTGGCACTAGGCGTTATTCAGTGGGCCCT TTTGATGGACATGTGACCTGTAGCCCAGTGCCCAGAGCATATTATCATAACCACATTTCA

GGGGACGCCAACGTCCATCCACCTTTGCATCGCTACCTGCAGCGAGCACA GG

Nrpl Mouse Protein

MERGLPLLCATLALALALAGAFRSDKCGGTIKIENPGYLTSPGYPHSYHPSEKCEWLIQA PEPYQRIMINFNPHFDLEDRDCKYDYVEVIDGENEGGRLWGKFCGKIAPSPWSSGPFLF IKFVSDYETHGAGFSIRYEIFKRGPECSQNYTAPTGVIKSPGFPEKYPNSLECTYIIFAP KMSEIILEFESFDLEQDSNPPGGMFCRYDRLEIWDGFPEVGPHIGRYCGQKTPGRIRSSS GVLSMVFYTDSAIAKEGFSANYSVLQSSISEDFKCMEALGMESGEIHSDQITASSQYGTN WSVERSRLNYPENGWTPGEDSYKEWIQVDLGLLRFVTAVGTQGAISKETKKKYYVKTYRV DI SSNGEDWI SLKEGNKAI I FQGNTNPTDWLGVFSKPLITRFVRIKPVSWETGI SMRFE VYGCKITDYPCSGMLGMVSGLISDSQITASNQADRNWMPENIRLVTSRTGWALPPSPHPY TNEWLQVDLGDEKIVRGVIIQGGKHRENKVFMRKFKIAYSNNGSDWKTIMDDSKRKAKSF EGNNNYDTPELRTFSPLSTRFIRIYPERATHSGLGLRMELLGCEVEAPTAGPTTPNGNPV DECDDDQANCHSGTGDDFQLTGGTTVLATEKPTIIDSTIQSEFPTYGFNCEFGWGSHKTF CHWEHDSHAQLRWSVLTSKTGPIQDHTGDGNFIYSQADENQKGKVARLVSPWYSQSSAH CMTFWYHMSGSHVGTLRVKLRYQKPEEYDQLVWMWGHQGDHWKEGRVLLHKSLKLYQVI FEGEIGKGNLGGIAVDDISINNHISQEDCAKPTDLDKKNTEIKIDETGSTPGYEGEGEGD KNI SRKPGNVLKTLDPI LITI IAMSALGVLLGAVCGWLYCACWHNGMSERNLSALENYN

FELVDGVKLKKDKLNPQ SNYSEA

Mcam Human DNA

GGGAAGCATGGGGCTTCCCAGGCTGGTCTGCGCCTTCTTGCTCGCCGCCTGCTGCTGCTG TCCTCGCGTCGCGGGTGTGCCCGGAGAGGCTGAGCAGCCTGCGCCTGAGCTGGTGGAGGT GGAAGTGGGCAGCACAGCCCTTCTGAAGTGCGGCCTCTCCCAGTCCCAAGGCAACCTCAG CCATGTCGACTGGTTTTCTGTCCACAAGGAGAAGCGGACGCTCATCTTCCGTGTGCGCCA GGGCCAGGGCCAGAGCGAACCTGGGGAGTACGAGCAGCGGCTCAGCCTCCAGGACAGAGG GGCTACTCTGGCCCTGACTCAAGTCACCCCCCAAGACGAGCGCATCTTCTTGTGCCAGGG CAAGCGCCCTCGGTCCCAGGAGTACCGCATCCAGCTCCGCGTCTACAAAGCTCCGGAGGA GCCAAACATCCAGGTCAACCCCCTGGGCATCCCTGTGAACAGTAAGGAGCCTGAGGAGGT CGCTACCTGTGTAGGGAGGAACGGGTACCCCATTCCTCAAGTCATCTGGTACAAGAATGG CCGGCCTCTGAAGGAGGAGAAGAACCGGGTCCACATTCAGTCGTCCCAGACTGTGGAGTC GAGTGGTTTGTACACCTTGCAGAGTATTCTGAAGGCACAGCTGGTTAAAGAAGACAAAGA TGCCCAGTTTTACTGTGAGCTCAACTACCGGCTGCCCAGTGGGAACCACATGAAGGAGTC CAGGGAAGTCACCGTCCCTGTTTTCTACCCGACAGAAAAAGTGTGGCTGGAAGTGGAGCC CGTGGGAATGCTGAAGGAAGGGGACCGCGTGGAAATCAGGTGTTTGGCTGATGGCAACCC T C C AC C AC AC T T C AG CAT C AG C AAG CAGAAC C C C AG C AC C AG G GAG G C AGAG GAAGAGAC AACCAACGACAACGGGGTCCTGGTGCTGGAGCCTGCCCGGAAGGAACACAGTGGGCGCTA TGAATGTCAGGCCTGGAACTTGGACACCATGATATCGCTGCTGAGTGAACCACAGGAACT ACTGGTGAACTATGTGTCTGACGTCCGAGTGAGTCCCGCAGCCCCTGAGAGACAGGAAGG CAGCAGCCTCACCCTGACCTGTGAGGCAGAGAGTAGCCAGGACCTCGAGTTCCAGTGGCT GAGAGAAGAGACAGACCAGGTGCTGGAAAGGGGGCCTGTGCTTCAGTTGCATGACCTGAA ACGGGAGGCAGGAGGCGGCTATCGCTGCGTGGCGTCTGTGCCCAGCATACCCGGCCTGAA CCGCACACAGCTGGTCAAGCTGGCCATTTTTGGCCCCCCTTGGATGGCATTCAAGGAGAG GAAGGTGTGGGTGAAAGAGAATATGGTGTTGAATCTGTCTTGTGAAGCGTCAGGGCACCC CCGGCCCACCATCTCCTGGAACGTCAACGGCACGGCAAGTGAACAAGACCAAGATCCACA GCGAGTCCTGAGCACCCTGAATGTCCTCGTGACCCCGGAGCTGTTGGAGACAGGTGTTGA ATGCACGGCCTCCAACGACCTGGGCAAAAACACCAGCATCCTCTTCCTGGAGCTGGTCAA T T T AAC C AC C C T C AC AC C AGAC T C C AAC AC AAC C AC T G G C C T C AG C AC T T C C AC T G C C AG T C C T CAT AC C AGAG C C AAC AG C AC C T C C AC AGAGAGAAAG C T G C C G GAG C C G GAGAG C C G GGGCGTGGTCATCGTGGCTGTGATTGTGTGCATCCTGGTCCTGGCGGTGCTGGGCGCTGT CCTCTATTTCCTCTATAAGAAGGGCAAGCTGCCGTGCAGGCGCTCAGGGAAGCAGGAGAT CACGCTGCCCCCGTCTCGTAAGACCGAACTTGTAGTTGAAGTTAAGTCAGATAAGCTCCC AGAAGAGATGGGCCTCCTGCAGGGCAGCAGCGGTGACAAGAGGGCTCCGGGAGACCAGGG AGAGAAATACATCGATCTGAGGCATTAGCCCCGAATCACTTCAGCTCCCTTCCCTGCCTG GACCATTCCCAGCTCCCTGCTCACTCTTCTCTCAGCCAAAGCTCAAAGGGACTAGAGAGA AGCCTCCTGCTCCCCTCGCCTGCACACCCCCTTTCAGAGGGCCACTGGGTTAGGACCTGA GGACCTCACTTGGCCCTGCAAGGCCCGCTTTTCAGGGACCAGTCCACCACCATCTCCTCC ACGTTGAGTGAAGCTCATCCCAAGCAAGGAGCCCCAGTCTCCCGAGCGGGTAGGAGAGTT TCTTGCAGAACGTGTTTTTTCTTTACACACATTATGCTGTAAATACGCTCGTCCTGCCAG CAGCTGAGCTGGGTAGCCTCTCTGAGCTGGTTTCCTGCCCCAAAGGCTGGCATTCCACCA TCCAGGTGCACCACTGAAGTGAGGACACACCGGAGCCAGGCGCCTGCTCATGTTGAAGTG CGCTGTTCACACCCGCTCCGGAGAGCACCCCAGCAGCATCCAGAAGCAGCTGCAGTGCAA GCTTGCATGCCTGCGTGTTGCTGCACCACCCTCCTGTCTGCCTCTTCAAAGTCTCCTGTG ACATTTTTTCTTTGGTCAGAGGCCAGGAACTGTGTCATTCCTTAAAGATACGTGCCGGGG CCAGGTGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGCGGATCACAA AGT C AGAC GAGAC CAT C C T G G C T AACAC G GT GAAAC CCTGTCTCTAC T AAAAAT AC AAAA AAAAATTAGCTAGGCGTAGTGGTTGGCACCTATAGTCCCAGCTACTCGGAAGGCTGAAGC AGGAGAATGGTATGAATCCAGGAGGTGGAGCTTGCAGTGAGCCGAGACCGTGCCACTGCA CTCCAGCCTGGGCAACACAGCGAGACTCCGTCTCGAGCCGGCCGGTTGCGCGGGCCCTCG GACCCTCAGAGAGGCGAGGGTTCGAGGGCACGAGTTCGAGGCCAACCTGGTCCACATGGG

TTG

Mcam Mouse DNA

CGCCCTCCGTCGGGGAAGCATGGGGCTGCCCAAACTGGTGTGCGTCTTCTTGTTCGCTGC CTGCTGCTGCTGTCGCCGTGCCGCGGGTGTGCCAGGAGAGGAAAAGCAGCCAGTACCCAC GCCCGACCTGGTGGAGGCAGAAGTGGGCAGCACAGCCCTTCTCAAGTGTGGCCCCTCACG GGCCTCAGGCAACTTCAGCCAAGTGGACTGGTTTTTGATTCACAAGGAGAGGCAGATACT GATTTTCCGTGTGCACCAAGGCAAGGGCCAGCGGGAACCTGGTGAATATGAGCACCGCCT TAGCCTCCAAGACTCGGTGGCTACTCTGGCCCTGAGTCACGTCACTCCCCATGATGAGCG AATGTTCCTGTGTAAGAGCAAGCGACCACGGCTCCAGGATCACTACGTTGAGCTTCAGGT CTTCAAAGCCCCAGAGGAACCAACTATTCAAGCCAATGTCGTGGGCATCCATGTGGACAG GCAAGAGCTCAGGGAGGTTGCTACCTGTGTGGGGAGAAACGGCTACCCCATTCCTCAAGT C C TAT G GT AC AAGAAC AGT CTGCCCTTG C AAGAG GAG GAGAAC C GAGT T CAT AT C C AGT C ATCACAGATTGTCGAGTCCAGTGGCTTGTACACCTTGAAGAGTGTTCTGAGTGCACGCCT AGT T AAG GAAGAC AAAGAT G C C C AGT T T T AC T GT GAAC T C AG CTACCGGCTACC C AGT G G GAACCACATGAAGGAATCTAAGGAGGTCACTGTCCCTGTTTTCTACCCTGCAGAAAAAGT GTGGGTGGAGGTAGAGCCTGTGGGGCTGCTGAAGGAAGGGGATCATGTGACAATCAGGTG T C T GAC AGAT G G C AAC C C T C AAC C C CAC T T C AC TAT C AAC AAGAAG GAC C C C AG C AC T G G GGAGATGGAAGAGGAGAGCACCGATGAAAATGGGCTCCTGTCCTTGGAGCCTGCCGAAAA GCACCATAGCGGGCTCTACCAGTGTCAGAGTCTGGACCTGGAAACTACCATCACACTGTC AAGTGACCCCCTGGAGCTGCTGGTGAACTATGTGTCTGATGTTCAAGTGAATCCAACTGC C C C T GAAGT C C AG GAAG GT GAGAG C CT CAC G C T GAC C T G C GAG G C AGAAAGT AAC C AG GA CCTTGAGTTTGAGTGGCTGAGAGACAAGACAGGCCAGCTGCTGGGAAAGGGTCCCGTCCT CCAGCTAAACAACGTGAGACGGGAAGCAGGGGGACGGTATCTCTGCATGGCATCTGTCCC CAGAGTTCCTGGCTTGAATCGTACCCAGCTGGTCAGCGTGGGCATTTTTGGGTCCCCATG GAT GGCATTAAAGGAGAGGAAGGT GTGGGT GCAAGAGAAT GCAGT GCT GAAT CT GT CTT G TGAGGCTTCAGGACATCCTCAGCCCACCATCTCCTGGAATGTCAATGGTTCGGCAACTGA AT G GAAC C C AGAT C C AC AGAC AGT AGT GAG CAC CTT GAAT GTCCTTGT GAC G C C AGAG C T T C T G GAGAC AG GT G C AGAGT GT AC AGC C T C C AAC TCCCTGGGCT C AAAC AC CAC CAC CAT TGTTCTGAAGCTGGTCACTTTAACCACCCTCATACCTGACTCCAGCCAAACCACTGGCCT C AG CAC C C T CAC AGT C AGT C C T CAC AC C AGAG C C AAC AG CAC C T C C AC AGAGAAAAAG C T GCCACAGCCAGAGAGCAAAGGTGTGGTCATCGTGGCTGTGATAGTGTGTACCTTGGTGCT TGCTGTGCTGGGTGCTGCTCTCTATTTCCTCTACAAGAAGGGCAAGCTGCCATGTGGACG CTCGGGAAAACAGGAGATCACGCTGCCCCCGACTCGTAAGAGTGAATTTGTAGTTGAAGT T AAGT C AGAT AAG C T C C C AGAAGAGAT GGCTCTCCTT C AG G G C AG C AAC G GT GAC AAGAG G G C T C C AG GAGAC C AG G GAGAGAAAT AC AT C GAT C T GAG G CAT T AGAT G G C T C C CAT T G C ACTGCTCGCAGCTCCCTGCTCAGACTTCACCCCAAGCTGAAGCCTCCAGAGGGACAGCAG GGACGAGCCACACTCAACCCCCCCCCTGCACATCAGGTCTGAGAGCTAGGAGCTGGGACA GGAGTCGTCTGCAGGAGCTCAGTTGGCCACAGAGGCCTGGTTTTAGAGACCAAGCCCTCC TCTGTGTCCAGTAAATAATGCTTATCCCAAGGGGCCCGTCTCCCAGGGCATTTCCCCCTC CCGTGCACAGCCATTGGTGGCAAATCCTTCTGCCATCAGCTGTGTGGGCTTGCCTCTTTG AGCTCATCTCCCCTCACAGGCTGTCTTCATGATGCAGGACCTGGGCACATGGTCACATTA TTCCGTTCACATTGGTCCTTGTGAGAACCTCACAGTCTGGAGGCGGCTGCTTTTGTACCT TCCTGCCTGCTACTAATTCAGGGTCTCATTTGGAACATTTTTCCTTTGGGTAGTGGTCAG GAACTGGTGTAAGTCCTCCAGACACATCCCTGTGTAAGGAAGCCAGGGCACTGTTTCTCT GAGTTTTGTTGTTTTGTTTTCTTTGAAGGCTACTGAGCCCAAGCTTCCCGCATTCCCTTA GT AAC AAGAGAC AG GAC AGAGAGAAGGT CTACTGTT CAT G G G GAT T AG G C T TAT AG GAAT GTTAGTACCAAATTTCTACATGTGAGCTTTGGGGGCCAGGTCCTAGAGAGCCCAAGTGGG AGAATGGTATTTAGGAGATGAAAAACCTGGCCTAGCAAGAGCTTTTGAGGTGTGTGTGTG T GT GT GT GT AT ACAT AT AT GT GT GT AT AT AT AT AT AT AT AT AT AT AGGT T T T GT CT GT AA AT T T GCAAAT T T T T C CT T T TAT AT GT GT GT T AGAAAAAT AAAGT GT TAT T GT C C CAAAAA

AAAAAAAAAA

Mcam Mouse Protein

MGLPKLVCVFLFAAC C C C RRAAGVP GEEKQPVPTPD L VEAE VG S T AL LKCGPSRASGNFS QVDWFLIHKERQI LI FRVHQGKGQREPGEYEHRLSLQDSVATLALSHVTPHDERMFLCKS KRPRLQDHYVELQVFKAPEEPTIQANWGIHVDRQELREVATCVGRNGYPI PQVLWYKNS LPLQEEENRVHIQS SQIVES SGLYTLKSVLSARLVKEDKDAQFYCELSYRLPSGNHMKES KEVTVPVFYPAEKVWVEVEPVGLLKEGDHVTI RCLTDGNPQPHFTINKKDPSTGEMEEES TDENGLLSLEPAEKHHSGLYQCQSLDLETTITLS SDPLELL YVSDVQ PTAPEVQEG ESLTLTCEAESNQDLEFEWLRDKTGQLLGKGPVLQLNNVRREAGGRYLCMASVPRVPGLN RTQLVSVGI FGS PWMALKERKVWVQENAVLNLSCEASGHPQPTI SWN GSATEWNPDPQ TWSTLNVLVTPELLETGAECTASNSLGSNTTTIVLKLVTLTTLI PDS SQTTGLSTLTVS PHTRANSTSTEKKLPQPESKGWIVAVIVCTLVLAVLGAALYFFYKKGKLPCGRSGKQEI

TLPPTRKSEFVVEVKSDKLPEEMALLQGSNGDKRAPGDQGEKYIDLRH

Pbk Human DNA

GTAAGAAAGCCAGGAGGGTTCGAATTGCAACGGCAGCTGCCGGGCGTATGTGTTGGTGCT AGAGGCAGCTGCAGGGTCTCGCTGGGGGCCGCTCGGGACCAATTTTGAAGAGGTACTTGG CCACGACTTATTTTCACCTCCGACCTTTCCTTCCAGGCGGTGAGACTCTGGACTGAGAGT G G C T T T C AC AAT G GAAG G GAT C AGT AAT T T C AAGAC AC C AAG C AAAT TAT C AGAAAAAAA GAAATCTGTATTATGTTCAACTCCAACTATAAATATCCCGGCCTCTCCGTTTATGCAGAA GCTTGGCTTTGGTACTGGGGTAAATGTGTACCTAATGAAAAGATCTCCAAGAGGTTTGTC TCATTCTCCTTGGGCTGTAAAAAAGATTAATCCTATATGTAATGATCATTATCGAAGTGT GT AT C AAAAGAGAC T AAT G GAT GAAGC T AAGAT T T T GAAAAG C C T T CAT CAT C C AAAC AT TGTTGGTTATCGTGCTTTTACTGAAGCCAATGATGGCAGTCTGTGTCTTGCTATGGAATA TGGAGGT GAAAAGT CT CTAAAT GAC T T AAT AGAAGAAC GAT AT AAAG C C AG C C AAGAT C C TTTTCCAGCAGCCATAATTTTAAAAGTTGCTTTGAATATGGCAAGAGGGTTAAAGTATCT G C AC C AAGAAAAGAAAC T G C T T CAT GGAGAC AT AAAGT C T T C AAAT GT T GT AAT T AAAG G C GAT T T T GAAAC AAT T AAAAT C T GT GAT GT AG GAGT CTCTCTAC C AC T G GAT GAAAAT AT GAC T GT GAC T GAC C C T GAG G C T T GT T AC AT T G G C AC AGAG C CAT G GAAAC C C AAAGAAG C TGTGGAGGAGAATGGTGTTATTACTGACAAGGCAGACATATTTGCCTTTGGCCTTACTTT GT G G GAAAT GAT GAC T T TAT C GAT T C C AC AC AT T AAT C T T T C AAAT GAT GAT GAT GAT GA AGAT AAAAC T T T T GAT GAAAGT GAT T T T GAT GAT GAAG CAT AC TAT G C AG C C T T G G GAAC T AG G C C AC C TAT T AAT AT G GAAGAACT G GAT GAAT CAT AC C AGAAAGT AAT T GAAC T C T T CTCTGTATGCACTAATGAAGACCCTAAAGATCGTCCTTCTGCTGCACACATTGTTGAAGC TCTGGAAACAGATGTCTAGTGATCATCTCAGCTGAAGTGTGGCTTGCGTAAATAACTGTT TAT T C C AAAAT AT T T AC AT AGT T AC TAT C AGT AGT TAT T AGAC T C T AAAAT T G G CAT AT T T GAG GAC C AT AGT T T C T T GT T AAC AT AT G GAT AAC TAT T T C T AAT AT GAAAT AT G C T TAT ATTGGCTATAAGCACTTGGAATTGTACTGGGTTTTCTGTAAAGTTTTAGAAACTAGCTAC AT AAGT AC T T T GAT AC T G C T CAT G C T GAC T T AAAAC AC TAG C AGT AAAAC G C T GT AAAC T GT AAC AT T AAAT T GAAT GAC CAT TACTTTTAT T AAT GAT C T T T C T T AAAT AT T C T AT AT T T T AAT G GAT C T AC T GAC AT TAG C AC T T T GT AC AGT AC AAAAT AAAGT C T AC AT T T GT T T A

AAACAAAAAAAAAAAAAAAAAA

Pbk Mouse DNA

GAGGGGAGCTGTTCCTGCATTTTCTGGAGCGAGTCTTCTGACTGCTTTTAGTTAGAACTC CAGTGCCCCTCGGCGGGCCGCGGCCTTTGAAAATGCGCGCGCCCTAAACGCTGCGGCGGT TACGCTGTTGGCGGGAGGGAGCTGAGCCTGCACTTTCCGGACTAGGTGTCCAGACAGCTT TGAGCCAGCCCGTCACTTTCACCTTTTTACCCGAGCGTGCGAGCGTGGACCTAACGTGAT T G C T AC AAT G GAAG GAAT T AAT AAT T T C AAGAC G C C AAAC AAAT C T GAAAAAAG GAAAT C TGTATTATGTTCCACTCCATGTGTAAATATCCCTGCCTCTCCATTTATGCAGAAGCTTGG CTTTGGGACTGGGGTCAGCGTTTACCTAATGAAAAGATCTCCAAGAGGGTTGTCTCATTC TCCTTGGGCCGTGAAAAAGATAAGTCTTTTATGCGATGATCATTATCGAACTGTGTATCA GAAGAGAC T AAC T GAT GAAG C T AAGAT T T T AAAAAAC C T T AAT C AC C C AAAC AT TAT AG G ATATCGTGCTTTTACTGAAGCCAGTGATGGTAGTCTGTGCCTTGCTATGGAGTATGGAGG T GAAAAGT C T C T GAAT GAC T T AAT AGAAGAG C G GAAC AAAGAC AGT G GAAGT CCTTTTCC AGCAGCTGTAATTCTCAGAGTTGCTTTGCACATGGCCAGAGGGCTAAAGTACCTGCACCA AGAAAAGAAG C T G C T T CAT G GAGAC AT AAAGT C T T C AAAT GT T GT AAT T AAAG GT GAT T T T GAAAC AAT T AAAAT CT GT GAT GTAGGAGT CT CT CT GCCATT GGAT GAAAAT AT GACT GT GACTGATCCTGAGGCCTGTTATATTGGTACTGAGCCATGGAAACCCAAGGAAGCGTTGGA AGAAAATGGCATCATTACTGACAAGGCAGATGTGTTTGCTTTTGGCCTTACTCTGTGGGA AAT GAT GAC T T T AT GT AT T C C AC AC GT C AAT C T T C C AGAT GAT GAT GT T GAT GAAGAT G C AACCTTTGATGAGAGTGACTTCGATGATGAAGCATATTATGCAGCTCTGGGGACAAGGCC ATCCATCAACATGGAAGAGCTGGATGACTCCTACCAGAAGGCCATTGAACTCTTCTGTGT GTGCACTAATGAGGATCCTAAAGATCGCCCGTCTGCTGCACACATCGTTGAAGCTTTGGA ACTAGATGGCCAATGTTGTGGTCTAAGCTCAAAGCATTAACTTGTATGGGAACTGTTAAC T AGAT AT AT GT AGT T AAT AT AAC T TAT G GT AG C T AGAT T C T AGAAGT AG C T T T AAC AC T A GTGACCCCTGTCTAAGATGACTTAAGAATCAAGGGACCATTGCTTTGTTACAGATCTTTT TAGATATTCTTGCTTCTTTAGTGGGTTACTAAAAATTTCACTACGTACATGTGGTACAGA TATCTGTCTGCTCATAGTGTCAGTCCTTCAGCTGGCCTGTCAGCCCATGCGCCCTGGGAC TTGAGAAGAGTTCATAAACGTAGCTCCTAGGGTGTCTTGCCTCTCTACACTTAGCTTCTA ATTTATTACTTTGTTTCTACTGATTGTGTCTTAAGTCTTTTAAAATAAATGTAAGAATAA

ACAATAAAAGACAGTTTTAGTACCAGGCAAAAAAAAAAAAAAAAAA

Pbk Mouse Protein

MEGINNFKTPNKSEKRKSVLCSTPCVNI PAS PFMQKLGFGTGVSVYLMKRS PRGLSHS PW AVKKI SLLCDDHYRTVYQKRLTDEAKI LKNLNHPNI I GYRAFTEASDGSLCLAMEYGGEK SLNDLI EERNKDSGS PFPAAVI LRVALHMARGLKYLHQEKKLLHGDI KS SNWI KGDFET I KI CDVGVSLPLDENMTVTDPEACYIGTEPWKPKEALEENGI ITDKADVFAFGLTLWEMM TLCI PH LPDDDVDEDATFDESDFDDEAYYAALGTRPS INMEELDDSYQKAI ELFCVCT EDPKDRPSAAHIVEALELDGQCCGLSSKH

Akrlcl Human DNA CCAGAAATGGATTCGAAATATCAGTGTGTGAAGCTGAATGATGGTCACTTCATGCCTGTC CTGGGATTTGGCACCTATGCGCCTGCAGAGGTTCCTAAAAGTAAAGCTTTAGAGGCCACC AAATTGGCAATTGAAGCTGGCTTCCGCCATATTGATTCTGCTCATTTATACAATAATGAG GAGCAGGTTGGACTGGCCATCCGAAGCAAGATTGCAGATGGCAGTGTGAAGAGAGAAGAC ATATTCTACACTTCAAAGCTTTGGTGCAATTCCCATCGACCAGAGTTGGTCCGACCAGCC TTGGAAAGGTCACTGAAAAATCTTCAATTGGATTATGTTGACCTCTACCTTATTCATTTT CCAGTGTCTGTAAAGCCAGGTGAGGAAGTGATCCCAAAAGATGAAAATGGAAAAATACTA TTTGACACAGTGGATCTCTGTGCCACGTGGGAGGCCGTGGAGAAGTGTAAAGATGCAGGA TTGGCCAAGTCCATCGGGGTGTCCAACTTCAACCGCAGGCAGCTGGAGATGATCCTCAAC AAGCCAGGGCTCAAGTACAAGCCTGTCTGCAACCAGGTGGAATGTCATCCTTACTTCAAC CAGAGAAAACTGCTGGATTTCTGCAAGTCAAAAGACATTGTTCTGGTTGCCTATAGTGCT CTGGGATCCCACCGAGAAGAACCATGGGTGGACCCGAACTCCCCGGTGCTCTTGGAGGAC CCAGTCCTTTGTGCCTTGGCAAAAAAGCACAAGCGAACCCCAGCCCTGATTGCCCTGCGC TACCAGCTACAGCGTGGGGTTGTGGTCCTGGCCAAGAGCTACAATGAGCAGCGCATCAGA CAGAACGTGCAGGTGTTTGAATTCCAGTTGACTTCAGAGGAGATGAAAGCCATAGATGGC CTAAACAGAAATGTGCGATATTTGACCCTTGATATTTTTGCTGGCCCCCCTAATTATCCA TTTTCTGATGAATATTAACATGGAGGGCATTGCATGAGGTCTGCCAGAAGGCCCTGCGTG TGGATGGTGACACAGAGGATGGCTCTATGCTGGTGACTGGACACATCGCCTCTGGTTAAA TCTCTCCTGCTTGGTGATTTCAGCAAGCTACAGCAAAGCCCATTGGCCAGAAAGGAAAGA CAATAATTTTGTTTTTTCATTTTGAAAAAATTAAATGCTCTCTCCTAAAGATTCTTCACC

TAAAAAA

Akrlcl Human Protein

MDSKYQCVKLNDGHFMPVLGFGTYAPAEVPKSKALEATKLAIEAGFRHIDSAHLYNNEEQ VGLAIRSKIADGSVKREDIFYTSKLWCNSHRPELVRPALERSLKNLQLDYVDLYLIHFPV SVKPGEEVIPKDENGKILFDTVDLCATWEAVEKCKDAGLAKSIGVSNFNRRQLEMILNKP GLKYKPVCNQVECHPYFNQRKLLDFCKSKDIVLVAYSALGSHREEPWVDPNSPVLLEDPV LCALAKKHKRTPALIALRYQLQRGVWLAKSYNEQRIRQNVQVFEFQLTSEEMKAIDGLN

RNVRYLTLDIF AGPPNYPF SDE Y

Akrlcl Mouse DNA

TTGTCCTGACTCTGTTCTGCAGCCCTGATTGATTAGTAGCAGCTTGGTTACAATACATTT TTGTCATCTGCATTGACCTGGTCTTTAAGTTATATTGGATTTATGTTGGATTTAAGTGGA CCCACAACACTTTGAGGAAGAAGAAGACACTCTTCTTACTTTGGAGTACCCAGTGATATC AGGAAAGTCAGAGGCAGAGCCTGCAGATGAATCCCAAGCGCTACATGGAACTAAGTGATG GCCACCACATTCCTGTGCTTGGCTTTGGAACCTTTGTCCCAGGAGAGGTTTCCAAGAGTA TGGTTGCAAAAGCCACCAAAATAGCTATAGATGCTGGATTCCGCCATATTGACTCAGCTT ATTTCTACCAAAATGAGGAGGAAGTAGGGCTGGCCATCCGAAGCAAGGTTGCTGATGGCA CTGTGAGGAGAGAAGATATATTCTACACTTCAAAGCTTCCCTGCACATGTCATAGACCAG AGCTGGTCCAGCCTTGCTTGGAACAATCCCTGAGAAAGCTTCAGCTGGATTATGTTGATC TGTACCTTATTCACTGCCCAGTGTCCATGAAGCCAGGCAATGATCTTATTCCAACAGATG AAAATGGGAAATTATTATTTGACACAGTGGATCTCTGTGACACATGGGAGGCCATGGAGA AGTGTAAGGATTCAGGGTTAGCCAAGTCCATTGGTGTGTCCAACTTTAACCGGAGGCAGC TGGAGATGATCCTGAACAAGCCAGGGCTCAGGTACAAGCCTGTGTGCAACCAGGTAGAGT GTCACCCTTATCTGAACCAGAGCAAGCTCCTGGACTACTGCAAGTCAAAAGACATCGTTC TGGTTGCCTATGGTGCTCTTGGCAGCCAACGGTGTAAGAACTGGATAGAGGAGAATGCCC CATATCTCTTGGAAGACCCAACTCTGTGTGCCATGGCGGAAAAGCACAAGCAAACTCCGG CCCTAATTTCCCTCCGGTATCTGCTGCAGCGTGGGATTGTCATTGTCACCAAGAGTTTCA ATGAGAAGCGGATCAAGGAGAACCTGAAGGTCTTTGAGTTCCACTTGCCAGCAGAGGACA TGGCAGTTATAGATAGGCTGAACAGAAACTACCGATATGCTACTGCTCGTATTATTTCTG CTCACCCCAATTATCCATTTTTGGATGAATATTAACGCGGAAGCCTTTGTTGTGACATCG CTCAGAGGGAGCAATGTGGGAGATGCTGTGGATGTTGATCAGCATCACCTCTGGTCGACG TCGACATCACCGTCAACCCACACTGAACTGGATGGAGAGGGGTGGCCATGGTGTTTTGTG

ATACTTTGAAGACAATAAAGTTTTGGTCTATGAGGT

Akrlcl Mouse Protein

MNPKRYMELSDGHHIPVLGFGTFVPGEVSKSMVAKATKIAIDAGFRHIDSAYFYQNEEEV GLAIRSKVADGTVRREDIFYTSKLPCTCHRPELVQPCLEQSLRKLQLDYVDLYLIHCPVS MKPGNDLIPTDENGKLLFDTVDLCDTWEAMEKCKDSGLAKSIGVSNFNRRQLEMILNKPG LRYKPVCNQVECHPYLNQSKLLDYCKSKDIVLVAYGALGSQRCKNWIEENAPYLLEDPTL CAMAEKHKQTPALISLRYLLQRGIVIVTKSFNEKRIKENLKVFEFHLPAEDMAVIDRLNR

NYRYATARIISAHPNYPFLDEY Cypl lal Human DNA

GGGCGCTGAAGTGGAGCAGGTACAGTCACAGCTGTGGGGACAGCATGCTGGCCAAGGGTC TTCCCCCACGCTCAGTCCTGGTCAAAGGCTACCAGACCTTTCTGAGTGCCCCCAGGGAGG GGCTGGGGCGTCTCAGGGTGCCCACTGGCGAGGGAGCTGGCATCTCCACCCGCAGTCCTC GCCCCTTCAATGAGATCCCCTCTCCTGGTGACAATGGCTGGCTAAACCTGTACCATTTCT G GAG G GAGAC G G G C AC AC AC AAAGT C C AC C T T C AC CAT GT C C AGAAT T T C C AGAAGT AT G GCCCGATTTACAGGGAGAAGCTCGGCAACGTGGAGTCGGTTTATGTCATCGACCCTGAAG ATGTGGCCCTTCTCTTTAAGTCCGAGGGCCCCAACCCAGAACGATTCCTCATCCCGCCCT GGGTCGCCTATCACCAGTATTACCAGAGACCCATAGGAGTCCTGTTGAAGAAGTCGGCAG CCTGGAAGAAAGACCGGGTGGCCCTGAACCAGGAGGTGATGGCTCCAGAGGCCACCAAGA ACTTTTTGCCCCTGTTGGATGCAGTGTCTCGGGACTTCGTCAGTGTCCTGCACAGGCGCA TCAAGAAGGCGGGCTCCGGAAATTACTCGGGGGACATCAGTGATGACCTGTTCCGCTTTG CCTTTGAGTCCATCACTAACGTCATTTTTGGGGAGCGCCAGGGGATGCTGGAGGAAGTAG TGAACCCCGAGGCCCAGCGATTCATTGATGCCATCTACCAGATGTTCCACACCAGCGTCC CCATGCTCAACCTTCCCCCAGACCTGTTCCGTCTGTTCAGGACCAAGACCTGGAAGGACC AT GT G G C T G CAT G G GAC GT GAT T T T CAGT AAAG C T GAC AT AT AC AC C C AGAAC T T C T AC T G G GAAT T GAGAC AGAAAG GAAGT GT T C AC C AC GAT TACCGTGG CAT G C T C T AC AGAC T C C T G G GAGAC AG C AAGAT GT C C T T C GAGGAC AT C AAG G C C AAC GT C AC AGAGAT G C T G G C AG GAGGGGTGGACACGACGTCCATGACCCTGCAGTGGCACTTGTATGAGATGGCACGCAACC TGAAGGTGCAGGATATGCTGCGGGCAGAGGTCTTGGCTGCGCGGCACCAGGCCCAGGGAG ACATGGCCACGATGCTACAGCTGGTCCCCCTCCTCAAAGCCAGCATCAAGGAGACACTAA GACTTCACCCCATCTCCGTGACCCTGCAGAGATATCTTGTAAATGACTTGGTTCTTCGAG ATTACATGATTCCTGCCAAGACACTGGTGCAAGTGGCCATCTATGCTCTGGGCCGAGAGC CCACCTTCTTCTTCGACCCGGAAAATTTTGACCCAACCCGATGGCTGAGCAAAGACAAGA ACATCACCTACTTCCGGAACTTGGGCTTTGGCTGGGGTGTGCGGCAGTGTCTGGGACGGC G GAT C G C T GAG C T AGAGAT GAC CAT CT T C C T CAT C AAT AT G C T G GAGAAC T T C AGAGT T G AAATCCAACACCTCAGCGATGTGGGCACCACATTCAACCTCATTCTGATGCCTGAAAAGC CCATCTCCTTCACCTTCTGGCCCTTTAACCAGGAAGCAACCCAGCAGTGATCAGAGAGGA TGGCCTGCAGCCACATGGGAGGAAGGCCCAGGGGTGGGGCCCATGGGGTCTCTGCATCTT CAGTCGTCTGTCCCAAGTCCTGCTCCTTTCTGCCCAGCCTGCTCAGCAGGTTGAATGGGT TCTCAGTGGTCACCTTCCTCAGCTCAGCTGGGCCACTCCTCTTCACCCACCCCATGGAGA

CAATAAACAGCTGAACCATCG

Cypl lal Mouse DNA

AAGTGGCAGTCGTGGGGACAGTATGCTGGCTAAAGGACTTTCCCTGCGCTCAGTGCTGGT CAAAGGCTGCCAACCTTTCCTGAGCCCTACGTGGCAGGGTCCAGTGCTGAGTACTGGAAA GGGAGCTGGTACCTCTACTAGCAGTCCTAGGTCCTTCAATGAGATCCCTTCCCCTGGCGA C AAT G GT T G G C T AAAC C T GT AC C AC T T C T G GAG G GAGAGT G G C AC AC AGAAAAT C CAT T A CCATCAGATGCAGAGTTTCCAAAAGTATGGCCCCATTTACAGGGAGAAGCTGGGCACTTT GGAGTCAGTTTACATCGTGGACCCCAAGGATGCGTCGATACTCTTCTCATGCGAGGGTCC CAACCCGGAGCGGTTCCTTGTGCCCCCCTGGGTGGCCTATCACCAGTATTATCAGAGGCC CATTGGGGTCCTGTTTAAGAGTTCAGATGCCTGGAAGAAAGACCGAATCGTCCTAAACCA AGAGGTGATGGCGCCTGGAGCCATCAAGAACTTCGTGCCCCTGCTGGAAGGTGTAGCTCA G GAC T T CAT C AAAGT C T T AC AC AGAC G CAT C AAG C AG C AAAAT T C T G GAAAT T T C T C AG G GGTCATCAGTGATGACCTATTCCGCTTTTCCTTTGAGTCCATCAGCAGTGTTATATTTGG GGAGCGCATGGGGATGCTGGAGGAGATCGTGGATCCCGAGGCCCAGCGGTTCATCAATGC TGTCTACCAGATGTTCCACACCAGTGTCCCCATGCTCAACCTGCCTCCAGACTTCTTTCG ACTCCTCAGAACTAAGACCTGGAAGGACCATGCAGCTGCCTGGGATGTGATTTTCAATAA AG C T GAT GAGT AC AC C C AGAAC T T C T AC T G G GAC T T AAG G C AGAAG C GAGAC T T C AG C C A GTACCCTGGTGTCCTTTATAGCCTCCTGGGGGGCAACAAGCTGCCCTTCAAGAACATCCA GGCCAACATTACCGAGATGCTGGCAGGAGGGGTGGACACGACCTCCATGACCCTGCAGTG GAACCTTTATGAGATGGCACACAACTTGAAGGTACAGGAGATGCTGCGGGCTGAAGTCCT GGCTGCCCGGCGCCAGGCCCAGGGAGACATGGCCAAGATGGTACAGTTGGTTCCACTCCT C AAAG C C AG CAT C AAG GAGAC AC T GAGAC T C C AC C C CAT C T C C GT GAC C T T G C AGAG GT A CACTGTGAATGACCTGGTGCTTCGTAATTACAAGATTCCAGCCAAGACTTTGGTACAGGT GGCTAGCTTTGCCATGGGTCGAGATCCGGGCTTCTTTCCCAATCCAAACAAGTTTGACCC AACTCGTTGGCTGGAAAAAAGCCAAAATACCACCCACTTCCGGTACTTGGGCTTTGGCTG GGGTGTTCGGCAGTGTCTGGGCCGGCGGATTGCGGAGCTGGAGATGACCATCCTCCTTAT CAATCTGCTGGAGAACTTCAGAATTGAAGTTCAAAATCTCCGTGATGTGGGGACCAAGTT CAGCCTCATCCTGATGCCTGAGAACCCCATCCTCTTCAACTTCCAGCCTCTCAAGCAGGA CCTGGGCCCAGCCGTGACCAGAAAAGACAACACTGTGAACTGAAGGCTGGAGTCACATGG GGAGGTGGCCCATGGGGCATTTGAGGGTGGTATCTCTGTATCTTCAGAAACAGCACTCTG TGATTACCTGCCCAGGTTAGCTGGGCTCTCCTCTCCTTCATCCTCTTTCCCTCTTTCCCT

ACCCAGGGAGTTAATAAACACTTGAACACTGAGG

Cypl lal Mouse Protein

MLAKGLSLRSVLVKGCQPFLSPTWQGPVLSTGKGAGTSTSSPRSFNEIPSPGDNGWL NLY HFWRESGTQKIHYHQMQSFQKYGPIYREKLGTLESVYIVDPKDASILFSCEGPNPERFLV PPWVAYHQYYQRPIGVLFKSSDAWKKDRIVLNQEVMAPGAIKNFVPLLEGVAQDFIKVLH RRIKQQNSGNFSGVISDDLFRFSFESISSVIFGERMGMLEEIVDPEAQRFINAVYQMFHT SVPMLNLPPDFFRLLRTKTWKDHAAAWDVI FNKADEYTQNFYWDLRQKRDFSQYPGVLYS LLGGNKLPFKNIQANITEMLAGGVDTTSMTLQWNLYEMAHNLKVQEMLRAEVLAARRQAQ GDMAKMVQLVPLLKASIKETLRLHPISVTLQRYT DLVLRNYKIPAKTLVQVASFAMGR DPGFFPNPNKFDPTRWLEKSQNTTHFRYLGFGWGVRQCLGRRIAELEMTILLINLLENFR

IEVQNLRDVGTKFSLILMPE PILF FQPLKQDLGPAVTRKDNTVN