ID EPHA2_MOUSE Reviewed; 977 AA. AC Q03145; Q3UNI2; Q60633; Q62212; DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot. DT 27-JUL-2011, sequence version 3. DT 27-MAR-2024, entry version 219. DE RecName: Full=Ephrin type-A receptor 2; DE EC=2.7.10.1; DE AltName: Full=Epithelial cell kinase; DE AltName: Full=Tyrosine-protein kinase receptor ECK; DE AltName: Full=Tyrosine-protein kinase receptor MPK-5; DE AltName: Full=Tyrosine-protein kinase receptor SEK-2; DE Flags: Precursor; GN Name=Epha2; Synonyms=Eck, Myk2, Sek2; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], GLYCOSYLATION, CATALYTIC ACTIVITY, AND RP DEVELOPMENTAL STAGE. RX PubMed=8183555; RA Ganju P., Shigemoto K., Brennan J., Entwistle A., Reith A.D.; RT "The Eck receptor tyrosine kinase is implicated in pattern formation during RT gastrulation, hindbrain segmentation and limb development."; RL Oncogene 9:1613-1624(1994). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE. RX PubMed=7918100; DOI=10.1016/0925-4773(94)90078-7; RA Ruiz J.C., Robertson E.J.; RT "The expression of the receptor-protein tyrosine kinase gene, eck, is RT highly restricted during early mouse development."; RL Mech. Dev. 46:87-100(1994). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; TISSUE=Bone marrow, and Vagina; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 552-977, AND DEVELOPMENTAL STAGE. RC STRAIN=C57BL/6J; TISSUE=Embryo; RX PubMed=7947319; DOI=10.1016/0925-4773(94)90091-4; RA Becker N., Seitanidou T., Murphy P., Mattei M.-G., Topilko P., Nieto A., RA Wilkinson D.G., Charnay P., Gilardi P.; RT "Several receptor tyrosine kinase genes of the Eph family are segmentally RT expressed in the developing hindbrain."; RL Mech. Dev. 47:3-17(1994). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 742-799. RC TISSUE=Embryonic brain; RX PubMed=1281307; RA Gilardi-Hebenstreit P., Nieto M.A., Frain M., Mattei M.-G., Chestier A., RA Wilkinson D.G., Charnay P.; RT "An Eph-related receptor protein tyrosine kinase gene segmentally expressed RT in the developing mouse hindbrain."; RL Oncogene 7:2499-2506(1992). RN [9] RP INTERACTION WITH SLA. RC TISSUE=Embryonic brain; RX PubMed=7543898; DOI=10.1074/jbc.270.33.19201; RA Pandey A., Duan H., Dixit V.M.; RT "Characterization of a novel Src-like adapter protein that associates with RT the Eck receptor tyrosine kinase."; RL J. Biol. Chem. 270:19201-19204(1995). RN [10] RP DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY. RX PubMed=11287184; DOI=10.1016/s0925-4773(01)00290-8; RA Naruse-Nakajima C., Asano M., Iwakura Y.; RT "Involvement of EphA2 in the formation of the tail notochord via RT interaction with ephrinA1."; RL Mech. Dev. 102:95-105(2001). RN [11] RP FUNCTION IN ANGIOGENESIS, AND DISRUPTION PHENOTYPE. RX PubMed=15054110; DOI=10.1242/jcs.01061; RA Brantley-Sieders D.M., Caughron J., Hicks D., Pozzi A., Ruiz J.C., Chen J.; RT "EphA2 receptor tyrosine kinase regulates endothelial cell migration and RT vascular assembly through phosphoinositide 3-kinase-mediated Rac1 GTPase RT activation."; RL J. Cell Sci. 117:2037-2049(2004). RN [12] RP FUNCTION IN CELL PROLIFERATION, AND DISRUPTION PHENOTYPE. RX PubMed=16849550; DOI=10.1158/0008-5472.can-06-0004; RA Guo H., Miao H., Gerber L., Singh J., Denning M.F., Gilliam A.C., Wang B.; RT "Disruption of EphA2 receptor tyrosine kinase leads to increased RT susceptibility to carcinogenesis in mouse skin."; RL Cancer Res. 66:7050-7058(2006). RN [13] RP FUNCTION IN ANGIOGENESIS, INTERACTION WITH VAV2 AND VAV3, AND MUTAGENESIS RP OF TYR-589; TYR-595 AND ASP-740. RX PubMed=16782872; DOI=10.1128/mcb.02215-05; RA Hunter S.G., Zhuang G., Brantley-Sieders D.M., Swat W., Cowan C.W., RA Chen J.; RT "Essential role of Vav family guanine nucleotide exchange factors in EphA RT receptor-mediated angiogenesis."; RL Mol. Cell. Biol. 26:4830-4842(2006). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, INTERACTION WITH VAV2; VAV3 RP AND PI3-KINASE P85 SUBUNIT, PHOSPHORYLATION AT TYR-589; TYR-595; TYR-736 RP AND TYR-773, AND MUTAGENESIS OF TYR-589; TYR-595; TYR-736; TYR-773 AND RP TYR-931. RX PubMed=18387945; DOI=10.1074/jbc.m709934200; RA Fang W.B., Brantley-Sieders D.M., Hwang Y., Ham A.-J.L., Chen J.; RT "Identification and functional analysis of phosphorylated tyrosine residues RT within EphA2 receptor tyrosine kinase."; RL J. Biol. Chem. 283:16017-16026(2008). RN [15] RP FUNCTION IN LENS FIBER CELLS MORPHOGENESIS. RX PubMed=18948590; DOI=10.1073/pnas.0808987105; RA Cooper M.A., Son A.I., Komlos D., Sun Y., Kleiman N.J., Zhou R.; RT "Loss of ephrin-A5 function disrupts lens fiber cell packing and leads to RT cataract."; RL Proc. Natl. Acad. Sci. U.S.A. 105:16620-16625(2008). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-595 AND TYR-773, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic fibroblast; RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200; RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.; RT "Large scale localization of protein phosphorylation by use of electron RT capture dissociation mass spectrometry."; RL Mol. Cell. Proteomics 8:904-912(2009). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Heart, Kidney, Liver, and Lung; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [18] RP FUNCTION IN BONE IN REMODELING. RX PubMed=19299512; DOI=10.1074/jbc.m807598200; RA Irie N., Takada Y., Watanabe Y., Matsuzaki Y., Naruse C., Asano M., RA Iwakura Y., Suda T., Matsuo K.; RT "Bidirectional signaling through ephrinA2-EphA2 enhances osteoclastogenesis RT and suppresses osteoblastogenesis."; RL J. Biol. Chem. 284:14637-14644(2009). RN [19] RP FUNCTION IN MAMMARY GLAND DEVELOPMENT. RX PubMed=19321667; DOI=10.1091/mbc.e08-04-0378; RA Vaught D., Chen J., Brantley-Sieders D.M.; RT "Regulation of mammary gland branching morphogenesis by EphA2 receptor RT tyrosine kinase."; RL Mol. Biol. Cell 20:2572-2581(2009). RN [20] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-408 AND ASN-436. RC TISSUE=Myoblast; RX PubMed=19656770; DOI=10.1074/mcp.m900195-mcp200; RA Gundry R.L., Raginski K., Tarasova Y., Tchernyshyov I., Bausch-Fluck D., RA Elliott S.T., Boheler K.R., Van Eyk J.E., Wollscheid B.; RT "The mouse C2C12 myoblast cell surface N-linked glycoproteome: RT identification, glycosite occupancy, and membrane orientation."; RL Mol. Cell. Proteomics 8:2555-2569(2009). RN [21] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-408 AND ASN-436. RX PubMed=19349973; DOI=10.1038/nbt.1532; RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., RA Schiess R., Aebersold R., Watts J.D.; RT "Mass-spectrometric identification and relative quantification of N-linked RT cell surface glycoproteins."; RL Nat. Biotechnol. 27:378-386(2009). RN [22] RP UBIQUITINATION, AND INTERACTION WITH ANKS1A. RX PubMed=20100865; DOI=10.1128/mcb.01605-09; RA Kim J., Lee H., Kim Y., Yoo S., Park E., Park S.; RT "The SAM domains of Anks family proteins are critically involved in RT modulating the degradation of EphA receptors."; RL Mol. Cell. Biol. 30:1582-1592(2010). RN [23] RP DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY. RX PubMed=27446912; DOI=10.3389/fcell.2016.00058; RA Alonso-Martin S., Rochat A., Mademtzoglou D., Morais J., de Reynies A., RA Aurade F., Chang T.H., Zammit P.S., Relaix F.; RT "Gene expression profiling of muscle stem cells identifies novel regulators RT of postnatal myogenesis."; RL Front. Cell Dev. Biol. 4:58-58(2016). RN [24] {ECO:0007744|PDB:5ZRX} RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 900-977 IN COMPLEX WITH INPPL1, RP FUNCTION, AND MUTAGENESIS OF LYS-918; LYS-957 AND ARG-958. RX PubMed=29749928; DOI=10.7554/elife.35677; RA Wang Y., Shang Y., Li J., Chen W., Li G., Wan J., Liu W., Zhang M.; RT "Specific Eph receptor-cytoplasmic effector signaling mediated by SAM-SAM RT domain interactions."; RL Elife 7:0-0(2018). CC -!- FUNCTION: Receptor tyrosine kinase which binds promiscuously membrane- CC bound ephrin-A family ligands residing on adjacent cells, leading to CC contact-dependent bidirectional signaling into neighboring cells. The CC signaling pathway downstream of the receptor is referred to as forward CC signaling while the signaling pathway downstream of the ephrin ligand CC is referred to as reverse signaling. Activated by the ligand ephrin- CC A1/EFNA1 regulates migration, integrin-mediated adhesion, proliferation CC and differentiation of cells (PubMed:29749928). Regulates cell adhesion CC and differentiation through DSG1/desmoglein-1 and inhibition of the CC ERK1/ERK2 signaling pathway. May also participate in UV radiation- CC induced apoptosis and have a ligand-independent stimulatory effect on CC chemotactic cell migration. During development, may function in CC distinctive aspects of pattern formation and subsequently in CC development of several fetal tissues. Involved for instance in CC angiogenesis, in early hindbrain development and epithelial CC proliferation and branching morphogenesis during mammary gland CC development. Engaged by the ligand ephrin-A5/EFNA5 may regulate lens CC fiber cells shape and interactions and be important for lens CC transparency development and maintenance. With ephrin-A2/EFNA2 may play CC a role in bone remodeling through regulation of osteoclastogenesis and CC osteoblastogenesis. {ECO:0000269|PubMed:15054110, CC ECO:0000269|PubMed:16782872, ECO:0000269|PubMed:16849550, CC ECO:0000269|PubMed:18387945, ECO:0000269|PubMed:18948590, CC ECO:0000269|PubMed:19299512, ECO:0000269|PubMed:19321667, CC ECO:0000269|PubMed:29749928}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl- CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1; CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028, CC ECO:0000269|PubMed:8183555}; CC -!- SUBUNIT: Homodimer. Interacts with INPPL1; regulates activated EPHA2 CC endocytosis and degradation (PubMed:29749928). Interacts (inactivated CC form) with PTK2/FAK1 and interacts (EFNA1 ligand-activated form) with CC PTPN11; regulates integrin-mediated adhesion. Interacts with ARHGEF16, CC DOCK4 and ELMO2; mediates ligand-independent activation of RAC1 which CC stimulates cell migration. Interacts with CLDN4; phosphorylates CLDN4 CC and may regulate tight junctions. Interacts with ACP1. Interacts with CC CEMIP. Interacts with NCK1; may regulate EPHA2 activity in cell CC migration and adhesion. Interacts with SLA. Interacts (phosphorylated CC form) with VAV2, VAV3 and PI3-kinase p85 subunit (PIK3R1, PIK3R2 or CC PIK3R3); critical for the EFNA1-induced activation of RAC1 which CC stimulates cell migration. Interacts with ANKS1A. Interacts with TIMD4 CC (By similarity). {ECO:0000250|UniProtKB:P29317, CC ECO:0000269|PubMed:16782872, ECO:0000269|PubMed:18387945, CC ECO:0000269|PubMed:20100865, ECO:0000269|PubMed:29749928, CC ECO:0000269|PubMed:7543898}. CC -!- INTERACTION: CC Q03145; Q03137: Epha4; NbExp=3; IntAct=EBI-529701, EBI-1539152; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P29317}; CC Single-pass type I membrane protein {ECO:0000255}. Cell projection, CC ruffle membrane {ECO:0000250|UniProtKB:P29317}; Single-pass type I CC membrane protein {ECO:0000255}. Cell projection, lamellipodium membrane CC {ECO:0000250|UniProtKB:P29317}; Single-pass type I membrane protein CC {ECO:0000255}. Cell junction, focal adhesion CC {ECO:0000250|UniProtKB:P29317}. Note=Present at regions of cell-cell CC contacts but also at the leading edge of migrating cells. Relocates CC from the plasma membrane to the cytoplasmic and perinuclear regions in CC cancer cells. {ECO:0000250|UniProtKB:P29317}. CC -!- TISSUE SPECIFICITY: Expressed in the lung, intestine and liver CC (PubMed:11287184). Expressed in myogenic progenitor cells CC (PubMed:27446912). {ECO:0000269|PubMed:11287184, CC ECO:0000269|PubMed:27446912}. CC -!- DEVELOPMENTAL STAGE: First detected in gastrulation stage embryos (6.5- CC 7.5 dpc) in ectodermal cells adjacent to the distal region of the CC primitive streak. By the neural plate stage (approximately 7.5 dpc), CC EPHA2 expression becomes restricted to the extreme distal end or node CC of the primitive streak. After the beginning of somitogenesis CC (approximately 8.0 dpc), expression persists in the node as this CC structure regresses toward the caudal end of the embryo. In addition, CC beginning at the mid head fold stage (approximately 7.75 dpc), we CC observe that EPHA2 exhibits a dynamic and spatially restricted CC expression pattern in the prospective hindbrain region. EPHA2 CC transcripts are initially detected in a 5-cell wide strip of mesodermal CC cells underlying prospective rhombomere 4 (R4). Subsequently at the CC beginning of somitogenesis, expression is observed in prospective R4. CC At the 4-8-somite stage, EPHA2 transcripts are observed in R4, CC mesenchymal cells underlying R4, and surface ectoderm in the vicinity CC of the developing second branchial arch. By the 10-somite stage, CC expression in these cells is down-regulated. Additionally, at the 5-8- CC somite stage, EPHA2 transcripts are detected initially in the lateral CC mesenchyme immediately underlying the surface ectoderm adjacent to R5 CC and R6, and subsequently in surface ectoderm overlying the developing CC third branchial arch. In myogenic progenitor cells, expressed during CC the acquisition of muscle stem cell properties, from 18.5 dpc to CC adulthood (PubMed:27446912). {ECO:0000269|PubMed:11287184, CC ECO:0000269|PubMed:27446912, ECO:0000269|PubMed:7918100, CC ECO:0000269|PubMed:7947319, ECO:0000269|PubMed:8183555}. CC -!- PTM: Autophosphorylates. Phosphorylated at Ser-898 by PKB; serum- CC induced phosphorylation which targets EPHA2 to the cell leading edge CC and stimulates cell migration. Phosphorylation by PKB is inhibited by CC EFNA1-activated EPHA2 which regulates PKB activity via a reciprocal CC regulatory loop. Phosphorylated on tyrosine upon binding and activation CC by EFNA1. Phosphorylated residues Tyr-589 and Tyr-595 are required for CC binding VAV2 and VAV3 while phosphorylated residues Tyr-736 and Tyr-931 CC are required for binding PI3-kinase p85 subunit (PIK3R1, PIK3R2 or CC PIK3R3). These phosphorylated residues are critical for recruitment of CC VAV2 and VAV3 and PI3-kinase p85 subunit which transduce downstream CC signaling to activate RAC1 GTPase and cell migration. Dephosphorylation CC of Tyr-931 by PTPRF prevents the interaction of EPHA2 with NCK1. CC Phosphorylated at Ser-898 in response to TNF by RPS6KA1 and RPS6KA3; CC RPS6KA-EPHA2 signaling pathway controls cell migration. Phosphorylated CC at Ser-898 by PKA; blocks cell retraction induced by EPHA2 kinase CC activity. Dephosphorylated by ACP1. {ECO:0000250|UniProtKB:P29317, CC ECO:0000269|PubMed:18387945}. CC -!- PTM: Ubiquitinated by CHIP/STUB1. Ubiquitination is regulated by the CC HSP90 chaperone and regulates the receptor stability and activity CC through proteasomal degradation. ANKS1A prevents ubiquitination and CC degradation. {ECO:0000269|PubMed:20100865}. CC -!- DISRUPTION PHENOTYPE: Mice are viable, fertile but exhibit aberrant CC development of tail vertebra and susceptibility to carcinogenesis. CC {ECO:0000269|PubMed:11287184, ECO:0000269|PubMed:15054110, CC ECO:0000269|PubMed:16849550}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. Ephrin receptor subfamily. {ECO:0000255|PROSITE- CC ProRule:PRU00159}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X78339; CAA55135.1; -; mRNA. DR EMBL; U07634; AAA82113.1; -; mRNA. DR EMBL; AK137704; BAE23470.1; -; mRNA. DR EMBL; AK144202; BAE25765.1; -; mRNA. DR EMBL; AL607087; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL670285; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH466615; EDL13361.1; -; Genomic_DNA. DR EMBL; BC140960; AAI40961.1; -; mRNA. DR EMBL; X76010; CAA53597.1; -; mRNA. DR EMBL; X57243; CAA40519.1; -; mRNA. DR CCDS; CCDS18869.1; -. DR PIR; I48759; I48759. DR PIR; I48974; I48974. DR PIR; S49004; S49004. DR RefSeq; NP_034269.2; NM_010139.3. DR PDB; 5ZRX; X-ray; 1.50 A; A/B=900-977. DR PDBsum; 5ZRX; -. DR AlphaFoldDB; Q03145; -. DR SMR; Q03145; -. DR BioGRID; 199469; 3. DR CORUM; Q03145; -. DR DIP; DIP-829N; -. DR IntAct; Q03145; 4. DR MINT; Q03145; -. DR STRING; 10090.ENSMUSP00000006614; -. DR BindingDB; Q03145; -. DR ChEMBL; CHEMBL4105859; -. DR GuidetoPHARMACOLOGY; 1822; -. DR GlyCosmos; Q03145; 2 sites, No reported glycans. DR GlyGen; Q03145; 2 sites. DR iPTMnet; Q03145; -. DR PhosphoSitePlus; Q03145; -. DR EPD; Q03145; -. DR MaxQB; Q03145; -. DR PaxDb; 10090-ENSMUSP00000006614; -. DR PeptideAtlas; Q03145; -. DR ProteomicsDB; 275752; -. DR Pumba; Q03145; -. DR ABCD; Q03145; 35 sequenced antibodies. DR Antibodypedia; 4183; 1532 antibodies from 47 providers. DR DNASU; 13836; -. DR Ensembl; ENSMUST00000006614.3; ENSMUSP00000006614.3; ENSMUSG00000006445.4. DR GeneID; 13836; -. DR KEGG; mmu:13836; -. DR UCSC; uc008voc.2; mouse. DR AGR; MGI:95278; -. DR CTD; 1969; -. DR MGI; MGI:95278; Epha2. DR VEuPathDB; HostDB:ENSMUSG00000006445; -. DR eggNOG; KOG0196; Eukaryota. DR GeneTree; ENSGT00940000160786; -. DR HOGENOM; CLU_000288_141_0_1; -. DR InParanoid; Q03145; -. DR OMA; CLECPVH; -. DR OrthoDB; 1614410at2759; -. DR PhylomeDB; Q03145; -. DR TreeFam; TF315608; -. DR BRENDA; 2.7.10.1; 3474. DR Reactome; R-MMU-2682334; EPH-Ephrin signaling. DR Reactome; R-MMU-3928663; EPHA-mediated growth cone collapse. DR Reactome; R-MMU-3928665; EPH-ephrin mediated repulsion of cells. DR Reactome; R-MMU-9013149; RAC1 GTPase cycle. DR Reactome; R-MMU-9013404; RAC2 GTPase cycle. DR Reactome; R-MMU-9013408; RHOG GTPase cycle. DR Reactome; R-MMU-9013420; RHOU GTPase cycle. DR Reactome; R-MMU-9013423; RAC3 GTPase cycle. DR Reactome; R-MMU-9013424; RHOV GTPase cycle. DR Reactome; R-MMU-9696264; RND3 GTPase cycle. DR Reactome; R-MMU-9696270; RND2 GTPase cycle. DR Reactome; R-MMU-9696273; RND1 GTPase cycle. DR BioGRID-ORCS; 13836; 1 hit in 80 CRISPR screens. DR ChiTaRS; Epha2; mouse. DR PRO; PR:Q03145; -. DR Proteomes; UP000000589; Chromosome 4. DR RNAct; Q03145; Protein. DR Bgee; ENSMUSG00000006445; Expressed in neural plate and 154 other cell types or tissues. DR GO; GO:0009986; C:cell surface; IDA:MGI. DR GO; GO:0005925; C:focal adhesion; ISS:UniProtKB. DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB. DR GO; GO:0031258; C:lamellipodium membrane; IEA:UniProtKB-SubCell. DR GO; GO:0031256; C:leading edge membrane; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0043235; C:receptor complex; IBA:GO_Central. DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell. DR GO; GO:0070160; C:tight junction; ISO:MGI. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0005003; F:ephrin receptor activity; IEA:InterPro. DR GO; GO:0019838; F:growth factor binding; ISO:MGI. DR GO; GO:0140677; F:molecular function activator activity; ISO:MGI. DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; ISS:UniProtKB. DR GO; GO:0090630; P:activation of GTPase activity; ISS:UniProtKB. DR GO; GO:0048320; P:axial mesoderm formation; IMP:MGI. DR GO; GO:0001568; P:blood vessel development; IMP:MGI. DR GO; GO:0002043; P:blood vessel endothelial cell proliferation involved in sprouting angiogenesis; IMP:MGI. DR GO; GO:0048514; P:blood vessel morphogenesis; IMP:MGI. DR GO; GO:0046849; P:bone remodeling; IMP:UniProtKB. DR GO; GO:0060444; P:branching involved in mammary gland duct morphogenesis; IMP:UniProtKB. DR GO; GO:0046058; P:cAMP metabolic process; ISS:UniProtKB. DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW. DR GO; GO:0060326; P:cell chemotaxis; ISS:UniProtKB. DR GO; GO:0016477; P:cell migration; ISS:UniProtKB. DR GO; GO:0048870; P:cell motility; ISS:UniProtKB. DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IMP:MGI. DR GO; GO:0048013; P:ephrin receptor signaling pathway; IDA:MGI. DR GO; GO:0006954; P:inflammatory response; IMP:MGI. DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; ISO:MGI. DR GO; GO:0030216; P:keratinocyte differentiation; ISO:MGI. DR GO; GO:0070309; P:lens fiber cell morphogenesis; IDA:UniProtKB. DR GO; GO:0033598; P:mammary gland epithelial cell proliferation; IMP:UniProtKB. DR GO; GO:0016525; P:negative regulation of angiogenesis; IMP:MGI. DR GO; GO:0032682; P:negative regulation of chemokine production; IMP:MGI. DR GO; GO:0001818; P:negative regulation of cytokine production; IMP:MGI. DR GO; GO:1901491; P:negative regulation of lymphangiogenesis; IMP:MGI. DR GO; GO:0051898; P:negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISS:UniProtKB. DR GO; GO:0021915; P:neural tube development; IMP:MGI. DR GO; GO:0030182; P:neuron differentiation; IDA:MGI. DR GO; GO:0060035; P:notochord cell development; IMP:MGI. DR GO; GO:0014028; P:notochord formation; IMP:MGI. DR GO; GO:0048570; P:notochord morphogenesis; IMP:MGI. DR GO; GO:0001649; P:osteoblast differentiation; IMP:UniProtKB. DR GO; GO:0030316; P:osteoclast differentiation; IDA:UniProtKB. DR GO; GO:1904238; P:pericyte cell differentiation; IMP:MGI. DR GO; GO:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISS:UniProtKB. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:1903348; P:positive regulation of bicellular tight junction assembly; ISO:MGI. DR GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI. DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; ISS:UniProtKB. DR GO; GO:0036342; P:post-anal tail morphogenesis; IMP:MGI. DR GO; GO:0072659; P:protein localization to plasma membrane; ISO:MGI. DR GO; GO:0045765; P:regulation of angiogenesis; IDA:UniProtKB. DR GO; GO:0043535; P:regulation of blood vessel endothelial cell migration; IDA:UniProtKB. DR GO; GO:0033628; P:regulation of cell adhesion mediated by integrin; ISS:UniProtKB. DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; ISO:MGI. DR GO; GO:0010591; P:regulation of lamellipodium assembly; ISS:UniProtKB. DR GO; GO:0070848; P:response to growth factor; ISS:UniProtKB. DR GO; GO:0001501; P:skeletal system development; IMP:MGI. DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central. DR GO; GO:0001570; P:vasculogenesis; IMP:MGI. DR CDD; cd10480; EphR_LBD_A2; 1. DR CDD; cd00063; FN3; 2. DR CDD; cd09543; SAM_EPH-A2; 1. DR Gene3D; 2.60.40.1770; ephrin a2 ectodomain; 1. DR Gene3D; 2.60.120.260; Galactose-binding domain-like; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 2. DR Gene3D; 1.20.5.510; Single helix bin; 1. DR Gene3D; 1.10.150.50; Transcription Factor, Ets-1; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR Gene3D; 2.10.50.10; Tumor Necrosis Factor Receptor, subunit A, domain 2; 1. DR InterPro; IPR027936; Eph_TM. DR InterPro; IPR034263; EphA2_rcpt_lig-bd. DR InterPro; IPR001090; Ephrin_rcpt_lig-bd_dom. DR InterPro; IPR003961; FN3_dom. DR InterPro; IPR036116; FN3_sf. DR InterPro; IPR008979; Galactose-bd-like_sf. DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR001660; SAM. DR InterPro; IPR013761; SAM/pointed_sf. DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom. DR InterPro; IPR008266; Tyr_kinase_AS. DR InterPro; IPR020635; Tyr_kinase_cat_dom. DR InterPro; IPR016257; Tyr_kinase_ephrin_rcpt. DR InterPro; IPR001426; Tyr_kinase_rcpt_V_CS. DR PANTHER; PTHR46877; EPH RECEPTOR A5; 1. DR PANTHER; PTHR46877:SF12; EPHRIN TYPE-A RECEPTOR 3; 1. DR Pfam; PF14575; EphA2_TM; 1. DR Pfam; PF01404; Ephrin_lbd; 1. DR Pfam; PF00041; fn3; 2. DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1. DR Pfam; PF00536; SAM_1; 1. DR PIRSF; PIRSF000666; TyrPK_ephrin_receptor; 1. DR PRINTS; PR00109; TYRKINASE. DR SMART; SM00615; EPH_lbd; 1. DR SMART; SM01411; Ephrin_rec_like; 1. DR SMART; SM00060; FN3; 2. DR SMART; SM00454; SAM; 1. DR SMART; SM00219; TyrKc; 1. DR SUPFAM; SSF49265; Fibronectin type III; 1. DR SUPFAM; SSF49785; Galactose-binding domain-like; 1. DR SUPFAM; SSF57184; Growth factor receptor domain; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF47769; SAM/Pointed domain; 1. DR PROSITE; PS01186; EGF_2; 1. DR PROSITE; PS51550; EPH_LBD; 1. DR PROSITE; PS50853; FN3; 2. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. DR PROSITE; PS00790; RECEPTOR_TYR_KIN_V_1; 1. DR PROSITE; PS00791; RECEPTOR_TYR_KIN_V_2; 1. DR PROSITE; PS50105; SAM_DOMAIN; 1. DR Genevisible; Q03145; MM. PE 1: Evidence at protein level; KW 3D-structure; Angiogenesis; Apoptosis; ATP-binding; Cell adhesion; KW Cell junction; Cell membrane; Cell projection; Differentiation; KW Disulfide bond; Glycoprotein; Kinase; Membrane; Nucleotide-binding; KW Phosphoprotein; Receptor; Reference proteome; Repeat; Signal; Transferase; KW Transmembrane; Transmembrane helix; Tyrosine-protein kinase; KW Ubl conjugation. FT SIGNAL 1..25 FT /evidence="ECO:0000255" FT CHAIN 26..977 FT /note="Ephrin type-A receptor 2" FT /id="PRO_0000016801" FT TOPO_DOM 26..538 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 539..559 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 560..977 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 27..205 FT /note="Eph LBD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00883" FT DOMAIN 329..433 FT /note="Fibronectin type-III 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 439..530 FT /note="Fibronectin type-III 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 614..876 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT DOMAIN 905..969 FT /note="SAM" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184" FT REGION 1..205 FT /note="Mediates interaction with CLDN4" FT /evidence="ECO:0000250" FT REGION 607..907 FT /note="Mediates interaction with ARHGEF16" FT /evidence="ECO:0000250" FT REGION 887..977 FT /note="Negatively regulates interaction with ARHGEF16" FT /evidence="ECO:0000250" FT MOTIF 975..977 FT /note="PDZ-binding" FT /evidence="ECO:0000255" FT ACT_SITE 740 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10028" FT BINDING 620..628 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 647 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 571 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P29317" FT MOD_RES 580 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P29317" FT MOD_RES 589 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000250" FT MOD_RES 595 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:18387945, FT ECO:0007744|PubMed:19131326" FT MOD_RES 629 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P29317" FT MOD_RES 648 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P29317" FT MOD_RES 736 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:18387945" FT MOD_RES 773 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:18387945, FT ECO:0007744|PubMed:19131326" FT MOD_RES 870 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P29317" FT MOD_RES 893 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P29317" FT MOD_RES 898 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P29317" FT MOD_RES 902 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P29317" FT MOD_RES 922 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000255" FT MOD_RES 931 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P29317" FT CARBOHYD 408 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19349973, FT ECO:0000269|PubMed:19656770" FT CARBOHYD 436 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19349973, FT ECO:0000269|PubMed:19656770" FT DISULFID 69..187 FT /evidence="ECO:0000250" FT DISULFID 104..114 FT /evidence="ECO:0000250" FT MUTAGEN 589 FT /note="Y->E: No significant effect on kinase activity and FT loss of binding to VAV2 and VAV3. Inhibits EFNA1-induced FT vascular assembly and RAC1 activation in endothelial cells, FT no significant effect on kinase activity, significant FT reduction in phosphorylation and binding to VAV3; when FT associated with E-595." FT /evidence="ECO:0000269|PubMed:16782872, FT ECO:0000269|PubMed:18387945" FT MUTAGEN 589 FT /note="Y->F: Inhibits EFNA1-induced vascular assembly and FT kinase activity." FT /evidence="ECO:0000269|PubMed:16782872, FT ECO:0000269|PubMed:18387945" FT MUTAGEN 595 FT /note="Y->E: No significant effect on kinase activity and FT loss of binding to VAV2 and VAV3. Inhibits EFNA1-induced FT vascular assembly and RAC1 activation in endothelial cells, FT no significant effect on kinase activity, significant FT reduction in phosphorylation and binding to VAV3; when FT associated with E-589." FT /evidence="ECO:0000269|PubMed:16782872, FT ECO:0000269|PubMed:18387945" FT MUTAGEN 595 FT /note="Y->F: Inhibits EFNA1-induced vascular assembly and FT abolishes kinase activity." FT /evidence="ECO:0000269|PubMed:16782872, FT ECO:0000269|PubMed:18387945" FT MUTAGEN 736 FT /note="Y->F: Inhibits EFNA1-induced vascular assembly and FT RAC1 activation in endothelial cells. No significant effect FT on kinase activity. Loss of binding to PI3-kinase p85 FT subunit." FT /evidence="ECO:0000269|PubMed:18387945" FT MUTAGEN 740 FT /note="D->N: Loss of kinase activity and binding to VAV3." FT /evidence="ECO:0000269|PubMed:16782872" FT MUTAGEN 773 FT /note="Y->F: No significant effect on kinase activity. FT Significant reduction in phosphorylation." FT /evidence="ECO:0000269|PubMed:18387945" FT MUTAGEN 918 FT /note="K->A: Strongly reduced binding affinity for INPPL1 FT SAM domain." FT /evidence="ECO:0000269|PubMed:29749928" FT MUTAGEN 931 FT /note="Y->F: Inhibits EFNA1-induced vascular assembly and FT RAC1 activation in endothelial cells. Inhibits kinase FT activity. Loss of binding to VAV3 and PI3-kinase p85 FT subunit." FT /evidence="ECO:0000269|PubMed:18387945" FT MUTAGEN 957 FT /note="K->A: Strongly reduced binding affinity for INPPL1 FT SAM domain." FT /evidence="ECO:0000269|PubMed:29749928" FT MUTAGEN 958 FT /note="R->C,K: Abolishes interaction with INPPL1 SAM FT domain." FT /evidence="ECO:0000269|PubMed:29749928" FT CONFLICT 5 FT /note="A -> T (in Ref. 1; CAA55135)" FT /evidence="ECO:0000305" FT CONFLICT 112..113 FT /note="SS -> HA (in Ref. 2; AAA82113)" FT /evidence="ECO:0000305" FT CONFLICT 189 FT /note="A -> R (in Ref. 2; AAA82113)" FT /evidence="ECO:0000305" FT CONFLICT 209 FT /note="R -> C (in Ref. 2; AAA82113)" FT /evidence="ECO:0000305" FT CONFLICT 244 FT /note="P -> A (in Ref. 2; AAA82113)" FT /evidence="ECO:0000305" FT CONFLICT 258..260 FT /note="IGQ -> SE (in Ref. 2; AAA82113)" FT /evidence="ECO:0000305" FT CONFLICT 291 FT /note="C -> S (in Ref. 2; AAA82113)" FT /evidence="ECO:0000305" FT CONFLICT 339..340 FT /note="IG -> C (in Ref. 2; AAA82113)" FT /evidence="ECO:0000305" FT CONFLICT 371..372 FT /note="WP -> CA (in Ref. 2; AAA82113)" FT /evidence="ECO:0000305" FT CONFLICT 383 FT /note="S -> T (in Ref. 2; AAA82113)" FT /evidence="ECO:0000305" FT CONFLICT 457 FT /note="W -> R (in Ref. 2; AAA82113)" FT /evidence="ECO:0000305" FT CONFLICT 485 FT /note="V -> G (in Ref. 2; AAA82113)" FT /evidence="ECO:0000305" FT CONFLICT 511 FT /note="L -> W (in Ref. 2; AAA82113)" FT /evidence="ECO:0000305" FT CONFLICT 534 FT /note="A -> R (in Ref. 2; AAA82113)" FT /evidence="ECO:0000305" FT CONFLICT 678 FT /note="R -> P (in Ref. 1; CAA55135)" FT /evidence="ECO:0000305" FT CONFLICT 681 FT /note="G -> A (in Ref. 2; AAA82113)" FT /evidence="ECO:0000305" FT CONFLICT 819..820 FT /note="YW -> LL (in Ref. 2; AAA82113)" FT /evidence="ECO:0000305" FT CONFLICT 878 FT /note="A -> R (in Ref. 2; AAA82113)" FT /evidence="ECO:0000305" FT CONFLICT 919..920 FT /note="MQ -> IE (in Ref. 2; AAA82113)" FT /evidence="ECO:0000305" FT HELIX 910..916 FT /evidence="ECO:0007829|PDB:5ZRX" FT HELIX 920..922 FT /evidence="ECO:0007829|PDB:5ZRX" FT HELIX 923..928 FT /evidence="ECO:0007829|PDB:5ZRX" FT HELIX 934..937 FT /evidence="ECO:0007829|PDB:5ZRX" FT HELIX 942..947 FT /evidence="ECO:0007829|PDB:5ZRX" FT HELIX 953..969 FT /evidence="ECO:0007829|PDB:5ZRX" SQ SEQUENCE 977 AA; 108852 MW; 66338CE7EF2DEE02 CRC64; MELRAVGFCL ALLWGCALAA AAAQGKEVVL LDFAAMKGEL GWLTHPYGKG WDLMQNIMDD MPIYMYSVCN VVSGDQDNWL RTNWVYREEA ERIFIELKFT VRDCNSFPGG ASSCKETFNL YYAESDVDYG TNFQKRQFTK IDTIAPDEIT VSSDFEARNV KLNVEERMVG PLTRKGFYLA FQDIGACVAL LSVRVYYKKC PEMLQSLARF PETIAVAVSD TQPLATVAGT CVDHAVVPYG GEGPLMHCTV DGEWLVPIGQ CLCQEGYEKV EDACRACSPG FFKSEASESP CLECPEHTLP STEGATSCQC EEGYFRAPED PLSMSCTRPP SAPNYLTAIG MGAKVELRWT APKDTGGRQD IVYSVTCEQC WPESGECGPC EASVRYSEPP HALTRTSVTV SDLEPHMNYT FAVEARNGVS GLVTSRSFRT ASVSINQTEP PKVRLEDRST TSLSVTWSIP VSQQSRVWKY EVTYRKKGDA NSYNVRRTEG FSVTLDDLAP DTTYLVQVQA LTQEGQGAGS KVHEFQTLST EGSANMAVIG GVAVGVVLLL VLAGVGLFIH RRRRNLRARQ SSEDVRFSKS EQLKPLKTYV DPHTYEDPNQ AVLKFTTEIH PSCVARQKVI GAGEFGEVYK GTLKASSGKK EIPVAIKTLK AGYTEKQRVD FLSEASIMGQ FSHHNIIRLE GVVSKYKPMM IITEYMENGA LDKFLREKDG EFSVLQLVGM LRGIASGMKY LANMNYVHRD LAARNILVNS NLVCKVSDFG LSRVLEDDPE ATYTTSGGKI PIRWTAPEAI SYRKFTSASD VWSYGIVMWE VMTYGERPYW ELSNHEVMKA INDGFRLPTP MDCPSAIYQL MMQCWQQERS RRPKFADIVS ILDKLIRAPD SLKTLADFDP RVSIRLPSTS GSEGVPFRTV SEWLESIKMQ QYTEHFMVAG YTAIEKVVQM SNEDIKRIGV RLPGHQKRIA YSLLGLKDQV NTVGIPI //