EPHA1_HUMAN
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 03-AUG-2022, entry version 225.
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="http://atlasgeneticsoncology.org/Genes/EPHA1ID40461ch7q35.html";
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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; 128.
DR CORUM; P21709; -.
DR DIP; DIP-34886N; -.
DR IntAct; P21709; 119.
DR MINT; P21709; -.
DR STRING; 9606.ENSP00000275815; -.
DR BindingDB; P21709; -.
DR ChEMBL; CHEMBL5810; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; P21709; -.
DR GuidetoPHARMACOLOGY; 1821; -.
DR GlyGen; P21709; 1 site.
DR iPTMnet; P21709; -.
DR PhosphoSitePlus; 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; P21709; -.
DR PeptideAtlas; P21709; -.
DR PRIDE; P21709; -.
DR ProteomicsDB; 53891; -. [P21709-1]
DR Antibodypedia; 32658; 629 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 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; YQRCPEA; -.
DR OrthoDB; 933071at2759; -.
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 1107 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 91 other tissues.
DR Genevisible; P21709; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:ARUK-UCL.
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; IEA:UniProtKB-KW.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IDA:UniProtKB.
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:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
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 GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd10479; EphR_LBD_A1; 1.
DR CDD; cd00063; FN3; 2.
DR Gene3D; 1.10.150.50; -; 1.
DR Gene3D; 2.60.40.10; -; 2.
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 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; SM00060; FN3; 2.
DR SMART; SM00454; SAM; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF47769; SSF47769; 1.
DR SUPFAM; SSF49265; SSF49265; 1.
DR SUPFAM; SSF49785; SSF49785; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57184; SSF57184; 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.
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
