HIGHLY ENGRAFTABLE HEMATOPOIETIC STEM CELLS
20190060366 ยท 2019-02-28
Inventors
Cpc classification
C12N2501/21
CHEMISTRY; METALLURGY
A61K31/7088
HUMAN NECESSITIES
A61K31/7088
HUMAN NECESSITIES
A61K2035/124
HUMAN NECESSITIES
A61K45/06
HUMAN NECESSITIES
C12N2501/22
CHEMISTRY; METALLURGY
C12N5/0647
CHEMISTRY; METALLURGY
A61K31/395
HUMAN NECESSITIES
A61K2300/00
HUMAN NECESSITIES
A61K2300/00
HUMAN NECESSITIES
A61K31/395
HUMAN NECESSITIES
International classification
Abstract
The present inventions relates to highly engraftable hematopoietic stem cell (heHSC) and related methods of production and use for the treatment of stem cell and progenitor cell disorders.
Claims
1. An isolated, non-native highly engraftable hematopoietic stem cell (heHSC), wherein the heHSC is Sca-1+, c-kit+ and Lin (SKL).
2.-7. (canceled)
8. The isolated heHSC of claim 1, wherein the heHSC is prepared by contacting hematopoietic stem cells and/or progenitor cells with at least one CXCR2 agonist and at least one CXCR4 antagonist, VLA-4 antagonist, a t antagonist, .sub.9.sub.1 integrin/VLA-4 antagonist or combination thereof.
9.-14. (canceled)
15. The isolated heHSC of claim 8, wherein the at least one CXCR2 agonist is GRO or an analog or derivative thereof, and wherein the at least one CXCR4 antagonist is plerixafor or an analog or derivative thereof.
16.-20. (canceled)
21. The isolated heHSC of claim 1, wherein the heHSC is substantially pure.
22.-26. (canceled)
27. An isolated population of cells comprising a plurality of heHSC's of claim 1, wherein the isolated population has a unique cell surface marker expression profile as compared to a naturally occurring population of HSC.
28.-36. (canceled)
37. A method of treating a stem cell or progenitor cell disorder comprising administering a cell population comprising the isolated heHSC of claim 1 to a subject in need thereof, wherein the administered heHSC population engrafts in the subject's bone marrow compartment, thereby treating the stem cell or progenitor cell disorder.
38.-42. (canceled)
43. The method of claim 37, wherein the stem cell or progenitor cell disorder is a malignant hematologic disease or a non-malignant disease.
44-73. (canceled)
74. The isolated heHSC of claim 1; 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, .sub.9.sub.1 antagonist, .sub.9.sub.1 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.
75.-82. (canceled)
83. The isolated heHSC of claim 74, wherein the at least one CXCR2 agonist is GRO or an analog or derivative thereof, and wherein the CXCR4 antagonist is plerixafor or an analog or derivative thereof.
84.-92. (canceled)
93. The isolated heHSC of claim 74, wherein the heHSC differentially express one or more of the genes selected from the group consisting of Fos, CD93, Fosb, Dusp1, Jun, Dusp6, Cdk1, Fignl1, Plk2, Rsad2, Sgk1, Sdc1, Serpine2, Spp1, Cdca8, Nrp1, Mcam, Pbk, Akr1cl and Cyp11a1, relative to one or more genes expressed in hematopoietic stem cells (HSCs) mobilized using G-CSF.
94.-101. (canceled)
102. A method of identifying an heHSC cell population comprising a. 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, .sub.9.sub.1 antagonist, .sub.9.sub.1 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; b. mobilizing hematopoietic stem cells and/or progenitor cells from a bone marrow compartment of a subject to a peripheral compartment of the subject by a mobilization regimen not comprising a CXCR2 agonist, and isolating the mobilized hematopoietic stem cells and/or progenitor cells from the peripheral compartment of the subject; c. comparing one or more immunophenotypical and/or functional properties of the isolated cell population of step (a) to the isolated cell population of step (b); and d. identifying a subpopulation of the mobilized cell population of step (a) with one or more immunophenotypical and/or functional properties different than the isolated cell population of step (b).
103. The method of claim 102, wherein step (a) comprises administering at least one CXCR2 agonist and at least one CXCR4 antagonist.
104. The method of claim 102, wherein the mobilization regimen not comprising a CXCR2 agonist consists of G-CSF.
105.-173. (canceled)
174. A method of identifying an heHSC cell population comprising determining a transcriptomic signature of a population of hematopoietic stem cells (HSCs) and comparing the transcriptomic signature with a transcriptomic signature from a G-CSF mobilized population of HSCs, wherein the population of HSCs is identified as an heHSC population when the transcriptomic signature comprises a differential signature of one or more genes selected from the group consisting of Fos, CD93, Fosb, Dusp1, Jun, Dusp6, Cdk1, Fignl1, Plk2, Rsad2, Sgk1, Sdc1, Serpine2, Spp1, Cdca8, Nrp1, Mcam, Pbk, Akr1cl and Cyp11a1, relative to one or more of the genes expressed by hematopoietic stem cells mobilized using G-CSF.
175. The method of claim 174, wherein the transcriptomic signature is determined using FACs.
176. The method of claim 174, wherein the heHSC population is administered to a human subject having a stem cell or progenitor cell disorder.
177. The method of claim 176, wherein the stem cell or progenitor cell disorder is a malignant hematologic disease.
178. The method claim 177, wherein 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.
179. The method of claim 174, further comprising transforming the population of heHSCs with an expression vector comprising a polynucleotide.
180. The method of claim 179, wherein the transformed heHSC population is administered to a human subject in need thereof.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
[0031] 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.
[0032]
[0033]
[0034]
[0035]
DETAILED DESCRIPTION OF THE INVENTION
[0036] 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.
[0037] 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., GRO) 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., GRO) 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.
[0038] 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., GRO) and at least one CXCR4 antagonist, VLA-4 antagonist, .sub.9.sub.1 antagonist, .sub.9.sub.1 integrin/VLA-4 antagonist or combination thereof.
[0039] 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., GRO) 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., GRO) 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.
[0040] 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.
[0041] 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., GRO) and a CXCR4 antagonist (e.g., plerixafor), VLA-4 antagonist, .sub.9.sub.1 antagonist, .sub.9.sub.1 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.
[0042] 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 GRO, GRO, GRO, 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.
[0043] In certain aspects, the CXCR2 agonist comprises GRO.
[0044] In some embodiments, the at least one CXCR2 agonist is the chemokine GRO or an analog or derivative thereof. An exemplary form of GRO is the human GRO polypeptide (GenBank Accession: AAP13104; SEQ ID NO: 1). In certain aspects, an exemplary form of GRO is the human GRO (UniProt ID No. P19875; SEQ ID NO: 2).
[0045] An exemplary GRO analog or derivative is the desamino GRO 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 GRO analog or derivative is the dimeric modified GRO protein described in U.S. Pat. No. 6,413,510, the contents of which are incorporated herein by reference in their entirety. Still another exemplary GRO analog or derivative is SB-251353, a GRO 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.
[0046] In some embodiments of the present inventions, the at least one CXCR2 agonist is or comprises GRO-4 (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 GRO or an analog or derivative thereof and GRO-4 or an analog or derivative thereof.
[0047] 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.
[0048] 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.
##STR00001##
[0049] 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 entirety.
##STR00002## ##STR00003## ##STR00004##
[0050] In some embodiments, the at least one CXCR4 antagonist comprises ALT1188, ALT1187, 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 CXCR4, Theranostics 2013; 3(1):47-75, incorporated herein by reference.
[0051] 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., GRO) and at least one .sub.9.sub.1 integrin/VLA-4 antagonist. In some embodiments, the .sub.9.sub.1 integrin/VLA-4 antagonist is N-(benzenesulfonyl)-L-prolyl-L-O-(1-pyrrolidinylcarbonyl)tyrosine (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., GRO) and at least one VLA-4 antagonist. In some embodiments, the VLA-4 antagonist is BIO 5192, Natalizumab, or an analog or derivative thereof.
[0052] In some embodiments, the at least one CXCR2 agonist is or comprises GRO 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 GRO-4 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.
[0053] The combination of at least one CXCR2 agonist and at least one CXCR4 antagonist, VLA-4 antagonist, .sub.9.sub.1 antagonist, .sub.9.sub.1 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, .sub.9.sub.1 antagonist, .sub.9.sub.1 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.
[0054] 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-4 or an analog or derivative thereof) and at least one CXCR4 antagonist (e.g., plerixafor or an analog or derivative thereof), VLA-4 antagonist, .sub.9.sub.1 antagonist, .sub.9.sub.1 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
[0055] 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.
[0056] 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, .sub.9.sub.1 antagonist, .sub.9.sub.1 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, .sub.9.sub.1 antagonist, .sub.9.sub.1 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.
[0057] 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.
[0058] 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, NK-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+, Sca1+, and lack of lineage markers (negative for B220, CD3, CD4, CD8, Mac1, Gr1, and Ter119, among others).
[0059] 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+, Ter119, CD16/32, CD127, cKit, Sca1) using assays known to those of skill in the art.
[0060] 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.
[0061] 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.sup.mid cells. In some embodiments, the mobilized hematopoietic stem cells and/or progenitor cells comprise Sca-1, c-kit+, Lin, CD34, CD16/32.sup.low cells. In some embodiments, the isolated heHSC does not express an immunophenotypic means of identifying human hematopoietic stem cells.
[0062] 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
[0063] 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, .sub.9.sub.1 antagonist, .sub.9.sub.1 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., GRO or an analog or derivative thereof) and one or more CXCR4 antagonists (e.g., plerixafor or an analog or derivative thereof), VLA-4 antagonist, .sub.9.sub.1 antagonist, .sub.9.sub.1 integrin/VLA-4 antagonist or combination thereof. In certain aspects, such heHSCs are substantially pure.
[0064] 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
[0065] 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., GRO) and at least one CXCR4 antagonist, VLA-4 antagonist, .sub.9.sub.1 antagonist, .sub.9.sub.1 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.
[0066] 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.
[0067] 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, .sub.9.sub.1 antagonist, .sub.9.sub.1 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, .sub.9.sub.1 antagonist, .sub.9.sub.1 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, .sub.9.sub.1 antagonist, .sub.9.sub.1 integrin/VLA-4 antagonist or combination thereof.
[0068] 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., GRO or GRO-4) and at least one CXCR4 antagonist (e.g., plerixafor), VLA-4 antagonist, .sub.9.sub.1 antagonist, .sub.9.sub.1 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, .sub.9.sub.1 antagonist, .sub.9.sub.1 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., GRO or GRO-4) and at least one CXCR4 antagonist, VLA-4 antagonist, .sub.9.sub.1 antagonist, .sub.9.sub.1 integrin/VLA-4 antagonist or combination thereof is administered to the subject.
[0069] In some embodiments, administration of the at least one CXCR2 agonist (e.g., GRO or GRO-4) and the at least one CXCR4 antagonist, VLA-4 antagonist, .sub.9.sub.1 antagonist, .sub.9.sub.1 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 110.sup.6/kg body weight and 1010.sup.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 110.sup.6/kg and 1010.sup.6/kg of the recipient's body weight. In some embodiments, administration of the at least one CXCR2 agonist (e.g., GRO or GRO-4) and the at least one CXCR4 antagonist, VLA-4 antagonist, .sub.9.sub.1 antagonist, .sub.9.sub.1 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 210.sup.6/kg body weight and 810.sup.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 210.sup.6/kg and 810.sup.6/kg of the recipient's body weight. In some embodiments, administration of the at least one CXCR2 agonist (e.g., GRO or GRO-4) and the at least one CXCR4 antagonist, VLA-4 antagonist, .sub.9.sub.1 antagonist, .sub.9.sub.1 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 310.sup.6/kg body weight and 610.sup.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 110.sup.6/kg and 1010.sup.6/kg of the recipient's body weight.
[0070] 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.
[0071] 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.
[0072] 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.
[0073] 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.
[0074] 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.
[0075] 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.
[0076] 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.
[0077] 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.
[0078] In some other embodiments, the heHSCs disclosed herein can be used as carriers for gene therapy.
[0079] 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.
[0080] 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.
[0081] 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.
[0082] 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.
[0083] 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
[0084] 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.
[0085] 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.
[0086] 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.
[0087] 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, .sub.9.sub.1 antagonist, .sub.9.sub.1 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).
[0088] 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.
[0089] 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.
[0090] 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.
[0091] 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.
[0092] 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.
[0093] 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.
[0094] 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.
[0095] 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, 91 antagonist, 91 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.
[0096] 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 CD150+ 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.
[0097] 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
[0098] 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, 91 antagonist, 91 integrin/VLA-4 antagonist or combination thereof is performed in vivo. In some embodiments, the contacting is performed in vitro.
[0099] In some embodiments, the at least one CXCR2 agonist comprises GRO or an analog or derivative thereof. In some embodiments, the at least one CXCR2 agonist comprises GRO-4 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 GRO or an analog or derivative thereof, and wherein the at least one CXCR4 antagonist is plerixafor or an analog or derivative thereof.
[0100] 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.
[0101] 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, five-fold, six-fold, or more. In some embodiments, donor chimerism is increased by at least about 50%.
[0102] In some embodiments, the heHSC product is non-quiescent.
[0103] 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.
[0104] 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, Dusp1, Jun, Dusp6, Cdk1, Fignl1, Plk2, Rsad2, Sgk1, Sdc1, Serpine2, Spp1, Cdca8, Nrp1, Mcam, Pbk, Akr1cl and Cyp11a1, 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.
[0105] 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.
[0106] In some embodiments, the heHSC product comprises at least 40% CD93+ cells. In some embodiments, the heHSC product comprises at least about 2106 cells. In some embodiments, the hematopoietic stem cells and/or progenitor cells are human or mouse cells.
[0107] 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, 91 antagonist, 91 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.
[0108] 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 CD150+ 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.
[0109] 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
[0110] 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, 91 antagonist, 91 integrin/VLA-4 antagonist or combination thereof is performed in vivo. In some embodiments, the contacting is performed in vitro.
[0111] In some embodiments, the at least one CXCR2 agonist comprises GRO or an analog or derivative thereof. In some embodiments, the at least one CXCR2 agonist comprises GRO-4 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 GRO or an analog or derivative thereof, and wherein the at least one CXCR4 antagonist is plerixafor or an analog or derivative thereof.
[0112] 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.
[0113] 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, five-fold, six-fold, or more. In some embodiments, donor chimerism is increased by at least about 50%.
[0114] In some embodiments, the heHSC product is non-quiescent.
[0115] 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.
[0116] 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, Dusp1, Jun, Dusp6, Cdk1, Fignl1, Plk2, Rsad2, Sgk1, Sdc1, Serpine2, Spp1, Cdca8, Nrp1, Mcam, Pbk, Akr1cl and Cyp11a1, 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.
[0117] 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.
[0118] In some embodiments, the heHSC product comprises at least 40% CD93+ cells. In some embodiments, the heHSC product comprises at least about 2106 cells. In some embodiments, the hematopoietic stem cells and/or progenitor cells are human or mouse cells.
[0119] 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.
[0120] 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.
[0121] 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.
[0122] 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.
[0123] 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
[0124] 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, GRO. GRO and GRO-4 (collectively referred to herein as GRO) rapidly mobilize hematopoietic stem cells (HSC), including all classes of short-term progenitor cells as well as long-term repopulating cells. In mice, peak GRO-induced mobilization occurs within 15-30 minutes of administration. Moreover, not only was the observed mobilization faster following GRO 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.
[0125] To assess this, the present inventors mobilized large cohorts of mice (15-20 per group) with either G-CSF (125 ug/kg/day, five days) or with a combination of GRO (2.5 mg/kg) and plerixafor (AMD-3100) (5 mg/kg), and then sorted the peripheral blood for highly purified SLAM SKL cells (CD150+, CD48, Sca-1+, c-kit+, lineage negative)
[0126] 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 GRO plus plerixafor-mobilized donors, went into the irradiated recipients. As illustrated in
Example 2 Transcriptome Signatures
[0127] 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.
[0128] Much like panning for gold, the present inventors can now use the differential mobilization properties of the mobilization regimen using GRO 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.
[0129] 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 GRO and plerixafor (AMD-3100), as described in Example 1.
[0130] 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 GRO 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 GRO plus plerixafor-treated mice, and a drug spike control, which consisted of G-CSF mobilized blood spiked with GRO (350 ng/ml) plus AMD-3100 (10 ug/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 GRO 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
[0131] Surprisingly, as illustrated in
Example 3 Generation of Unique Stem Cell Populations
[0132] 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 MIP-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.
[0133] 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, TIMP-1 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.
[0134] Transplantation of 210.sup.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, P<0.001). 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 CD150+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.
[0135] The foregoing data suggest that a unique subset of highly engraftable HSCs (heHSCs) are mobilized by the rapid regimen comprising an N-terminal truncated MIP-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
[0136] 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 (2.5 mg/kg) and AMD-3100 (5 mg/kg), or G-CSF (125 ug/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=11 mice/group, P<0.0004). See
Example 5 Molecular Cell Sorting and Signature Determination
[0137] 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.
TABLE-US-00001 SEQUENCELISTING <120> HIGHLYENGRAFTABLEHEMATOPOIETICSTEMCELLS <130> HRVY-078-WO1 <150> 62/300,694 <151> 2016Feb.26 <150> 62/413,821 <151> 2016Oct.27 <160> 23 <210> 1 <211> 73 <212> PRT <213> Homosapiens <220> <221> MISC_FEATURE <223> HumanGro-beta <400> 1 AlaProLeuAlaThrGluLeuArgCysGlnCysLeuGlnThrLeuGln 151015 GlyIleHisLeuLysAsnIleGlnSerValLysValLysSerProGly 202530 ProHisCysAlaGlnThrGluValIleAlaThrLeuLysAsnGlyGln 354045 LysAlaCysLeuAsnProAlaSerProMetValLysLysIleIleGlu 505560 LysMetLeuLysAsnGlyLysSerAsn 6570 <210> 2 <211> 107 <212> PRT <213> Homosapiens <220> <221> MISC_FEATURE <223> UniProtIDNo.P19875-humanGRO-beta <400> 2 MetAlaArgAlaThrLeuSerAlaAlaProSerAsnProArgLeuLeu 151015 ArgValAlaLeuLeuLeuLeuLeuLeuValAlaAlaSerArgArgAla 202530 AlaGlyAlaProLeuAlaThrGluLeuArgCysGlnCysLeuGlnThr 354045 LeuGlnGlyIleHisLeuLysAsnIleGlnSerValLysValLysSer 505560 ProGlyProHisCysAlaGlnThrGluValIleAlaThrLeuLysAsn 65707580 GlyGlnLysAlaCysLeuAsnProAlaSerProMetValLysLysIle 859095 IleGluLysMetLeuLysAsnGlyLysSerAsn 100105 <210> 3 <211> 69 <212> PRT <213> Homosapiens <220> <221> MISC_FEATURE <223> GRO-beta-delta-4 <400> 3 ThrGluLeuArgCysGlnCysLeuGlnThrLeuGlnGlyIleHisLeu 151015 LysAsnIleGlnSerValLysValLysSerProGlyProHisCysAla 202530 GlnThrGluValIleAlaThrLeuLysAsnGlyGlnLysAlaCysLeu 354045 AsnProAlaSerProMetValLysLysIleIleGluLysMetLeuLys 505560 AsnGlyLysSerAsn 65 <210> 4 <211> 380 <212> PRT <213> Homosapiens <220> <221> MISC_FEATURE <223> FOS <400> 4 MetMetPheSerGlyPheAsnAlaAspTyrGluAlaSerSerSerArg 151015 CysSerSerAlaSerProAlaGlyAspSerLeuSerTyrTyrHisSer 202530 ProAlaAspSerPheSerSerMetGlySerProValAsnAlaGlnAsp 354045 PheCysThrAspLeuAlaValSerSerAlaAsnPheIleProThrVal 505560 ThrAlaIleSerThrSerProAspLeuGlnTrpLeuValGlnProAla 65707580 LeuValSerSerValAlaProSerGlnThrArgAlaProHisProPhe 859095 GlyValProAlaProSerAlaGlyAlaTyrSerArgAlaGlyValVal 100105110 LysThrMetThrGlyGlyArgAlaGlnSerIleGlyArgArgGlyLys 115120125 ValGluGlnLeuSerProGluGluGluGluLysArgArgIleArgArg 130135140 GluArgAsnLysMetAlaAlaAlaLysCysArgAsnArgArgArgGlu 145150155160 LeuThrAspThrLeuGlnAlaGluThrAspGlnLeuGluAspGluLys 165170175 SerAlaLeuGlnThrGluIleAlaAsnLeuLeuLysGluLysGluLys 180185190 LeuGluPheIleLeuAlaAlaHisArgProAlaCysLysIleProAsp 195200205 AspLeuGlyPheProGluGluMetSerValAlaSerLeuAspLeuThr 210215220 GlyGlyLeuProGluValAlaThrProGluSerGluGluAlaPheThr 225230235240 LeuProLeuLeuAsnAspProGluProLysProSerValGluProVal 245250255 LysSerIleSerSerMetGluLeuLysThrGluProPheAspAspPhe 260265270 LeuPheProAlaSerSerArgProSerGlySerGluThrAlaArgSer 275280285 ValProAspMetAspLeuSerGlySerPheTyrAlaAlaAspTrpGlu 290295300 ProLeuHisSerGlySerLeuGlyMetGlyProMetAlaThrGluLeu 305310315320 GluProLeuCysThrProValValThrCysThrProSerCysThrAla 325330335 TyrThrSerSerPheValPheThrTyrProGluAlaAspSerPhePro 340345350 SerCysAlaAlaAlaHisArgLysGlySerSerSerAsnGluProSer 355360365 SerAspSerLeuSerSerProThrLeuLeuAlaLeu 370375380 <210> 5 <211> 652 <212> PRT <213> Homosapiens <220> <221> MISC_FEATURE <223> CD93 <400> 5 MetAlaThrSerMetGlyLeuLeuLeuLeuLeuLeuLeuLeuLeuThr 151015 GlnProGlyAlaGlyThrGlyAlaAspThrGluAlaValValCysVal 202530 GlyThrAlaCysTyrThrAlaHisSerGlyLysLeuSerAlaAlaGlu 354045 AlaGlnAsnHisCysAsnGlnAsnGlyGlyAsnLeuAlaThrValLys 505560 SerLysGluGluAlaGlnHisValGlnArgValLeuAlaGlnLeuLeu 65707580 ArgArgGluAlaAlaLeuThrAlaArgMetSerLysPheTrpIleGly 859095 LeuGlnArgGluLysGlyLysCysLeuAspProSerLeuProLeuLys 100105110 GlyPheSerTrpValGlyGlyGlyGluAspThrProTyrSerAsnTrp 115120125 HisLysGluLeuArgAsnSerCysIleSerLysArgCysValSerLeu 130135140 LeuLeuAspLeuSerGlnProLeuLeuProSerArgLeuProLysTrp 145150155160 SerGluGlyProCysGlySerProGlySerProGlySerAsnIleGlu 165170175 GlyPheValCysLysPheSerPheLysGlyMetCysArgProLeuAla 180185190 LeuGlyGlyProGlyGlnValThrTyrThrThrProPheGlnThrThr 195200205 SerSerSerLeuGluAlaValProPheAlaSerAlaAlaAsnValAla 210215220 CysGlyGluGlyAspLysAspGluThrGlnSerHisTyrPheLeuCys 225230235240 LysGluLysAlaProAspValPheAspTrpGlySerSerGlyProLeu 245250255 CysValSerProLysTyrGlyCysAsnPheAsnAsnGlyGlyCysHis 260265270 GlnAspCysPheGluGlyGlyAspGlySerPheLeuCysGlyCysArg 275280285 ProGlyPheArgLeuLeuAspAspLeuValThrCysAlaSerArgAsn 290295300 ProCysSerSerSerProCysArgGlyGlyAlaThrCysValLeuGly 305310315320 ProHisGlyLysAsnTyrThrCysArgCysProGlnGlyTyrGlnLeu 325330335 AspSerSerGlnLeuAspCysValAspValAspGluCysGlnAspSer 340345350 ProCysAlaGlnGluCysValAsnThrProGlyGlyPheArgCysGlu 355360365 CysTrpValGlyTyrGluProGlyGlyProGlyGluGlyAlaCysGln 370375380 AspValAspGluCysAlaLeuGlyArgSerProCysAlaGlnGlyCys 385390395400 ThrAsnThrAspGlySerPheHisCysSerCysGluGluGlyTyrVal 405410415 LeuAlaGlyGluAspGlyThrGlnCysGlnAspValAspGluCysVal 420425430 GlyProGlyGlyProLeuCysAspSerLeuCysPheAsnThrGlnGly 435440445 SerPheHisCysGlyCysLeuProGlyTrpValLeuAlaProAsnGly 450455460 ValSerCysThrMetGlyProValSerLeuGlyProProSerGlyPro 465470475480 ProAspGluGluAspLysGlyGluLysGluGlySerThrValProArg 485490495 AlaAlaThrAlaSerProThrArgGlyProGluGlyThrProLysAla 500505510 ThrProThrThrSerArgProSerLeuSerSerAspAlaProIleThr 515520525 SerAlaProLeuLysMetLeuAlaProSerGlySerProGlyValTrp 530535540 ArgGluProSerIleHisHisAlaThrAlaAlaSerGlyProGlnGlu 545550555560 ProAlaGlyGlyAspSerSerValAlaThrGlnAsnAsnAspGlyThr 565570575 AspGlyGlnLysLeuLeuLeuPheTyrIleLeuGlyThrValValAla 580585590 IleLeuLeuLeuLeuAlaLeuAlaLeuGlyLeuLeuValTyrArgLys 595600605 ArgArgAlaLysArgGluGluLysLysGluLysLysProGlnAsnAla 610615620 AlaAspSerTyrSerTrpValProGluArgAlaGluSerArgAlaMet 625630635640 GluAsnGlnTyrSerProThrProGlyThrAspCys 645650 <210> 6 <211> 338 <212> PRT <213> Homosapiens <220> <221> MISC_FEATURE <223> FOSB <400> 6 MetPheGlnAlaPheProGlyAspTyrAspSerGlySerArgCysSer 151015 SerSerProSerAlaGluSerGlnTyrLeuSerSerValAspSerPhe 202530 GlySerProProThrAlaAlaAlaSerGlnGluCysAlaGlyLeuGly 354045 GluMetProGlySerPheValProThrValThrAlaIleThrThrSer 505560 GlnAspLeuGlnTrpLeuValGlnProThrLeuIleSerSerMetAla 65707580 GlnSerGlnGlyGlnProLeuAlaSerGlnProProValValAspPro 859095 TyrAspMetProGlyThrSerTyrSerThrProGlyMetSerGlyTyr 100105110 SerSerGlyGlyAlaSerGlySerGlyGlyProSerThrSerGlyThr 115120125 ThrSerGlyProGlyProAlaArgProAlaArgAlaArgProArgArg 130135140 ProArgGluGluThrLeuThrProGluGluGluGluLysArgArgVal 145150155160 ArgArgGluArgAsnLysLeuAlaAlaAlaLysCysArgAsnArgArg 165170175 ArgGluLeuThrAspArgLeuGlnAlaGluThrAspGlnLeuGluGlu 180185190 GluLysAlaGluLeuGluSerGluIleAlaGluLeuGlnLysGluLys 195200205 GluArgLeuGluPheValLeuValAlaHisLysProGlyCysLysIle 210215220 ProTyrGluGluGlyProGlyProGlyProLeuAlaGluValArgAsp 225230235240 LeuProGlySerAlaProAlaLysGluAspGlyPheSerTrpLeuLeu 245250255 ProProProProProProProLeuProPheGlnThrSerGlnAspAla 260265270 ProProAsnLeuThrAlaSerLeuPheThrHisSerGluValGlnVal 275280285 LeuGlyAspProPheProValValAsnProSerTyrThrSerSerPhe 290295300 ValLeuThrCysProGluValSerAlaPheAlaGlyAlaGlnArgThr 305310315320 SerGlySerAspGlnProSerAspProLeuAsnSerProSerLeuLeu 325330335 AlaLeu <210> 7 <211> 367 <212> PRT <213> Homosapiens <220> <221> MISC_FEATURE <223> Dusp1 <400> 7 MetValMetGluValGlyThrLeuAspAlaGlyGlyLeuArgAlaLeu 151015 LeuGlyGluArgAlaAlaGlnCysLeuLeuLeuAspCysArgSerPhe 202530 PheAlaPheAsnAlaGlyHisIleAlaGlySerValAsnValArgPhe 354045 SerThrIleValArgArgArgAlaLysGlyAlaMetGlyLeuGluHis 505560 IleValProAsnAlaGluLeuArgGlyArgLeuLeuAlaGlyAlaTyr 65707580 HisAlaValValLeuLeuAspGluArgSerAlaAlaLeuAspGlyAla 859095 LysArgAspGlyThrLeuAlaLeuAlaAlaGlyAlaLeuCysArgGlu 100105110 AlaArgAlaAlaGlnValPhePheLeuLysGlyGlyTyrGluAlaPhe 115120125 SerAlaSerCysProGluLeuCysSerLysGlnSerThrProMetGly 130135140 LeuSerLeuProLeuSerThrSerValProAspSerAlaGluSerGly 145150155160 CysSerSerCysSerThrProLeuTyrAspGlnGlyGlyProValGlu 165170175 IleLeuProPheLeuTyrLeuGlySerAlaTyrHisAlaSerArgLys 180185190 AspMetLeuAspAlaLeuGlyIleThrAlaLeuIleAsnValSerAla 195200205 AsnCysProAsnHisPheGluGlyHisTyrGlnTyrLysSerIlePro 210215220 ValGluAspAsnHisLysAlaAspIleSerSerTrpPheAsnGluAla 225230235240 IleAspPheIleAspSerIleLysAsnAlaGlyGlyArgValPheVal 245250255 HisCysGlnAlaGlyIleSerArgSerAlaThrIleCysLeuAlaTyr 260265270 LeuMetArgThrAsnArgValLysLeuAspGluAlaPheGluPheVal 275280285 LysGlnArgArgSerIleIleSerProAsnPheSerPheMetGlyGln 290295300 LeuLeuGlnPheGluSerGlnValLeuAlaProHisCysSerAlaGlu 305310315320 AlaGlySerProAlaMetAlaValLeuAspArgGlyThrSerThrThr 325330335 ThrValPheAsnPheProValSerIleProValHisSerThrAsnSer 340345350 AlaLeuSerTyrLeuGlnSerProIleThrThrSerProSerCys 355360365 <210> 8 <211> 331 <212> PRT <213> Homosapiens <220> <221> MISC_FEATURE <223> Jun <400> 8 MetThrAlaLysMetGluThrThrPheTyrAspAspAlaLeuAsnAla 151015 SerPheLeuProSerGluSerGlyProTyrGlyTyrSerAsnProLys 202530 IleLeuLysGlnSerMetThrLeuAsnLeuAlaAspProValGlySer 354045 LeuLysProHisLeuArgAlaLysAsnSerAspLeuLeuThrSerPro 505560 AspValGlyLeuLeuLysLeuAlaSerProGluLeuGluArgLeuIle 65707580 IleGlnSerSerAsnGlyHisIleThrThrThrProThrProThrGln 859095 PheLeuCysProLysAsnValThrAspGluGlnGluGlyPheAlaGlu 100105110 GlyPheValArgAlaLeuAlaGluLeuHisSerGlnAsnThrLeuPro 115120125 SerValThrSerAlaAlaGlnProValAsnGlyAlaGlyMetValAla 130135140 ProAlaValAlaSerValAlaGlyGlySerGlySerGlyGlyPheSer 145150155160 AlaSerLeuHisSerGluProProValTyrAlaAsnLeuSerAsnPhe 165170175 AsnProGlyAlaLeuSerSerGlyGlyGlyAlaProSerTyrGlyAla 180185190 AlaGlyLeuAlaPheProAlaGlnProGlnGlnGlnGlnGlnProPro 195200205 HisHisLeuProGlnGlnMetProValGlnHisProArgLeuGlnAla 210215220 LeuLysGluGluProGlnThrValProGluMetProGlyGluThrPro 225230235240 ProLeuSerProIleAspMetGluSerGlnGluArgIleLysAlaGlu 245250255 ArgLysArgMetArgAsnArgIleAlaAlaSerLysCysArgLysArg 260265270 LysLeuGluArgIleAlaArgLeuGluGluLysValLysThrLeuLys 275280285 AlaGlnAsnSerGluLeuAlaSerThrAlaAsnMetLeuArgGluGln 290295300 ValAlaGlnLeuLysGlnLysValMetAsnHisValAsnSerGlyCys 305310315320 GlnLeuMetLeuThrGlnGlnLeuGlnThrPhe 325330 <210> 9 <211> 381 <212> PRT <213> Homosapiens <220> <221> MISC_FEATURE <223> DUSP6 <400> 9 MetIleAspThrLeuArgProValProPheAlaSerGluMetAlaIle 151015 SerLysThrValAlaTrpLeuAsnGluGlnLeuGluLeuGlyAsnGlu 202530 ArgLeuLeuLeuMetAspCysArgProGlnGluLeuTyrGluSerSer 354045 HisIleGluSerAlaIleAsnValAlaIleProGlyIleMetLeuArg 505560 ArgLeuGlnLysGlyAsnLeuProValArgAlaLeuPheThrArgGly 65707580 GluAspArgAspArgPheThrArgArgCysGlyThrAspThrValVal 859095 LeuTyrAspGluSerSerSerAspTrpAsnGluAsnThrGlyGlyGlu 100105110 SerValLeuGlyLeuLeuLeuLysLysLeuLysAspGluGlyCysArg 115120125 AlaPheTyrLeuGluGlyGlyPheSerLysPheGlnAlaGluPheSer 130135140 LeuHisCysGluThrAsnLeuAspGlySerCysSerSerSerSerPro 145150155160 ProLeuProValLeuGlyLeuGlyGlyLeuArgIleSerSerAspSer 165170175 SerSerAspIleGluSerAspLeuAspArgAspProAsnSerAlaThr 180185190 AspSerAspGlySerProLeuSerAsnSerGlnProSerPheProVal 195200205 GluIleLeuProPheLeuTyrLeuGlyCysAlaLysAspSerThrAsn 210215220 LeuAspValLeuGluGluPheGlyIleLysTyrIleLeuAsnValThr 225230235240 ProAsnLeuProAsnLeuPheGluAsnAlaGlyGluPheLysTyrLys 245250255 GlnIleProIleSerAspHisTrpSerGlnAsnLeuSerGlnPhePhe 260265270 ProGluAlaIleSerPheIleAspGluAlaArgGlyLysAsnCysGly 275280285 ValLeuValHisCysLeuAlaGlyIleSerArgSerValThrValThr 290295300 ValAlaTyrLeuMetGlnLysLeuAsnLeuSerMetAsnAspAlaTyr 305310315320 AspIleValLysMetLysLysSerAsnIleSerProAsnPheAsnPhe 325330335 MetGlyGlnLeuLeuAspPheGluArgThrLeuGlyLeuSerSerPro 340345350 CysAspAsnArgValProAlaGlnGlnLeuTyrPheThrThrProSer 355360365 AsnGlnAsnValTyrGlnValAspSerLeuGlnSerThr 370375380 <210> 10 <211> 297 <212> PRT <213> Homosapiens <220> <221> MISC_FEATURE <223> CDK1 <400> 10 MetGluAspTyrThrLysIleGluLysIleGlyGluGlyThrTyrGly 151015 ValValTyrLysGlyArgHisLysThrThrGlyGlnValValAlaMet 202530 LysLysIleArgLeuGluSerGluGluGluGlyValProSerThrAla 354045 IleArgGluIleSerLeuLeuLysGluLeuArgHisProAsnIleVal 505560 SerLeuGlnAspValLeuMetGlnAspSerArgLeuTyrLeuIlePhe 65707580 GluPheLeuSerMetAspLeuLysLysTyrLeuAspSerIleProPro 859095 GlyGlnTyrMetAspSerSerLeuValLysSerTyrLeuTyrGlnIle 100105110 LeuGlnGlyIleValPheCysHisSerArgArgValLeuHisArgAsp 115120125 LeuLysProGlnAsnLeuLeuIleAspAspLysGlyThrIleLysLeu 130135140 AlaAspPheGlyLeuAlaArgAlaPheGlyIleProIleArgValTyr 145150155160 ThrHisGluValValThrLeuTrpTyrArgSerProGluValLeuLeu 165170175 GlySerAlaArgTyrSerThrProValAspIleTrpSerIleGlyThr 180185190 IlePheAlaGluLeuAlaThrLysLysProLeuPheHisGlyAspSer 195200205 GluIleAspGlnLeuPheArgIlePheArgAlaLeuGlyThrProAsn 210215220 AsnGluValTrpProGluValGluSerLeuGlnAspTyrLysAsnThr 225230235240 PheProLysTrpLysProGlySerLeuAlaSerHisValLysAsnLeu 245250255 AspGluAsnGlyLeuAspLeuLeuSerLysMetLeuIleTyrAspPro 260265270 AlaLysArgIleSerGlyLysMetAlaLeuAsnHisProTyrPheAsn 275280285 AspLeuAspAsnGlnIleLysLysMet 290295 <210> 11 <211> 674 <212> PRT <213> Homosapiens <220> <221> MISC_FEATURE <223> Fignl1 <400> 11 MetGlnThrSerSerSerArgSerValHisLeuSerGluTrpGlnLys 151015 AsnTyrPheAlaIleThrSerGlyIleCysThrGlyProLysAlaAsp 202530 AlaTyrArgAlaGlnIleLeuArgIleGlnTyrAlaTrpAlaAsnSer 354045 GluIleSerGlnValCysAlaThrLysLeuPheLysLysTyrAlaGlu 505560 LysTyrSerAlaIleIleAspSerAspAsnValGluSerGlyLeuAsn 65707580 AsnTyrAlaGluAsnIleLeuThrLeuAlaGlySerGlnGlnThrAsp 859095 SerAspLysTrpGlnSerGlyLeuSerIleAsnAsnValPheLysMet 100105110 SerSerValGlnLysMetMetGlnAlaGlyLysLysPheLysAspSer 115120125 LeuLeuGluProAlaLeuAlaSerValValIleHisLysGluAlaThr 130135140 ValPheAspLeuProLysPheSerValCysGlySerSerGlnGluSer 145150155160 AspSerLeuProAsnSerAlaHisAspArgAspArgThrGlnAspPhe 165170175 ProGluSerAsnArgLeuLysLeuLeuGlnAsnAlaGlnProProMet 180185190 ValThrAsnThrAlaArgThrCysProThrPheSerAlaProValGly 195200205 GluSerAlaThrAlaLysPheHisValThrProLeuPheGlyAsnVal 210215220 LysLysGluAsnHisSerSerAlaLysGluAsnIleGlyLeuAsnVal 225230235240 PheLeuSerAsnGlnSerCysPheProAlaAlaCysGluAsnProGln 245250255 ArgLysSerPheTyrGlySerGlyThrIleAspAlaLeuSerAsnPro 260265270 IleLeuAsnLysAlaCysSerLysThrGluAspAsnGlyProLysGlu 275280285 AspSerSerLeuProThrPheLysThrAlaLysGluGlnLeuTrpVal 290295300 AspGlnGlnLysLysTyrHisGlnProGlnArgAlaSerGlySerSer 305310315320 TyrGlyGlyValLysLysSerLeuGlyAlaSerArgSerArgGlyIle 325330335 LeuGlyLysPheValProProIleProLysGlnAspGlyGlyGluGln 340345350 AsnGlyGlyMetGlnCysLysProTyrGlyAlaGlyProThrGluPro 355360365 AlaHisProValAspGluArgLeuLysAsnLeuGluProLysMetIle 370375380 GluLeuIleMetAsnGluIleMetAspHisGlyProProValAsnTrp 385390395400 GluAspIleAlaGlyValGluPheAlaLysAlaThrIleLysGluIle 405410415 ValValTrpProMetLeuArgProAspIlePheThrGlyLeuArgGly 420425430 ProProLysGlyIleLeuLeuPheGlyProProGlyThrGlyLysThr 435440445 LeuIleGlyLysCysIleAlaSerGlnSerGlyAlaThrPhePheSer 450455460 IleSerAlaSerSerLeuThrSerLysTrpValGlyGluGlyGluLys 465470475480 MetValArgAlaLeuPheAlaValAlaArgCysGlnGlnProAlaVal 485490495 IlePheIleAspGluIleAspSerLeuLeuSerGlnArgGlyAspGly 500505510 GluHisGluSerSerArgArgIleLysThrGluPheLeuValGlnLeu 515520525 AspGlyAlaThrThrSerSerGluAspArgIleLeuValValGlyAla 530535540 ThrAsnArgProGlnGluIleAspGluAlaAlaArgArgArgLeuVal 545550555560 LysArgLeuTyrIleProLeuProGluAlaSerAlaArgLysGlnIle 565570575 ValIleAsnLeuMetSerLysGluGlnCysCysLeuSerGluGluGlu 580585590 IleGluGlnIleValGlnGlnSerAspAlaPheSerGlyAlaAspMet 595600605 ThrGlnLeuCysArgGluAlaSerLeuGlyProIleArgSerLeuGln 610615620 ThrAlaAspIleAlaThrIleThrProAspGlnValArgProIleAla 625630635640 TyrIleAspPheGluAsnAlaPheArgThrValArgProSerValSer 645650655 ProLysAspLeuGluLeuTyrGluAsnTrpAsnLysThrPheGlyCys 660665670 GlyLys <210> 12 <211> 685 <212> PRT <213> Homosapiens <220> <221> MISC_FEATURE <223> Plk2 <400> 12 MetGluLeuLeuArgThrIleThrTyrGlnProAlaAlaSerThrLys 151015 MetCysGluGlnAlaLeuGlyLysGlyCysGlyAlaAspSerLysLys 202530 LysArgProProGlnProProGluGluSerGlnProProGlnSerGln 354045 AlaGlnValProProAlaAlaProHisHisHisHisHisHisSerHis 505560 SerGlyProGluIleSerArgIleIleValAspProThrThrGlyLys 65707580 ArgTyrCysArgGlyLysValLeuGlyLysGlyGlyPheAlaLysCys 859095 TyrGluMetThrAspLeuThrAsnAsnLysValTyrAlaAlaLysIle 100105110 IleProHisSerArgValAlaLysProHisGlnArgGluLysIleAsp 115120125 LysGluIleGluLeuHisArgIleLeuHisHisLysHisValValGln 130135140 PheTyrHisTyrPheGluAspLysGluAsnIleTyrIleLeuLeuGlu 145150155160 TyrCysSerArgArgSerMetAlaHisIleLeuLysAlaArgLysVal 165170175 LeuThrGluProGluValArgTyrTyrLeuArgGlnIleValSerGly 180185190 LeuLysTyrLeuHisGluGlnGluIleLeuHisArgAspLeuLysLeu 195200205 GlyAsnPhePheIleAsnGluAlaMetGluLeuLysValGlyAspPhe 210215220 GlyLeuAlaAlaArgLeuGluProLeuGluHisArgArgArgThrIle 225230235240 CysGlyThrProAsnTyrLeuSerProGluValLeuAsnLysGlnGly 245250255 HisGlyCysGluSerAspIleTrpAlaLeuGlyCysValMetTyrThr 260265270 MetLeuLeuGlyArgProProPheGluThrThrAsnLeuLysGluThr 275280285 TyrArgCysIleArgGluAlaArgTyrThrMetProSerSerLeuLeu 290295300 AlaProAlaLysHisLeuIleAlaSerMetLeuSerLysAsnProGlu 305310315320 AspArgProSerLeuAspAspIleIleArgHisAspPhePheLeuGln 325330335 GlyPheThrProAspArgLeuSerSerSerCysCysHisThrValPro 340345350 AspPheHisLeuSerSerProAlaLysAsnPhePheLysLysAlaAla 355360365 AlaAlaLeuPheGlyGlyLysLysAspLysAlaArgTyrIleAspThr 370375380 HisAsnArgValSerLysGluAspGluAspIleTyrLysLeuArgHis 385390395400 AspLeuLysLysThrSerIleThrGlnGlnProSerLysHisArgThr 405410415 AspGluGluLeuGlnProProThrThrThrValAlaArgSerGlyThr 420425430 ProAlaValGluAsnLysGlnGlnIleGlyAspAlaIleArgMetIle 435440445 ValArgGlyThrLeuGlySerCysSerSerSerSerGluCysLeuGlu 450455460 AspSerThrMetGlySerValAlaAspThrValAlaArgValLeuArg 465470475480 GlyCysLeuGluAsnMetProGluAlaAspCysIleProLysGluGln 485490495 LeuSerThrSerPheGlnTrpValThrLysTrpValAspTyrSerAsn 500505510 LysTyrGlyPheGlyTyrGlnLeuSerAspHisThrValGlyValLeu 515520525 PheAsnAsnGlyAlaHisMetSerLeuLeuProAspLysLysThrVal 530535540 HisTyrTyrAlaGluLeuGlyGlnCysSerValPheProAlaThrAsp 545550555560 AlaProGluGlnPheIleSerGlnValThrValLeuLysTyrPheSer 565570575 HisTyrMetGluGluAsnLeuMetAspGlyGlyAspLeuProSerVal 580585590 ThrAspIleArgArgProArgLeuTyrLeuLeuGlnTrpLeuLysSer 595600605 AspLysAlaLeuMetMetLeuPheAsnAspGlyThrPheGlnValAsn 610615620 PheTyrHisAspHisThrLysIleIleIleCysSerGlnAsnGluGlu 625630635640 TyrLeuLeuThrTyrIleAsnGluAspArgIleSerThrThrPheArg 645650655 LeuThrThrLeuLeuMetSerGlyCysSerSerGluLeuLysAsnArg 660665670 MetGluTyrAlaLeuAsnMetLeuLeuGlnArgCysAsn 675680685 <210> 13 <211> 361 <212> PRT <213> Homosapiens <220> <221> MISC_FEATURE <223> RSAD2 <400> 13 MetTrpValLeuThrProAlaAlaPheAlaGlyLysLeuLeuSerVal 151015 PheArgGlnProLeuSerSerLeuTrpArgSerLeuValProLeuPhe 202530 CysTrpLeuArgAlaThrPheTrpLeuLeuAlaThrLysArgArgLys 354045 GlnGlnLeuValLeuArgGlyProAspGluThrLysGluGluGluGlu 505560 AspProProLeuProThrThrProThrSerValAsnTyrHisPheThr 65707580 ArgGlnCysAsnTyrLysCysGlyPheCysPheHisThrAlaLysThr 859095 SerPheValLeuProLeuGluGluAlaLysArgGlyLeuLeuLeuLeu 100105110 LysGluAlaGlyMetGluLysIleAsnPheSerGlyGlyGluProPhe 115120125 LeuGlnAspArgGlyGluTyrLeuGlyLysLeuValArgPheCysLys 130135140 ValGluLeuArgLeuProSerValSerIleValSerAsnGlySerLeu 145150155160 IleArgGluArgTrpPheGlnAsnTyrGlyGluTyrLeuAspIleLeu 165170175 AlaIleSerCysAspSerPheAspGluGluValAsnValLeuIleGly 180185190 ArgGlyGlnGlyLysLysAsnHisValGluAsnLeuGlnLysLeuArg 195200205 ArgTrpCysArgAspTyrArgValAlaPheLysIleAsnSerValIle 210215220 AsnArgPheAsnValGluGluAspMetThrGluGlnIleLysAlaLeu 225230235240 AsnProValArgTrpLysValPheGlnCysLeuLeuIleGluGlyGlu 245250255 AsnCysGlyGluAspAlaLeuArgGluAlaGluArgPheValIleGly 260265270 AspGluGluPheGluArgPheLeuGluArgHisLysGluValSerCys 275280285 LeuValProGluSerAsnGlnLysMetLysAspSerTyrLeuIleLeu 290295300 AspGluTyrMetArgPheLeuAsnCysArgLysGlyArgLysAspPro 305310315320 SerLysSerIleLeuAspValGlyValGluGluAlaIleLysPheSer 325330335 GlyPheAspGluLysMetPheLeuLysArgGlyGlyLysTyrIleTrp 340345350 SerLysAlaAspLeuLysLeuAspTrp 355360 <210> 14 <211> 431 <212> PRT <213> Homosapiens <220> <221> MISC_FEATURE <223> SGK1 <400> 14 MetThrValLysThrGluAlaAlaLysGlyThrLeuThrTyrSerArg 151015 MetArgGlyMetValAlaIleLeuIleAlaPheMetLysGlnArgArg 202530 MetGlyLeuAsnAspPheIleGlnLysIleAlaAsnAsnSerTyrAla 354045 CysLysHisProGluValGlnSerIleLeuLysIleSerGlnProGln 505560 GluProGluLeuMetAsnAlaAsnProSerProProProSerProSer 65707580 GlnGlnIleAsnLeuGlyProSerSerAsnProHisAlaLysProSer 859095 AspPheHisPheLeuLysValIleGlyLysGlySerPheGlyLysVal 100105110 LeuLeuAlaArgHisLysAlaGluGluValPheTyrAlaValLysVal 115120125 LeuGlnLysLysAlaIleLeuLysLysLysGluGluLysHisIleMet 130135140 SerGluArgAsnValLeuLeuLysAsnValLysHisProPheLeuVal 145150155160 GlyLeuHisPheSerPheGlnThrAlaAspLysLeuTyrPheValLeu 165170175 AspTyrIleAsnGlyGlyGluLeuPheTyrHisLeuGlnArgGluArg 180185190 CysPheLeuGluProArgAlaArgPheTyrAlaAlaGluIleAlaSer 195200205 AlaLeuGlyTyrLeuHisSerLeuAsnIleValTyrArgAspLeuLys 210215220 ProGluAsnIleLeuLeuAspSerGlnGlyHisIleValLeuThrAsp 225230235240 PheGlyLeuCysLysGluAsnIleGluHisAsnSerThrThrSerThr 245250255 PheCysGlyThrProGluTyrLeuAlaProGluValLeuHisLysGln 260265270 ProTyrAspArgThrValAspTrpTrpCysLeuGlyAlaValLeuTyr 275280285 GluMetLeuTyrGlyLeuProProPheTyrSerArgAsnThrAlaGlu 290295300 MetTyrAspAsnIleLeuAsnLysProLeuGlnLeuLysProAsnIle 305310315320 ThrAsnSerAlaArgHisLeuLeuGluGlyLeuLeuGlnLysAspArg 325330335 ThrLysArgLeuGlyAlaLysAspAspPheMetGluIleLysSerHis 340345350 ValPhePheSerLeuIleAsnTrpAspAspLeuIleAsnLysLysIle 355360365 ThrProProPheAsnProAsnValSerGlyProAsnAspLeuArgHis 370375380 PheAspProGluPheThrGluGluProValProAsnSerIleGlyLys 385390395400 SerProAspSerValLeuValThrAlaSerValLysGluAlaAlaGlu 405410415 AlaPheLeuGlyPheSerTyrAlaProProThrAspSerPheLeu 420425430 <210> 15 <211> 310 <212> PRT <213> Homosapiens <220> <221> MISC_FEATURE <223> Sdc1 <400> 15 MetArgArgAlaAlaLeuTrpLeuTrpLeuCysAlaLeuAlaLeuSer 151015 LeuGlnProAlaLeuProGlnIleValAlaThrAsnLeuProProGlu 202530 AspGlnAspGlySerGlyAspAspSerAspAsnPheSerGlySerGly 354045 AlaGlyAlaLeuGlnAspIleThrLeuSerGlnGlnThrProSerThr 505560 TrpLysAspThrGlnLeuLeuThrAlaIleProThrSerProGluPro 65707580 ThrGlyLeuGluAlaThrAlaAlaSerThrSerThrLeuProAlaGly 859095 GluGlyProLysGluGlyGluAlaValValLeuProGluValGluPro 100105110 GlyLeuThrAlaArgGluGlnGluAlaThrProArgProArgGluThr 115120125 ThrGlnLeuProThrThrHisLeuAlaSerThrThrThrAlaThrThr 130135140 AlaGlnGluProAlaThrSerHisProHisArgAspMetGlnProGly 145150155160 HisHisGluThrSerThrProAlaGlyProSerGlnAlaAspLeuHis 165170175 ThrProHisThrGluAspGlyGlyProSerAlaThrGluArgAlaAla 180185190 GluAspGlyAlaSerSerGlnLeuProAlaAlaGluGlySerGlyGlu 195200205 GlnAspPheThrPheGluThrSerGlyGluAsnThrAlaValValAla 210215220 ValGluProAspArgArgAsnGlnSerProValAspGlnGlyAlaThr 225230235240 GlyAlaSerGlnGlyLeuLeuAspArgLysGluValLeuGlyGlyVal 245250255 IleAlaGlyGlyLeuValGlyLeuIlePheAlaValCysLeuValGly 260265270 PheMetLeuTyrArgMetLysLysLysAspGluGlySerTyrSerLeu 275280285 GluGluProLysGlnAlaAsnGlyGlyAlaTyrGlnLysProThrLys 290295300 GlnGluGluPheTyrAla 305310 <210> 16 <211> 398 <212> PRT <213> Homosapiens <220> <221> MISC_FEATURE <223> Serpine2 <400> 16 MetAsnTrpHisLeuProLeuPheLeuLeuAlaSerValThrLeuPro 151015 SerIleCysSerHisPheAsnProLeuSerLeuGluGluLeuGlySer 202530 AsnThrGlyIleGlnValPheAsnGlnIleValLysSerArgProHis 354045 AspAsnIleValIleSerProHisGlyIleAlaSerValLeuGlyMet 505560 LeuGlnLeuGlyAlaAspGlyArgThrLysLysGlnLeuAlaMetVal 65707580 MetArgTyrGlyValAsnGlyValGlyLysIleLeuLysLysIleAsn 859095 LysAlaIleValSerLysLysAsnLysAspIleValThrValAlaAsn 100105110 AlaValPheValLysAsnAlaSerGluIleGluValProPheValThr 115120125 ArgAsnLysAspValPheGlnCysGluValArgAsnValAsnPheGlu 130135140 AspProAlaSerAlaCysAspSerIleAsnAlaTrpValLysAsnGlu 145150155160 ThrArgAspMetIleAspAsnLeuLeuSerProAspLeuIleAspGly 165170175 ValLeuThrArgLeuValLeuValAsnAlaValTyrPheLysGlyLeu 180185190 TrpLysSerArgPheGlnProGluAsnThrLysLysArgThrPheVal 195200205 AlaAlaAspGlyLysSerTyrGlnValProMetLeuAlaGlnLeuSer 210215220 ValPheArgCysGlySerThrSerAlaProAsnAspLeuTrpTyrAsn 225230235240 PheIleGluLeuProTyrHisGlyGluSerIleSerMetLeuIleAla 245250255 LeuProThrGluSerSerThrProLeuSerAlaIleIleProHisIle 260265270 SerThrLysThrIleAspSerTrpMetSerIleMetValProLysArg 275280285 ValGlnValIleLeuProLysPheThrAlaValAlaGlnThrAspLeu 290295300 LysGluProLeuLysValLeuGlyIleThrAspMetPheAspSerSer 305310315320 LysAlaAsnPheAlaLysIleThrThrGlySerGluAsnLeuHisVal 325330335 SerHisIleLeuGlnLysAlaLysIleGluValSerGluAspGlyThr 340345350 LysAlaSerAlaAlaThrThrAlaIleLeuIleAlaArgSerSerPro 355360365 ProTrpPheIleValAspArgProPheLeuPhePheIleArgHisAsn 370375380 ProThrGlyAlaValLeuPheMetGlyGlnIleAsnLysPro 385390395 <210> 17 <211> 314 <212> PRT <213> Homosapiens <220> <221> MISC_FEATURE <223> Spp1 <400> 17 MetArgIleAlaValIleCysPheCysLeuLeuGlyIleThrCysAla 151015 IleProValLysGlnAlaAspSerGlySerSerGluGluLysGlnLeu 202530 TyrAsnLysTyrProAspAlaValAlaThrTrpLeuAsnProAspPro 354045 SerGlnLysGlnAsnLeuLeuAlaProGlnAsnAlaValSerSerGlu 505560 GluThrAsnAspPheLysGlnGluThrLeuProSerLysSerAsnGlu 65707580 SerHisAspHisMetAspAspMetAspAspGluAspAspAspAspHis 859095 ValAspSerGlnAspSerIleAspSerAsnAspSerAspAspValAsp 100105110 AspThrAspAspSerHisGlnSerAspGluSerHisHisSerAspGlu 115120125 SerAspGluLeuValThrAspPheProThrAspLeuProAlaThrGlu 130135140 ValPheThrProValValProThrValAspThrTyrAspGlyArgGly 145150155160 AspSerValValTyrGlyLeuArgSerLysSerLysLysPheArgArg 165170175 ProAspIleGlnTyrProAspAlaThrAspGluAspIleThrSerHis 180185190 MetGluSerGluGluLeuAsnGlyAlaTyrLysAlaIleProValAla 195200205 GlnAspLeuAsnAlaProSerAspTrpAspSerArgGlyLysAspSer 210215220 TyrGluThrSerGlnLeuAspAspGlnSerAlaGluThrHisSerHis 225230235240 LysGlnSerArgLeuTyrLysArgLysAlaAsnAspGluSerAsnGlu 245250255 HisSerAspValIleAspSerGlnGluLeuSerLysValSerArgGlu 260265270 PheHisSerHisGluPheHisSerHisGluAspMetLeuValValAsp 275280285 ProLysSerLysGluGluAspLysHisLeuLysPheArgIleSerHis 290295300 GluLeuAspSerAlaSerSerGluValAsn 305310 <210> 18 <211> 280 <212> PRT <213> Homosapiens <220> <221> MISC_FEATURE <223> Cdca8 <400> 18 MetAlaProArgLysGlySerSerArgValAlaLysThrAsnSerLeu 151015 ArgArgArgLysLeuAlaSerPheLeuLysAspPheAspArgGluVal 202530 GluIleArgIleLysGlnIleGluSerAspArgGlnAsnLeuLeuLys 354045 GluValAspAsnLeuTyrAsnIleGluIleLeuArgLeuProLysAla 505560 LeuArgGluMetAsnTrpLeuAspTyrPheAlaLeuGlyGlyAsnLys 65707580 GlnAlaLeuGluGluAlaAlaThrAlaAspLeuAspIleThrGluIle 859095 AsnLysLeuThrAlaGluAlaIleGlnThrProLeuLysSerAlaLys 100105110 ThrArgLysValIleGlnValAspGluMetIleValGluGluGluGlu 115120125 GluGluGluAsnGluArgLysAsnLeuGlnThrAlaArgValLysArg 130135140 CysProProSerLysLysArgThrGlnSerIleGlnGlyLysGlyLys 145150155160 GlyLysArgSerSerArgAlaAsnThrValThrProAlaValGlyArg 165170175 LeuGluValSerMetValLysProThrProGlyLeuThrProArgPhe 180185190 AspSerArgValPheLysThrProGlyLeuArgThrProAlaAlaGly 195200205 GluArgIleTyrAsnIleSerGlyAsnGlySerProLeuAlaAspSer 210215220 LysGluIlePheLeuThrValProValGlyGlyGlyGluSerLeuArg 225230235240 LeuLeuAlaSerAspLeuGlnArgHisSerIleAlaGlnLeuAspPro 245250255 GluAlaLeuGlyAsnIleLysLysLeuSerAsnArgLeuAlaGlnIle 260265270 CysSerSerIleArgThrHisLys 275280 <210> 19 <211> 923 <212> PRT <213> Homosapiens <220> <221> MISC_FEATURE <223> Nrp1 <400> 19 MetGluArgGlyLeuProLeuLeuCysAlaValLeuAlaLeuValLeu 151015 AlaProAlaGlyAlaPheArgAsnAspLysCysGlyAspThrIleLys 202530 IleGluSerProGlyTyrLeuThrSerProGlyTyrProHisSerTyr 354045 HisProSerGluLysCysGluTrpLeuIleGlnAlaProAspProTyr 505560 GlnArgIleMetIleAsnPheAsnProHisPheAspLeuGluAspArg 65707580 AspCysLysTyrAspTyrValGluValPheAspGlyGluAsnGluAsn 859095 GlyHisPheArgGlyLysPheCysGlyLysIleAlaProProProVal 100105110 ValSerSerGlyProPheLeuPheIleLysPheValSerAspTyrGlu 115120125 ThrHisGlyAlaGlyPheSerIleArgTyrGluIlePheLysArgGly 130135140 ProGluCysSerGlnAsnTyrThrThrProSerGlyValIleLysSer 145150155160 ProGlyPheProGluLysTyrProAsnSerLeuGluCysThrTyrIle 165170175 ValPheValProLysMetSerGluIleIleLeuGluPheGluSerPhe 180185190 AspLeuGluProAspSerAsnProProGlyGlyMetPheCysArgTyr 195200205 AspArgLeuGluIleTrpAspGlyPheProAspValGlyProHisIle 210215220 GlyArgTyrCysGlyGlnLysThrProGlyArgIleArgSerSerSer 225230235240 GlyIleLeuSerMetValPheTyrThrAspSerAlaIleAlaLysGlu 245250255 GlyPheSerAlaAsnTyrSerValLeuGlnSerSerValSerGluAsp 260265270 PheLysCysMetGluAlaLeuGlyMetGluSerGlyGluIleHisSer 275280285 AspGlnIleThrAlaSerSerGlnTyrSerThrAsnTrpSerAlaGlu 290295300 ArgSerArgLeuAsnTyrProGluAsnGlyTrpThrProGlyGluAsp 305310315320 SerTyrArgGluTrpIleGlnValAspLeuGlyLeuLeuArgPheVal 325330335 ThrAlaValGlyThrGlnGlyAlaIleSerLysGluThrLysLysLys 340345350 TyrTyrValLysThrTyrLysIleAspValSerSerAsnGlyGluAsp 355360365 TrpIleThrIleLysGluGlyAsnLysProValLeuPheGlnGlyAsn 370375380 ThrAsnProThrAspValValValAlaValPheProLysProLeuIle 385390395400 ThrArgPheValArgIleLysProAlaThrTrpGluThrGlyIleSer 405410415 MetArgPheGluValTyrGlyCysLysIleThrAspTyrProCysSer 420425430 GlyMetLeuGlyMetValSerGlyLeuIleSerAspSerGlnIleThr 435440445 SerSerAsnGlnGlyAspArgAsnTrpMetProGluAsnIleArgLeu 450455460 ValThrSerArgSerGlyTrpAlaLeuProProAlaProHisSerTyr 465470475480 IleAsnGluTrpLeuGlnIleAspLeuGlyGluGluLysIleValArg 485490495 GlyIleIleIleGlnGlyGlyLysHisArgGluAsnLysValPheMet 500505510 ArgLysPheLysIleGlyTyrSerAsnAsnGlySerAspTrpLysMet 515520525 IleMetAspAspSerLysArgLysAlaLysSerPheGluGlyAsnAsn 530535540 AsnTyrAspThrProGluLeuArgThrPheProAlaLeuSerThrArg 545550555560 PheIleArgIleTyrProGluArgAlaThrHisGlyGlyLeuGlyLeu 565570575 ArgMetGluLeuLeuGlyCysGluValGluAlaProThrAlaGlyPro 580585590 ThrThrProAsnGlyAsnLeuValAspGluCysAspAspAspGlnAla 595600605 AsnCysHisSerGlyThrGlyAspAspPheGlnLeuThrGlyGlyThr 610615620 ThrValLeuAlaThrGluLysProThrValIleAspSerThrIleGln 625630635640 SerGluPheProThrTyrGlyPheAsnCysGluPheGlyTrpGlySer 645650655 HisLysThrPheCysHisTrpGluHisAspAsnHisValGlnLeuLys 660665670 TrpSerValLeuThrSerLysThrGlyProIleGlnAspHisThrGly 675680685 AspGlyAsnPheIleTyrSerGlnAlaAspGluAsnGlnLysGlyLys 690695700 ValAlaArgLeuValSerProValValTyrSerGlnAsnSerAlaHis 705710715720 CysMetThrPheTrpTyrHisMetSerGlySerHisValGlyThrLeu 725730735 ArgValLysLeuArgTyrGlnLysProGluGluTyrAspGlnLeuVal 740745750 TrpMetAlaIleGlyHisGlnGlyAspHisTrpLysGluGlyArgVal 755760765 LeuLeuHisLysSerLeuLysLeuTyrGlnValIlePheGluGlyGlu 770775780 IleGlyLysGlyAsnLeuGlyGlyIleAlaValAspAspIleSerIle 785790795800 AsnAsnHisIleSerGlnGluAspCysAlaLysProAlaAspLeuAsp 805810815 LysLysAsnProGluIleLysIleAspGluThrGlySerThrProGly 820825830 TyrGluGlyGluGlyGluGlyAspLysAsnIleSerArgLysProGly 835840845 AsnValLeuLysThrLeuAspProIleLeuIleThrIleIleAlaMet 850855860 SerAlaLeuGlyValLeuLeuGlyAlaValCysGlyValValLeuTyr 865870875880 CysAlaCysTrpHisAsnGlyMetSerGluArgAsnLeuSerAlaLeu 885890895 GluAsnTyrAsnPheGluLeuValAspGlyValLysLeuLysLysAsp 900905910 LysLeuAsnThrGlnSerThrTyrSerGluAla 915920 <210> 20 <211> 646 <212> PRT <213>Homosapiens <220> <221> MISC_FEATURE <223> Mcam <400> 20 MetGlyLeuProArgLeuValCysAlaPheLeuLeuAlaAlaCysCys 151015 CysCysProArgValAlaGlyValProGlyGluAlaGluGlnProAla 202530 ProGluLeuValGluValGluValGlySerThrAlaLeuLeuLysCys 354045 GlyLeuSerGlnSerGlnGlyAsnLeuSerHisValAspTrpPheSer 505560 ValHisLysGluLysArgThrLeuIlePheArgValArgGlnGlyGln 65707580 GlyGlnSerGluProGlyGluTyrGluGlnArgLeuSerLeuGlnAsp 859095 ArgGlyAlaThrLeuAlaLeuThrGlnValThrProGlnAspGluArg 100105110 IlePheLeuCysGlnGlyLysArgProArgSerGlnGluTyrArgIle 115120125 GlnLeuArgValTyrLysAlaProGluGluProAsnIleGlnValAsn 130135140 ProLeuGlyIleProValAsnSerLysGluProGluGluValAlaThr 145150155160 CysValGlyArgAsnGlyTyrProIleProGlnValIleTrpTyrLys 165170175 AsnGlyArgProLeuLysGluGluLysAsnArgValHisIleGlnSer 180185190 SerGlnThrValGluSerSerGlyLeuTyrThrLeuGlnSerIleLeu 195200205 LysAlaGlnLeuValLysGluAspLysAspAlaGlnPheTyrCysGlu 210215220 LeuAsnTyrArgLeuProSerGlyAsnHisMetLysGluSerArgGlu 225230235240 ValThrValProValPheTyrProThrGluLysValTrpLeuGluVal 245250255 GluProValGlyMetLeuLysGluGlyAspArgValGluIleArgCys 260265270 LeuAlaAspGlyAsnProProProHisPheSerIleSerLysGlnAsn 275280285 ProSerThrArgGluAlaGluGluGluThrThrAsnAspAsnGlyVal 290295300 LeuValLeuGluProAlaArgLysGluHisSerGlyArgTyrGluCys 305310315320 GlnGlyLeuAspLeuAspThrMetIleSerLeuLeuSerGluProGln 325330335 GluLeuLeuValAsnTyrValSerAspValArgValSerProAlaAla 340345350 ProGluArgGlnGluGlySerSerLeuThrLeuThrCysGluAlaGlu 355360365 SerSerGlnAspLeuGluPheGlnTrpLeuArgGluGluThrGlyGln 370375380 ValLeuGluArgGlyProValLeuGlnLeuHisAspLeuLysArgGlu 385390395400 AlaGlyGlyGlyTyrArgCysValAlaSerValProSerIleProGly 405410415 LeuAsnArgThrGlnLeuValAsnValAlaIlePheGlyProProTrp 420425430 MetAlaPheLysGluArgLysValTrpValLysGluAsnMetValLeu 435440445 AsnLeuSerCysGluAlaSerGlyHisProArgProThrIleSerTrp 450455460 AsnValAsnGlyThrAlaSerGluGlnAspGlnAspProGlnArgVal 465470475480 LeuSerThrLeuAsnValLeuValThrProGluLeuLeuGluThrGly 485490495 ValGluCysThrAlaSerAsnAspLeuGlyLysAsnThrSerIleLeu 500505510 PheLeuGluLeuValAsnLeuThrThrLeuThrProAspSerAsnThr 515520525 ThrThrGlyLeuSerThrSerThrAlaSerProHisThrArgAlaAsn 530535540 SerThrSerThrGluArgLysLeuProGluProGluSerArgGlyVal 545550555560 ValIleValAlaValIleValCysIleLeuValLeuAlaValLeuGly 565570575 AlaValLeuTyrPheLeuTyrLysLysGlyLysLeuProCysArgArg 580585590 SerGlyLysGlnGluIleThrLeuProProSerArgLysSerGluLeu 595600605 ValValGluValLysSerAspLysLeuProGluGluMetGlyLeuLeu 610615620 GlnGlySerSerGlyAspLysArgAlaProGlyAspGlnGlyGluLys 625630635640 TyrIleAspLeuArgHis 645 <210> 21 <211> 322 <212> PRT <213>Homosapiens <220> <221> MISC_FEATURE <223> Pbk <400> 21 MetGluGlyIleSerAsnPheLysThrProSerLysLeuSerGluLys 151015 LysLysSerValLeuCysSerThrProThrIleAsnIleProAlaSer 202530 ProPheMetGlnLysLeuGlyPheGlyThrGlyValAsnValTyrLeu 354045 MetLysArgSerProArgGlyLeuSerHisSerProTrpAlaValLys 505560 LysIleAsnProIleCysAsnAspHisTyrArgSerValTyrGlnLys 65707580 ArgLeuMetAspGluAlaLysIleLeuLysSerLeuHisHisProAsn 859095 IleValGlyTyrArgAlaPheThrGluAlaAsnAspGlySerLeuCys 100105110 LeuAlaMetGluTyrGlyGlyGluLysSerLeuAsnAspLeuIleGlu 115120125 GluArgTyrLysAlaSerGlnAspProPheProAlaAlaIleIleLeu 130135140 LysValAlaLeuAsnMetAlaArgGlyLeuLysTyrLeuHisGlnGlu 145150155160 LysLysLeuLeuHisGlyAspIleLysSerSerAsnValValIleLys 165170175 GlyAspPheGluThrIleLysIleCysAspValGlyValSerLeuPro 180185190 LeuAspGluAsnMetThrValThrAspProGluAlaCysTyrIleGly 195200205 ThrGluProTrpLysProLysGluAlaValGluGluAsnGlyValIle 210215220 ThrAspLysAlaAspIlePheAlaPheGlyLeuThrLeuTrpGluMet 225230235240 MetThrLeuSerIleProHisIleAsnLeuSerAsnAspAspAspAsp 245250255 GluAspLysThrPheAspGluSerAspPheAspAspGluAlaTyrTyr 260265270 AlaAlaLeuGlyThrArgProProIleAsnMetGluGluLeuAspGlu 275280285 SerTyrGlnLysValIleGluLeuPheSerValCysThrAsnGluAsp 290295300 ProLysAspArgProSerAlaAlaHisIleValGluAlaLeuGluThr 305310315320 AspVal <210> 22 <211> 262 <212> PRT <213> Musmusculus <220> <221> MISC_FEATURE <223> Akr1c1 <400> 22 GlyLeuAlaIleArgSerLysValAlaAspGlyThrValArgArgGlu 151015 AspIlePheTyrThrSerLysLeuProCysThrCysHisArgProGlu 202530 LeuValGlnProCysLeuGluGlnSerLeuArgLysLeuGlnLeuAsp 354045 TyrValAspLeuTyrLeuIleHisCysProValSerMetLysProGly 505560 AsnAspLeuIleProThrAspGluAsnGlyLysLeuLeuPheAspThr 65707580 ValAspLeuCysAspThrTrpGluAlaMetGluLysCysLysAspSer 859095 GlyLeuAlaLysSerIleGlyValSerAsnPheAsnArgArgGlnLeu 100105110 GluMetIleLeuAsnLysProGlyLeuArgTyrLysProValCysAsn 115120125 GlnValGluCysHisProTyrLeuAsnGlnSerLysLeuLeuAspTyr 130135140 CysLysSerLysAspIleValLeuValAlaTyrGlyAlaLeuGlySer 145150155160 GlnArgCysLysAsnTrpIleGluGluAsnAlaProTyrLeuLeuGlu 165170175 AspProThrLeuCysAlaMetAlaGluLysHisLysGlnThrProAla 180185190 LeuIleSerLeuArgTyrLeuLeuGlnArgGlyIleValIleValThr 195200205 LysSerPheAsnGluLysArgIleLysGluAsnLeuLysValPheGlu 210215220 PheHisLeuProAlaGluAspMetAlaValIleAspArgLeuAsnArg 225230235240 AsnTyrArgTyrAlaThrAlaArgIleIleSerAlaHisProAsnTyr 245250255 ProPheLeuAspGluTyr 260 <210> 23 <211> 521 <212> PRT <213> Homosapiens <220> <221> MISC_FEATURE <223> Cypl1a1 <400> 23 MetLeuAlaLysGlyLeuProProArgSerValLeuValLysGlyCys 151015 GlnThrPheLeuSerAlaProArgGluGlyLeuGlyArgLeuArgVal 202530 ProThrGlyGluGlyAlaGlyIleSerThrArgSerProArgProPhe 354045 AsnGluIleProSerProGlyAspAsnGlyTrpLeuAsnLeuTyrHis 505560 PheTrpArgGluThrGlyThrHisLysValHisLeuHisHisValGln 65707580 AsnPheGlnLysTyrGlyProIleTyrArgGluLysLeuGlyAsnVal 859095 GluSerValTyrValIleAspProGluAspValAlaLeuLeuPheLys 100105110 SerGluGlyProAsnProGluArgPheLeuIleProProTrpValAla 115120125 TyrHisGlnTyrTyrGlnArgProIleGlyValLeuLeuLysLysSer 130135140 AlaAlaTrpLysLysAspArgValAlaLeuAsnGlnGluValMetAla 145150155160 ProGluAlaThrLysAsnPheLeuProLeuLeuAspAlaValSerArg 165170175 AspPheValSerValLeuHisArgArgIleLysLysAlaGlySerGly 180185190 AsnTyrSerGlyAspIleSerAspAspLeuPheArgPheAlaPheGlu 195200205 SerIleThrAsnValIlePheGlyGluArgGlnGlyMetLeuGluGlu 210215220 ValValAsnProGluAlaGlnArgPheIleAspAlaIleTyrGlnMet 225230235240 PheHisThrSerValProMetLeuAsnLeuProProAspLeuPheArg 245250255 LeuPheArgThrLysThrTrpLysAspHisValAlaAlaTrpAspVal 260265270 IlePheSerLysAlaAspIleTyrThrGlnAsnPheTyrTrpGluLeu 275280285 ArgGlnLysGlySerValHisHisAspTyrArgGlyIleLeuTyrArg 290295300 LeuLeuGlyAspSerLysMetSerPheGluAspIleLysAlaAsnVal 305310315320 ThrGluMetLeuAlaGlyGlyValAspThrThrSerMetThrLeuGln 325330335 TrpHisLeuTyrGluMetAlaArgAsnLeuLysValGlnAspMetLeu 340345350 ArgAlaGluValLeuAlaAlaArgHisGlnAlaGlnGlyAspMetAla 355360365 ThrMetLeuGlnLeuValProLeuLeuLysAlaSerIleLysGluThr 370375380 LeuArgLeuHisProIleSerValThrLeuGlnArgTyrLeuValAsn 385390395400 AspLeuValLeuArgAspTyrMetIleProAlaLysThrLeuValGln 405410415 ValAlaIleTyrAlaLeuGlyArgGluProThrPhePhePheAspPro 420425430 GluAsnPheAspProThrArgTrpLeuSerLysAspLysAsnIleThr 435440445 TyrPheArgAsnLeuGlyPheGlyTrpGlyValArgGlnCysLeuGly 450455460 ArgArgIleAlaGluLeuGluMetThrIlePheLeuIleAsnMetLeu 465470475480 GluAsnPheArgValGluIleGlnHisLeuSerAspValGlyThrThr 485490495 PheAsnLeuIleLeuMetProGluLysProIleSerPheThrPheTrp 500505510 ProPheAsnGlnGluAlaThrGlnGln 515520 ThefollowingDNA arefrommRNA FOSHumanDNA AACCGCATCTGCAGCGAGCAACTGAGAAGCCAAGACTGAGCCGGCGGCCGCGGCGCAGCG AACGAGCAGTGACCGTGCTCCTACCCAGCTCTGCTTCACAGCGCCCACCTGTCTCCGCCC CTCGGCCCCTCGCCCGGCTTTGCCTAACCGCCACGATGATGTTCTCGGGCTTCAACGCAG ACTACGAGGCGTCATCCTCCCGCTGCAGCAGCGCGTCCCCGGCCGGGGATAGCCTCTCTT ACTACCACTCACCCTTTCGGAGTCCCCGCCCCCTCCGCTGGGGCTTACTCCAGGGCTGGC GTTGTGAAGACCATGACAGGAGGCCGAGCGCAGAGCATTGGCAGGAGGGGCAAGGTGGAA CAGTTATCTCCTGAAGAAGAAGAGAAAAGGAGAATCCGAAGGGAAAGGAATAAGATGGCT GCAGCCAAATGCCGCAACCGGAGGAGGGAGCTGACTGATACACTCCAAGCGGAGACAGAC CAACTAGAAGATGAGAAGTCTGCTTTGCAGACCGAGATTGCCAACCTGCTGAAGGAGAAG GAAAAACTAGAGTTCATCCTGGCAGCTCACCGACCTGCCTGCAAGATCCCTGATGACCTG GGCTTCCCAGAAGAGATGTCTGTGGCTTCCCTTGATCTGACTGGGGGCCTGCCAGAGGTT GCCACCCCGGAGTCTGAGGAGGCCTTCACCCTGCCTCTCCTCAATGACCCTGAGCCCAAG CCCTCAGTGGAACCTGTCAAGAGCATCAGCAGCATGGAGCTGAAGACCGAGCCCTTTGAT GACTTCCTGTTCCCAGCATCATCCAGGCCCAGTGGCTCTGAGACAGCCCGCTCCGTGCCA GACATGGACCTATCTGGGTCCTTCTATGCAGCAGACTGGGAGCCTCTGCACAGTGGCTCC CTGGGGATGGGGCCCATGGCCACAGAGCTGGAGCCCCTGTGCACTCCGGTGGTCACCTGT ACTCCCAGCTGCACTGCTTACACGTCTTCCTTCGTCTTCACCTACCCCGAGGCTGACTCC TTCCCCAGCTGTGCAGCTGCCCACCGCAAGGGCAGCAGCAGCAATGAGCCTTCCTCTGAC TCGCTCAGCTCACCCACGCTGCTGGCCCTGTGAGGGGGCAGGGAAGGGGAGGCAGCCGGC ACCCACAAGTGCCACTGCCCGAGCTGGTGCATTACAGAGAGGAGAAACACATCTTCCCTA GAGGGTTCCTGTAGACCTAGGGAGGACCTTATCTGTGCGTGAAACACACCAGGCTGTGGG CCTCAAGGACTTGAAAGCATCCATGTGTGGACTCAAGTCCTTACCTCTTCCGGAGATGTA GCAAAACGCATGGAGTGTGTATTGTTCCCAGTGACACTTCAGAGAGCTGGTAGTTAGTAG CATGTTGAGCCAGGCCTGGGTCTGTGTCTCTTTTCTCTTTCTCCTTAGTCTTCTCATAGC ATTAACTAATCTATTGGGTTCATTATTGGAATTAACCTGGTGCTGGATATTTTCAAATTG TATCTAGTGCAGCTGATTTTAACAATAACTACTGTGTTCCTGGCAATAGTGTGTTCTGAT TAGAAATGACCAATATTATACTAAGAAAAGATACGACTTTATTTTCTGGTAGATAGAAAT AAATAGCTATATCCATGTACTGTAGTTTTTCTTCAACATCAATGTTCATTGTAATGTTAC TGATCATGCATTGTTGAGGTGGTCTGAATGTTCTGACATTAACAGTTTTCCATGAAAACG TTTTATTGTGTTTTTAATTTATTTATTAAGATGGATTCTCAGATATTTATATTTTTATTT TATTTTTTTCTACCTTGAGGTCTTTTGACATGTGGAAAGTGAATTTGAATGAAAAATTTA AGCATTGTTTGCTTATTGTTCCAAGACATTGTCAATAAAAGCATTTAAGTT GAATGCG FOSMouseProtein MMFSGFNADYEASSSRCSSASPAGDSLSYYHSPADSFSSMGSPVNTQDFCADLSVSSANF IPTVTAISTSPDLQWLVQPTLVSSVAPSQTRAPHPYGLPTQSAGAYARAGMVKTVSGGRA QSIGRRGKVEQLSPEEEEKRRIRRERNKMAAAKCRNRRRELTDTLQAETDQLEDEKSALQ TEIANLLKEKEKLEFILAAHRPACKIPDDLGFPEEMSVASLDLTGGLPEASTPESEEAFT LPLLNDPEPKPSLEPVKSISNVELKAEPFDDFLFPASSRPSGSETSRSVPDVDLSGSFYA ADWEPLHSNSLGMGPMVTELEPLCTPVVTCTPGCTTYTSSFVFTYPEADSFPSCAAAHRK GSSSNEPSSDSLSSPTLLAL FOSMouseDNA CAGCGAGCAACTGAGAAGACTGGATAGAGCCGGCGGTTCCGCGAACGAGCAGTGACCGCG CTCCCACCCAGCTCTGCTCTGCAGCTCCCACCAGTGTCTACCCCTGGACCCCTTGCCGGG CTTTCCCCAAACTTCGACCATGATGTTCTCGGGTTTCAACGCCGACTACGAGGCGTCATC CTCCCGCTGCAGTAGCGCCTCCCCGGCCGGGGACAGCCTTTCCTACTACCATTCCCCAGC CGACTCCTTCTCCAGCATGGGCTCTCCTGTCAACACACAGGACTTTTGCGCAGATCTGTC CGTCTCTAGTGCCAACTTTATCCCCACGGTGACAGCCATCTCCACCAGCCCAGACCTGCA GTGGCTGGTGCAGCCCACTCTGGTCTCCTCCGTGGCCCCATCGCAGACCAGAGCGCCCCA TCCTTACGGACTCCCCACCCAGTCTGCTGGGGCTTACGCCAGAGCGGGAATGGTGAAGAC CGTGTCAGGAGGCAGAGCGCAGAGCATCGGCAGAAGGGGCAAAGTAGAGCAGCTATCTCC TGAAGAGGAAGAGAAACGGAGAATCCGAAGGGAACGGAATAAGATGGCTGCAGCCAAGTG CCGGAATCGGAGGAGGGAGCTGACAGATACACTCCAAGCGGAGACAGATCAACTTGAAGA TGAGAAGTCTGCGTTGCAGACTGAGATTGCCAATCTGCTGAAAGAGAAGGAAAAACTGGA GTTTATTTTGGCAGCCCACCGACCTGCCTGCAAGATCCCCGATGACCTTGGCTTCCCAGA GGAGATGTCTGTGGCCTCCCTGGATTTGACTGGAGGTCTGCCTGAGGCTTCCACCCCAGA GTCTGAGGAGGCCTTCACCCTGCCCCTTCTCAACGACCCTGAGCCCAAGCCATCCTTGGA GCCAGTCAAGAGCATCAGCAACGTGGAGCTGAAGGCAGAACCCTTTGATGACTTCTTGTT TCCGGCATCATCTAGGCCCAGTGGCTCAGAGACCTCCCGCTCTGTGCCAGATGTGGACCT GTCCGGTTCCTTCTATGCAGCAGACTGGGAGCCTCTGCACAGCAATTCCTTGGGGATGGG GCCCATGGTCACAGAGCTGGAGCCCCTGTGTACTCCCGTGGTCACCTGTACTCCGGGCTG CACTACTTACACGTCTTCCTTTGTCTTCACCTACCCTGAAGCTGACTCCTTCCCAAGCTG TGCCGCTGCCCACCGAAAGGGCAGCAGCAGCAACGAGCCCTCCTCCGACTCCCTGAGCTC ACCCACGCTGCTGGCCCTGTGAGCAGTCAGAGAAGGCAAGGCAGCCGGCATCCAGACGTG CCACTGCCCGAGCTGGTGCATTACAGAGAGGAGAAACACGTCTTCCCTCGAAGGTTCCCG TCGACCTAGGGAGGACCTTACCTGTTCGTGAAACACACCAGGCTGTGGGCCTCAAGGACT TGCAAGCATCCACATCTGGCCTCCAGTCCTCACCTCTTCCAGAGATGTAGCAAAAACAAA ACAAAACAAAACAAAAAACCGCATGGAGTGTGTTGTTCCTAGTGACACCTGAGAGCTGGT AGTTAGTAGAGCATGTGAGTCAAGGCCTGGTCTGTGTCTCTTTTCTCTTTCTCCTTAGTT TTCTCATAGCACTAACTAATCTGTTGGGTTCATTATTGGAATTAACCTGGTGCTGGATTG TATCTAGTGCAGCTGATTTTAACAATACCTACTGTGTTCCTGGCAATAGCGTGTTCCAAT TAGAAACGACCAATATTAAACTAAGAAAAGATAGGACTTTATTTTCCAGTAGATAGAAAT CAATAGCTATATCCATGTACTGTAGTCCTTCAGCGTCAATGTTCATTGTCATGTTACTGA TCATGCATTGTCGAGGTGGTCTGAATGTTCTGACATTAACAGTTTTCCATGAAAACGTTT TTATTGTGTTTTCAATTTATTTATTAAGATGGATTCTCAGATATTTATATTTTTATTTTA TTTTTTTCTACCCTGAGGTCTTTCGACATGTGGAAAGTGAATTTGAATGAAAAATTTTAA GCATTGTTTGCTTATTGTTCCAAGACATTGTCAATAAAAGCATTTAAGTTGAAAAAAAAA AAAAAAA CD93HumanDNA 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 CD93MouseProtein MAISTGLFLLLGLLGQPWAGAAADSQAVVCEGTACYTAHWGKLSAAEAQHRCNENGGNLA TVKSEEEARHVQQALTQLLKTKAPLEAKMGKFWIGLQREKGNCTYHDLPMRGFSWVGGGE DTAYSNWYKASKSSCIFKRCVSLILDLSLTPHPSHLPKWHESPCGTPEAPGNSIEGFLCK FNFKGMCRPLALGGPGRVTYTTPFQATTSSLEAVPFASVANVACGDEAKSETHYFLCNEK TPGIFHWGSSGPLCVSPKFGCSFNNGGCQQDCFEGGDGSFRCGCRPGFRLLDDLVTCASR NPCSSNPCTGGGMCHSVPLSENYTCRCPSGYQLDSSQVHCVDIDECQDSPCAQDCVNTLG SFHCECWVGYQPSGPKEEACEDVDECAAANSPCAQGCINTDGSFYCSCKEGYIVSGEDST QCEDIDECSDARGNPCDSLCFNTDGSFRCGCPPGWELAPNGVFCSRGTVFSELPARPPQK EDNDDRKESTMPPTEMPSSPSGSKDVSNRAQTTGLFVQSDIPTASVPLEIEIPSEVSDVW FELGTYLPTTSGHSKPTHEDSVSAHSDTDGQNLLLFYILGTVVAISLLLVLALGILIYHK RRAKKEEIKEKKPQNAADSYSWVPERAESQAPENQYSPTPGTDC CD93MouseDNA GAAAGCAGCAGTGCGCCTCTGCTCCCTTCAGAGCACAGCCTGGTGTCAAGGTCCAGGTTC CACCGGCTGCTGCTGTCACCGCAGGGGAGTCTAGCCCCTCCCAGAAGGAGACACAGAAGA ATGGCCATCTCAACTGGTTTGTTCCTGCTGCTGGGGCTCCTTGGCCAGCCCTGGGCAGGG GCTGCTGCTGATTCACAGGCTGTGGTGTGCGAGGGGACTGCCTGCTATACAGCCCATTGG GGCAAGCTGAGTGCCGCTGAAGCCCAGCATCGCTGCAATGAGAATGGAGGCAATCTTGCC ACCGTGAAGAGTGAGGAGGAGGCCCGGCATGTTCAGCAAGCCCTGACTCAGCTCCTGAAG ACCAAGGCACCCTTGGAAGCAAAGATGGGCAAATTCTGGATCGGGCTCCAGCGAGAGAAG GGCAACTGTACGTACCATGATTTGCCAATGAGGGGCTTCAGCTGGGTGGGTGGTGGAGAG GACACAGCTTATTCAAACTGGTACAAAGCCAGCAAGAGCTCCTGTATCTTTAAACGCTGT GTGTCCCTCATACTGGACCTGTCCTTGACACCTCACCCCAGCCATCTGCCCAAGTGGCAT GAGAGTCCCTGTGGGACCCCCGAAGCTCCAGGTAACAGCATTGAAGGTTTCCTGTGCAAG TTCAACTTCAAAGGCATGTGTAGGCCACTGGCGCTGGGTGGTCCAGGGCGGGTGACCTAT ACCACCCCTTTCCAGGCCACTACCTCCTCTCTGGAGGCTGTGCCTTTTGCCTCTGTAGCC AATGTAGCTTGTGGGGATGAAGCTAAGAGTGAAACCCACTATTTCCTATGCAATGAAAAG ACTCCAGGAATATTTCACTGGGGCAGCTCAGGCCCACTCTGTGTCAGCCCCAAGTTTGGT TGCAGTTTCAACAACGGGGGCTGCCAGCAGGATTGCTTCGAAGGTGGCGATGGCTCCTTC CGCTGCGGCTGCCGGCCTGGATTTCGACTGCTGGATGATCTAGTAACTTGTGCCTCCAGG AACCCCTGCAGCTCAAACCCATGCACAGGAGGTGGCATGTGCCATTCTGTACCACTCAGT GAAAACTACACTTGCCGTTGTCCCAGCGGCTACCAGCTGGACTCTAGCCAAGTGCACTGT GTGGATATAGATGAGTGCCAGGACTCCCCCTGTGCCCAGGATTGTGTCAACACTCTAGGG AGCTTCCACTGTGAATGTTGGGTTGGTTACCAACCCAGTGGCCCCAAGGAAGAGGCCTGT GAAGATGTGGATGAGTGTGCAGCTGCCAACTCGCCCTGTGCCCAAGGCTGCATCAACACT GATGGCTCTTTCTACTGCTCCTGTAAAGAGGGCTATATTGTGTCTGGGGAAGACAGTACC CAGTGTGAGGATATAGATGAGTGTTCGGACGCAAGGGGCAATCCATGTGATTCCCTGTGC TTCAACACAGATGGTTCCTTCAGGTGTGGCTGCCCGCCAGGCTGGGAGCTGGCTCCCAAT GGGGTCTTTTGTAGCAGGGGCACTGTGTTTTCTGAACTACCAGCCAGGCCTCCCCAAAAG GAAGACAACGATGACAGAAAGGAGAGTACTATGCCTCCTACTGAAATGCCCAGTTCTCCT AGTGGCTCTAAGGATGTCTCCAACAGAGCACAGACAACAGGTCTCTTCGTCCAATCAGAT ATTCCCACTGCCTCTGTTCCACTAGAAATAGAAATCCCTAGTGAAGTATCTGATGTCTGG TTCGAGTTGGGCACATACCTCCCCACGACCTCCGGCCACAGCAAGCCGACACATGAAGAT TCTGTGTCTGCACACAGTGACACCGATGGGCAGAACCTGCTTCTGTTTTACATCCTGGGG ACGGTGGTGGCCATCTCACTCTTGCTGGTGCTGGCCCTAGGGATTCTCATTTATCATAAA CGGAGAGCCAAGAAGGAGGAGATAAAAGAGAAGAAGCCTCAGAATGCAGCCGACAGCTAT TCCTGGGTTCCAGAGCGAGCAGAGAGCCAAGCCCCGGAGAATCAGTACAGCCCAACACCA GGGACAGACTGCTGAAGACTATGTGGCCTTAGAGACAGCTGCCACTACCTTCAGAGCTAC CTTCTTAGATGAGGGGGAAGCCACATCATTCTGAATGACTTGACTGGACTCTCAGCAAAA AAATTGTGCACCTTCCACTTAAGAACCTGGTGGCTTGGGATAGGCAGGTATTTTCTTGGT GCCTTTGATATGTCTGGGGGTGAAAGCTGTGTGTTGGTTTGTCATTGTGGGGAGTTTTGT GGATATTGACAGACCTCACTCAAACACCCTTTTCAAATCCAATAGCAACTGGTTCCTCTG GTTCCTAATTAGGGGGAAAGGAGTCAGAGGGGTGGGACAGGGTGGGGGGATGGGGCTTCA AAGTTTTTTCTTATCACTTGATTTATCATCGAAGGAGTTACTGGTGCTAATTACAATGGA AACAGTTCCTTTCCATCACAGGACAGACACACCTCAATCCTCCATGGGGTCAACAACTAT ATACCCCCAGTGACCCCTTAGGCAAGGACTTGTTGAGAACTGCATCACATTTTGACCTGT TCTCAACAGTACCCATCTATTTCAGGTGGGATCTCTGGACCTTTCCTCCTTCCCATCTTG TCTGCAATGTGGCAAATGGCTTCTTTTTGCATTTTTACTCCGCCCCCACCCCAAGCTGAA GTTCATTTGCAGATCAGCGATTAAGTCTGAATTGTGTGGTGGTCAGTCTTGTTTCCTTTT GTCAGGGGTTATTGTAAATGTTAGTAATTTCGCCTCAAGCCCTCAGTAAGAACATAAATA TTTTAAAATATGTGCGTTTGAAATCTGTTTCATGCATCCTGGAACTGTGGGATGCTCAGG CAAGAGTGACTTTAGTCTTTCAGTGAATGTTGCCCAGAATGTGGGTAGGGAAGGCTCACA GGTTACTCTCCTCCTTAGAGCTACAACATAACATTCTGAGGGGAGTCACAGGGTTGCCTT TAAAAAGTGGGAGCTATGTCATGCTTTGAGCTTTCTGTTAAGCACCTCTCCTAATAAACT CTGAAAAAAT FOSBHumanDNA CATTCATAAGACTCAGAGCTACGGCCACGGCAGGGACACGCGGAACCAAGACTTGGAAAC TTGATTGTTGTGGTTCTTCTTGGGGGTTATGAAATTTCATTAATCTTTTTTTTTTCCGGG GAGAAAGTTTTTGGAAAGATTCTTCCAGATATTTCTTCATTTTCTTTTGGAGGACCGACT TACTTTTTTTGGTCTTCTTTATTACTCCCCTCCCCCCGTGGGACCCGCCGGACGCGTGGA GGAGACCGTAGCTGAAGCTGATTCTGTACAGCGGGACAGCGCTTTCTGCCCCTGGGGGAG CAACCCCTCCCTCGCCCCTGGGTCCTACGGAGCCTGCACTTTCAAGAGGTACAGCGGCAT CCTGTGGGGGCCTGGGCACCGCAGGAAGACTGCACAGAAACTTTGCCATTGTTGGAACGG GACGTTGCTCCTTCCCCGAGCTTCCCCGGACAGCGTACTTTGAGGACTCGCTCAGCTCAC CGGGGACTCCCACGGCTCACCCCGGACTTGCACCTTACTTCCCCAACCCGGCCATAGCCT TGGCTTCCCGGCGACCTCAGCGTGGTCACAGGGGCCCCCCTGTGCCCAGGGAAATGTTTC AGGCTTTCCCCGGAGACTACGACTCCGGCTCCCGGTGCAGCTCCTCACCCTCTGCCGAGT CTCAATATCTGTCTTCGGTGGACTCCTTCGGCAGTCCACCCACCGCCGCGGCCTCCCAGG AGTGCGCCGGTCTCGGGGAAATGCCCGGTTCCTTCGTGCCCACGGTCACCGCGATCACAA CCAGCCAGGACCTCCAGTGGCTTGTGCAACCCACCCTCATCTCTTCCATGGCCCAGTCCC AGGGGCAGCCACTGGCCTCCCAGCCCCCGGTCGTCGACCCCTACGACATGCCGGGAACCA GCTACTCCACACCAGGCATGAGTGGCTACAGCAGTGGCGGAGCGAGTGGCAGTGGTGGGC CTTCCACCAGCGGAACTACCAGTGGGCCTGGGCCTGCCCGCCCAGCCCGAGCCCGGCCTA GGAGACCCCGAGAGGAGACGCTCACCCCAGAGGAAGAGGAGAAGCGAAGGGTGCGCCGGG AACGAAATAAACTAGCAGCAGCTAAATGCAGGAACCGGCGGAGGGAGCTGACCGACCGAC TCCAGGCGGAGACAGATCAGTTGGAGGAAGAAAAAGCAGAGCTGGAGTCGGAGATCGCCG AGCTCCAAAAGGAGAAGGAACGTCTGGAGTTTGTGCTGGTGGCCCACAAACCGGGCTGCA AGATCCCCTACGAAGAGGGGCCCGGGCCGGGCCCGCTGGCGGAGGTGAGAGATTTGCCGG GCTCAGCACCGGCTAAGGAAGATGGCTTCAGCTGGCTGCTGCCGCCCCCGCCACCACCGC CCCTGCCCTTCCAGACCAGCCAAGACGCACCCCCCAACCTGACGGCTTCTCTCTTTACAC ACAGTGAAGTTCAAGTCCTCGGCGACCCCTTCCCCGTTGTTAACCCTTCGTACACTTCTT CGTTTGTCCTCACCTGCCCGGAGGTCTCCGCGTTCGCCGGCGCCCAACGCACCAGCGGCA GTGACCAGCCTTCCGATCCCCTGAACTCGCCCTCCCTCCTCGCTCGGTGAACTCTTTAGA CACACAAAACAAACAAACACATGGGGGAGAGAGACTTGGAAGAGGAGGAGGAGGAGGAGA 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 TATGTATAAGTAAATATATTATATATGGATGTGTGTGTGTGCGTGCGCGTGAGTGTGTGA GCGCTTCTGCAGCCTCGGCCTAGGTCACGTTGGCCCTCAAAGCGAGCCGTTGAATTGGAA ACTGCTTCTAGAAACTCTGGCTCAGCCTGTCTCGGGCTGACCCTTTTCTGATCGTCTCGG CCCCTCTGATTGTTCCCGATGGTCTCTCTCCCTCTGTCTTTTCTCCTCCGCCTGTGTCCA TCTGACCGTTTTCACTTGTCTCCTTTCTGACTGTCCCTGCCAATGCTCCAGCTGTCGTCT GACTCTGGGTTCGTTGGGGACATGAGATTTTATTTTTTGTGAGTGAGACTGAGGGATCGT AGATTTTTACAATCTGTATCTTTGACAATTCTGGGTGCGAGTGTGAGAGTGTGAGCAGGG CTTGCTCCTGCCAACCACAATTCAATGAATCCCCGACCCCCCTACCCCATGCTGTACTTG TGGTTCTCTTTTTGTATTTTGCATCTGACCCCGGGGGGCTGGGACAGATTGGCAATGGGC CGTCCCCTCTCCCCTTGGTTCTGCACTGTTGCCAATAAAAAGCTCTTAAAA ACGC FOSBMouseDNA ATAAATTCTTATTTTGACACTCACCAAAATAGTCACCTGGAAAACCCGCTTTTTGTGACA AAGTACAGAAGGCTTGGTCACATTTAAATCACTGAGAACTAGAGAGAAATACTATCGCAA ACTGTAATAGACATTACATCCATAAAAGTTTCCCCAGTCCTTATTGTAATATTGCACAGT GCAATTGCTACATGGCAAACTAGTGTAGCATAGAAGTCAAAGCAAAAACAAACCAAAGAA AGGAGCCACAAGAGTAAAACTGTTCAACAGTTAATAGTTCAAACTAAGCCATTGAATCTA TCATTGGGATCGTTAAAATGAATCTTCCTACACCTTGCAGTGTATGATTTAACTTTTACA GAACACAAGCCAAGTTTAAAATCAGCAGTAGAGATATTAAAATGAAAAGGTTTGCTAATA GAGTAACATTAAATACCCTGAAGGAAAAAAAACCTAAATATCAAAATAACTGATTAAAAT TCACTTGCAAATTAGCACACGAATATGCAACTTGGAAATCATGCAGTGTTTTATTTAAGA AAACATAAAACAAAACTATTAAAATAGTTTTAGAGGGGGTAAAATCCAGGTCCTCTGCCA GGATGCTAAAATTAGACTTCAGGGGAATTTTGAAGTCTTCAATTTTGAAACCTATTAAAA AGCCCATGATTACAGTTAATTAAGAGCAGTGCACGCAACAGTGACACGCCTTTAGAGAGC ATTACTGTGTATGAACATGTTGGCTGCTACCAGCCACAGTCAATTTAACAAGGCTGCTCA GTCATGAACTTAATACAGAGAGAGCACGCCTAGGCAGCAAGCACAGCTTGCTGGGCCACT TTCCTCCCTGTCGTGACACAATCAATCCGTGTACTTGGTGTATCTGAAGCGCACGCTGCA CCGCGGCACTGCCCGGCGGGTTTCTGGGCGGGGAGCGATCCCCGCGTCGCCCCCCGTGAA ACCGACAGAGCCTGGACTTTCAGGAGGTACAGCGGCGGTCTGAAGGGGATCTGGGATCTT GCAGAGGGAACTTGCATCGAAACTTGGGCAGTTCTCCGAACCGGAGACTAAGCTTCCCCG AGCAGCGCACTTTGGAGACGTGTCCGGTCTACTCCGGACTCGCATCTCATTCCACTCGGC CATAGCCTTGGCTTCCCGGCGACCTCAGCGTGGTCACAGGGGCCCCCCTGTGCCCAGGGA AATGTTTCAAGCTTTTCCCGGAGACTACGACTCCGGCTCCCGGTGTAGCTCATCACCCTC CGCCGAGTCTCAGTACCTGTCTTCGGTGGACTCCTTCGGCAGTCCACCCACCGCCGCCGC CTCCCAGGAGTGCGCCGGTCTCGGGGAAATGCCCGGCTCCTTCGTGCCAACGGTCACCGC AATCACAACCAGCCAGGATCTTCAGTGGCTCGTGCAACCCACCCTCATCTCTTCCATGGC CCAGTCCCAGGGGCAGCCACTGGCCTCCCAGCCTCCAGCTGTTGACCCTTATGACATGCC AGGAACCAGCTACTCAACCCCAGGCCTGAGTGCCTACAGCACTGGCGGGGCAAGCGGAAG TGGTGGGCCTTCAACCAGCACAACCACCAGTGGACCTGTGTCTGCCCGTCCAGCCAGAGC CAGGCCTAGAAGACCCCGAGAAGAGACACTTACCCCAGAAGAAGAAGAAAAGCGAAGGGT TCGCAGAGAGCGGAACAAGCTGGCTGCAGCTAAGTGCAGGAACCGTCGGAGGGAGCTGAC AGATCGACTTCAGGCGGAAACTGATCAGCTTGAAGAGGAAAAGGCAGAGCTGGAGTCGGA GATCGCCGAGCTGCAAAAAGAGAAGGAACGCCTGGAGTTTGTCCTGGTGGCCCACAAACC GGGCTGCAAGATCCCCTACGAAGAGGGGCCGGGGCCAGGCCCGCTGGCCGAGGTGAGAGA TTTGCCAGGGTCAACATCCGCTAAGGAAGACGGCTTCGGCTGGCTGCTGCCGCCCCCTCC ACCACCCCCCCTGCCCTTCCAGAGCAGCCGAGACGCACCCCCCAACCTGACGGCTTCTCT CTTTACACACAGTGAAGTTCAAGTCCTCGGCGACCCCTTCCCCGTTGTTAGCCCTTCGTA CACTTCCTCGTTTGTCCTCACCTGCCCGGAGGTCTCCGCGTTCGCCGGCGCCCAACGCAC CAGCGGCAGCGAGCAGCCGTCCGACCCGCTGAACTCGCCCTCCCTTCTTGCTCTGTAAAC TCTTTAGACAAACAAAACAAACAAACCCGCAAGGAACAAGGAGGAGGAAGATGAGGAGGA GAGGGGAGGAAGCAGTCCGGGGGTGTGTGTGTGGACCCTTTGACTCTTCTGTCTGACCAC CTGCCGCCTCTGCCATCGGACATGACGGAAGGACCTCCTTTGTGTTTTGTGCTCCGTCTC TGGTTTTCTGTGCCCCGGCGAGACCGGAGAGCTGGTGACTTTGGGGACAGGGGGTGGGGC GGGGATGGACACCCCTCCTGCATATCTTTGTCCTGTTACTTCAACCCAACTTCTGGGGAT AGATGGCTGGCTGGGTGGGTAGGGTGGGGTGCAACGCCCACCTTTGGCGTCTTGCGTGAG GCTGGAGGGGAAAGGGTGCTGAGTGTGGGGTGCAGGGTGGGTTGAGGTCGAGCTGGCATG CACCTCCAGAGAGACCCAACGAGGAAATGACAGCACCGTCCTGTCCTTCTTTTCCCCCAC CCACCCATCCACCCTCAAGGGTGCAGGGTGACCAAGATAGCTCTGTTTTGCTCCCTCGGG CCTTAGCTGATTAACTTAACATTTCCAAGAGGTTACAACCTCCTCCTGGACGAATTGAGC CCCCGACTGAGGGAAGTCGATGCCCCCTTTGGGAGTCTGCTAACCCCACTTCCCGCTGAT TCCAAAATGTGAACCCCTATCTGACTGCTCAGTCTTTCCCTCCTGGGAAAACTGGCTCAG GTTGGATTTTTTTCCTCGTCTGCTACAGAGCCCCCTCCCAACTCAGGCCCGCTCCCACCC CTGTGCAGTATTATGCTATGTCCCTCTCACCCTCACCCCCACCCCAGGCGCCCTTGGCCG TCCTCGTTGGGCCTTACTGGTTTTGGGCAGCAGGGGGCGCTGCGACGCCCATCTTGCTGG AGCGCTTTATACTGTGAATGAGTGGTCGGATTGCTGGGTGCGCCGGATGGGATTGACCCC CAGCCCTCCAAAACTTTCCCTGGGCCTCCCCTTCTTCCACTTGCTTCCTCCCTCCCCTTG ACAGGGAGTTAGACTCGAAAGGATGACCACGACGCATCCCGGTGGCCTTCTTGCTCAGGC CCCAGACTTTTTCTCTTTAAGTCCTTCGCCTTCCCCAGCCTAGGACGCCAACTTCTCCCC ACCCTGGGAGCCCCGCATCCTCTCACAGAGGTCGAGGCAATTTTCAGAGAAGTTTTCAGG GCTGAGGCTTTGGCTCCCCTATCCTCGATATTTGAATCCCCAAATATTTTTGGACTAGCA TACTTAAGAGGGGGCTGAGTTCCCACTATCCCACTCCATCCAATTCCTTCAGTCCCAAAG ACGAGTTCTGTCCCTTCCCTCCAGCTTTCACCTCGTGAGAATCCCACGAGTCAGATTTCT ATTTTTTAATATTGGGGAGATGGGCCCTACCGCCCGTCCCCCGTGCTGCATGGAACATTC CATACCCTGTCCTGGGCCCTAGGTTCCAAACCTAATCCCAAACCCCACCCCCAGCTATTT ATCCCTTTCCTGGTTCCCAAAAAGCACTTATATCTATTATGTATAAATAAATATATTATA TATGAGTGTGCGTGTGTGTGCGTGTGCGTGCGTGCGTGCGTGCGTGCGAGCTTCCTTGTT TTCAAGTGTGCTGTGGAGTTCAAAATCGCTTCTGGGGATTTGAGTCAGACTTTCTGGCTG TCCCTTTTTGTCACCTTTTTGTTGTTGTCTCGGCTCCTCTGGCTGTTGGAGACAGTCCCG GCCTCTCCCTTTATCCTTTCTCAAGTCTGTCTCGCTCAGACCACTTCCAACATGTCTCCA CTCTCAATGACTCTGATCTCCGGTNTGTCTGTTAATTCTGGATTTGTCGGGGACATGCAA TTTTACTTCTGTAAGTAAGTGTGACTGGGTGGTAGATTTTTTACAATCTATATCGTTGAG AATTC FOSBMouseProtein MFQAFPGDYDSGSRCSSSPSAESQYLSSVDSFGSPPTAAASQECAGLGEMPGSFVPTVTA ITTSQDLQWLVQPTLISSMAQSQGQPLASQPPAVDPYDMPGTSYSTPGLSAYSTGGASGS GGPSTSTTTSGPVSARPARARPRRPREETLTPEEEEKRRVRRERNKLAAAKCRNRRRELT DRLQAETDQLEEEKAELESEIAELQKEKERLEFVLVAHKPGCKIPYEEGPGPGPLAEVRD LPGSTSAKEDGFGWLLPPPPPPPLPFQSSRDAPPNLTASLFTHSEVQVLGDPFPVVSPSY TSSFVLTCPEVSAFAGAQRTSGSEQPSDPLNSPSLLAL Dusp1HumanDNA TTTGGGCTGTGTGTGCGACGCGGGTCGGAGGGGCAGTCGGGGGAACCGCGAAGAAGCCGA GGAGCCCGGAGCCCCGCGTGACGCTCCTCTCTCAGTCCAAAAGCGGCTTTTGGTTCGGCG CAGAGAGACCCGGGGGTCTAGCTTTTCCTCGAAAAGCGCCGCCCTGCCCTTGGCCCCGAG AACAGACAAAGAGCACCGCAGGGCCGATCACGCTGGGGGCGCTGAGGCCGGCCATGGTCA TGGAAGTGGGCACCCTGGACGCTGGAGGCCTGCGGGCGCTGCTGGGGGAGCGAGCGGCGC AATGCCTGCTGCTGGACTGCCGCTCCTTCTTCGCTTTCAACGCCGGCCACATCGCCGGCT CTGTCAACGTGCGCTTCAGCACCATCGTGCGGCGCCGGGCCAAGGGCGCCATGGGCCTGG AGCACATCGTGCCCAACGCCGAGCTCCGCGGCCGCCTGCTGGCCGGCGCCTACCACGCCG TGGTGTTGCTGGACGAGCGCAGCGCCGCCCTGGACGGCGCCAAGCGCGACGGCACCCTGG CCCTGGCGGCCGGCGCGCTCTGCCGCGAGGCGCGCGCCGCGCAAGTCTTCTTCCTCAAAG GAGGATACGAAGCGTTTTCGGCTTCCTGCCCGGAGCTGTGCAGCAAACAGTCGACCCCCA TGGGGCTCAGCCTTCCCCTGAGTACTAGCGTCCCTGACAGCGCGGAATCTGGGTGCAGTT CCTGCAGTACCCCACTCTACGATCAGGGTGGCCCGGTGGAAATCCTGCCCTTTCTGTACC TGGGCAGTGCGTATCACGCTTCCCGCAAGGACATGCTGGATGCCTTGGGCATAACTGCCT TGATCAACGTCTCAGCCAATTGTCCCAACCATTTTGAGGGTCACTACCAGTACAAGAGCA TCCCTGTGGAGGACAACCACAAGGCAGACATCAGCTCCTGGTTCAACGAGGCCATTGACT TCATAGACTCCATCAAGAATGCTGGAGGAAGGGTGTTTGTCCACTGCCAGGCAGGCATTT CCCGGTCAGCCACCATCTGCCTTGCTTACCTTATGAGGACTAATCGAGTCAAGCTGGACG AGGCCTTTGAGTTTGTGAAGCAGAGGCGAAGCATCATCTCTCCCAACTTCAGCTTCATGG GCCAGCTGCTGCAGTTTGAGTCCCAGGTGCTGGCTCCGCACTGTTCGGCAGAGGCTGGGA GCCCCGCCATGGCTGTGCTCGACCGAGGCACCTCCACCACCACCGTGTTCAACTTCCCCG TCTCCATCCCTGTCCACTCCACGAACAGTGCGCTGAGCTACCTTCAGAGCCCCATTACGA CCTCTCCCAGCTGCTGAAAGGCCACGGGAGGTGAGGCTCTTCACATCCCATTGGGACTCC ATGCTCCTTGAGAGGAGAAATGCAATAACTCTGGGAGGGGCTCGAGAGGGCTGGTCCTTA TTTATTTAACTTCACCCGAGTTCCTCTGGGTTTCTAAGCAGTTATGGTGATGACTTAGCG TCAAGACATTTGCTGAACTCAGCACATTCGGGACCAATATATAGTGGGTACATCAAGTCC ATCTGACAAAATGGGGCAGAAGAGAAAGGACTCAGTGTGTGATCCGGTTTCTTTTTGCTC GCCCCTGTTTTTTGTAGAATCTCTTCATGCTTGACATACCTACCAGTATTATTCCCGACG ACACATATACATATGAGAATATACCTTATTTATTTTTGTGTAGGTGTCTGCCTTCACAAA TGTCATTGTCTACTCCTAGAAGAACCAAATACCTCAATTTTTGTTTTTGAGTACTGTACT ATCCTGTAAATATATCTTAAGCAGGTTTGTTTTCAGCACTGATGGAAAATACCAGTGTTG GGTTTTTTTTTAGTTGCCAACAGTTGTATGTTTGCTGATTATTTATGACCTGAAATAATA TATTTCTTCTTCTAAGAAGACATTTTGTTACATAAGGATGACTTTTTTATACAATGGAAT AAATTATGGCATTTCTATTG Dusp1MouseDNA CGGCGGGAGGAAAGCGCGGTGAAGCCAGATTAGGAGCAGCGAGCACTTGGGGACTTAGGG CCACAGGACACCGCACAAGATCGACCGACTTTTTCTGGAGAACCGCAGAACGGGCACGCT GGGGTCGCTGGGGCTGGCCATGGTGATGGAGGTGGGCATCCTGGACGCCGGGGGGCTGCG CGCGCTGCTGCGAGAGGGCGCCGCGCAGTGCCTGTTGTTGGATTGTCGCTCCTTCTTCGC TTTCAACGCCGGCCACATCGCGGGCTCAGTGAACGTGCGCTTCAGCACCATCGTGCGGCG CCGCGCCAAGGGCGCCATGGGCCTGGAGCATATCGTGCCCAACGCTGAACTGCGTGGCCG CCTGCTGGCCGGAGCCTACCACGCCGTGGTGCTGCTGGACGAGCGCAGCGCCTCCCTGGA CGGCGCCAAGCGCGACGGCACCCTGGCCCTGGCCGCGGGCGCGCTCTGCCGAGAGGCGCG CTCCACTCAAGTCTTCTTTCTCCAAGGAGGATATGAAGCGTTTTCGGCTTCCTGCCCTGA GCTGTGCAGCAAACAGTCCACCCCCACGGGGCTCAGCCTCCCCCTGAGTACTAGTGTGCC TGACAGTGCAGAATCCGGATGCAGCTCCTGTAGTACCCCTCTCTACGATCAGGGGGGCCC AGTGGAGATCCTGTCCTTCCTGTACCTGGGCAGTGCCTATCACGCTTCTCGGAAGGATAT GCTTGACGCCTTGGGCATCACCGCCTTGATCAACGTCTCAGCCAATTGTCCTAACCACTT TGAGGGTCACTACCAGTACAAGAGCATCCCTGTGGAGGACAACCACAAGGCAGACATCAG CTCCTGGTTCAACGAGGCTATTGACTTCATAGACTCCATCAAGGATGCTGGAGGGAGAGT GTTTGTTCATTGCCAGGCCGGCATCTCCCGGTCAGCCACCATCTGCCTTGCTTACCTCAT GAGGACTAACCGGGTAAAGCTGGACGAGGCCTTTGAGTTTGTGAAGCAGAGGCGGAGTAT CATCTCCCCGAACTTCAGCTTCATGGGCCAGCTGCTGCAGTTTGAGTCCCAAGTGCTAGC CCCTCACTGCTCTGCTGAAGCTGGGAGCCCTGCCATGGCTGTCCTTGACCGGGGCACCTC TACTACCACAGTCTTCAACTTCCCTGTTTCCATCCCCGTCCACCCCACGAACAGTGCCCT GAACTACCTTAAAAGCCCCATCACCACCTCTCCAAGCTGCTGAAGGGCAAGGGGAGGTGT GGAGTTTCACTTGCCACCGGGTCGCCACTCCTCCTGTGGGAGGAGCAATGCAATAACTCT GGGAGAGGCTCATGGGAGCTGGTCCTTATTTATTTAACACCCCCCTCACCCCCCAACTCC TCCTGAGTTCCACTGAGTTCCTAAGCAGTCACAACAATGACTTGACCGCAAGACATTTGC TGAACTCGGCACATTCGGGACCAATATATTGTGGGTACATCAAGTCCCTCTGACAAAACA GGGCAGAAGAGAAAGGACTCTGTTTGAGGCAGTTTCTTCGCTTGCCTGTTTTTTTTTTCT AGAAACTTCATGCTTGACACACCCACCAGTATTAACCATTCCCGATGACATGCGCGTATG AGAGTTTTTACCTTTATTTATTTTTGTGTAGGTCGGTGGTTTCTGCCTTCACAAATGTCA TTGTCTACTCATAGAAGAACCAAATACCTCAATTTTGTGTTTGCGTACTGTACTATCTTG TAAATAGACCCAGAGCAGGTTTGCTTTCGGCACTGACAGACAAAGCCAGTGTAGGTTTGT AGCTTTCAGTTATCGACAGTTGTATGTTTGTTTATTTATGATCTGAAGTAATATATTTCT TCTTCTGTGAAGACATTTTGTTACTGGGATGACTTTTTTTATACAACAGAATAAATTATG ACGTTTCTATTGA Dusp1MouseProtein MVMEVGILDAGGLRALLREGAAQCLLLDCRSFFAFNAGHIAGSVNVRFSTIVRRRAKGAM GLEHIVPNAELRGRLLAGAYHAVVLLDERSASLDGAKRDGTLALAAGALCREARSTQVFF LQGGYEAFSASCPELCSKQSTPTGLSLPLSTSVPDSAESGCSSCSTPLYDQGGPVEILSF LYLGSAYHASRKDMLDALGITALINVSANCPNHFEGHYQYKSIPVEDNHKADISSWFNEA IDFIDSIKDAGGRVFVHCQAGISRSATICLAYLMRTNRVKLDEAFEFVKQRRSIISPNFS FMGQLLQFESQVLAPHCSAEAGSPAMAVLDRGTSTTTVFNFPVSIPVHPTNSALNYLKSP ITTSPSC JunHumanDNA ATGACTGCAAAGATGGAAACGACCTTCTATGACGATGCCCTCAACGCCTCGTTCCTCCCG TCCGAGAGCGGACCTTATGGCTACAGTAACCCCAAGATCCTGAAACAGAGCATGACCCTG AACCTGGCCGACCCAGTGGGGAGCCTGAAGCCGCACCTCCGCGCCAAGAACTCGGACCTC CTCACCTCGCCCGACGTGGGGCTGCTCAAGCTGGCGTCGCCCGAGCTGGAGCGCCTGATA ATCCAGTCCAGCAACGGGCACATCACCACCACGCCGACCCCCACCCAGTTCCTGTGCCCC AAGAACGTGACAGATGAGCAGGAGGGCTTCGCCGAGGGCTTCGTGCGCGCCCTGGCCGAA CTGCACAGCCAGAACACGCTGCCCAGCGTCACGTCGGCGGCGCAGCCGGTCAACGGGGCA GGCATGGTGGCTCCCGCGGTAGCCTCGGTGTCAGGGGGCAGCGGCAGCGGCGGCTTCAGC GCCAGCCTGCACAGCGAGCCGCCGGTCTACGCAAACCTCAGCAACTTCAACCCAGGCGCG CTGAGCAGCGGCGGCGGGGCGCCCTCCTACGGCGCGGCCGGCCTGGCCTTTCCCGCGCAA CCCCAGCAGCAGCAGCAGCCGCCGCACCACCTGCCCCAGCAGATGCCCGTGCAGCACCCG CGGCTGCAGGCCCTGAAGGAGGAGCCTCAGACAGTGCCCGAGATGCCCGGCGAGACACCG CCCCTGTCCCCCATCGACATGGAGTCCCAGGAGCGGATCAAGGCGGAGAGGAAGCGCATG AGGAACCGCATCGCTGCCTCCAAGTGCCGAAAAAGGAAGCTGGAGAGAATCGCCCGGCTG GAGGAAAAAGTGAAAACCTTGAAAGCTCAGAACTCGGAGCTGGCGTCCACGGCCAACATG CTCAGGGAACAGGTGGCACAGCTTAAACAGAAAGTCATGAACCACGTTAACAGTGGGTGC CAACTCATGCTAACGCAGCAGTTGCAAACATTTTGA JunMouseDNA 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 JunMouseProtein MTAKMETTFYDDALNASFLQSESGAYGYSNPKILKQSMTLNLADPVGSLKPHLRAKNSDL LTSPDVGLLKLASPELERLIIQSSNGHITTTPTPTQFLCPKNVTDEQEGFAEGFVRALAE LHSQNTLPSVTSAAQPVSGAGMVAPAVASVAGAGGGGGYSASLHSEPPVYANLSNFNPGA LSSGGGAPSYGAAGLAFPSQPQQQQQPPQPPHHLPQQIPVQHPRLQALKEEPQTVPEMPG ETPPLSPIDMESQERIKAERKRMRNRIAASKCRKRKLERIARLEEKVKTLKAQNSELAST ANMLREQVAQLKQKVMNHVNSGCQLMLTQQLQTF Dusp6HumanDNA CCAGCCTCGGAGGGAGGGATTAGAAGCCGCTAGACTTTTTTTCCTCCCCTCTCAGTAGCA CGGAGTCCGAATTAATTGGATTTCATTCACTGGGGAGGAACAAAAACTATCTGGGCAGCT TCATTGAGAGAGATTCATTGACACTAAGAGCCAGCGCTGCAGCTGGTGCAGAGAGAACCT CCGGCTTTGACTTCTGTCTCGTCTGCCCCAAGGCCGCTAGCCTCGGCTTGGGAAGGCGAG GCGGAATTAAACCCCGCTCCGAGAGCGCACGTTCGCGCGCGGTGCGTCGGCCATTGCCTG CCCCGAGGGGCGTCTGGTAGGCACCCCGCCCTCTCCCGCAGCTCGACCCCCATGATAGAT ACGCTCAGACCCGTGCCCTTCGCGTCGGAAATGGCGATCAGCAAGACGGTGGCGTGGCTC AACGAGCAGCTGGAGCTGGGCAACGAGCGGCTGCTGCTGATGGACTGCCGGCCGCAGGAG CTATACGAGTCGTCGCACATCGAGTCGGCCATCAACGTGGCCATCCCGGGCATCATGCTG CGGCGCCTGCAGAAGGGTAACCTGCCGGTGCGCGCGCTCTTCACGCGCGGCGAGGACCGG GACCGCTTCACCCGGCGCTGTGGCACCGACACAGTGGTGCTCTACGACGAGAGCAGCAGC GACTGGAACGAGAATACGGGCGGCGAGTCGTTGCTCGGGCTGCTGCTCAAGAAGCTCAAG GACGAGGGCTGCCGGGCGTTCTACCTGGAAGGTGGCTTCAGTAAGTTCCAAGCCGAGTTC TCCCTGCATTGCGAGACCAATCTAGACGGCTCGTGTAGCAGCAGCTCGCCGCCGTTGCCA GTGCTGGGGCTCGGGGGCCTGCGGATCAGCTCTGACTCTTCCTCGGACATCGAGTCTGAC CTTGACCGAGACCCCAATAGTGCAACAGACTCGGATGGTAGTCCGCTGTCCAACAGCCAG CCTTCCTTCCCAGTGGAGATCTTGCCCTTCCTCTACTTGGGCTGTGCCAAAGACTCCACC AACTTGGACGTGTTGGAGGAATTCGGCATCAAGTACATCTTGAACGTCACCCCCAATTTG CCGAATCTCTTTGAGAACGCAGGAGAGTTTAAATACAAGCAAATCCCCATCTCGGATCAC TGGAGCCAAAACCTGTCCCAGTTTTTCCCTGAGGCCATTTCTTTCATAGATGAAGCCCGG GGCAAGAACTGTGGTGTCTTGGTACATTGCTTGGCTGGCATTAGCCGCTCAGTCACTGTG ACTGTGGCTTACCTTATGCAGAAGCTCAATCTGTCGATGAACGATGCCTATGACATTGTC AAAATGAAAAAATCCAACATATCCCCTAACTTCAACTTCATGGGTCAGCTGCTGGACTTC GAGAGGACGCTGGGACTCAGCAGCCCATGTGACAACAGGGTTCCAGCACAGCAGCTGTAT TTTACCACCCCTTCCAACCAGAATGTATACCAGGTGGACTCTCTGCAATCTACGTGAAAG ACCCCACACCCCTCCTTGCTGGAATGTGTCTGGCCCTTCAGCAGTTTCTCTTGGCAGCAT CAGCTGGGCTGCTTTCTTTGTGTGTGGCCCCAGGTGTCAAAATGACACCAGCTGTCTGTA CTAGACAAGGTTACCAAGTGCGGAATTGGTTAATACTAACAGAGAGATTTGCTCCATTCT CTTTGGAATAACAGGACATGCTGTATAGATACAGGCAGTAGGTTTGCTCTGTACCCATGT GTACAGCCTACCCATGCAGGGACTGGGATTCGAGGACTTCCAGGCGCATAGGGTAGAACC AAATGATAGGGTAGGAGCATGTGTTCTTTAGGGCCTTGTAAGGCTGTTTCCTTTTGCATC TGGAACTGACTATATAATTGTCTTCAATGAAGACTAATTCAATTTTGCATATAGAGGAGC CAAAGAGAGATTTCAGCTCTGTATTTGTGGTATCAGTTTGGAAAAAAAAATCTGATACTC CATTTGATTATTGTAAATATTTGATCTTGAATCACTTGACAGTGTTTGTTTGAATTGTGT TTGTTTTTTCCTTTGATGGGCTTAAAAGAAATTATCCAAAGGGAGAAAGAGCAGTATGCC ACTTCTTAA Dusp6MouseDNA GATCCATTGAGGAGCTGCCTCGCACAGGGGGTGTGCTCTCGCGGAGTCCTAGGGACTGTG AGCAAACCCAGTCTTGAATAATCCGGCGAGAAACACCGGGTTGGATCCGAGGTGCAGCCT CAGAGGGAAGGATTAAGAGCCGCTAGACTTTTTTTCTTTTCCCTTTTTCTCCTCTCAGTG GCACGGAGTCCGAATTAATTGGATTTCATTCACTGGGTAGGAACAAAACTGGGCACCTTC ATTCAGAGAGAGAGATTCATTGACTCGGAGAGTGATCTGGTGCAGAGGGACCACCGACTT GACTTCTGTGTCGCTTTCCCTAACCGCTAGCCTCGGCTTGGGAAAGGCGAGGCGGAATCA AACCCCGCTCCGAGAGCGGGAGCTTCGCGCAGCGTGCTCGGCCTATGCCTGCCTCGAGGG GCGTCTGCTAGGCACCCCGCCTTCTCCTGCAGCTCGACCCCCATGATAGATACGCTCAGA CCCGTGCCCTTCGCGTCGGAAATGGCGATCTGCAAGACGGTGTCGTGGCTCAACGAGCAG CTGGAGCTGGGCAACGAACGGCTTCTGCTGATGGACTGCCGACCACAGGAGCTGTACGAG TCGTCACACATCGAATCTGCCATTAATGTGGCCATCCCCGGCATCATGCTGCGGCGTCTG CAGAAGGGCAACCTGCCCGTGCGTGCGCTCTTCACGCGCTGCGAGGACCGGGACCGCTTT ACCAGGCGCTGCGGCACCGACACCGTGGTGCTGTACGACGAGAATAGCAGCGACTGGAAT GAGAACACTGGTGGAGAGTCGGTCCTCGGGCTGCTGCTCAAGAAACTCAAAGACGAGGGC TGCCGGGCGTTCTACCTGGAAGGTGGCTTCAGTAAGTTCCAGGCCGAGTTCGCCCTGCAC TGCGAGACCAATCTAGACGGCTCGTGCAGCAGCAGTTCCCCGCCTTTGCCAGTGCTGGGG CTCGGGGGCCTGCGGATCAGCTCGGACTCTTCCTCGGACATTGAGTCTGACCTTGACCGA GACCCCAATAGTGCAACGGACTCTGATGGCAGCCCGCTGTCCAACAGCCAGCCTTCCTTC CCGGTGGAGATTTTGCCCTTCCTTTACCTGGGCTGTGCCAAGGACTCGACCAACTTGGAC GTGTTGGAAGAGTTTGGCATCAAGTACATCTTGAATGTCACCCCCAATTTGCCCAATCTG TTTGAGAATGCGGGCGAGTTCAAATACAAGCAAATTCCTATCTCGGATCACTGGAGCCAA AACCTGTCCCAGTTTTTCCCTGAGGCCATTTCTTTCATAGATGAAGCCCGAGGCAAAAAC TGTGGTGTCCTGGTGCATTGCTTGGCAGGTATCAGCCGCTCTGTCACCGTGACAGTGGCG TACCTCATGCAGAAGCTCAACCTGTCCATGAACGATGCTTACGACATTGTTAAGATGAAG AAGTCCAACATCTCCCCCAACTTCAACTTCATGGGCCAGCTGCTTGACTTCGAAAGGACC CTGGGACTGAGCAGCCCTTGTGACAACCGTGTCCCCACTCCGCAGCTGTACTTCACCACG CCCTCCAACCAGAACGTCTACCAGGTGGACTCCCTGCAGTCTACGTGAAAGGCACCCACC TCTCCTAGCCGGGAGTTGTCCCCATTCCTTCAGTTCCTCTTGAGCAGCATCGACCAGGCT GCTTTCTTTCTGTGTGTGGCCCCGGGTGTCAAAAGTGTCACCAGCTGTCTGTGTTAGACA AGGTTGCCAAGTGCAAAATTGGTTATTACGGAGGGAGAGATTTGCTCCATTCATTGTTTT TTTGGAAGGACAGGACATGCTGTCTCTAGATCCAGCAATAGGTTTGCTTCTGTACCCCAG CCTACCCAAGCAGGGACTGGACATCCATCCAGATAGAGGGTAGCATAGGAATAGGGACAG GAGCATCTGTTCTTTAAGGCCTTGTATGGCTGTTTCCTGTTGCATCTGGAACTAACTATA TATATTGTCTTCAGTGAAGACTGATTCAACTTTGGGTATAGTGGAGCCAAAGAGATTTTT AGCTCTGTATTTGCGGTATCGGTTTAGAAGACAAAAAAAATTAAAACCTGATACTTTTAT CTGATTATTGTAAATATTTGATCTTCAATCACTTGACAGTGTTTGTTTGGCTTGTATTTG TTTTTTATCTTTGGGCTTAAAAGAGATCCAAAGAGAGAAAGAGCAGTATGCCACTTCTTA GAACAAAAGTATAAGGAAAAAAATGTTCTTTTTAATCCAAAGGGTATATTTGCAGCATGC TTGACCTTGATGTACCAATTCTGACGGCATTTTCGTGGATATTATTATCACTAAGACTTT GTTATGATGAGGTCTTCAGTCTCTTTCATATATCTTCCTTGTAACTTTTTTTTTCCTCTT AATGTAGTTTTGACTCTGCCTTACCTTTGTAAATATTTGGCTTACAGTGTCTCAAGGGGT ATTTTGGAAAGACACCAAAATTGTGGGTTCACTTTTTTTTTTTTTTTAAATAACTTCAGC TGTGCTAAACAGCATATTACCTCTGTACAAAATTCTTCAGGGAGTGTCACCTCAAATGCA ATACTTTGGGTTGGTTTCTTTCCTTTTAAAAAAAAAATACGAAACTGGAAGTGTGTGTAT GTGTGCGAGTATGAGCGCCCATTTGGTGGATGCAACAGGTTGAGAGGAAGGGAGAATTAA CTTGCTCCATGATGTTCGTGGTGTAAAGTTTTGAGCTGGAATTTATTATAAGAATGTAAA ACCTTAAATTATTAATAAATAACTATTTTGGCT Dusp6MouseProtein MIDTLRPVPFASEMAICKTVSWLNEQLELGNERLLLMDCRPQELYESSHIESAINVAIPG IMLRRLQKGNLPVRALFTRCEDRDRFTRRCGTDTVVLYDENSSDWNENTGGESVLGLLLK KLKDEGCRAFYLEGGFSKFQAEFALHCETNLDGSCSSSSPPLPVLGLGGLRISSDSSSDI ESDLDRDPNSATDSDGSPLSNSQPSFPVEILPFLYLGCAKDSTNLDVLEEFGIKYILNVT PNLPNLFENAGEFKYKQIPISDHWSQNLSQFFPEAISFIDEARGKNCGVLVHCLAGISRS VTVTVAYLMQKLNLSMNDAYDIVKMKKSNISPNFNFMGQLLDFERTLGLSSPCDNRVPTP QLYFTTPSNQNVYQVDSLQST Cdk1HumanDNA GGGGGGGGGGGGCACTTGGCTTCAAAGCTGGCTCTTGGAAATTGAGCGGAGACGAGCGGC TTGTTGTAGCTGCCGTGCGGCCGCCGCGGAATAATAAGCCGGGATCTACCATACCATTGA CTAACTATGGAAGATTATACCAAAATAGAGAAAATTGGAGAAGGTACCTATGGAGTTGTG TATAAGGGTAGACACAAAACTACAGGTCAAGTGGTAGCCATGAAAAAAATCAGACTAGAA AGTGAAGAGGAAGGGGTTCCTAGTACTGCAATTCGGGAAATTTCTCTATTAAAGGAACTT CGTCATCCAAATATAGTCAGTCTTCAGGATGTGCTTATGCAGGATTCCAGGTTATATCTC ATCTTTGAGTTTCTTTCCATGGATCTGAAGAAATACTTGGATTCTATCCCTCCTGGTCAG TACATGGATTCTTCACTTGTTAAGAGTTATTTATACCAAATCCTACAGGGGATTGTGTTT TGTCACTCTAGAAGAGTTCTTCACAGAGACTTAAAACCTCAAAATCTCTTGATTGATGAC AAAGGAACAATTAAACTGGCTGATTTTGGCCTTGCCAGAGCTTTTGGAATACCTATCAGA GTATATACACATGAGGTAGTAACACTCTGGTACAGATCTCCAGAAGTATTGCTGGGGTCA GCTCGTTACTCAACTCCAGTTGACATTTGGAGTATAGGCACCATATTTGCTGAACTAGCA ACTAAGAAACCACTTTTCCATGGGGATTCAGAAATTGATCAACTCTTCAGGATTTTCAGA GCTTTGGGCACTCCCAATAATGAAGTGTGGCCAGAAGTGGAATCTTTACAGGACTATAAG AATACATTTCCCAAATGGAAACCAGGAAGCCTAGCATCCCATGTCAAAAACTTGGATGAA AATGGCTTGGATTTGCTCTCGAAAATGTTAATCTATGATCCAGCCAAACGAATTTCTGGC AAAATGGCACTGAATCATCCATATTTTAATGATTTGGACAATCAGATTAAGAAGATGTAG CTTTCTGACAAAAAGTTTCCATATGTTATG Cdk1MouseDNA TCCGTCGTAACCTGTTGAGTAACTATGGAAGACTATATCAAAATAGAGAAAATTGGAGAA GGTACTTACGGTGTGGTGTATAAGGGTAGACACAGAGTCACTGGCCAGATAGTGGCCATG AAGAAGATCAGACTTGAAAGCGAGGAAGAAGGAGTGCCCAGTACTGCAATTCGGGAAATC TCTCTATTAAAAGAACTTCGACATCCAAATATAGTCAGCCTGCAGGATGTGCTCATGCAG GACTCCAGGCTGTATCTCATCTTTGAGTTCCTGTCCATGGACCTCAAGAAGTACCTGGAC TCCATCCCTCCTGGGCAGTTCATGGATTCTTCACTCGTTAAGAGTTACTTACACCAAATC CTCCAGGGAATTGTGTTTTGCCACTCCCGGCGAGTTCTTCACAGAGACTTGAAACCTCAA AATCTATTGATTGATGACAAAGGAACAATCAAACTGGCTGATTTCGGCCTTGCCAGAGCG TTTGGAATACCGATACGAGTGTACACACACGAGGTAGTGACGCTGTGGTACCGATCTCCA GAAGTGTTGCTGGGCTCGGCTCGTTACTCCACTCCGGTTGACATCTGGAGTATAGGGACC ATATTTGCAGAACTGGCCACCAAGAAGCCGCTTTTCCACGGCGACTCAGAGATTGACCAG CTCTTCAGGATCTTCAGAGCTCTGGGCACTCCTAACAACGAAGTGTGGCCAGAAGTCGAG TCCCTGCAGGACTACAAGAACACCTTTCCCAAGTGGAAGCCGGGGAGCCTCGCATCCCAC GTCAAGAACCTGGACGAGAACGGCTTGGATTTGCTCTCAAAAATGCTAGTCTATGATCCT GCCAAACGAATCTCTGGCAAAATGGCCCTGAAGCACCCGTACTTTGATGACTTGGACAAT CAGATTAAGAAGATGTAGCCCTCTGGATGGATGTCCCTGTCTGCTGGTCGTAGGGGAAGA TCG Cdk1MouseProtein MEDYIKIEKIGEGTYGVVYKGRHRVTGQIVAMKKIRLESEEEGVPSTAIREISLLKELRH PNIVSLQDVLMQDSRLYLIFEFLSMDLKKYLDSIPPGQFMDSSLVKSYLHQILQGIVFCH SRRVLHRDLKPQNLLIDDKGTIKLADFGLARAFGIPIRVYTHEVVTLWYRSPEVLLGSAR YSTPVDIWSIGTIFAELATKKPLFHGDSEIDQLFRIFRALGTPNNEVWPEVESLQDYKNT FPKWKPGSLASHVKNLDENGLDLLSKMLVYDPAKRISGKMALKHPYFDDLD NQIKKM Fignl1HumanDNA GTCAGTCCCCGCGCTTTTCGGAGGCTGCCAGCGTCCCACACCAGCCGCAGGTGAAAACCG GCAGAAAGACATTAAGAGATTTTCCTGCAGTCACTGCTGGCAGATGATAGAGCCAGGATT TGAAAGCAGGCAGCCTGGCTCCAGACCCTGTGCTCTTAACTCCCGTTTTGCATCAAGAAC AGAATCCTATGAAAGGCTTGTACAGTGCTTGGATAGCAGCATCAAGGAGCATTGTGTACA TGCAGAAGTGCACAGTACCTGGAGTGAAACTGCTTGTGTTCGATTTCTGATACCATTCAT AACTGGCTGTGTGATCTCAAAACCTCTAAAATGCAGACCTCCAGCTCTAGATCTGTGCAC CTGAGTGAATGGCAGAAGAATTACTTCGCAATTACATCTGGCATATGTACCGGACCGAAG GCAGATGCATACCGTGCACAGATATTACGCATTCAGTATGCATGGGCAAACTCTGAGATT TCCCAGGTCTGTGCTACCAAACTGTTCAAAAAATATGCAGAGAAATATTCTGCAATTATT GATTCTGACAATGTTGAATCTGGGTTGAATAATTATGCAGAAAACATTTTAACTTTGGCA GGATCTCAACAAACAGATAGTGACAAGTGGCAGTCTGGATTGTCAATAAATAATGTTTTC AAAATGAGTAGTGTACAGAAGATGATGCAAGCTGGCAAAAAATTCAAAGACTCTCTGTTG GAACCTGCTCTTGCATCAGTGGTAATCCATAAGGAGGCCACTGTCTTTGATCTTCCTAAA TTTAGTGTTTGTGGTAGTTCTCAAGAGAGTGACTCATTACCTAACTCAGCTCATGATCGA GACCGGACCCAAGACTTCCCGGAGAGCAATCGTTTGAAACTCCTTCAGAATGCCCAGCCA CCTATGGTGACTAACACTGCTAGGACTTGTCCTACATTCTCAGCACCTGTAGGTGAGTCA GCTACTGCAAAATTCCATGTCACACCATTGTTTGGAAATGTCAAAAAGGAAAATCACAGC TCTGCAAAAGAAAACATAGGACTTAATGTGTTCTTATCTAACCAGTCTTGTTTTCCTGCT GCCTGTGAAAATCCACAGAGGAAGTCTTTTTATGGTTCTGGCACCATTGATGCACTTTCC AATCCAATACTGAATAAGGCTTGTAGTAAAACAGAAGATAATGGCCCAAAGGAGGATAGC AGCCTGCCTACATTTAAAACTGCAAAAGAACAATTATGGGTAGATCAGCAAAAAAAGTAC CACCAACCTCAGCGTGCATCAGGGTCTTCATATGGTGGTGTAAAAAAGTCTCTAGGAGCT AGTAGATCCCGAGGGATACTTGGAAAGTTTGTTCCTCCTATACCCAAGCAAGATGGGGGA GAGCAGAATGGAGGAATGCAATGTAAGCCTTATGGGGCAGGACCTACAGAACCAGCACAT CCAGTTGATGAGCGTCTGAAGAACTTGGAGCCAAAGATGATTGAACTTATTATGAATGAG ATTATGGATCATGGACCTCCAGTAAATTGGGAAGATATTGCAGGAGTAGAATTTGCTAAA GCCACCATAAAGGAAATAGTTGTGTGGCCCATGTTGAGGCCAGACATCTTTACTGGTTTA AGGGGACCCCCTAAAGGAATTTTGCTCTTTGGTCCTCCTGGGACTGGTAAAACTCTAATT GGCAAGTGCATTGCTAGTCAGTCTGGGGCAACATTCTTTAGCATCTCTGCTTCATCCTTA ACTTCTAAATGGGTAGGTGAGGGGGAGAAAATGGTCCGTGCATTGTTTGCTGTTGCAAGG TGTCAGCAACCAGCTGTGATATTTATTGACGAAATTGATTCCTTGTTATCTCAACGGGGA GATGGTGAGCATGAATCTTCTAGAAGGATAAAAACAGAATTTTTAGTTCAATTAGATGGA GCAACAACATCTTCTGAAGATCGTATCCTAGTGGTGGGAGCAACAAATCGGCCACAAGAA ATTGATGAGGCTGCCCGGAGAAGATTGGTGAAAAGGCTTTATATTCCCCTCCCAGAAGCT TCAGCCAGGAAACAGATAGTAATTAATCTAATGTCCAAAGAGCAGTGTTGCCTCAGTGAA GAAGAAATTGAACAGATTGTACAGCAGTCTGATGCGTTTTCAGGAGCAGACATGACACAG CTTTGCAGGGGGGCTTCTCTTGGTCCTATTCGCAGTTTACAAACTGCTGACATTGCTACC ATAACACCGGATCAAGTTCGACCCATAGCTTACATTGATTTTGAAAATGCTTTTAGAACT GTGCGACCTAGTGTTTCTCCAAAAGATTTAGAGCTTTATGAAAACTGGAACAAAACTTTT GGTTGTGGAAAGTAAGTGGGATACTTGGAATCAAGGCATCTCTGTATTACAGTCTTCTTT ATTTTTTAGCATAGAAAGTTGGGGATGTGTTAATTGTATTTTTAAGAATATATTCTAAAT TCTGTACTTCAAATAATAGCACAGATTTTACATCTG Fignl1MouseDNA CATCGAGAAGTGTTCAGTGCCTGGTAAAGTACATAGACCTTGCTTCACTTGGAACTCGGC CTTGATTTCTGCCGTTGGTCATAATCAGCAGAGTTCTCTCTAAACCTTTGACATGGAGAC GTCCAGCTCCATGTCTGTGGAGACGACTAGGTCTGTGCAGGTGGACGAATGGCAGAAGAA TTACTGTGTGGTTACATCCAGCATATGTACACCAAAGCAGAAGGCCGATGCATACCGTGC ACTACTACTGCATATTCAGTATGCATATGCCAACTCCGAGATCTCTCAGGTCTTTGCTAC CAACCTGTTCAAAAGGTATACAGAAAAATACTCTGCAATTATTGATTCTGACAATGTTGT AACTGGCTTGAATAACTATGCAGAGAGCATTTTTGCTTTGGCAGGATCTCGACAGGCTGA CAGTAACAAGTGGCAGTCTGGATTGTCAATAGATAATGTTTTCAAAATGAGTTGTGTACA GGAGATGATGCAGGCTGGCAAGAAATTTGAAGAGTCTCTGTTGGAACCTGCTGATGCATC AGTAGTCCTGTGTAAAGAGCCCACCGCCTTTGAGGTTCCTCAGCTTAGTGTTTGTGGAGG TTCTGAAGACGCTGACATATTATCCAGTTCAGGTCATGACACAGATAAGACCCAAGCCAT TCCAGGGAGCAGTCTGAGATGTTCCCCTTTTCAGAGTGCTCGGCTGCCTAAGGAAACTAA TACCACTAAGACATGCCTCACCTCCTCAACATCTTTAGGTGAGTCAGCCACTGCAGCATT TCACATGACACCATTATTTGGAAACACCGAAAAGGACACTCAAAGCTTTCCTAAAACCAG CACAGGACTAAATATGTTCTTATCTAATCTGTCTTGTGTTCCTTCTGGCTGTGAAAACCC TCAAGAAAGGAAGGCTTTTAATGACTCTGACATCATTGACATACTTTCCAATCCAACACT GAACAAGGCTCCTAGTAAAACAGAAGACAGAGGCCGAAGGGAAGATAATAGCCTGCCTAC CTTTAAAACTGCAAAAGAACAATTATGGGTAGATCAAAAGAAAAAGGGCCATCAATCCCA GCATACATCTAAATCTTCTAATGGTGTTATGAAAAAGTCTCTGGGAGCTGGGAGGTCGAG AGGGATATTTGGCAAGTTTGTTCCTCCTGTATCTAATAAGCAAGACGGAAGTGAGCAGCA TGCCAAGAAGCACAAGTCTAGTAGGGCAGGGTCTGCAGAACCAGCACACCTCACTGATGA TTGTCTGAAGAACGTGGAGCCAAGGATGGTTGAACTTGTTATGAATGAAATTATGGACCA TGGGCCTCCAGTACATTGGGACGATATTGCTGGAGTAGAATTTGCCAAAGCCACAATAAA GGAAATCGTTGTGTGGCCCATGATGAGGCCAGATATCTTTACTGGATTGCGAGGGCCCCC TAAAGGAATTCTACTCTTTGGCCCTCCAGGGACTGGTAAAACTCTGATTGGCAAGTGCAT TGCTAGCCAGTCTGGAGCAACATTCTTCAGCATCTCTGCTTCATCGCTGACTTCTAAGTG GGTAGGTGAGGGAGAAAAAATGGTCCGTGCACTGTTTGCTGTTGCCAGGTGTCAGCAGCC AGCTGTCATATTTATTGATGAAATTGATTCTTTATTGTCTCAACGAGGAGATGGTGAACA TGAATCTTCAAGAAGGATAAAAACGGAATTTTTAGTTCAGTTAGATGGAGCAACCACATC TTCTGAAGACCGGATTCTTGTGGTGGGAGCTACAAATCGGCCCCAAGAGATTGATGAAGC TGCCCGGAGAAGATTGGTGAAAAGACTTTATATTCCCCTCCCAGAAGCTTCAGCCAGGAA ACAGATAGTAGGTAATCTAATGTCTAAGGAGCAATGTTGTCTCAGTGATGAAGAAACTGA TCTGGTAGTGCAGCAGTCTGATGGGTTTTCTGGCGCAGATATGACACAGCTTTGCAGAGA GGCTTCTCTTGGTCCTATTCGCAGTTTGCACGCTGCTGACATTGCTACCATAAGTCCAGA TCAAGTTCGACCAATAGCTTATATTGATTTTGAAAATGCTTTTAAAACTGTGCGACCTAC TGTATCTCCAAAAGACTTGGAGCTTTATGAAAACTGGAATGAAACATTTGGTTGTGGAAA GTGAATATAGCGATTGAAAGGAGAAGCTGTTATCTAGTAGTCGTCTTTACCTTTAGCCTC GGAAGCTTGCTGTGCTACTTGTATTGTTTTGGAGTATATCCTGAATTCTGTGCCTCAGAT TAGAATGATAACAGCTTGACTACTGACTGATATATTAGTATGTTGTATTTG CC Fignl1MouseProtein METSSSMSVETTRSVQVDEWQKNYCVVTSSICTPKQKADAYRALLLHIQYAYANSEISQV FATNLFKRYTEKYSAIIDSDNVVTGLNNYAESIFALAGSRQADSNKWQSGLSIDNVFKMS CVQEMMQAGKKFEESLLEPADASVVLCKEPTAFEVPQLSVCGGSEDADILSSSGHDTDKT QAIPGSSLRCSPFQSARLPKETNTTKTCLTSSTSLGESATAAFHMTPLFGNTEKDTQSFP KTSTGLNMFLSNLSCVPSGCENPQERKAFNDSDIIDILSNPTLNKAPSKTEDRGRREDNS LPTFKTAKEQLWVDQKKKGHQSQHTSKSSNGVMKKSLGAGRSRGIFGKFVPPVSNKQDGS EQHAKKHKSSRAGSAEPAHLTDDCLKNVEPRMVELIMNEIMDHGPPVHWDDIAGVEFAKA TIKEIVVWPMMRPDIFTGLRGPPKGILLFGPPGTGKTLIGKCIASQSGATFFSISASSLT SKWVGEGEKMVRALFAVARCQQPAVIFIDEIDSLLSQRGDGEHESSRRIKTEFLVQLDGA TTSSEDRILVVGATNRPQEIDEAARRRLVKRLYIPLPEASARKQIVGNLMSKEQCCLSDE ETDLVVQQSDGFSGADMTQLCREASLGPIRSLHAADIATISPDQVRPIAYIDFENAFKTV RPTVSPKDLELYENWNETFGCGK P1k2HumanDNA GCGCGCGGCTCCGATGGGAAGCATGACCCGGGTGGCGGGACAAGACTTGCTTCCCGGCCA CGCGCGCTCGGCCGGCCGTGGGGCGGGGCATAGGCGTGACGTGGTGTCGCGTATCGAGTC TCCGCCCCCTTCCCGCCTCCCCGTATATAAGACTTCGCCGAGCACTCTCACTCGCACAAG TGGACCGGGGTGTTGGGTGCTAGTCGGCACCAGAGGCAAGGGTGCGAGGACCACGGCCGG CTCGGACGTGTGACCGCGCCTAGGGGGTGGCAGCGGGCAGTGCGGGGCGGCAAGGCGACC ATGGARCTTTTGCGGACTATCACCTACCAGCCAGCCGCCAGCACCAAAATGTGCGAGCAG GCGCTGGGCAAGGGTTGCGGAGGGGACTCGAAGAAGAAGCGGCCGCCGCAGCCCCCCGAG GAATCGCAGCCACCTCAGTCCCAGGCGCAAGTGCCCCCGGCGGCCCCTCACCACCATCAC CACCATTCGCACTCGGGGCCGGAGATCTCGCGGATTATCGTCGACCCCACGACTGGGAAG CGCTACTGCCGGGGCAAAGTGCTGGGAAAGGGTGGCTTTGCAAAATGTTACGAGATGACA GATTTGACAAATAACAAAGTCTACGCCGCAAAAATTATTCCTCACAGCAGAGTAGCTAAA CCTCATCAAAGGGAAAAGATTGACAAAGAAATAGAGCTTCACAGAATTCTTCATCATAAG CATGTAGTGCAGTTTTACCACTACTTCGAGGACAAAGAAAACATTTACATTCTCTTGGAA TACTGCAGTAGAAGGTCAATGGCTCATATTTTGAAAGCAAGAAAGGTGTTGACAGAGCCA GAAGTTCGATACTACCTCAGGCAGATTGTGTCTGGACTGAAATACCTTCATGAACAAGAA ATCTTGCACAGAGATCTCAAACTAGGGAACTTTTTTATTAATGAAGCCATGGAACTAAAA GTTGGGGACTTCGGTCTGGCAGCCAGGCTAGAACCCYTGGAACACAGAAGGAGAACGATA TGTGGTACCCCAAATTATCTCTCTCCTGAAGTCCTCAACAAACAAGGACATGGCTGTGAA TCAGACATTTGGGCCCTGGGCTGTGTAATGTATACAATGTTACTAGGGAGGCCCCCATTT GAAACTACAAATCTCAAAGAAACTTATAGGTGCATAAGGGAAGCAAGGTATACAATGCCG TCCTCATTGCTGGCTCCTGCCAAGCACTTAATTGCTAGTATGTTGTCCAAAAACCCAGAG GATCGTCCCAGTTTGGATGACATCATTCGACATGACTTTTTTTTGCAGGGCTTCACTCCG GACAGACTGTCTTCTAGCTGTTGTCATACAGTTCCAGATTTCCACTTATCAAGCCCAGCT AAGAATTTCTTTAAGAAAGCAGCTGCTGCTCTTTTTGGTGGCAAAAAAGACAAAGCAAGA TATATTGACACACATAATAGAGTGTCTAAAGAAGATGAAGACATCTACAAGCTTAGGCAT GATTTGAAAAAGACTTCAATAACTCAGCAACCCAGCAAACACAGGACAGATGAGGAGCTC CAGCCACCTACCACCACAGTTGCCAGGTCTGGAACACCCGCAGTAGAAAACAAGCAGCAG ATTGGGGATGCTATTCGGATGATAGTCAGAGGGACTCTTGGCAGCTGTAGCAGCAGCAGT GAATGCCTTGAAGACAGTACCATGGGAAGTGTTGCAGACACAGTGGCAAGGGTTCTTCGG GGATGTCTGGAAAACATGCCGGAAGCTGATTGCATTCCCAAAGAGCAGCTGAGCACATCA TTTCAGTGGGTCACCAAATGGGTTGATTACTCTAACAAATATGGCTTTGGGTACCAGCTC TCAGACCACACCGTCGGTGTCCTTTTCAACAATGGTGCTCACATGAGCCTCCTTCCAGAC AAAAAAACAGTTCACTATTACGCAGAGCTTGGCCAATGCTCAGTTTTCCCAGCAACAGAT GCTCCTGAGCAATTTATTAGTCAAGTGACGGTGCTGAAATACTTTTCTCATTACATGGAG GAGAACCTCATGGATGGTGGAGATCTGCCTAGTGTTACTGATATTCGAAGACCTCGGCTC TACCTCCTTCAGTGGCTAAAATCTGATAAGGCCCTAATGATGCTCTTTAATGATGGCACC TTTCAGGTGAATTTCTACCATGATCATACAAAAATCATCATCTGTAGCCAAAATGAAGAA TACCTTCTCACCTACATCAATGAGGATAGGATATCTACAACTTTCAGGCTGACAACTCTG CTGATGTCTGGCTGTTCATCAGAATTAAAAAATCGAATGGAATATGCCCTGAACATGCTC TTACAAAGATGTAACTGAAAGACTTTTCGAATGGACCCTATGGGACTCCTCTTTTCCACT GTGAGATCTACAGGGAAGCCAAAAGAATGATCTAGAGTATGTTGAAGAAGATGGACATGT GGTGGTACGAAAACAATTCCCCTGTGGCCTGCTGGACTGGGTGGAACCCAGAACCAGGCT AAGGCATACAGTTCTTGACTTTGGACAATCCCAAGAGTGAACCAGAATGCAGTTTTCCTT GAGATACCTGTTTTAAAAGGTTTTTCAGACAATTTTGCAGAAAGGTGCATTGATTCTTAA ATTCTCTCTGTTGAGAGCATTTCAGCCAGAGGACTTTGGAACTGTGAATATACTTCCTGA AGGGGAGGGAGAAGGGAGGAAGCTCCCATGTTGTTTAAAGGCTGTAATTGGAGCAGCTTT TGGCTGCGTAACTGTGAACTATGGCCATATATAATTTTTTTTCATTAATTTTTGAAGATA CTTGTGGCTGGAAAAGTGCATTCCTTGTTAATAAACTTTTTATTTATTACAGCCCAAAGA GCAGTATTTATTATCAAAATGTCTTTTTTTTTATGTTGACCATTTTAAACCGTTGGCAAT AAAGAGTATGAAAACGCAAAAAAAAAAAAAAA P1k2MouseDNA CGTAGGGAGAGAGACTGGTGCTCGAGGGACAGGGCTAGCCCGGACGCGTGTCCGCGCCTC GGAGGTGGCAAGTAGGCAGTGTCGGGTGGCGAGGCAACGATGGAGCTCCTGCGGACTATC ACCTACCAGCCGGCCGCCGGCACCAAGATGTGCGAGCAGGCTCTGGGCAAAGCTTGCGGC GGGGACTCAAAGAAGAAGCGACCACAGCAGCCTTCTGAAGATGGGCAGCCCCAAGCCCAG GTGACCCCGGCGGCCCCGCACCACCATCACCACCATTCCCACTCGGGACCCGAGATCTCG CGGATTATAGTCGACCCCACGACGGGGAAGCGCTACTGCCGGGGCAAAGTGCTGGGCAAG GGTGGATTTGCAAAGTGTTACGAAATGACAGATCTGACAAACAACAAAGTCTACGCTGCA AAAATTATTCCTCACAGCAGAGTAGCTAAACCTCATCAGAGGGAAAAGATCGACAAAGAA ATCGAGCTTCACAGACTACTGCACCATAAGCATGTCGTGCAGTTTTACCACTACTTTGAA GACAAAGAAAACATTTACATTCTCTTGGAATACTGCAGTAGAAGGTCCATGGCTCACATC TTGAAAGCAAGAAAGGTGTTGACAGAGCCAGAAGTCCGATACTACCTCAGGCAGATTGTG TCAGGACTCAAGTATCTTCACGAACAAGAAATCTTGCACAGGGATCTCAAGCTAGGGAAC TTTTTTATTAATGAAGCCATGGAGCTGAAGGTGGGAGACTTTGGTTTGGCAGCCAGACTG GAACCACTGGAACACAGAAGGAGAACAATATGTGGAACCCCAAATTATCTCTCCCCCGAA GTCCTCAACAAACAAGGACACGGCTGTGAATCAGACATCTGGGCCTTAGGCTGTGTAATG TATACGATGCTGCTAGGAAGACCTCCATTCGAAACCACAAATCTGAAAGAAACGTACAGG TGCATAAGGGAAGCAAGGTATACCATGCCGTCCTCATTGCTGGCCCCTGCTAAGCACTTG ATAGCTAGCATGCTGTCCAAAAACCCAGAGGACCGCCCCAGTTTGGATGACATCATTCGG CATGACTTCTTCCTGCAGGGTTTCACTCCGGACAGACTCTCTTCCAGCTGTTGCCACACA GTTCCAGATTTCCACTTGTCAAGCCCAGCCAAGAATTTCTTTAAGAAAGCCGCAGCCGCT CTTTTTGGTGGCAAGAAGGACAAAGCAAGATATAACGACACACACAATAAGGTGTCTAAG GAAGATGAAGACATTTACAAGCTTCGGCATGATTTGAAGAAAGTGTCGATAACCCAGCAG CCTAGCAAACACAGAGCAGACGAGGAGCCCCAGCCGCCTCCCACTACTGTTGCCAGATCT GGAACGTCCGCAGTGGAAAACAAACAGCAGATTGGGGATGCAATCCGGATGATAGTCAGG GGGACTCTCGGCAGCTGCAGCAGCAGCAGCGAATGCCTTGAAGACAGCACCATGGGAAGT GTTGCAGACACAGTGGCAAGAGTCCTTCGAGGATGTCTAGAAAACATGCCGGAAGCTGAC TGTATCCCCAAAGAGCAGCTGAGCACGTCCTTTCAGTGGGTCACCAAGTGGGTCGACTAC TCCAACAAATATGGCTTTGGGTACCAGCTCTCGGACCACACTGTTGGCGTCCTTTTCAAC AACGGGGCTCACATGAGCCTCCTTCCGGACAAAAAGACAGTTCACTATTATGCGGAACTT GGCCAATGCTCTGTTTTCCCAGCAACAGATGCCCCTGAACAATTTATTAGTCAAGTGACG GTGCTGAAATACTTTTCTCATTACATGGAGGAGAACCTCATGGATGGTGGTGATCTCCCG AGTGTTACTGACATTCGAAGACCTCGGCTCTACCTCCTGCAGTGGTTAAAGTCTGATAAA GCCTTAATGATGCTCTTCAATGACGGCACATTTCAGGTGAATTTCTACCACGATCATACA AAAATCATCATCTGTAACCAGAGTGAAGAATACCTTCTCACCTACATCAATGAGGACAGG ATCTCTACAACTTTCAGACTGACGACTCTGCTGATGTCTGGCTGTTCGTTAGAATTGAAA AATCGAATGGAATATGCCCTGAACATGCTCTTACAGAGATGTAACTGAAAACATTATTAT TATTATTATTATAATTATTTCGAGCGGACCTCATGGGACTCTTTTCCACTGTGAGATCAA CAGGGAAGCCAGCGGAAAGATACAGAGCATGTTAGAGAAGTCGGACAGGTGGTGGTACGA ATACAATTCCTCTGTGGCCTGCTGGACTGCTGGAACCAGACCAGCCTAAGGTGTAGAGTT GACTTTGGACAATCCTGAGTGTGGAGCCGAGTGCAGTTTTCCCTGAGATACCTGTCGTGA AAAGGTTTATGGGACAGTTTTTCAGAAAGATGCATTGACTCTGAAGTTCTCTCTGTTGAG AGCGTCTTCAGTTGGAAGACTTGGAACTGTGAATACACTTCCTGAAGGGGAGGGAGAAGG GAGGTTGCTCCCTTGCTGTTTAAAGGCTACAATCAGAGCAGCTTTTGGCTGCTTAACTGT GAACTATGGCCATACATTTTTTTTTTTTTTGGTTATTTTTGAATACACTTGTGGTTGGAA AAGTGCATTCCTTGTTAATAAACTTTTTATTTATTACAGCCCCAAGAGCAGTATTTATTA TCAAGATGTTCTCTTTTTTTATGTTGACCATTTCAAACTCTTGGCAATAAAGAGTATGAC ATAGAAAAAAAA P1k2MouseProtein MELLRTITYQPAAGTKMCEQALGKACGGDSKKKRPQQPSEDGQPQAQVTPAAPHHHHHHS HSGPEISRIIVDPTTGKRYCRGKVLGKGGFAKCYEMTDLTNNKVYAAKIIPHSRVAKPHQ REKIDKEIELHRLLHHKHVVQFYHYFEDKENIYILLEYCSRRSMAHILKARKVLTEPEVR YYLRQIVSGLKYLHEQEILHRDLKLGNFFINEAMELKVGDFGLAARLEPLEHRRRTICGT PNYLSPEVLNKQGHGCESDIWALGCVMYTMLLGRPPFETTNLKETYRCIREARYTMPSSL LAPAKHLIASMLSKNPEDRPSLDDIIRHDFFLQGFTPDRLSSSCCHTVPDFHLSSPAKNF FKKAAAALFGGKKDKARYNDTHNKVSKEDEDIYKLRHDLKKVSITQQPSKHRADEEPQPP PTTVARSGTSAVENKQQIGDAIRMIVRGTLGSCSSSSECLEDSTMGSVADTVARVLRGCL ENMPEADCIPKEQLSTSFQWVTKWVDYSNKYGFGYQLSDHTVGVLFNNGAHMSLLPDKKT VHYYAELGQCSVFPATDAPEQFISQVTVLKYFSHYMEENLMDGGDLPSVTDIRRPRLYLL QWLKSDKALMMLFNDGTFQVNFYHDHTKIIICNQSEEYLLTYINEDRISTTFRLTTLLMS GCSLELKNRMEYALNMLLQRCN Rsad2HumanDNA CAGGAAGGGCCATGAAGATTAATAAAGATTTGGACTCAGGGCAAATATTTACTTAGTAGC AATAACTCAAAGAATTACTGTTGAATAAATAAGCCAATTAAGCAGCCAATCACGTACTAT GCGGATGCACACAAATGAAACCCTCACTTCAACCTGAAGACATTCGCACATGAGTTACGT AGAGGGACCTGCAGGAAGCGGTAGAGAAAACATAAGGCTTATGCGTTTAATTTCCACACC AATTTCAGGATCTTTGTCACTGACAGCAGCACTAAGACTTGTTAACTTTATATAGTTAAG AAGAACAAGGCTGAGCGCGATGACTCACGCCTGTAAGCCTAGAACTTTGGGAGGCCAAAG CAGGCAGACTGCTTGAGCCCAGGAGTTCCAGACCAGCCTGGGCAACATGGCAACACCCCA TCTCTACAAAAAAATACAAGAATCAGCTGGGCGTGGTGATGTGTTCCTGTAATCTCAGCT ACTCGGGAGGCAGAGGCAGGAGGATTGCTTGAACCCGGGAGGCAGAGGTTGTAGTTAGCC GAGATCTCGCCACTGCACTCCAGTCTGGACGACAGAGTGAGACTCAGTCTCAAATAAATA AATAAATACATAAATATAAGGAAAAAAATAAAGCTGCTTTCTCCTCTTCCTCCTCTTTGG TCTCATCTGGCTCTGCTCCAGGCATCTGCCACAATGTGGGTGCTTACACCTGCTGCTTTT GCTGGGAAGTTCTTGAGTGTGTTCAGGCAACCTCTGAGCTCTCTGTGGAGGAGCCTGGTC CCGCTGTTCTGCTGGCTGAGGGCAACCTTCTGGCTGCTAGCTACCAAGAGGAGAAAGCAG CAGCTGGTCCTGAGAGGGCCAGATGAGACCAAAGAGGAGGAAGAGGACCCTCCTCTGCCC ACCACCCCAACCAGCGTCAACTATCACTTCACTCGCCAGTGCAACTACAAATGCGGCTTC TGTTTCCACACAGCCAAAACATCCTTTGTGCTGCCCCTTGAGGAAGCAAAGAGAGGATTG CTTTTGCTTAAGGAAGCTGGTATGGAGAAGATCAACTTTTCAGGTGGAGAGCCATTTCTT CAAGACCGGGGAGAATACCTGGGCAAGTTGGTGAGGTTCTGCAAAGTAGAGTTGCGGCTG CCCAGCGTGAGCATCGTGAGCAATGGAAGCCTGATCCGGGAGAGGTGGTTCCAGAATTAT GGTGAGTATTTGGACATTCTCGCTATCTCCTGTGACAGCTTTGACGAGGAAGTCAATGTC CTTATTGGCCGTGGCCAAGGAAAGAAGAACCATGTGGAAAACCTTCAAAAGCTGAGGAGG TGGTGTAGGGATTATAGAATCCCTTTCAAGATAAATTCTGTCATTAATCGTTTCAACGTG GAAGAGGACATGACGGAACAGATCAAAGCACTAAACCCTGTCCGCTGGAAAGTGTTCCAG TGCCTCTTAATTGAAGGTGAGAATTGTGGAGAAGATGCTCTAAGAGAAGCAGAAAGATTT GTTATTGGTGATGAAGAATTTGAAAGATTCTTGGAGCGCCACAAAGAAGTGTCCTGCTTG 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 Rsad2MouseDNA CCTATCACCATGGGGATGCTGGTGCCCACTGCTCTAGCTGCTCGGCTGCTGAGCCTGTTC CAGCAGCAGCTGGGTTCCCTCTGGAGTGGCCTGGCCATCCTGTTCTGCTGGCTGAGAATA GCATTAGGGTGGCTAGATCCCGGGAAGGAACAGCCACAGGTCCGGGGTGAGCTGGAGGAG ACCCAGGAGACCCAGGAAGATGGGAACAGCACTCAGCGCACAACCCCCGTGAGTGTCAAC TACCACTTCACTCGTCAGTGCAACTACAAATGTGGCTTCTGCTTCCACACAGCCAAGACA TCCTTCGTGCTGCCCCTGGAGGAGGCCAAGCGAGGACTGCTTCTGCTCAAACAGGCTGGT TTGGAGAAGATCAACTTTTCTGGAGGAGAACCCTTCCTTCAGGACAGGGGTGAATACTTG GGCAAGCTTGTGAGATTCTGCAAGGAGGAGCTAGCCCTGCCCTCTGTGAGCATAGTGAGC AATGGCAGCCTTATCCAGGAGAGATGGTTCAAGGACTATGGGGAGTATTTGGACATTCTT GCTATCTCCTGCGACAGCTTCGATGAGCAGGTTAATGCTCTGATTGGCCGTGGTCAAGGA AAAAAGAACCACGTGGAAAACCTTCAAAAGCTGAGGAGGTGGTGCAGGGATTACAAGGTG GCTTTCAAGATCAACTCTGTCATTAATCGCTTCAACGTGGACGAAGACATGAATGAACAC ATCAAGGCCCTGAGCCCTGTGCGCTGGAAGGTTTTCCAGTGCCTCCTAATTGAGGGTGAG AACTCAGGAGAAGATGCCCTGAGGGAAGCAGAAAGATTTCTTATAAGCAATGAAGAATTT GAAACATTCTTGGAGCGTCACAAAGAGGTGTCCTGTTTGGTGCCTGAATCTAACCAGAAG ATGAAAGACTCCTACCTTATCCTAGATGAATATATGCGCTTTCTGAACTGTACCGGTGGC CGGAAGGACCCTTCCAAGTCTATTCTGGATGTTGGCGTGGAAGAAGCAATAAAGTTCAGT GGATTTGATGAGAAGATGTTTCTGAAGCGTGGCGGAAAGTATGTGTGGAGTAAAGCTGAC CTGAAGCTGGACTGGTGAGGCTGAGATGGGAAGGAAACTCCGACCAGCTACAGGGACATT CACGCCCAGCTATCCTTCAACAAGCTACATCTTCTGGCTGTCTACAGACTG TTGTT Rsad2MouseProtein MGMLVPTALAARLLSLFQQQLGSLWSGLAILFCWLRIALGWLDPGKEQPQVRGEPEDTQE TQEDGNSTQPTTPVSVNYHFTRQCNYKCGFCFHTAKTSFVLPLEEAKRGLLLLKQAGLEK INFSGGEPFLQDRGEYLGKLVRFCKEELALPSVSIVSNGSLIRERWFKDYGEYLDILAIS CDSFDEQVNALIGRGQGKKNHVENLQKLRRWCRDYKVAFKINSVINRFNVDEDMNEHIKA LSPVRWKVFQCLLIEGENSGEDALREAERFLISNEEFETFLERHKEVSCLVPESNQKMKD SYLILDEYMRFLNCTGGRKDPSKSILDVGVEEAIKFSGFDEKMFLKRGGKYVWSKADLKL DW Sgk1HumanDNA CACGAGGGAGCGCTAACGTCTTTCTGTCTCCCCGCGGTGGTGATGACGGTGAAAACTGAG GCTGCTAAGGGCACCCTCACTTACTCCAGGATGAGGGGCATGGTGGCAATTCTCATCGCT TTCATGAAGCAGAGGAGGATGGGTCTGAACGACTTTATTCAGAAGATTGCCAATAACTCC TATGCATGCAAACACCCTGAAGTTCAGTCCATCTTGAAGATCTCCCAACCTCAGGAGCCT GAGCTTATGAATGCCAACCCTTCTCCTCCACCAAGTCCTTCTCAGCAAATCAACCTTGGC CCGTCGTCCAATCCTCATGCTAAACCATCTGACTTTCACTTCTTGAAAGTGATCGGAAAG GGCAGTTTTGGAAAGGTTCTTCTAGCAAGACACAAGGCAGAAGAAGTGTTCTATGCAGTC AAAGTTTTACAGAAGAAAGCAATCCTGAAAAAGAAAGAGGAGAAGCATATTATGTCGGAG CGGAATGTTCTGTTGAAGAATGTGAAGCACCCTTTCCTGGTGGGCCTTCACTTCTCTTTC CAGACTGCTGACAAATTGTACTTTGTCCTAGACTACATTAATGGTGGAGAGTTGTTCTAC CATCTCCAGAGGGAACGCTGCTTCCTGGAACCACGGGCTCGTTTCTATGCTGCTGAAATA GCCAGTGCCTTGGGCTACCTGCATTCACTGAACATCGTTTATAGAGACTTAAAACCAGAG AATATTTTGCTAGATTCACAGGGACACATTGTCCTTACTGATTTCGGACTCTGCAAGGAG AACATTGAACACAACAGCACAACATCCACCTTCTGTGGCACGCCGGAGTATCTCGCACCT GAGGTGCTTCATAAGCAGCCTTATGACAGGACTGTGGACTGGTGGTGCCTGGGAGCTGTC TTGTATGAGATGCTGTATGGCCTGCCGCCTTTTTATAGCCGAAACACAGCTGAAATGTAC GACAACATTCTGAACAAGCCTCTCCAGCTGAAACCAAATATTACAAATTCCGCAAGACAC CTCCTGGAGGGCCTCCTGCAGAAGGACAGGACAAAGCGGCTCGGGGCCAAGGATGACTTC ATGGAGATTAAGAGTCATGTCTTCTTCTCCTTAATTAACTGGGATGATCTCATTAATAAG AAGATTACTCCCCCTTTTAACCCAAATGTGAGTGGGCCCAACGAGCTACGGCACTTTGAC CCCGAGTTTACCGAAGAGCCTGTCCCCAACTCCATTGGCAAGTCCCCTGACAGCGTCCTC GTCACAGCCAGCGTCAAGGAAGCTGCCGAGGCTTTCCTAGGCTTTTCCTATGCGCCTCCC ACGGACTCTTTCCTCTGAACCCTGTTAGGGCTTGGTTTTAAAGGATTTTATGTGTGTTTC CGAATGTTTTAGTTAGCCTTTTGGTGGAGCCGCCAGCTGACAGGACATCTTACAAGAGAA TTTGCACATCTCTGGAAGCTTAGCAATCTTATTGCACACTGTTCGCTGGAATTTTTTGAA GAGCACATTCTCCTCAGTGAGCTCATGAGGTTTTCATTTTTATTCTTCCTTCCAACGTGG TGCTATCTCTGAAACGAGCGTTAGAGTGCCGCCTTAGACGGAGGCAGGAGTTTCGTTAGA AAGCGGACCTGTTCTAAAAAAGGTCTCCTGCAGATCTGTCTGGGCTGTGATGACGAATAT TATGAAATGTGCCTTTTCTGAAGAGATTGTGTTAGCTCCAAAGCTTTTCCTATCGCAGTG TTTCAGTTCTTTATTTTCCCTTGTGGATATGCTGTGTGAACCGTCGTGTGAGTGTGGTAT GCCTGATCACAGATGGATTTTGTTATAAGCATCAATGTGACACTTGCAGGACACTACAAC GTGGGACATTGTTTGTTTCTTCCATATTTGGAAGATAAATTTATGTGTAGACTTTTTTGT AAGATACGGTTAATAACTAAAATTTATTGAAATGGTCTTGCAATGACTCGTATTCAGATG CCTAAAGAAAGCATTGCTGCTACAAATATTTCTATTTTTAGAAAGGGTTTTTATGGACCA ATGCCCCAGTTGTCAGTCAGAGCCGTTGGTGTTTTTCATTGTTTAAAATGTCACCTGTAA AATGGGCATTATTTATGTTTTTTTTTTTGCATTCCTGATAATTGTATGTATTGTATAAAG AACGTCTGTACATTGGGTTATAACACTAGTATATTTAAACTTACAGGCTTATTTGTAATG TAAACCACCATTTTAATGTACTGTAATTAACATGGTTATAATACGTACAATCCTTCCCTC ATCCCATCACACAACTTTTTTTGTGTGTGATAAACTGATTTTGGTTTGCAATAAAACCTT GAAAAATAAAAAAAAAAAAAAAAAAAAAAA Sgk1MouseDNA ACCCACGCGTCCGGCCGGTTTCACTGCTCCCCTCAGTCTCTTTTGGGCTCTTTCCGGGCA TCGGGACGATGACCGTCAAAGCCGAGGCTGCTCGAAGCACCCTTACCTACTCCAGAATGA GGGGAATGGTAGCGATTCTCATCGCTTTTATGAAACAGAGAAGGATGGGCCTGAACGATT TTATTCAGAAGATTGCCAGCAACACCTATGCATGCAAACACGCTGAAGTTCAGTCCATTT TGAAAATGTCCCATCCTCAGGAGCCGGAGCTTATGAACGCTAACCCCTCTCCTCCGCCAA GTCCCTCTCAACAAATCAACCTGGGTCCGTCCTCCAACCCTCACGCCAAACCCTCCGACT TTCACTTCTTGAAAGTGATCGGAAAGGGCAGTTTTGGAAAGGTTCTTCTGGCTAGGCACA AGGCAGAAGAAGTATTCTATGCAGTCAAAGTTTTACAGAAGAAAGCCATCCTGAAGAAGA AAGAGGAGAAGCATATTATGTCAGAGCGGAATGTTCTGTTGAAGAATGTGAAGCACCCTT TCCTGGTGGGCCTTCACTTCTCATTCCAGACCGCTGACAAACTCTACTTTGTCCTGGACT ACATTAATGGTGGAGAGCTGTTCTACCATCTCCAGAGGGAGCGCTGCTTCCTGGAACCAC GGGCTCGATTCTACGCAGCTGAAATAGCCAGTGCCTTGGGCTATCTGCACTCCCTAAACA TCGTTTATAGAGACTTAAAACCTGAGAATATTCTCCTAGACTCCCAGGGGCACATCGTCC TCACTGACTTTGGGCTCTGCAAAGAGAATATTGAGCATAACGGGACAACATCTACCTTCT GTGGCACGCCTGAGTATCTGGCTCCTGAGGTCCTCCATAAGCAGCCGTATGACCGGACGG TGGACTGGTGGTGTCTTGGGGCTGTCCTGTATGAGATGCTCTACGGCCTGCCCCCGTTTT ATAGCCGGAACACGGCTGAGATGTACGACAATATTCTGAACAAGCCTCTCCAGTTGAAAC CAAATATTACAAACTCGGCAAGGCACCTCCTGGAAGGCCTCCTGCAGAAGGACCGGACCA AGAGGCTGGGTGCCAAGGATGACTTTATGGAGATTAAGAGTCATATTTTCTTCTCTTTAA TTAACTGGGATGATCTCATCAATAAGAAGATTACACCCCCATTTAACCCAAATGTGAGTG GGCCCAGTGACCTTCGGCACTTTGATCCCGAGTTTACCGAGGAGCCGGTCCCCAGCTCCA TCGGCAGGTCCCCTGACAGCATCCTTGTCACGGCCAGTGTGAAGGAAGCAGCAGAAGCCT TCCTCGGCTTCTCCTATGCACCTCCTGTGGATTCCTTCCTCTGAGTGCTCCCGGGATGGT TCTGAAGGACTTCCTCAGCGTTTCCTAAAGTGTTTTCCTTACCCTTTGGTGGAGGTTGCC AGCTGACAGAACATTTTAAAAGAATTTGCACACCTGGAAGCTTGGCAGTCTCGCCTGCCC GGCGTGGCGCGACGCAGCGCGCGCTGCTTGATGGGAGCTTTCCGAAGAGCACACCCTCCT CTCAATGAGCTTGTGAGGTCTTCTTTTCTTCTCTTCCTTCCAACGTGGTGCTAGCTCCAG GCGAGCGAGCGTGAGAGTGCCGCCTGAGACAGACACCTTGGTCTCAGTTAGAAGGAAGAT GCAGGTCTAAGAGGAATCCCCGCAGTCTGTCTGAGCTGTGATCAAGAATATTCTGCAATG TGCCTTTTCTGAGATCGTGTTAGCTCCAAAGCTTTTTCCTATCGCAGAGTGTTCAGTTTG TGTTTGTTTGTTTTTGTTTTGTTTTGTTTTTCCCTTGGCGGATTTCCCGTGTGTGCAGTG GCGTGAGTGTGCTATGCCTGATCACAGACGGTTTTGTTGTGAGCATCAATGTGACACTTG CAGGACACTACAATGTGGGACATTGTTTGTTTCTTCCACATTTGGAAGATAAATTTATGT GTAGACTGTTTTGTAAGATATAGTTAATAACTAAAACCTATTGAAACGGTCTTGCAATGA CGAGCATTCAGATGCTTAAGGAAAGCATTGCTGCTACAAATATTTCTATTTTTAGAAAGG GTTTTTATGGACCAATGCCCCAGTTGTCAGTCAAAGCCGTTGGTGTTTTCATTGTTTAAA ATGTCACCTATAAAACGGGCATTATTTATGTTTTTTTTCCCTTTGTTCATATTCTTTTGC ATTCCTGATTATTGTATGTATCGTGTAAAGGAAGTCTGTACATTGGGTTATAACACTAGA TATTTAAACTTACAGGCTTATTTGTAAACCATCATTTTAATGTACTGTAATTAACATGGG TTATAATATGTACAATTCCTCCTCCTTACCACACAACTTTTTTTGTGTGCGATAAACCAA TTTTGGTTTGCAATAAAATCTTGAAACCT Sgk1MouseProtein MTVKAEAARSTLTYSRMRGMVAILIAFMKQRRMGLNDFIQKIASNTYACKHAEVQSILKM SHPQEPELMNANPSPPPSPSQQINLGPSSNPHAKPSDFHFLKVIGKGSFGKVLLARHKAE EVFYAVKVLQKKAILKKKEEKHIMSERNVLLKNVKHPFLVGLHFSFQTADKLYFVLDYIN GGELFYHLQRERCFLEPRARFYAAEIASALGYLHSLNIVYRDLKPENILLDSQGHIVLTD FGLCKENIEHNGTTSTFCGTPEYLAPEVLHKQPYDRTVDWWCLGAVLYEMLYGLPPFYSR NTAEMYDNILNKPLQLKPNITNSARHLLEGLLQKDRTKRLGAKDDFMEIKSHIFFSLINW DDLINKKITPPFNPNVSGPSDLRHFDPEFTEEPVPSSIGRSPDSILVTASVKEAAEAFLG FSYAPPVDSFL Sdc1HumanDNA ATGAGACGCGCGGCGCTCTGGCTCTGGCTCTGCGCGCTGGCGCTGAGCCTGCAGCCGGCC CTGCCGCAAATTGTGGCTACTAATTTGCCCCCTGAAGATCAAGATGGCTCTGGGGATGAC TCTGACAACTTCTCCGGCTCAGGTGCAGGTGCTTTGCAAGATATCACCTTGTCACAGCAG ACCCCCTCCACTTGGAAGGACACGCAGCTCCTGACGGCTATTCCCACGTCTCCAGAACCC ACCGGCCTGGAAGCTACAGCTGCCTCCACCTCCACCCTGCCGGCTGGAGAGGGGCCCAAG GAGGGAGAGGCTGTAGTCCTGCCAGAAGTGGAGCCTGGCCTCACCGCCCGGGAGCAGGAG GCCACCCCCCGACCCAGGGAGACCACACAGCTCCCGACCACTCATCAGGCCTCAACGACC ACAGCCACCACGGCCCAGGAGCCCGCCACCTCCCACCCCCACAGGGACATGCAGCCTGGC CACCATGAGACCTCAACCCCTGCAGGACCCAGCCAAGCTGACCTTCACACTCCCCACACA GAGGATGGAGGTCCTTCTGCCACCGAGAGGGCTGCTGAGGATGGAGCCTCCAGTCAGCTC CCAGCAGCAGAGGGCTCTGGGGAGCAGGACTTCACCTTTGAAACCTCGGGGGAGAATACG GCTGTAGTGGCCGTGGAGCCTGACCGCCGGAACCAGTCCCCAGTGGATCAGGGGGCCACG GGGGCCTCACAGGGCCTCCTGGACAGGAAAGAGGTGCTGGGAGGGGTCATTGCCGGAGGC CTCGTGGGGCTCATCTTTGCTGTGTGCCTGGTGGGTTTCATGCTGTACCGCATGAAGAAG AAGGACGAAGGCAGCTACTCCTTGGAGGAGCCGAAACAAGCCAACGGCGGTGCCTACCAG AAACCCACCAAGCAGGAGGAGTTCTACGCC Sdc1MouseDNA ACTCCGCGGGAGAGGTGCGGGCCAGAGGAGACAGAGCCTAACGCAGAGGAAGGGACCTGG CAGTCGGGAGCTGACTCCAGCCGGCGAAACCTACAGCCCTCGCTCGAGAGAGCAGCGAGC TGGGCAGGAGCCTGGGACAGCAAAGCGCAGAGCAATCAGCAGAGCCGGCCCGGAGCTCCG TGCAACCGGCAACTCGGATCCACGAAGCCCACCGAGCTCCCGCCGCCGGTCTGGGCAGCA TGAGACGCGCGGCGCTCTGGCTCTGGCTCTGCGCGCTGGCGCTGCGCCTGCAGCCTGCCC TCCCGCAAATTGTGGCTGTAAATGTTCCTCCTGAAGATCAGGATGGCTCTGGGGATGACT CTGACAACTTCTCTGGCTCTGGCACAGGTGCTTTGCCAGATACTTTGTCACGGCAGACAC CTTCCACTTGGAAGGACGTGTGGCTGTTGACAGCCACGCCCACAGCTCCAGAGCCCACCA GCAGCAACACCGAGACTGCTTTTACCTCTGTCCTGCCAGCCGGAGAGAAGCCCGAGGAGG GAGAGCCTGTGCTCCATGTAGAAGCAGAGCCTGGCTTCACTGCTCGGGACAAGGAAAAGG AGGTCACCACCAGGCCCAGGGAGACCGTGCAGCTCCCCATCACCCAACGGGCCTCAACAG TCAGAGTCACCACAGCCCAGGCAGCTGTCACATCTCATCCGCACGGGGGCATGCAACCTG 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 Sdc1MouseProtein MRRAALWLWLCALALRLQPALPQIVAVNVPPEDQDGSGDDSDNFSGSGTGALPDTLSRQT PSTWKDVWLLTATPTAPEPTSSNTETAFTSVLPAGEKPEEGEPVLHVEAEPGFTARDKEK EVTTRPRETVQLPITQRASTVRVTTAQAAVTSHPHGGMQPGLHETSAPTAPGQPDHQPPR VEGGGTSVIKEVVEDGTANQLPAGEGSGEQDFTFETSGENTAVAAVEPGLRNQPPVDEGA TGASQSLLDRKEVLGGVIAGGLVGLIFAVCLVAFMLYRMKKKDEGSYSLEEPKQANGGAY QKPTKQEEFYA Serpine2HumanDNA ATGAACTGGCATCTCCCCCTCTTCCTCTTGGCCTCTGTGACGCTGCCTTCCATCTGCTCC CACTTCAATCCTCTGTCTCTCGAGGAACTAGGCTCCAACACGGGGATCCAGGTTTTCAAT CAGATTGTGAAGTCGAGGCCTCATGACAACATCGTGATCTCTCCCCATGGGATTGCGTCG GTCCTGGGGATGCTTCAGCTGGGGGCGGACGGCAGGACCAAGAAGCAGCTCGCCATGGTG ATGAGATACGGCGTAAATGGAGTTGGTAAAATATTAAAGAAGATCAACAAGGCCATCGTC TCCAAGAAGAATAAAGACATTGTGACAGTGGCTAACGCCGTGTTTGTTAAGAATGCCTCT GAAATTGAAGTGCCTTTTGTTACAAGGAACAAAGATGTGTTCCAGTGTGAGGTCCGGAAT GTGAACTTTGAGGATCCAGCCTCTGCCTGTGATTCCATCAATGCATGGGTTAAAAACGAA ACCAGGGATATGATTGACAATCTGCTGTCCCCAGATCTTATTGATGGTGTGCTCACCAGA CTGGTCCTCGTCAACGCAGTGTATTTCAAGGGTCTGTGGAAATCACGGTTCCAACCCGAG AACACAAAGAAACGCACTTTCGTGGCAGCCGACGGGAAATCCTATCAAGTGCCAATGCTG GCCCAGCTCTCCGTGTTCCGGTGTGGGTCGACAAGTGCCCCCAATGATTTATGGTACAAC TTCATTGAACTGCCCTACCACGGGGAAAGCATCAGCATGCTGATTGCACTGCCGACTGAG AGCTCCACTCCGCTGTCTGCCATCATCCCACACATCAGCACCAAGACCATAGACAGCTGG ATGAGCATCATGGTCCCCAAGAGGGTGCAGGTGATCCTGCCCAAGTTCACAGCTGTAGCA CAAACAGATTTGAAGGAGCCGCTGAAAGTTCTTGGCATTACTGACATGTTTGATTCATCA AAGGCAAATTTTGCAAAAATAACAAGGTCAGAAAACCTCCATGTTTCTCATATCTTGCAA AAAGCAAAAATTGAAGTCAGTGAAGATGGAACCAAAGCTTCAGCAGCAACAACTGCAATT CTCATTGCAAGATCATCGCCTCCCTGGTTTATAGTAGACAGACCTTTTCTGTTTTTCATC CGACATAATCCTACAGGTGCTGTGTTATTCATGGGGCAGATAAACAAACC C Serpine2MouseDNA AGTGCAGTGGTTGCACGGGAGTGCGGGCTGCACGCGTCACCGTCACCGCCGCCTGTCCCC CACCGCCGCGCAGCGCCGATCTCCCTCCCGGTTTCGGCCGCCACCTGGGGATCCAAGCGA GGACGGGCTGTCCTTGTTGGAAGGAACCATGAATTGGCATTTTCCTTTCTTCATCTTGAC CACAGTGACTTTATACTCTGTGCACTCCCAGTTCAACTCTCTGTCACTGGAGGAACTAGG CTCCAACACAGGGATCCAGGTCTTCAATCAGATCATCAAGTCACGGCCTCATGAGAACGT TGTTGTCTCCCCACATGGGATCGCGTCCATCTTGGGCATGCTGCAGCTCGGGGCTGACGG CAAGACAAAGAAGCAGCTCTCCACGGTGATGCGATATAATGTAAACGGAGTTGGTAAAGT GCTGAAGAAGATCAACAAGGCTATTGTCTCCAAGAAAAATAAAGACATTGTGACCGTGGC CAATGCTGTGTTTCTCAGGAATGGCTTTAAAATGGAAGTGCCTTTTGCAGTAAGGAACAA AGATGTGTTTCAGTGTGAAGTGCAGAATGTGAACTTCCAGGACCCAGCCTCTGCCTCTGA GTCCATCAATTTTTGGGTCAAAAATGAGACCAGGGGCATGATTGATAATCTGCTTTCCCC AAATCTGATCGATGGTGCCCTTACCAGGCTGGTCCTCGTTAATGCAGTGTATTTCAAGGG TTTGTGGAAGTCTCGGTTTCAACCAGAGAGCACAAAGAAACGGACATTCGTGGCAGGTGA TGGGAAATCCTACCAAGTACCCATGTTGGCTCAGCTCTCTGTGTTCCGCTCAGGGTCTAC CAGGACCCCGAATGGCTTATGGTACAACTTCATTGAGCTGCCCTACCATGGTGAGAGCAT CAGCATGCTGATCGCCCTGCCAACAGAGAGCTCCACCCCACTGTCTGCCATCATCCCTCA CATCACTACCAAGACCATTGATAGCTGGATGAACACCATGGTACCCAAGAGGATGCAGCT GGTCCTACCCAAGTTCACAGCTGTGGCACAAACAGATCTGAAGGAGCCACTGAAAGCCCT TGGCATTACTGAGATGTTTGAGCCATCAAAGGCAAATTTTACAAAAATAACAAGGTCAGA GAGCCTTCATGTCTCTCACATCTTGCAAAAAGCAAAAATTGAAGTCAGTGAAGATGGAAC CAAAGCTTCAGCAGCAACAACTGCAATCCTAATTGCAAGGTCATCACCTCCCTGGTTTAT AGTAGACAGGCCTTTCCTGTTTTCCATCCGACACAATCCCACAGGTGCCATCTTGTTCCT GGGCCAGGTGAACAAGCCCTGAAGGACAGACAAAGGAAAGCCACGCAAAGCCAAGACGAC TTGGCTCTGAAGAGAGACTCCCTCCCCACATCTTTCATAGTTCTGTTAAATATTTTTATA TACTGCTTTCTTTTTTGAAACTGGTTCATAGCAGCAGTTAAGTGACGCAAGTGTTTCTGG TCGGGGCTGTGTCAGAAGAAAGGGCTGGATGCCTGGGATGCTGGATGCCTGGGATGCTGG ATGCCTGGGATGCTGGATGCCTGGGATGCTGGATGCCTGGGATGCTGGATGCCTGGGATG CTGTAGTGAAGGATGAGCAGGCCGGTTTCACGATGTCTAGAAGATTTCTTTAAACTACTG ATCAGTTATCTAGGTTAACAACCCTCTCGAGTATTTGCTGTCTGTCAAGTTCAGCATCTT TGTTTCATTCCTGTTGATATGTGTGACTTTCCAGGAGAGGATTAATCAGTGTGGCAGGAG AGGTTAAAAAAAAAAAAGACATTTTATAGTAGTTTTTATGTTTTTATGGAAAACAATATC ATTTGCCTTTTTAATTCTTTTTCCTCTCACTTCCACCCAAAGGCTTGAGGGTGGCAAGGG ATGGAGCTAGCAAAAGCCGTAGCCTCTTCGTGTGTTGTTTCTGTTGCTGTTGCTCTTGTT GTTTTATATACTGCATGTGTTCACTAAAATAAAGTTGGAAAACT Serpine2MouseProtein MNWHFPFFILTTVTLYSVHSQFNSLSLEELGSNTGIQVFNQIIKSRPHENVVVSPHGIAS ILGMLQLGADGKTKKQLSTVMRYNVNGVGKVLKKINKAIVSKKNKDIVTVANAVFLRNGF KMEVPFAVRNKDVFQCEVQNVNFQDPASASESINFWVKNETRGMIDNLLSPNLIDGALTR LVLVNAVYFKGLWKSRFQPESTKKRTFVAGDGKSYQVPMLAQLSVFRSGSTRTPNGLWYN FIELPYHGESISMLIALPTESSTPLSAIIPHITTKTIDSWMNTMVPKRMQLVLPKFTAVA QTDLKEPLKALGITEMFEPSKANFTKITRSESLHVSHILQKAKIEVSEDGTKASAATTAI LIARSSPPWFIVDRPFLFSIRHNPTGAILFLGQVNKP Spp1HumanDNA GACCAGACTCGTCTCAGGCCAGTTGCAGCCTTCTCAGCCAAACGCCGACCAAGGAAAACT CACTACCATGAGAATTGCAGTGATTTGCTTTTGCCTCCTAGGCATCACCTGTGCCATACC AGTTAAACAGGCTGATTCTGGAAGTTCTGAGGAAAAGCAGCTTTACAACAAATACCCAGA TGCTGTGGCCACATGGCTAAACCCTGACCCATCTCAGAAGCAGAATCTCCTAGCCCCACA GAATGCTGTGTCCTCTGAAGAAACCAATGACTTTAAACAAGAGACCCTTCCAAGTAAGTC CAACGAAAGCCATGACCACATGGATGATATGGATGATGAAGATGATGATGACCATGTGGA CAGCCAGGACTCCATTGACTCGAACGACTCTGATGATGTAGATGACACTGATGATTCTCA CCAGTCTGATGAGTCTCACCATTCTGATGAATCTGATGAACTGGTCACTGATTTTCCCAC GGACCTGCCAGCAACCGAAGTTTTCACTCCAGTTGTCCCCACAGTAGACACATATGATGG CCGAGGTGATAGTGTGGTTTATGGACTGAGGTCAAAATCTAAGAAGTTTCGCAGACCTGA CATCCAGTACCCTGATGCTACAGACGAGGACATCACCTCACACATGGAAAGCGAGGAGTT GAATGGTGCATACAAGGCCATCCCCGTTGCCCAGGACCTGAACGCGCCTTCTGATTGGGA CAGCCGTGGGAAGGACAGTTATGAAACGAGTCAGCTGGATGACCAGAGTGCTGAAACCCA CAGCCACAAGCAGTCCAGATTATATAAGCGGAAAGCCAATGATGAGAGCAATGAGCATTC CGATGTGATTGATAGTCAGGAACTTTCCAAAGTCAGCCGTGAATTCCACAGCCATGAATT TCACAGCCATGAAGATATGCTGGTTGTAGACCCCAAAAGTAAGGAAGAAGATAAACACCT GAAATTTCGTATTTCTCATGAATTAGATAGTGCATCTTCTGAGGTCAATTAAAAGGAGAA AAAATACAATTTCTCACTTTGCATTTAGTCAAAAGAAAAAATGCTTTATAGCAAAATGAA AGAGAACATGAAATGCTTCTTTCTCAGTTTATTGGTTGAATGTGTATCTATTTGAGTCTG GAAATAACTAATGTGTTTGATAATTAGTTTAGTTTGTGGCTTCATGGAAACTCCCTGTAA ACTAAAAGCTTCAGGGTTATGTCTATGTTCATTCTATAGAAGAAATGCAAACTATCACTG TATTTTAATATTTGTTATTCTCTCATGAATAGAAATTTATGTAGAAGCAAACAAAATACT TTTACCCACTTAAAAAGAGAATATAACATTTTATGTCACTATAATCTTTTGTTTTTTAAG TTAGTGTATATTTTGTTGTGATTATCTTTTTGTGGTGTGAATAA Spp1MouseDNA CTTGCTTGGGTTTGCAGTCTTCTGCGGCAGGCATTCTCGGAGGAAACCAGCCAAGGACTA ACTACGACCATGAGATTGGCAGTGATTTGCTTTTGCCTGTTTGGCATTGCCTCCTCCCTC CCGGTGAAAGTGACTGATTCTGGCAGCTCAGAGGAGAAGCTTTACAGCCTGCACCCAGAT CCTATAGCCACATGGCTGGTGCCTGACCCATCTCAGAAGCAGAATCTCCTTGCGCCACAG AATGCTGTGTCCTCTGAAGAAAAGGATGACTTTAAGCAAGAAACTCTTCCAAGCAATTCC AATGAAAGCCATGACCACATGGACGACGATGATGACGATGATGATGACGATGGAGACCAT GCAGGGAGCGAGGATTCTGTGGACTCGGATGAATCTGACGAATCTCACCATTCGGATGAG TCTGATGAGACCGTCACTGCTAGTACACAAGCAGACACTTTCACTCCAATCGTCCCTACA GTCGATGTCCCCAACGGCCGAGGTGATAGCTTGGCTTATGGACTGAGGTCAAAGTCTAGG AGTTTCCAGGTTTCTGATGAACAGTATCCTGATGCCACAGATGAGGACCTCACCTCTCAC ATGAAGAGCGGTGAGTCTAAGGAGTCCCTCGATGTCATCCCTGTTGCCCAGCTTCTGAGC ATGCCCTCTGATCAGGACAACAACGGAAAGGGCAGCCATGAGTCAAGTCAGCTGGATGAA CCAAGTCTGGAAACACACAGACTTGAGCATTCCAAAGAGAGCCAGGAGAGTGCCGATCAG TCGGATGTGATCGATAGTCAAGCAAGTTCCAAAGCCAGCCTGGAACATCAGAGCCACAAG TTTCACAGCCACAAGGACAAGCTAGTCCTAGACCCTAAGAGTAAGGAAGATGATAGGTAT CTGAAATTCCGAATTTCTCATGAATTAGAGAGTTCATCTTCTGAGGTCAACTAAAGAAGA GGCAAAAACACAGTTCCTTACTTTGCATTTAGTAAAAACAAGAAAAAGTGTTAGTGAGGA TTAAGCAGGAATACTAACTGCTCATTTCTCAGTTCAGTGGATATATGTATGTAGAGAAAG AGAGGTAATATTTTGGGCTCTTAGCTTAGTCTGTTGTTTCATGCAAACAACCGTTGTAAC CAAAAGCTTCTGCACTTTGCTTCTGTTCTTCCTGTACAAGAAATGCAAACGGCCACTGCA TTTTAATGATTGTTATTCTTTTATGAATAAAATGTATGTAGAAACAAGCAAATTTACTGA AACAAGCAGAATTAAAAGAGAAACTGTAACAGTCTATATCACTATACCCTTTTAGTTTTA TAATTAGCATATATTTTGTTGTGATTATTTTTTTTGTTGGTGTGAATAAATCTTGTAACG AATGT Spp1MouseProtein MRLAVICFCLFGIASSLPVKVTDSGSSEEKLYSLHPDPIATWLVPDPSQKQNLLAPQNAV SSEEKDDFKQETLPSNSNESHDHMDDDDDDDDDDGDHAESEDSVDSDESDESHHSDESDE TVTASTQADTFTPIVPTVDVPNGRGDSLAYGLRSKSRSFQVSDEQYPDATDEDLTSHMKS GESKESLDVIPVAQLLSMPSDQDNNGKGSHESSQLDEPSLETHRLEHSKESQESADQSDV IDSQASSKASLEHQSHKFHSHKDKLVLDPKSKEDDRYLKFRISHELESSSSEVN Cdca8HumanDNA GGTTGACTGTAGAGCCGCTCTCTCTCACTGGCACAGCGAGGTTTTGCTCAGCCCTTGTCT CGGGACCGCAGGTACGTGTCTGGCGACTTCTTCGGGTGGTCCCCGTCCGCCCTCCTCGTC CCTACCCAGTTTCTTGCTTCCCTGCCCCATCTCCGCCGCTCCCCGCAGCCTCCGCCGAGC GCCATGGCTCCTAGGAAGGGCAGTAGTCGGGTGGCCAAGACCAACTCCTTACGGAGGCGG AAGCTCGCCTCCTTTCTGAAAGACTTCGACCGTGAAGTGGAAATACGAATCAAGCAAATT GAGTCAGACAGGCAGAACCTCCTCAAGGAGGTGGATAACCTCTACAACATCGAGATCCTG CGGCTCCCCAAGGCTCTGCGCGAGATGAACTGGCTTGACTACTTCGCCCTTGGAGGAAAC AAACAGGCCCTGGAAGAGGCGGCAACAGCTGACCTGGATATCACCGAAATAAACAAACTA ACAGCAGAAGCTATTCAGACACCCCTGAAATCTGCCAAAACACGAAAGGTAATACAGGTA GATGAAATGATAGTGGAAGAGGGAAGAAGGAGAAGGAAAATTTACGTAAGAATCTTCAAA CTGCAAGAGTCAAAAGGTGTCCTCCATCCAAGAAGAGAACTCAGTCCATACAAGGCAAAG GAAAAGGGAAAAGGTCAAGCCGTGCTAACACTGTTACCCCAGCCGTGGGCCGATTGGAGG TGTCCATGGTCAAACCAACTCCAGGCCTGACACCCAGGTTTGACTCAAGGGTCTTCAAGA CCCTGGCCTGCGTACTCCAGCAGCAGGAGAGCGGATTTACAACATCTCAGGGAATGGCAG CCCTCTTGCTGACAGCAAAGAGATCTTCCTCACTGTGCCAGTGGGCGGCGGAGAGAGCCT GCGATTATTGGCCAGTGACTTGCAGAGGCACAGTATTGCCCAGCTGGATCCAGAGGCCTT GGGAAACATTAAGAAGCTCTCCAACCGTCTCGCCCAAATCTGCAGCAGCATACGGACCCA CAAATGAGACACCAAAGTTGACAGGATGGACTTTTAATGGGCACTTCTGGGACCCTGAAG AGACTTCTTCCCTTCAGGCTTATTGTTTGAGTGTGAAGTTCCAGAGCAAGGAGCCATGTT CCTCTAAGGGAATTCAGGAATTCAGACGTGCTAGTCCCACACCAGTTAGGTAGAGCTGTC TGTTCACCCTCCCATCCCAGCTGATCCCAGTCACTGCTTGCTGGGGCCATGCCATGGAAG CTTCCCATCAGTCTCCCAGCTGAATCCTCCCTGCTCTCTGAGCTGCTGCCTTTTGCCTCC TGCAACTCAACATCCTCTTCACCCTGCCCTGCCTGCAGTTGAGGGGGCGAAGAAGAACCC TGTGTTCTCAGGAAGACTGCCTCCACCACCGCTACCCAGAGAACCTCTGCATCTGGCATT TCTGCTCTCTATGCTTGAGACCGGGAGGTTTAGGCTCAGATAAGTGAGCTCTGGGCCATG AGAGGGTAGGTCCAGAAGGTGGGGGGAACTGTACAGATCAGCAGAGCAGGACAGTTGGCA GCAGTGACCTCAGTAGGGAACATGTCCGTCTACCCTCTCGCACTCATGACACCTCCCCCT ACCAGCCTCTCTCTCTCTCACCTCCTCTGTGGGAGGTGGTCAGTGGGACTTAGGGATCTT TCACCTGCTGTGCCCAGTAGTTCTGAAGTCTGCTTGTGGAGCAGTGTTTTATGTTTATCC CTGTTTACTGAAGACCAAATACTGGTTTGGAGACAACTTCCATGTCTTGCTCTTCTACCT CCCTAGTTAGTGGAAATTTGGATAAGGGAACTGTAGGGCCCAGATTCTGGAGGTTTTATG TCATTGGCCACAGAATAACTGTCTCTAAGCTATCCATGGTCCAGTGGTCCCTGCCAAGTC TGTAGACTTCAGAGAGCACTTCTCTCTTATGGGGTTCATGGGAACAGGGGCGGGTGTGAC TTGCTTGGTGGCCTCATTCCATGTGTGCCTGTGCCTGGGGCATGGACTTTGTTAAGCAGA GTCAGCAGTGAGGTCCTCATTCTCCAGCCAGCCTCTCTGCCCTGGAGAATCATGTGCTAT GTTCTAAGAATTTGAGAACTAGAGTCCTCATCCCCAGGCTTGAAGGCACATGGCTTTCTC ATGTAGGGCTCTCTGTGGTATTTGTTATTATTTTGCAACAAGACCATTTTAGTAAAACAG TCCTGTTCAAGTTGTATTCTTTTAAGTTCTTTTATTCTCCTTTCCCTGAGATTTTTGTAT ATATTGTTCTGAGTAATGGTATCTTTGAGCTGATTGTTCTAATCAGAGCTGGTACCTACT TTCAATAAATTCTGGTTTTGTGTTTTCTTTTGT Cdca8MouseDNA 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 Cdca8MouseProtein MAPKKRSSRGTRTNTLRSRKLASFLKDFDREVQVRTKQIESDRQTLLKEVENLYNIEILR LPKALQGMKWLDYFALGGNKQALEEAAKADRDITEINNLTAEAIQTPLKSVKKRKVIEVE ESIKEEEEEEEEGGGGGGRTKKSHKNLRSAKVKRCLPSKKRTQSIQGRGRSKRLSHDFVT PAMSRLEPSLVKPTPGMTPRFDSRVFKTPGLRTPAAKEQVYNISINGSPLADSKEISLSV PIGGGASLRLLASDLQRIDIAQLNPEALGNIRKLSSRLAQICSSIRTGR Nrp1HumanDNA ATGGAGAGGGGGCTGCCGCTCCTCTGCGCCGTGCTCGCCCTCGTCCTCGCCCCGGCCGGC GCTTTTCGCAACGATGAATGTGGCGATACTATAAAAATTGAAAGCCCCGGGTACCTTACA TCTCCTGGTTATCCTCATTCTTATCACCCAAGTGAAAAATGCGAATGGCTGATTCAGGCT CCGGACCCATACCAGAGAATTATGATCAACTTCAACCCTCACTTCGATTTGGAGGACAGA GACTGCAAGTATGACTACGTGGAAGTCTTCGATGGAGAAAATGAAAATGGACATTTTAGG GGAAAGTTCTGTGGAAAGATAGCCCCTCCTCCTGTTGTGTCTTCAGGGCCATTTCTTTTT ATCAAATTTGTCTCTGACTACGAAACACATGGTGCAGGATTTTCCATACGTTATGAAATT TTCAAGAGAGGTCCTGAATGTTCCCAGAACTACACAACACCTAGTGGAGTGATAAAGTCC CCCGGATTCCCTGAAAAATATCCCAACAGCCTTGAATGCACTTATATTGTCTTTGCGCCA AAGATGTCAGAGATTATCCTGGAATTTGAAAGCTTTGACCTGGAGCCTGACTCAAATCCT CCAGGGGGGATGTTCTGTCGCTACGACCGGCTAGAAATCTGGGATGGATTCCCTGATGTT GGCCCTCACATTGGGCGTTACTGTGGACAGAAAACACCAGGTCGAATCCGATCCTCATCG GGCATTCTCTCCATGGTTTTTTACACCGACAGCGCGATAGCAAAAGAAGGTTTCTCAGCA AACTACAGTGTCTTGCAGAGCAGTGTCTCAGAAGATTTCAAATGTATGGAAGCTCTGGGC ATGGAATCAGGAGAAATTCATTCTGACCAGATCACAGCTTCTTCCCAGTATAGCACCAAC TGGTCTGCAGAGCGCTCCCGCCTGAACTACCCTGAGAATGGGTGGACTCCCGGAGAGGAT TCCTACCGAGAGTGGATACAGGTAGACTTGGGCCTTCTGCGCTTTGTCACGGCTGTCGGG ACACAGGGCGCCATTTCAAAAGAAACCAAGAAGAAATATTATGTCAAGACTTACAAGATC GACGTTAGCTCCAACGGGGAAGACTGGATCACCATAAAAGAAGGAAACAAACCTGTTCTC TTTCAGGGAAACACCAACCCCACAGATGTTGTGGTTGCAGTATTCCCCAAACCACTGATA ACTCGATTTGTCCGAATCAAGCCTGCAACTTGGGAAACTGGCATATCTATGAGATTTGAA GTATACGGTTGCAAGATAACAGATTATCCTTGCTCTGGAATGTTGGGTATGGTGTCTGGA CTTATTTCTGACTCCCAGATCACATCATCCAACCAAGGAGACAGAAACTGGATGCCTGAA AACATCCGCCTGGTAACCAGTCGCTCTGGCTGGGCACTTCCACCCGCACCTCATTCCTAC ATCAATGAGTGGCTCCAAATAGACCTGGGGGAGGAGAAGATCGTGAGGGGCATCATCATT CAGGGTGGGAAGCACCGAGAGAACAAGGTGTTCATGAGGAAGTTCAAGATCGGGTACAGC AACAACGGCTCGGACTGGAAGATGATCATGGATGACAGCAAACGCAAGGCGAAGTCTTTT GAGGGCAACAACAACTATGATACACCTGAGCTGCGGACTTTTCCAGCTCTCTCCACGCGA TTCATCAGGATCTACCCCGAGAGAGCCACTCATGGCGGACTGGGGCTCAGAATGGAGCTG CTGGGCTGTGAAGTGGAAGCCCCTACAGCTGGACCGACCACTCCCAACGGGAACTTGGTG GATGAATGTGATGACGACCAGGCCAACTGCCACAGTGGAACAGGTGATGACTTCCAGCTC ACAGGTGGCACCACTGTGCTGGCCACAGAAAAGCCCACGGTCATAGACAGCACCATACAA TCAGAGTTTCCAACATATGGTTTTAACTGTGAATTTGGCTGGGGCTCTCACAAGACCTTC TGCCACTGGGAACATGACAATCACGTGCAGCTCAAGTGGAGTGTGTTGACCAGCAAGACG GGACCCATTCAGGATCACACAGGAGATGGCAACTTCATCTATTCCCAAGCTGACGAAAAT CAGAAGGGCAAAGTGGCTCGCCTGGTGAGCCCTGTGGTTTATTCCCAGAACTCTGCCCAC TGCATGACCTTCTGGTATCACATGTCTGGGTCCCACGTCGGCACACTCAGGGTCAAACTG CGCTACCAGAAGCCAGAGGAGTACGATCAGCTGGTCTGGATGGCCATTGGACACCAAGGT GACCACTGGAAGGAAGGGCGTGTCTTGCTCCACAAGTCTCTGAAACTTTATCAGGTGATT TTCGAGGGCGAAATCGGAAAAGGAAACCTTGGTGGGATTGCTGTGGATGACATTAGTATT AATAACCACATTTCACAAGAAGATTGTGCAAAACCAGCAGACCTGGATAAAAAGAACCCA GAAATTAAAATTGATGAAACAGGGAGCACGCCAGGATACGAAGGTGAAGGAGAAGGTGAC AAGAACATCTCCAGGAAGCCAGGCAATGTGTTGAAGACCTTAGAACCCATCCTCATCACC ATCATAGCCATGAGCGCCCTGGGGGTCCTCCTGGGGGCTGTCTGTGGGGTCGTGCTGTAC TGTGCCTGTTGGCATAATGGGATGTCAGAAAGAAACTTGTCTGCCCTGGAGAACTATAAC TTTGAACTTGTGGATGGTGTGAAGTTGAAAAAAGACAAACTGAATACACAGAGTACTTAT TCGGAGGCATGA Nrp1MouseDNA TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTCCTCCTTCTTCTTCTTCCTGAGACA TGGCCCGGGCAGTGGCTCCTGGAAGAGGAACAAGTGTGGGAAAAGGGAGAGGAAATCGGA GCTAAATGACAGGATGCAGGCGACTTGAGACACAAAAAGAGAAGCGCTTCTCGCGAATTC AGGCATTGCCTCGCCGCTAGCCTTCCCCGCCAAGACCCGCTGAGGATTTTATGGTTCTTA GGCGGACTTAAGAGCGTTTCGGATTGTTAAGATTATCGTTTGCTGGTTTTTCGTCCGCGC AATCGTGTTCTCCTGCGGCTGCCTGGGGACTGGCTTGGCGAAGGAGGATGGAGAGGGGGC TGCCGTTGCTGTGCGCCACGCTCGCCCTTGCCCTCGCCCTGGCGGGCGCTTTCCGCAGCG ACAAATGTGGCGGGACCATAAAAATCGAAAACCCAGGGTACCTCACATCTCCCGGTTACC CTCATTCTTACCATCCAAGTGAGAAGTGTGAATGGCTAATCCAAGCTCCGGAACCCTACC AGAGAATCATAATCAACTTCAACCCACATTTCGATTTGGAGGACAGAGACTGCAAGTATG ACTACGTGGAAGTAATTGATGGGGAGAATGAAGGCGGCCGCCTGTGGGGGAAGTTCTGTG GGAAGATTGCACCTTCTCCTGTGGTGTCTTCAGGGCCCTTTCTCTTCATCAAATTTGTCT CTGACTATGAGACACATGGGGCAGGGTTTTCCATCCGCTATGAAATCTTCAAGAGAGGGC CCGAATGTTCTCAGAACTATACAGCACCTACTGGAGTGATAAAGTCCCCTGGGTTCCCTG AAAAATACCCCAACTGCTTGGAGTGCACCTACATCATCTTTGCACCAAAGATGTCTGAGA TAATCCTGGAGTTTGAAAGTTTTGACCTGGAGCAAGACTCGAATCCTCCCGGAGGAATGT TCTGTCGCTATGACCGGCTGGAGATCTGGGATGGATTCCCTGAAGTTGGCCCTCACATTG GGCGTTATTGTGGGCAGAAAACTCCTGGCCGGATCCGCTCCTCTTCAGGCGTTCTATCCA TGGTCTTTTACACTGACAGCGCAATAGCAAAAGAAGGTTTCTCAGCCAACTACAGTGTGC 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 Nrp1MouseProtein MERGLPLLCATLALALALAGAFRSDKCGGTIKIENPGYLTSPGYPHSYHPSEKCEWLIQA PEPYQRIMINFNPHFDLEDRDCKYDYVEVIDGENEGGRLWGKFCGKIAPSPVVSSGPFLF IKFVSDYETHGAGFSIRYEIFKRGPECSQNYTAPTGVIKSPGFPEKYPNSLECTYIIFAP KMSEIILEFESFDLEQDSNPPGGMFCRYDRLEIWDGFPEVGPHIGRYCGQKTPGRIRSSS GVLSMVFYTDSAIAKEGFSANYSVLQSSISEDFKCMEALGMESGEIHSDQITASSQYGTN WSVERSRLNYPENGWTPGEDSYKEWIQVDLGLLRFVTAVGTQGAISKETKKKYYVKTYRV DISSNGEDWISLKEGNKAIIFQGNTNPTDVVLGVFSKPLITRFVRIKPVSWETGISMRFE VYGCKITDYPCSGMLGMVSGLISDSQITASNQADRNWMPENIRLVTSRTGWALPPSPHPY TNEWLQVDLGDEKIVRGVIIQGGKHRENKVFMRKFKIAYSNNGSDWKTIMDDSKRKAKSF EGNNNYDTPELRTFSPLSTRFIRIYPERATHSGLGLRMELLGCEVEAPTAGPTTPNGNPV DECDDDQANCHSGTGDDFQLTGGTTVLATEKPTIIDSTIQSEEPTYGENCEFGWGSHKTF CHWEHDSHAQLRWSVLTSKTGPIQDHTGDGNFIYSQADENQKGKVARLVSPVVYSQSSAH CMTFWYHMSGSHVGTLRVKLRYQKPEEYDQLVWMVVGHQGDHWKEGRVLLHKSLKLYQVI FEGEIGKGNLGGIAVDDISINNHISQEDCAKPTDLDKKNTEIKIDETGSTPGYEGEGEGD KNISRKPGNVLKTLDPILITIIAMSALGVLLGAVCGVVLYCACWHNGMSERNLSALENYN FELVDGVKLKKDKLNPQSNYSEA McamHumanDNA GGGAAGCATGGGGCTTCCCAGGCTGGTCTGCGCCTTCTTGCTCGCCGCCTGCTGCTGCTG TCCTCGCGTCGCGGGTGTGCCCGGAGAGGCTGAGCAGCCTGCGCCTGAGCTGGTGGAGGT GGAAGTGGGCAGCACAGCCCTTCTGAAGTGCGGCCTCTCCCAGTCCCAAGGCAACCTCAG CCATGTCGACTGGTTTTCTGTCCACAAGGAGAAGCGGACGCTCATCTTCCGTGTGCGCCA GGGCCAGGGCCAGAGCGAACCTGGGGAGTACGAGCAGCGGCTCAGCCTCCAGGACAGAGG GGCTACTCTGGCCCTGACTCAAGTCACCCCCCAAGACGAGCGCATCTTCTTGTGCCAGGG CAAGCGCCCTCGGTCCCAGGAGTACCGCATCCAGCTCCGCGTCTACAAAGCTCCGGAGGA GCCAAACATCCAGGTCAACCCCCTGGGCATCCCTGTGAACAGTAAGGAGCCTGAGGAGGT CGCTACCTGTGTAGGGAGGAACGGGTACCCCATTCCTCAAGTCATCTGGTACAAGAATGG CCGGCCTCTGAAGGAGGAGAAGAACCGGGTCCACATTCAGTCGTCCCAGACTGTGGAGTC GAGTGGTTTGTACACCTTGCAGAGTATTCTGAAGGCACAGCTGGTTAAAGAAGACAAAGA TGCCCAGTTTTACTGTGAGCTCAACTACCGGCTGCCCAGTGGGAACCACATGAAGGAGTC CAGGGAAGTCACCGTCCCTGTTTTCTACCCGACAGAAAAAGTGTGGCTGGAAGTGGAGCC CGTGGGAATGCTGAAGGAAGGGGACCGCGTGGAAATCAGGTGTTTGGCTGATGGCAACCC TCCACCACACTTCAGCATCAGCAAGCAGAACCCCAGCACCAGGGAGGCAGAGGAAGAGAC AACCAACGACAACGGGGTCCTGGTGCTGGAGCCTGCCCGGAAGGAACACAGTGGGCGCTA TGAATGTCAGGCCTGGAACTTGGACACCATGATATCGCTGCTGAGTGAACCACAGGAACT ACTGGTGAACTATGTGTCTGACGTCCGAGTGAGTCCCGCAGCCCCTGAGAGACAGGAAGG CAGCAGCCTCACCCTGACCTGTGAGGCAGAGAGTAGCCAGGACCTCGAGTTCCAGTGGCT GAGAGAAGAGACAGACCAGGTGCTGGAAAGGGGGCCTGTGCTTCAGTTGCATGACCTGAA ACGGGAGGCAGGAGGCGGCTATCGCTGCGTGGCGTCTGTGCCCAGCATACCCGGCCTGAA CCGCACACAGCTGGTCAAGCTGGCCATTTTTGGCCCCCCTTGGATGGCATTCAAGGAGAG GAAGGTGTGGGTGAAAGAGAATATGGTGTTGAATCTGTCTTGTGAAGCGTCAGGGCACCC CCGGCCCACCATCTCCTGGAACGTCAACGGCACGGCAAGTGAACAAGACCAAGATCCACA GCGAGTCCTGAGCACCCTGAATGTCCTCGTGACCCCGGAGCTGTTGGAGACAGGTGTTGA ATGCACGGCCTCCAACGACCTGGGCAAAAACACCAGCATCCTCTTCCTGGAGCTGGTCAA TTTAACCACCCTCACACCAGACTCCAACACAACCACTGGCCTCAGCACTTCCACTGCCAG TCCTCATACCAGAGCCAACAGCACCTCCACAGAGAGAAAGCTGCCGGAGCCGGAGAGCCG GGGCGTGGTCATCGTGGCTGTGATTGTGTGCATCCTGGTCCTGGCGGTGCTGGGCGCTGT CCTCTATTTCCTCTATAAGAAGGGCAAGCTGCCGTGCAGGCGCTCAGGGAAGCAGGAGAT CACGCTGCCCCCGTCTCGTAAGACCGAACTTGTAGTTGAAGTTAAGTCAGATAAGCTCCC AGAAGAGATGGGCCTCCTGCAGGGCAGCAGCGGTGACAAGAGGGCTCCGGGAGACCAGGG AGAGAAATACATCGATCTGAGGCATTAGCCCCGAATCACTTCAGCTCCCTTCCCTGCCTG GACCATTCCCAGCTCCCTGCTCACTCTTCTCTCAGCCAAAGCTCAAAGGGACTAGAGAGA AGCCTCCTGCTCCCCTCGCCTGCACACCCCCTTTCAGAGGGCCACTGGGTTAGGACCTGA GGACCTCACTTGGCCCTGCAAGGCCCGCTTTTCAGGGACCAGTCCACCACCATCTCCTCC ACGTTGAGTGAAGCTCATCCCAAGCAAGGAGCCCCAGTCTCCCGAGCGGGTAGGAGAGTT TCTTGCAGAACGTGTTTTTTCTTTACACACATTATGCTGTAAATACGCTCGTCCTGCCAG CAGCTGAGCTGGGTAGCCTCTCTGAGCTGGTTTCCTGCCCCAAAGGCTGGCATTCCACCA TCCAGGTGCACCACTGAAGTGAGGACACACCGGAGCCAGGCGCCTGCTCATGTTGAAGTG CGCTGTTCACACCCGCTCCGGAGAGCACCCCAGCAGCATCCAGAAGCAGCTGCAGTGCAA GCTTGCATGCCTGCGTGTTGCTGCACCACCCTCCTGTCTGCCTCTTCAAAGTCTCCTGTG ACATTTTTTCTTTGGTCAGAGGCCAGGAACTGTGTCATTCCTTAAAGATACGTGCCGGGG CCAGGTGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGCGGATCACAA AGTCAGACGAGACCATCCTGGCTAACACGGTGAAACCCTGTCTCTACTAAAAATACAAAA AAAAATTAGCTAGGCGTAGTGGTTGGCACCTATAGTCCCAGCTACTCGGAAGGCTGAAGC AGGAGAATGGTATGAATCCAGGAGGTGGAGCTTGCAGTGAGCCGAGACCGTGCCACTGCA CTCCAGCCTGGGCAACACAGCGAGACTCCGTCTCGAGCCGGCCGGTTGCGCGGGCCCTCG GACCCTCAGAGAGGCGAGGGTTCGAGGGCACGAGTTCGAGGCCAACCTGGTCCACATGGG TTG McamMouseDNA CGCCCTCCGTCGGGGAAGCATGGGGCTGCCCAAACTGGTGTGCGTCTTCTTGTTCGCTGC CTGCTGCTGCTGTCGCCGTGCCGCGGGTGTGCCAGGAGAGGAAAAGCAGCCAGTACCCAC GCCCGACCTGGTGGAGGCAGAAGTGGGCAGCACAGCCCTTCTCAAGTGTGGCCCCTCACG GGCCTCAGGCAACTTCAGCCAAGTGGACTGGTTTTTGATTCACAAGGAGAGGCAGATACT GATTTTCCGTGTGCACCAAGGCAAGGGCCAGCGGGAACCTGGTGAATATGAGCACCGCCT TAGCCTCCAAGACTCGGTGGCTACTCTGGCCCTGAGTCACGTCACTCCCCATGATGAGCG AATGTTCCTGTGTAAGAGCAAGCGACCACGGCTCCAGGATCACTACGTTGAGCTTCAGGT CTTCAAAGCCCCAGAGGAACCAACTATTCAAGCCAATGTCGTGGGCATCCATGTGGACAG GCAAGAGCTCAGGGAGGTTGCTACCTGTGTGGGGAGAAACGGCTACCCCATTCCTCAAGT CCTATGGTACAAGAACAGTCTGCCCTTGCAAGAGGAGGAGAACCGAGTTCATATCCAGTC ATCACAGATTGTCGAGTCCAGTGGCTTGTACACCTTGAAGAGTGTTCTGAGTGCACGCCT AGTTAAGGAAGACAAAGATGCCCAGTTTTACTGTGAACTCAGCTACCGGCTACCCAGTGG GAACCACATGAAGGAATCTAAGGAGGTCACTGTCCCTGTTTTCTACCCTGCAGAAAAAGT GTGGGTGGAGGTAGAGCCTGTGGGGCTGCTGAAGGAAGGGGATCATGTGACAATCAGGTG TCTGACAGATGGCAACCCTCAACCCCACTTCACTATCAACAAGAAGGACCCCAGCACTGG GGAGATGGAAGAGGAGAGCACCGATGAAAATGGGCTCCTGTCCTTGGAGCCTGCCGAAAA GCACCATAGCGGGCTCTACCAGTGTCAGAGTCTGGACCTGGAAACTACCATCACACTGTC AAGTGACCCCCTGGAGCTGCTGGTGAACTATGTGTCTGATGTTCAAGTGAATCCAACTGC CCCTGAAGTCCAGGAAGGTGAGAGCCTCACGCTGACCTGCGAGGCAGAAAGTAACCAGGA CCTTGAGTTTGAGTGGCTGAGAGACAAGACAGGCCAGCTGCTGGGAAAGGGTCCCGTCCT CCAGCTAAACAACGTGAGACGGGAAGCAGGGGGACGGTATCTCTGCATGGCATCTGTCCC CAGAGTTCCTGGCTTGAATCGTACCCAGCTGGTCAGCGTGGGCATTTTTGGGTCCCCATG GATGGCATTAAAGGAGAGGAAGGTGTGGGTGCAAGAGAATGCAGTGCTGAATCTGTCTTG TGAGGCTTCAGGACATCCTCAGCCCACCATCTCCTGGAATGTCAATGGTTCGGCAACTGA ATGGAACCCAGATCCACAGACAGTAGTGAGCACCTTGAATGTCCTTGTGACGCCAGAGCT TCTGGAGACAGGTGCAGAGTGTACAGCCTCCAACTCCCTGGGCTCAAACACCACCACCAT TGTTCTGAAGCTGGTCACTTTAACCACCCTCATACCTGACTCCAGCCAAACCACTGGCCT CAGCACCCTCACAGTCAGTCCTCACACCAGAGCCAACAGCACCTCCACAGAGAAAAAGCT GCCACAGCCAGAGAGCAAAGGTGTGGTCATCGTGGCTGTGATAGTGTGTACCTTGGTGCT TGCTGTGCTGGGTGCTGCTCTCTATTTCCTCTACAAGAAGGGCAAGCTGCCATGTGGACG CTCGGGAAAACAGGAGATCACGCTGCCCCCGACTCGTAAGAGTGAATTTGTAGTTGAAGT TAAGTCAGATAAGCTCCCAGAAGAGATGGCTCTCCTTCAGGGCAGCAACGGTGACAAGAG GGCTCCAGGAGACCAGGGAGAGAAATACATCGATCTGAGGCATTAGATGGCTCCCATTGC ACTGCTCGCAGCTCCCTGCTCAGACTTCACCCCAAGCTGAAGCCTCCAGAGGGACAGCAG GGACGAGCCACACTCAACCCCCCCCCTGCACATCAGGTCTGAGAGCTAGGAGCTGGGACA GGAGTCGTCTGCAGGAGCTCAGTTGGCCACAGAGGCCTGGTTTTAGAGACCAAGCCCTCC TCTGTGTCCAGTAAATAATGCTTATCCCAAGGGGCCCGTCTCCCAGGGCATTTCCCCCTC CCGTGCACAGCCATTGGTGGCAAATCCTTCTGCCATCAGCTGTGTGGGCTTGCCTCTTTG AGCTCATCTCCCCTCACAGGCTGTCTTCATGATGCAGGACCTGGGCACATGGTCACATTA TTCCGTTCACATTGGTCCTTGTGAGAACCTCACAGTCTGGAGGCGGCTGCTTTTGTACCT TCCTGCCTGCTACTAATTCAGGGTCTCATTTGGAACATTTTTCCTTTGGGTAGTGGTCAG GAACTGGTGTAAGTCCTCCAGACACATCCCTGTGTAAGGAAGCCAGGGCACTGTTTCTCT GAGTTTTGTTGTTTTGTTTTCTTTGAAGGCTACTGAGCCCAAGCTTCCCGCATTCCCTTA GTAACAAGAGACAGGACAGAGAGAAGGTCTACTGTTCATGGGGATTAGGCTTATAGGAAT GTTAGTACCAAATTTCTACATGTGAGCTTTGGGGGCCAGGTCCTAGAGAGCCCAAGTGGG AGAATGGTATTTAGGAGATGAAAAACCTGGCCTAGCAAGAGCTTTTGAGGTGTGTGTGTG TGTGTGTGTATACATATATGTGTGTATATATATATATATATATATAGGTTTTGTCTGTAA ATTTGCAAATTTTTCCTTTTATATGTGTGTTAGAAAAATAAAGTGTTATTGTCCCAAAAA AAAAAAAAAA McamMouseProtein MGLPKLVCVFLFAACCCCRRAAGVPGEEKQPVPTPDLVEAEVGSTALLKCGPSRASGNFS QVDWFLIHKERQILIFRVHQGKGQREPGEYEHRLSLQDSVATLALSHVTPHDERMFLCKS KRPRLQDHYVELQVFKAPEEPTIQANVVGIHVDRQELREVATCVGRNGYPIPQVLWYKNS LPLQEEENRVHIQSSQIVESSGLYTLKSVLSARLVKEDKDAQFYCELSYRLPSGNHMKES KEVTVPVFYPAEKVWVEVEPVGLLKEGDHVTIRCLTDGNPQPHFTINKKDPSTGEMEEES TDENGLLSLEPAEKHHSGLYQCQSLDLETTITLSSDPLELLVNYVSDVQVNPTAPEVQEG ESLTLTCEAESNQDLEFEWLRDKTGQLLGKGPVLQLNNVRREAGGRYLCMASVPRVPGLN RTQLVSVGIFGSPWMALKERKVWVQENAVLNLSCEASGHPQPTISWNVNGSATEWNPDPQ TVVSTLNVLVTPELLETGAECTASNSLGSNTTTIVLKLVTLTTLIPDSSQTTGLSTLTVS PHTRANSTSTEKKLPQPESKGVVIVAVIVCTLVLAVLGAALYFFYKKGKLPCGRSGKQEI TLPPTRKSEFVVEVKSDKLPEEMALLQGSNGDKRAPGDQGEKYIDLRH PbkHumanDNA GTAAGAAAGCCAGGAGGGTTCGAATTGCAACGGCAGCTGCCGGGCGTATGTGTTGGTGCT AGAGGCAGCTGCAGGGTCTCGCTGGGGGCCGCTCGGGACCAATTTTGAAGAGGTACTTGG CCACGACTTATTTTCACCTCCGACCTTTCCTTCCAGGCGGTGAGACTCTGGACTGAGAGT GGCTTTCACAATGGAAGGGATCAGTAATTTCAAGACACCAAGCAAATTATCAGAAAAAAA GAAATCTGTATTATGTTCAACTCCAACTATAAATATCCCGGCCTCTCCGTTTATGCAGAA GCTTGGCTTTGGTACTGGGGTAAATGTGTACCTAATGAAAAGATCTCCAAGAGGTTTGTC TCATTCTCCTTGGGCTGTAAAAAAGATTAATCCTATATGTAATGATCATTATCGAAGTGT GTATCAAAAGAGACTAATGGATGAAGCTAAGATTTTGAAAAGCCTTCATCATCCAAACAT TGTTGGTTATCGTGCTTTTACTGAAGCCAATGATGGCAGTCTGTGTCTTGCTATGGAATA TGGAGGTGAAAAGTCTCTAAATGACTTAATAGAAGAACGATATAAAGCCAGCCAAGATCC TTTTCCAGCAGCCATAATTTTAAAAGTTGCTTTGAATATGGCAAGAGGGTTAAAGTATCT GCACCAAGAAAAGAAACTGCTTCATGGAGACATAAAGTCTTCAAATGTTGTAATTAAAGG CGATTTTGAAACAATTAAAATCTGTGATGTAGGAGTCTCTCTACCACTGGATGAAAATAT GACTGTGACTGACCCTGAGGCTTGTTACATTGGCACAGAGCCATGGAAACCCAAAGAAGC TGTGGAGGAGAATGGTGTTATTACTGACAAGGCAGACATATTTGCCTTTGGCCTTACTTT GTGGGAAATGATGACTTTATCGATTCCACACATTAATCTTTCAAATGATGATGATGATGA AGATAAAACTTTTGATGAAAGTGATTTTGATGATGAAGCATACTATGCAGCCTTGGGAAC TAGGCCACCTATTAATATGGAAGAACTGGATGAATCATACCAGAAAGTAATTGAACTCTT CTCTGTATGCACTAATGAAGACCCTAAAGATCGTCCTTCTGCTGCACACATTGTTGAAGC TCTGGAAACAGATGTCTAGTGATCATCTCAGCTGAAGTGTGGCTTGCGTAAATAACTGTT TATTCCAAAATATTTACATAGTTACTATCAGTAGTTATTAGACTCTAAAATTGGCATATT TGAGGACCATAGTTTCTTGTTAACATATGGATAACTATTTCTAATATGAAATATGCTTAT ATTGGCTATAAGCACTTGGAATTGTACTGGGTTTTCTGTAAAGTTTTAGAAACTAGCTAC ATAAGTACTTTGATACTGCTCATGCTGACTTAAAACACTAGCAGTAAAACGCTGTAAACT GTAACATTAAATTGAATGACCATTACTTTTATTAATGATCTTTCTTAAATATTCTATATT TTAATGGATCTACTGACATTAGCACTTTGTACAGTACAAAATAAAGTCTACATTTGTTTA AAACAAAAAAAAAAAAAAAAAA PbkMouseDNA GAGGGGAGCTGTTCCTGCATTTTCTGGAGCGAGTCTTCTGACTGCTTTTAGTTAGAACTC CAGTGCCCCTCGGCGGGCCGCGGCCTTTGAAAATGCGCGCGCCCTAAACGCTGCGGCGGT TACGCTGTTGGCGGGAGGGAGCTGAGCCTGCACTTTCCGGACTAGGTGTCCAGACAGCTT TGAGCCAGCCCGTCACTTTCACCTTTTTACCCGAGCGTGCGAGCGTGGACCTAACGTGAT TGCTACAATGGAAGGAATTAATAATTTCAAGACGCCAAACAAATCTGAAAAAAGGAAATC TGTATTATGTTCCACTCCATGTGTAAATATCCCTGCCTCTCCATTTATGCAGAAGCTTGG CTTTGGGACTGGGGTCAGCGTTTACCTAATGAAAAGATCTCCAAGAGGGTTGTCTCATTC TCCTTGGGCCGTGAAAAAGATAAGTCTTTTATGCGATGATCATTATCGAACTGTGTATCA GAAGAGACTAACTGATGAAGCTAAGATTTTAAAAAACCTTAATCACCCAAACATTATAGG ATATCGTGCTTTTACTGAAGCCAGTGATGGTAGTCTGTGCCTTGCTATGGAGTATGGAGG TGAAAAGTCTCTGAATGACTTAATAGAAGAGCGGAACAAAGACAGTGGAAGTCCTTTTCC AGCAGCTGTAATTCTCAGAGTTGCTTTGCACATGGCCAGAGGGCTAAAGTACCTGCACCA AGAAAAGAAGCTGCTTCATGGAGACATAAAGTCTTCAAATGTTGTAATTAAAGGTGATTT TGAAACAATTAAAATCTGTGATGTAGGAGTCTCTCTGCCATTGGATGAAAATATGACTGT GACTGATCCTGAGGCCTGTTATATTGGTACTGAGCCATGGAAACCCAAGGAAGCGTTGGA AGAAAATGGCATCATTACTGACAAGGCAGATGTGTTTGCTTTTGGCCTTACTCTGTGGGA AATGATGACTTTATGTATTCCACACGTCAATCTTCCAGATGATGATGTTGATGAAGATGC AACCTTTGATGAGAGTGACTTCGATGATGAAGCATATTATGCAGCTCTGGGGACAAGGCC ATCCATCAACATGGAAGAGCTGGATGACTCCTACCAGAAGGCCATTGAACTCTTCTGTGT GTGCACTAATGAGGATCCTAAAGATCGCCCGTCTGCTGCACACATCGTTGAAGCTTTGGA ACTAGATGGCCAATGTTGTGGTCTAAGCTCAAAGCATTAACTTGTATGGGAACTGTTAAC TAGATATATGTAGTTAATATAACTTATGGTAGCTAGATTCTAGAAGTAGCTTTAACACTA GTGACCCCTGTCTAAGATGACTTAAGAATCAAGGGACCATTGCTTTGTTACAGATCTTTT TAGATATTCTTGCTTCTTTAGTGGGTTACTAAAAATTTCACTACGTACATGTGGTACAGA TATCTGTCTGCTCATAGTGTCAGTCCTTCAGCTGGCCTGTCAGCCCATGCGCCCTGGGAC TTGAGAAGAGTTCATAAACGTAGCTCCTAGGGTGTCTTGCCTCTCTACACTTAGCTTCTA ATTTATTACTTTGTTTCTACTGATTGTGTCTTAAGTCTTTTAAAATAAATGTAAGAATAA ACAATAAAAGACAGTTTTAGTACCAGGCAAAAAAAAAAAAAAAAAA PbkMouseProtein MEGINNFKTPNKSEKRKSVLCSTPCVNIPASPFMQKLGFGTGVSVYLMKRSPRGLSHSPW AVKKISLLCDDHYRTVYQKRLTDEAKILKNLNHPNIIGYRAFTEASDGSLCLAMEYGGEK SLNDLIEERNKDSGSPFPAAVILRVALHMARGLKYLHQEKKLLHGDIKSSNVVIKGDFET IKICDVGVSLPLDENMTVTDPEACYIGTEPWKPKEALEENGIITDKADVFAFGLTLWEMM TLCIPHVNLPDDDVDEDATFDESDFDDEAYYAALGTRPSINMEELDDSYQKAIELFCVCT NEDPKDRPSAAHIVEALELDGQCCGLSSKH Akr1c1HumanDNA CCAGAAATGGATTCGAAATATCAGTGTGTGAAGCTGAATGATGGTCACTTCATGCCTGTC CTGGGATTTGGCACCTATGCGCCTGCAGAGGTTCCTAAAAGTAAAGCTTTAGAGGCCACC AAATTGGCAATTGAAGCTGGCTTCCGCCATATTGATTCTGCTCATTTATACAATAATGAG GAGCAGGTTGGACTGGCCATCCGAAGCAAGATTGCAGATGGCAGTGTGAAGAGAGAAGAC ATATTCTACACTTCAAAGCTTTGGTGCAATTCCCATCGACCAGAGTTGGTCCGACCAGCC TTGGAAAGGTCACTGAAAAATCTTCAATTGGATTATGTTGACCTCTACCTTATTCATTTT CCAGTGTCTGTAAAGCCAGGTGAGGAAGTGATCCCAAAAGATGAAAATGGAAAAATACTA TTTGACACAGTGGATCTCTGTGCCACGTGGGAGGCCGTGGAGAAGTGTAAAGATGCAGGA TTGGCCAAGTCCATCGGGGTGTCCAACTTCAACCGCAGGCAGCTGGAGATGATCCTCAAC AAGCCAGGGCTCAAGTACAAGCCTGTCTGCAACCAGGTGGAATGTCATCCTTACTTCAAC CAGAGAAAACTGCTGGATTTCTGCAAGTCAAAAGACATTGTTCTGGTTGCCTATAGTGCT CTGGGATCCCACCGAGAAGAACCATGGGTGGACCCGAACTCCCCGGTGCTCTTGGAGGAC CCAGTCCTTTGTGCCTTGGCAAAAAAGCACAAGCGAACCCCAGCCCTGATTGCCCTGCGC TACCAGCTACAGCGTGGGGTTGTGGTCCTGGCCAAGAGCTACAATGAGCAGCGCATCAGA CAGAACGTGCAGGTGTTTGAATTCCAGTTGACTTCAGAGGAGATGAAAGCCATAGATGGC CTAAACAGAAATGTGCGATATTTGACCCTTGATATTTTTGCTGGCCCCCCTAATTATCCA TTTTCTGATGAATATTAACATGGAGGGCATTGCATGAGGTCTGCCAGAAGGCCCTGCGTG TGGATGGTGACACAGAGGATGGCTCTATGCTGGTGACTGGACACATCGCCTCTGGTTAAA TCTCTCCTGCTTGGTGATTTCAGCAAGCTACAGCAAAGCCCATTGGCCAGAAAGGAAAGA CAATAATTTTGTTTTTTCATTTTGAAAAAATTAAATGCTCTCTCCTAAAGATTCTTCACC TAAAAAA Akr1c1HumanProtein MDSKYQCVKLNDGHFMPVLGFGTYAPAEVPKSKALEATKLAIEAGFRHIDSAHLYNNEEQ VGLAIRSKIADGSVKREDIFYTSKLWCNSHRPELVRPALERSLKNLQLDYVDLYLIHFPV SVKPGEEVIPKDENGKILFDTVDLCATWEAVEKCKDAGLAKSIGVSNFNRRQLEMILNKP GLKYKPVCNQVECHPYFNQRKLLDFCKSKDIVLVAYSALGSHREEPWVDPNSPVLLEDPV LCALAKKHKRTPALIALRYQLQRGVVVLAKSYNEQRIRQNVQVFEFQLTSEEMKAIDGLN RNVRYLTLDIFAGPPNYPFSDEY Akr1c1MouseDNA TTGTCCTGACTCTGTTCTGCAGCCCTGATTGATTAGTAGCAGCTTGGTTACAATACATTT TTGTCATCTGCATTGACCTGGTCTTTAAGTTATATTGGATTTATGTTGGATTTAAGTGGA CCCACAACACTTTGAGGAAGAAGAAGACACTCTTCTTACTTTGGAGTACCCAGTGATATC AGGAAAGTCAGAGGCAGAGCCTGCAGATGAATCCCAAGCGCTACATGGAACTAAGTGATG GCCACCACATTCCTGTGCTTGGCTTTGGAACCTTTGTCCCAGGAGAGGTTTCCAAGAGTA TGGTTGCAAAAGCCACCAAAATAGCTATAGATGCTGGATTCCGCCATATTGACTCAGCTT ATTTCTACCAAAATGAGGAGGAAGTAGGGCTGGCCATCCGAAGCAAGGTTGCTGATGGCA CTGTGAGGAGAGAAGATATATTCTACACTTCAAAGCTTCCCTGCACATGTCATAGACCAG AGCTGGTCCAGCCTTGCTTGGAACAATCCCTGAGAAAGCTTCAGCTGGATTATGTTGATC TGTACCTTATTCACTGCCCAGTGTCCATGAAGCCAGGCAATGATCTTATTCCAACAGATG AAAATGGGAAATTATTATTTGACACAGTGGATCTCTGTGACACATGGGAGGCCATGGAGA AGTGTAAGGATTCAGGGTTAGCCAAGTCCATTGGTGTGTCCAACTTTAACCGGAGGCAGC TGGAGATGATCCTGAACAAGCCAGGGCTCAGGTACAAGCCTGTGTGCAACCAGGTAGAGT GTCACCCTTATCTGAACCAGAGCAAGCTCCTGGACTACTGCAAGTCAAAAGACATCGTTC TGGTTGCCTATGGTGCTCTTGGCAGCCAACGGTGTAAGAACTGGATAGAGGAGAATGCCC CATATCTCTTGGAAGACCCAACTCTGTGTGCCATGGCGGAAAAGCACAAGCAAACTCCGG CCCTAATTTCCCTCCGGTATCTGCTGCAGCGTGGGATTGTCATTGTCACCAAGAGTTTCA ATGAGAAGCGGATCAAGGAGAACCTGAAGGTCTTTGAGTTCCACTTGCCAGCAGAGGACA TGGCAGTTATAGATAGGCTGAACAGAAACTACCGATATGCTACTGCTCGTATTATTTCTG CTCACCCCAATTATCCATTTTTGGATGAATATTAACGCGGAAGCCTTTGTTGTGACATCG CTCAGAGGGAGCAATGTGGGAGATGCTGTGGATGTTGATCAGCATCACCTCTGGTCGACG TCGACATCACCGTCAACCCACACTGAACTGGATGGAGAGGGGTGGCCATGGTGTTTTGTG ATACTTTGAAGACAATAAAGTTTTGGTCTATGAGGT Akr1c1MouseProtein MNPKRYMELSDGHHIPVLGFGTFVPGEVSKSMVAKATKIAIDAGFRHIDSAYFYQNEEEV GLAIRSKVADGTVRREDIFYTSKLPCTCHRPELVQPCLEQSLRKLQLDYVDLYLIHCPVS MKPGNDLIPTDENGKLLFDTVDLCDTWEAMEKCKDSGLAKSIGVSNFNRRQLEMILNKPG LRYKPVCNQVECHPYLNQSKLLDYCKSKDIVLVAYGALGSQRCKNWIEENAPYLLEDPTL CAMAEKHKQTPALISLRYLLQRGIVIVTKSFNEKRIKENLKVFEFHLPAEDMAVIDRLNR NYRYATARIISAHPNYPFLDEY Cyp11a1HumanDNA GGGCGCTGAAGTGGAGCAGGTACAGTCACAGCTGTGGGGACAGCATGCTGGCCAAGGGTC TTCCCCCACGCTCAGTCCTGGTCAAAGGCTACCAGACCTTTCTGAGTGCCCCCAGGGAGG GGCTGGGGCGTCTCAGGGTGCCCACTGGCGAGGGAGCTGGCATCTCCACCCGCAGTCCTC GCCCCTTCAATGAGATCCCCTCTCCTGGTGACAATGGCTGGCTAAACCTGTACCATTTCT GGAGGGAGACGGGCACACACAAAGTCCACCTTCACCATGTCCAGAATTTCCAGAAGTATG GCCCGATTTACAGGGAGAAGCTCGGCAACGTGGAGTCGGTTTATGTCATCGACCCTGAAG ATGTGGCCCTTCTCTTTAAGTCCGAGGGCCCCAACCCAGAACGATTCCTCATCCCGCCCT GGGTCGCCTATCACCAGTATTACCAGAGACCCATAGGAGTCCTGTTGAAGAAGTCGGCAG CCTGGAAGAAAGACCGGGTGGCCCTGAACCAGGAGGTGATGGCTCCAGAGGCCACCAAGA ACTTTTTGCCCCTGTTGGATGCAGTGTCTCGGGACTTCGTCAGTGTCCTGCACAGGCGCA TCAAGAAGGCGGGCTCCGGAAATTACTCGGGGGACATCAGTGATGACCTGTTCCGCTTTG CCTTTGAGTCCATCACTAACGTCATTTTTGGGGAGCGCCAGGGGATGCTGGAGGAAGTAG TGAACCCCGAGGCCCAGCGATTCATTGATGCCATCTACCAGATGTTCCACACCAGCGTCC CCATGCTCAACCTTCCCCCAGACCTGTTCCGTCTGTTCAGGACCAAGACCTGGAAGGACC ATGTGGCTGCATGGGACGTGATTTTCAGTAAAGCTGACATATACACCCAGAACTTCTACT GGGAATTGAGACAGAAAGGAAGTGTTCACCACGATTACCGTGGCATGCTCTACAGACTCC TGGGAGACAGCAAGATGTCCTTCGAGGACATCAAGGCCAACGTCACAGAGATGCTGGCAG GAGGGGTGGACACGACGTCCATGACCCTGCAGTGGCACTTGTATGAGATGGCACGCAACC TGAAGGTGCAGGATATGCTGCGGGCAGAGGTCTTGGCTGCGCGGCACCAGGCCCAGGGAG ACATGGCCACGATGCTACAGCTGGTCCCCCTCCTCAAAGCCAGCATCAAGGAGACACTAA GACTTCACCCCATCTCCGTGACCCTGCAGAGATATCTTGTAAATGACTTGGTTCTTCGAG ATTACATGATTCCTGCCAAGACACTGGTGCAAGTGGCCATCTATGCTCTGGGCCGAGAGC CCACCTTCTTCTTCGACCCGGAAAATTTTGACCCAACCCGATGGCTGAGCAAAGACAAGA ACATCACCTACTTCCGGAACTTGGGCTTTGGCTGGGGTGTGCGGCAGTGTCTGGGACGGC GGATCGCTGAGCTAGAGATGACCATCTTCCTCATCAATATGCTGGAGAACTTCAGAGTTG AAATCCAACACCTCAGCGATGTGGGCACCACATTCAACCTCATTCTGATGCCTGAAAAGC CCATCTCCTTCACCTTCTGGCCCTTTAACCAGGAAGCAACCCAGCAGTGATCAGAGAGGA TGGCCTGCAGCCACATGGGAGGAAGGCCCAGGGGTGGGGCCCATGGGGTCTCTGCATCTT CAGTCGTCTGTCCCAAGTCCTGCTCCTTTCTGCCCAGCCTGCTCAGCAGGTTGAATGGGT TCTCAGTGGTCACCTTCCTCAGCTCAGCTGGGCCACTCCTCTTCACCCACCCCATGGAGA CAATAAACAGCTGAACCATCG Cyp11a1MouseDNA AAGTGGCAGTCGTGGGGACAGTATGCTGGCTAAAGGACTTTCCCTGCGCTCAGTGCTGGT CAAAGGCTGCCAACCTTTCCTGAGCCCTACGTGGCAGGGTCCAGTGCTGAGTACTGGAAA GGGAGCTGGTACCTCTACTAGCAGTCCTAGGTCCTTCAATGAGATCCCTTCCCCTGGCGA CAATGGTTGGCTAAACCTGTACCACTTCTGGAGGGAGAGTGGCACACAGAAAATCCATTA CCATCAGATGCAGAGTTTCCAAAAGTATGGCCCCATTTACAGGGAGAAGCTGGGCACTTT GGAGTCAGTTTACATCGTGGACCCCAAGGATGCGTCGATACTCTTCTCATGCGAGGGTCC CAACCCGGAGCGGTTCCTTGTGCCCCCCTGGGTGGCCTATCACCAGTATTATCAGAGGCC CATTGGGGTCCTGTTTAAGAGTTCAGATGCCTGGAAGAAAGACCGAATCGTCCTAAACCA AGAGGTGATGGCGCCTGGAGCCATCAAGAACTTCGTGCCCCTGCTGGAAGGTGTAGCTCA GGACTTCATCAAAGTCTTACACAGACGCATCAAGCAGCAAAATTCTGGAAATTTCTCAGG GGTCATCAGTGATGACCTATTCCGCTTTTCCTTTGAGTCCATCAGCAGTGTTATATTTGG GGAGCGCATGGGGATGCTGGAGGAGATCGTGGATCCCGAGGCCCAGCGGTTCATCAATGC TGTCTACCAGATGTTCCACACCAGTGTCCCCATGCTCAACCTGCCTCCAGACTTCTTTCG ACTCCTCAGAACTAAGACCTGGAAGGACCATGCAGCTGCCTGGGATGTGATTTTCAATAA AGCTGATGAGTACACCCAGAACTTCTACTGGGACTTAAGGCAGAAGCGAGACTTCAGCCA GTACCCTGGTGTCCTTTATAGCCTCCTGGGGGGCAACAAGCTGCCCTTCAAGAACATCCA GGCCAACATTACCGAGATGCTGGCAGGAGGGGTGGACACGACCTCCATGACCCTGCAGTG GAACCTTTATGAGATGGCACACAACTTGAAGGTACAGGAGATGCTGCGGGCTGAAGTCCT GGCTGCCCGGCGCCAGGCCCAGGGAGACATGGCCAAGATGGTACAGTTGGTTCCACTCCT CAAAGCCAGCATCAAGGAGACACTGAGACTCCACCCCATCTCCGTGACCTTGCAGAGGTA CACTGTGAATGACCTGGTGCTTCGTAATTACAAGATTCCAGCCAAGACTTTGGTACAGGT GGCTAGCTTTGCCATGGGTCGAGATCCGGGCTTCTTTCCCAATCCAAACAAGTTTGACCC AACTCGTTGGCTGGAAAAAAGCCAAAATACCACCCACTTCCGGTACTTGGGCTTTGGCTG GGGTGTTCGGCAGTGTCTGGGCCGGCGGATTGCGGAGCTGGAGATGACCATCCTCCTTAT CAATCTGCTGGAGAACTTCAGAATTGAAGTTCAAAATCTCCGTGATGTGGGGACCAAGTT CAGCCTCATCCTGATGCCTGAGAACCCCATCCTCTTCAACTTCCAGCCTCTCAAGCAGGA CCTGGGCCCAGCCGTGACCAGAAAAGACAACACTGTGAACTGAAGGCTGGAGTCACATGG GGAGGTGGCCCATGGGGCATTTGAGGGTGGTATCTCTGTATCTTCAGAAACAGCACTCTG TGATTACCTGCCCAGGTTAGCTGGGCTCTCCTCTCCTTCATCCTCTTTCCCTCTTTCCCT ACCCAGGGAGTTAATAAACACTTGAACACTGAGG Cyp11a1MouseProtein MLAKGLSLRSVLVKGCQPFLSPTWQGPVLSTGKGAGTSTSSPRSFNEIPSPGDNGWLNLY HFWRESGTQKIHYHQMQSFQKYGPIYREKLGTLESVYIVDPKDASILFSCEGPNPERFLV PPWVAYHQYYQRPIGVLFKSSDAWKKDRIVLNQEVMAPGAIKNFVPLLEGVAQDFIKVLH RRIKQQNSGNFSGVISDDLFRFSFESISSVIFGERMGMLEEIVDPEAQRFINAVYQMFHT SVPMLNLPPDFFRLLRTKTWKDHAAAWDVIFNKADEYTQNFYWDLRQKRDFSQYPGVLYS LLGGNKLPFKNIQANITEMLAGGVDTTSMTLQWNLYEMAHNLKVQEMLRAEVLAARRQAQ GDMAKMVQLVPLLKASIKETLRLHPISVTLQRYTVNDLVLRNYKIPAKTLVQVASFAMGR DPGFFPNPNKFDPTRWLEKSQNTTHFRYLGFGWGVRQCLGRRIAELEMTILLINLLENFR IEVQNLRDVGTKFSLILMPENPILFNFQPLKQDLGPAVTRKDNTVN