ID EPHA1_HUMAN Reviewed; 976 AA. AC P21709; A1L3V3; B5A966; B5A967; Q15405; DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot. DT 11-JAN-2011, sequence version 4. DT 24-JAN-2024, entry version 233. DE RecName: Full=Ephrin type-A receptor 1; DE Short=hEpha1; DE EC=2.7.10.1; DE AltName: Full=EPH tyrosine kinase; DE AltName: Full=EPH tyrosine kinase 1; DE AltName: Full=Erythropoietin-producing hepatoma receptor; DE AltName: Full=Tyrosine-protein kinase receptor EPH; DE Flags: Precursor; GN Name=EPHA1; Synonyms=EPH, EPHT, EPHT1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS ALA-160 AND VAL-900. RX PubMed=2825356; DOI=10.1126/science.2825356; RA Hirai H., Maru Y., Hagiwara K., Nishida J., Takaku F.; RT "A novel putative tyrosine kinase receptor encoded by the eph gene."; RL Science 238:1717-1720(1987). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ALA-160 AND VAL-900. RX PubMed=10369740; DOI=10.1006/mcpr.1999.0228; RA Owshalimpur D., Kelley M.J.; RT "Genomic structure of the EPHA1 receptor tyrosine kinase gene."; RL Mol. Cell. Probes 13:169-173(1999). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), AND ALTERNATIVE SPLICING. RX PubMed=18593464; DOI=10.1186/ar2447; RA Jin P., Zhang J., Sumariwalla P.F., Ni I., Jorgensen B., Crawford D., RA Phillips S., Feldmann M., Shepard H.M., Paleolog E.M.; RT "Novel splice variants derived from the receptor tyrosine kinase RT superfamily are potential therapeutics for rheumatoid arthritis."; RL Arthritis Res. Ther. 10:R73-R73(2008). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANTS ALA-160 AND RP VAL-900. RX PubMed=12690205; DOI=10.1126/science.1083423; RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D., RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., RA Adams M.D., Tsui L.-C.; RT "Human chromosome 7: DNA sequence and biology."; RL Science 300:767-772(2003). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANTS ALA-160 AND RP VAL-900. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS ALA-160 RP AND VAL-900. 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 [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 286-976 (ISOFORM 1), AND VARIANT VAL-900. RC TISSUE=Placenta; RA Tuzi N.L.; RT "An EGFR/eph chimeric receptor possesses ligand stimulated tyrosine kinase RT activity and promotes cell growth."; RL Submitted (MAY-1994) to the EMBL/GenBank/DDBJ databases. RN [9] RP NOMENCLATURE. RX PubMed=9267020; DOI=10.1016/s0092-8674(00)80500-0; RG Eph nomenclature committee; RT "Unified nomenclature for Eph family receptors and their ligands, the RT ephrins."; RL Cell 90:403-404(1997). RN [10] RP FUNCTION IN MIGRATION OF T-LYMPHOCYTES, AND INTERACTION WITH LCK; RP PTK2B/PYK2 AND PI3-KINASE. RX PubMed=17634955; DOI=10.1002/eji.200737111; RA Hjorthaug H.S., Aasheim H.C.; RT "Ephrin-A1 stimulates migration of CD8+CCR7+ T lymphocytes."; RL Eur. J. Immunol. 37:2326-2336(2007). RN [11] RP FUNCTION IN CELL SPREADING, FUNCTION IN CELL MIGRATION, RP AUTOPHOSPHORYLATION, SUBCELLULAR LOCATION, AND INTERACTION WITH PTK2/FAK1 RP AND ILK. RX PubMed=19118217; DOI=10.1242/jcs.036467; RA Yamazaki T., Masuda J., Omori T., Usui R., Akiyama H., Maru Y.; RT "EphA1 interacts with integrin-linked kinase and regulates cell morphology RT and motility."; RL J. Cell Sci. 122:243-255(2009). RN [12] RP FUNCTION IN ANGIOGENESIS, AND FUNCTION IN CELL PROLIFERATION. RX PubMed=20043122; RA Chen G., Wang Y., Zhou M., Shi H., Yu Z., Zhu Y., Yu F.; RT "EphA1 receptor silencing by small interfering RNA has antiangiogenic and RT antitumor efficacy in hepatocellular carcinoma."; RL Oncol. Rep. 23:563-570(2010). RN [13] RP UBIQUITINATION. RX PubMed=20596523; DOI=10.1371/journal.pone.0011332; RA Del Rincon S.V., Rogers J., Widschwendter M., Sun D., Sieburg H.B., RA Spruck C.; RT "Development and validation of a method for profiling post-translational RT modification activities using protein microarrays."; RL PLoS ONE 5:E11332-E11332(2010). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-906 AND SER-910, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [15] RP STRUCTURE BY NMR OF 536-573, AND HOMODIMERIZATION. RX PubMed=18728013; DOI=10.1074/jbc.m803089200; RA Bocharov E.V., Mayzel M.L., Volynsky P.E., Goncharuk M.V., Ermolyuk Y.S., RA Schulga A.A., Artemenko E.O., Efremov R.G., Arseniev A.S.; RT "Spatial structure and pH-dependent conformational diversity of dimeric RT transmembrane domain of the receptor tyrosine kinase EphA1."; RL J. Biol. Chem. 283:29385-29395(2008). RN [16] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 911-974. RG Structural genomics consortium (SGC); RT "Sam domain of human ephrin type-a receptor 1 (epha1)."; RL Submitted (JUN-2009) to the PDB data bank. RN [17] RP VARIANTS [LARGE SCALE ANALYSIS] ALA-160; CYS-351; GLN-492; GLN-575; RP THR-585; LEU-697; LYS-703; ARG-807 AND VAL-900. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., RA Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). RN [18] RP VARIANT [LARGE SCALE ANALYSIS] VAL-900, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). 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. Binds with a low affinity EFNA3 CC and EFNA4 and with a high affinity to EFNA1 which most probably CC constitutes its cognate/functional ligand. Upon activation by EFNA1 CC induces cell attachment to the extracellular matrix inhibiting cell CC spreading and motility through regulation of ILK and downstream RHOA CC and RAC. Also plays a role in angiogenesis and regulates cell CC proliferation. May play a role in apoptosis. CC {ECO:0000269|PubMed:17634955, ECO:0000269|PubMed:19118217, CC ECO:0000269|PubMed:20043122}. 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 -!- SUBUNIT: Homodimer. Forms a signaling complex with LCK; PTK2B/PYK2 and CC PI3-kinase upon activation by EFNA1; regulates T-lymphocytes migration. CC Interacts (via SAM domain) with ILK (via ANK repeats); stimulated by CC EFNA1 but independent of the kinase activity of EPHA1. Interacts CC (kinase activity-dependent) with PTK2/FAK1. CC {ECO:0000269|PubMed:17634955, ECO:0000269|PubMed:19118217}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:19118217}; CC Single-pass type I membrane protein {ECO:0000269|PubMed:19118217}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P21709-1; Sequence=Displayed; CC Name=2; CC IsoId=P21709-2; Sequence=VSP_056010, VSP_056013; CC Name=3; CC IsoId=P21709-3; Sequence=VSP_056011, VSP_056012; CC -!- TISSUE SPECIFICITY: Overexpressed in several carcinomas. CC -!- PTM: Phosphorylated. Autophosphorylation is stimulated by its ligand CC EFNA1. CC -!- PTM: Ubiquitinated. {ECO:0000269|PubMed:20596523}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. Ephrin receptor subfamily. {ECO:0000255|PROSITE- CC ProRule:PRU00159}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA36747.1; Type=Frameshift; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/40461/EPHA1"; 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; M18391; AAA36747.1; ALT_FRAME; mRNA. DR EMBL; AF101171; AAD43440.1; -; Genomic_DNA. DR EMBL; AF101165; AAD43440.1; JOINED; Genomic_DNA. DR EMBL; AF101166; AAD43440.1; JOINED; Genomic_DNA. DR EMBL; AF101167; AAD43440.1; JOINED; Genomic_DNA. DR EMBL; AF101168; AAD43440.1; JOINED; Genomic_DNA. DR EMBL; AF101169; AAD43440.1; JOINED; Genomic_DNA. DR EMBL; AF101170; AAD43440.1; JOINED; Genomic_DNA. DR EMBL; EU826604; ACF47640.1; -; mRNA. DR EMBL; EU826605; ACF47641.1; -; mRNA. DR EMBL; AC092214; AAS07458.1; -; Genomic_DNA. DR EMBL; CH236959; EAL23789.1; -; Genomic_DNA. DR EMBL; CH471198; EAW51846.1; -; Genomic_DNA. DR EMBL; CH471198; EAW51847.1; -; Genomic_DNA. DR EMBL; BC130291; AAI30292.1; -; mRNA. DR EMBL; Z27409; CAA81796.1; -; mRNA. DR CCDS; CCDS5884.1; -. [P21709-1] DR PIR; A34076; A34076. DR RefSeq; NP_005223.4; NM_005232.4. [P21709-1] DR PDB; 2K1K; NMR; -; A/B=536-573. DR PDB; 2K1L; NMR; -; A/B=536-573. DR PDB; 3HIL; X-ray; 2.00 A; A/B=911-974. DR PDB; 3KKA; X-ray; 2.40 A; A/B=911-974. DR PDBsum; 2K1K; -. DR PDBsum; 2K1L; -. DR PDBsum; 3HIL; -. DR PDBsum; 3KKA; -. DR AlphaFoldDB; P21709; -. DR BMRB; P21709; -. DR SMR; P21709; -. DR BioGRID; 108355; 251. DR CORUM; P21709; -. DR DIP; DIP-34886N; -. DR IntAct; P21709; 236. DR MINT; P21709; -. DR STRING; 9606.ENSP00000275815; -. DR BindingDB; P21709; -. DR ChEMBL; CHEMBL5810; -. DR DrugBank; DB12010; Fostamatinib. DR DrugCentral; P21709; -. DR GuidetoPHARMACOLOGY; 1821; -. DR GlyCosmos; P21709; 1 site, No reported glycans. DR GlyGen; P21709; 1 site. DR iPTMnet; P21709; -. DR PhosphoSitePlus; P21709; -. DR SwissPalm; P21709; -. DR BioMuta; EPHA1; -. DR DMDM; 317373566; -. DR CPTAC; CPTAC-2782; -. DR EPD; P21709; -. DR jPOST; P21709; -. DR MassIVE; P21709; -. DR MaxQB; P21709; -. DR PaxDb; 9606-ENSP00000275815; -. DR PeptideAtlas; P21709; -. DR ProteomicsDB; 53891; -. [P21709-1] DR ABCD; P21709; 2 sequenced antibodies. DR Antibodypedia; 32658; 706 antibodies from 39 providers. DR DNASU; 2041; -. DR Ensembl; ENST00000275815.4; ENSP00000275815.3; ENSG00000146904.9. [P21709-1] DR Ensembl; ENST00000645847.2; ENSP00000494931.1; ENSG00000284816.2. [P21709-1] DR GeneID; 2041; -. DR KEGG; hsa:2041; -. DR MANE-Select; ENST00000275815.4; ENSP00000275815.3; NM_005232.5; NP_005223.4. DR UCSC; uc003wcz.3; human. [P21709-1] DR AGR; HGNC:3385; -. DR CTD; 2041; -. DR DisGeNET; 2041; -. DR GeneCards; EPHA1; -. DR HGNC; HGNC:3385; EPHA1. DR HPA; ENSG00000146904; Group enriched (esophagus, parathyroid gland). DR MIM; 179610; gene. DR neXtProt; NX_P21709; -. DR OpenTargets; ENSG00000146904; -. DR PharmGKB; PA27817; -. DR VEuPathDB; HostDB:ENSG00000146904; -. DR eggNOG; KOG0196; Eukaryota. DR GeneTree; ENSGT00940000160920; -. DR HOGENOM; CLU_000288_141_0_1; -. DR InParanoid; P21709; -. DR OMA; SCWSHDR; -. DR OrthoDB; 1614410at2759; -. DR PhylomeDB; P21709; -. DR TreeFam; TF315363; -. DR BRENDA; 2.7.10.1; 2681. DR PathwayCommons; P21709; -. DR Reactome; R-HSA-2682334; EPH-Ephrin signaling. DR Reactome; R-HSA-2892247; POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation. DR Reactome; R-HSA-3928663; EPHA-mediated growth cone collapse. DR Reactome; R-HSA-3928665; EPH-ephrin mediated repulsion of cells. DR SignaLink; P21709; -. DR SIGNOR; P21709; -. DR BioGRID-ORCS; 2041; 8 hits in 1187 CRISPR screens. DR ChiTaRS; EPHA1; human. DR EvolutionaryTrace; P21709; -. DR GeneWiki; EPH_receptor_A1; -. DR GenomeRNAi; 2041; -. DR Pharos; P21709; Tchem. DR PRO; PR:P21709; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; P21709; Protein. DR Bgee; ENSG00000146904; Expressed in lower esophagus mucosa and 93 other cell types or tissues. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0043235; C:receptor complex; IBA:GO_Central. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0001968; F:fibronectin binding; IDA:ARUK-UCL. DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB. DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central. DR GO; GO:0005005; F:transmembrane-ephrin receptor activity; IDA:UniProtKB. DR GO; GO:0090630; P:activation of GTPase activity; IDA:UniProtKB. DR GO; GO:0001525; P:angiogenesis; IBA:GO_Central. DR GO; GO:0007166; P:cell surface receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0048013; P:ephrin receptor signaling pathway; IBA:GO_Central. DR GO; GO:0030336; P:negative regulation of cell migration; IDA:UniProtKB. DR GO; GO:0006469; P:negative regulation of protein kinase activity; IDA:UniProtKB. DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB. DR GO; GO:0045766; P:positive regulation of angiogenesis; IMP:UniProtKB. DR GO; GO:0030335; P:positive regulation of cell migration; IMP:UniProtKB. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:UniProtKB. DR GO; GO:0001954; P:positive regulation of cell-matrix adhesion; IDA:UniProtKB. DR GO; GO:0051496; P:positive regulation of stress fiber assembly; ISS:UniProtKB. DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB. DR GO; GO:0043087; P:regulation of GTPase activity; IDA:UniProtKB. DR GO; GO:0034446; P:substrate adhesion-dependent cell spreading; IDA:UniProtKB. DR CDD; cd10479; EphR_LBD_A1; 1. DR CDD; cd00063; FN3; 2. DR CDD; cd09542; SAM_EPH-A1; 1. DR CDD; cd12841; TM_EphA1; 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; 1.10.150.50; 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; IPR034251; EphA1_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; IPR011641; Tyr-kin_ephrin_A/B_rcpt-like. 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; PF07699; Ephrin_rec_like; 1. DR Pfam; PF00041; fn3; 1. 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; P21709; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Angiogenesis; ATP-binding; KW Cell adhesion; Cell membrane; Glycoprotein; Kinase; Membrane; KW Nucleotide-binding; Phosphoprotein; Receptor; Reference proteome; Repeat; KW Signal; Transferase; Transmembrane; Transmembrane helix; KW Tyrosine-protein kinase; Ubl conjugation. FT SIGNAL 1..25 FT /evidence="ECO:0000255" FT CHAIN 26..976 FT /note="Ephrin type-A receptor 1" FT /id="PRO_0000016798" FT TOPO_DOM 26..547 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 548..568 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 569..976 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 27..209 FT /note="Eph LBD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00883" FT DOMAIN 332..445 FT /note="Fibronectin type-III 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 447..538 FT /note="Fibronectin type-III 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 624..884 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT DOMAIN 913..976 FT /note="SAM" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184" FT MOTIF 974..976 FT /note="PDZ-binding" FT /evidence="ECO:0000255" FT ACT_SITE 749 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10028" FT BINDING 630..638 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 656 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 599 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000255" FT MOD_RES 605 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000255" FT MOD_RES 781 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000255" FT MOD_RES 906 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 910 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 930 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000255" FT CARBOHYD 414 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VAR_SEQ 446..490 FT /note="ESLSGLSLRLVKKEPRQLELTWAGSRPRSPGANLTYELHVLNQDE -> DPT FT LSLWTPRVTVRPVSETGEERTEATRADLGGVPAPKPWGEPDL (in isoform 2)" FT /evidence="ECO:0000303|PubMed:18593464" FT /id="VSP_056010" FT VAR_SEQ 446..474 FT /note="ESLSGLSLRLVKKEPRQLELTWAGSRPRS -> GERLRGAGTGTWWRQKGLR FT PQNKLMGRKP (in isoform 3)" FT /evidence="ECO:0000303|PubMed:18593464" FT /id="VSP_056011" FT VAR_SEQ 475..976 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:18593464" FT /id="VSP_056012" FT VAR_SEQ 491..976 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:18593464" FT /id="VSP_056013" FT VARIANT 160 FT /note="V -> A (in dbSNP:rs4725617)" FT /evidence="ECO:0000269|PubMed:10369740, FT ECO:0000269|PubMed:12690205, ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:17344846, ECO:0000269|PubMed:2825356, FT ECO:0000269|Ref.6" FT /id="VAR_028265" FT VARIANT 351 FT /note="R -> C (in dbSNP:rs56006153)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042115" FT VARIANT 492 FT /note="R -> Q (in dbSNP:rs11768549)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_028266" FT VARIANT 575 FT /note="R -> Q (in dbSNP:rs35719334)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042116" FT VARIANT 585 FT /note="A -> T (in dbSNP:rs34178823)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042117" FT VARIANT 697 FT /note="P -> L (in dbSNP:rs34372369)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042118" FT VARIANT 703 FT /note="E -> K (in a breast pleomorphic lobular carcinoma FT sample; somatic mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042119" FT VARIANT 807 FT /note="S -> R (in dbSNP:rs56244405)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042120" FT VARIANT 900 FT /note="M -> V (in dbSNP:rs6967117)" FT /evidence="ECO:0000269|PubMed:10369740, FT ECO:0000269|PubMed:12690205, ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:17344846, ECO:0000269|PubMed:2825356, FT ECO:0000269|Ref.6, ECO:0000269|Ref.8, FT ECO:0007744|PubMed:19369195" FT /id="VAR_028267" FT CONFLICT 398 FT /note="G -> A (in Ref. 2; AAD43440 and 8; CAA81796)" FT /evidence="ECO:0000305" FT STRAND 538..540 FT /evidence="ECO:0007829|PDB:2K1K" FT HELIX 545..570 FT /evidence="ECO:0007829|PDB:2K1K" FT HELIX 918..924 FT /evidence="ECO:0007829|PDB:3HIL" FT HELIX 928..930 FT /evidence="ECO:0007829|PDB:3HIL" FT HELIX 931..936 FT /evidence="ECO:0007829|PDB:3HIL" FT HELIX 942..945 FT /evidence="ECO:0007829|PDB:3HIL" FT HELIX 950..955 FT /evidence="ECO:0007829|PDB:3HIL" FT HELIX 961..973 FT /evidence="ECO:0007829|PDB:3HIL" SQ SEQUENCE 976 AA; 108127 MW; 91EFCA69FFE17826 CRC64; MERRWPLGLG LVLLLCAPLP PGARAKEVTL MDTSKAQGEL GWLLDPPKDG WSEQQQILNG TPLYMYQDCP MQGRRDTDHW LRSNWIYRGE EASRVHVELQ FTVRDCKSFP GGAGPLGCKE TFNLLYMESD QDVGIQLRRP LFQKVTTVAA DQSFTIRDLV SGSVKLNVER CSLGRLTRRG LYLAFHNPGA CVALVSVRVF YQRCPETLNG LAQFPDTLPG PAGLVEVAGT CLPHARASPR PSGAPRMHCS PDGEWLVPVG RCHCEPGYEE GGSGEACVAC PSGSYRMDMD TPHCLTCPQQ STAESEGATI CTCESGHYRA PGEGPQVACT GPPSAPRNLS FSASGTQLSL RWEPPADTGG RQDVRYSVRC SQCQGTAQDG GPCQPCGVGV HFSPGARGLT TPAVHVNGLE PYANYTFNVE AQNGVSGLGS SGHASTSVSI SMGHAESLSG LSLRLVKKEP RQLELTWAGS RPRSPGANLT YELHVLNQDE ERYQMVLEPR VLLTELQPDT TYIVRVRMLT PLGPGPFSPD HEFRTSPPVS RGLTGGEIVA VIFGLLLGAA LLLGILVFRS RRAQRQRQQR QRDRATDVDR EDKLWLKPYV DLQAYEDPAQ GALDFTRELD PAWLMVDTVI GEGEFGEVYR GTLRLPSQDC KTVAIKTLKD TSPGGQWWNF LREATIMGQF SHPHILHLEG VVTKRKPIMI ITEFMENGAL DAFLREREDQ LVPGQLVAML QGIASGMNYL SNHNYVHRDL AARNILVNQN LCCKVSDFGL TRLLDDFDGT YETQGGKIPI RWTAPEAIAH RIFTTASDVW SFGIVMWEVL SFGDKPYGEM SNQEVMKSIE DGYRLPPPVD CPAPLYELMK NCWAYDRARR PHFQKLQAHL EQLLANPHSL RTIANFDPRM TLRLPSLSGS DGIPYRTVSE WLESIRMKRY ILHFHSAGLD TMECVLELTA EDLTQMGITL PGHQKRILCS IQGFKD //