ID EPHA3_HUMAN Reviewed; 983 AA. AC P29320; Q9H2V3; Q9H2V4; DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot. DT 17-OCT-2006, sequence version 2. DT 02-SEP-2026, entry version 242. DE RecName: Full=Ephrin type-A receptor 3; DE EC=2.7.10.1; DE AltName: Full=EPH-like kinase 4; DE Short=EK4; DE Short=hEK4; DE AltName: Full=HEK; DE Short=Human embryo kinase; DE AltName: Full=Tyrosine-protein kinase TYRO4; DE AltName: Full=Tyrosine-protein kinase receptor ETK1; DE Short=Eph-like tyrosine kinase 1; DE Flags: Precursor; GN Name=EPHA3; Synonyms=ETK, ETK1, HEK, TYRO4; 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 VARIANT ARG-924. RX PubMed=1311845; DOI=10.1073/pnas.89.5.1611; RA Wicks I.P., Wilkinson D., Salvaris E., Boyd A.W.; RT "Molecular cloning of HEK, the gene encoding a receptor tyrosine kinase RT expressed by human lymphoid tumor cell lines."; RL Proc. Natl. Acad. Sci. U.S.A. 89:1611-1615(1992). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Melanoma; RX PubMed=10987298; RA Chiari R., Hames G., Stroobant V., Texier C., Maillere B., Boon T., RA Coulie P.G.; RT "Identification of a tumor-specific shared antigen derived from an Eph RT receptor and presented to CD4 T cells on HLA class II molecules."; RL Cancer Res. 60:4855-4863(2000). RN [3] RP PROTEIN SEQUENCE OF 21-29 AND 840-860, AND CHARACTERIZATION. RX PubMed=1737782; DOI=10.1016/s0021-9258(19)50725-6; RA Boyd A.W., Ward L.D., Wicks I.P., Simpson R.J., Salvaris E., Wilks A., RA Welch K., Loudovaris M., Rockman S., Busmanis I.; RT "Isolation and characterization of a novel receptor-type protein tyrosine RT kinase (hek) from a human pre-B cell line."; RL J. Biol. Chem. 267:3262-3267(1992). RN [4] 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 [5] RP FUNCTION IN CELL-CELL ADHESION, EFNA5-BINDING, SUBCELLULAR LOCATION RP (ISOFORM 1), INTERACTION WITH CRK, AND PHOSPHORYLATION AT TYR-596; TYR-602 RP AND TYR-779. RX PubMed=11870224; DOI=10.1242/jcs.115.5.1059; RA Lawrenson I.D., Wimmer-Kleikamp S.H., Lock P., Schoenwaelder S.M., Down M., RA Boyd A.W., Alewood P.F., Lackmann M.; RT "Ephrin-A5 induces rounding, blebbing and de-adhesion of EphA3-expressing RT 293T and melanoma cells by CrkII and Rho-mediated signalling."; RL J. Cell Sci. 115:1059-1072(2002). RN [6] RP FUNCTION. RX PubMed=12794130; DOI=10.4049/jimmunol.170.12.6024; RA Sharfe N., Freywald A., Toro A., Roifman C.M.; RT "Ephrin-A1 induces c-Cbl phosphorylation and EphA receptor down-regulation RT in T cells."; RL J. Immunol. 170:6024-6032(2003). RN [7] RP INVOLVEMENT IN CRC. RX PubMed=12738854; DOI=10.1126/science.1082596; RA Bardelli A., Parsons D.W., Silliman N., Ptak J., Szabo S., Saha S., RA Markowitz S., Willson J.K., Parmigiani G., Kinzler K.W., Vogelstein B., RA Velculescu V.E.; RT "Mutational analysis of the tyrosine kinome in colorectal cancers."; RL Science 300:949-949(2003). RN [8] RP EPHRIN LIGAND-BINDING, OLIGOMERIZATION, MUTAGENESIS OF VAL-133 AND PHE-152, RP AND INTERACTION WITH CRK. RX PubMed=14660665; DOI=10.1074/jbc.m309326200; RA Smith F.M., Vearing C., Lackmann M., Treutlein H., Himanen J., Chen K., RA Saul A., Nikolov D., Boyd A.W.; RT "Dissecting the EphA3/Ephrin-A5 interactions using a novel functional RT mutagenesis screen."; RL J. Biol. Chem. 279:9522-9531(2004). RN [9] RP IDENTIFICATION IN A COMPLEX WITH ADAM10 AND EFNA5. RX PubMed=16239146; DOI=10.1016/j.cell.2005.08.014; RA Janes P.W., Saha N., Barton W.A., Kolev M.V., Wimmer-Kleikamp S.H., RA Nievergall E., Blobel C.P., Himanen J.P., Lackmann M., Nikolov D.B.; RT "Adam meets Eph: an ADAM substrate recognition module acts as a molecular RT switch for ephrin cleavage in trans."; RL Cell 123:291-304(2005). RN [10] RP EFNA5 LIGAND-BINDING. RX PubMed=15901737; DOI=10.1074/jbc.m504972200; RA Day B., To C., Himanen J.P., Smith F.M., Nikolov D.B., Boyd A.W., RA Lackmann M.; RT "Three distinct molecular surfaces in ephrin-A5 are essential for a RT functional interaction with EphA3."; RL J. Biol. Chem. 280:26526-26532(2005). RN [11] RP INTERACTION WITH PTPN1, PHOSPHORYLATION, DEPHOSPHORYLATION BY PTPN1, AND RP SUBCELLULAR LOCATION (ISOFORM 2). RX PubMed=21135139; DOI=10.1083/jcb.201005035; RA Nievergall E., Janes P.W., Stegmayer C., Vail M.E., Haj F.G., Teng S.W., RA Neel B.G., Bastiaens P.I., Lackmann M.; RT "PTP1B regulates Eph receptor function and trafficking."; RL J. Cell Biol. 191:1189-1203(2010). RN [12] RP X-RAY CRYSTALLOGRAPHY (1.07 ANGSTROMS) OF 577-947 IN COMPLEX WITH ATP RP ANALOG, IDENTIFICATION BY MASS SPECTROMETRY, PHOSPHORYLATION AT TYR-596; RP TYR-602 AND TYR-701, AND MUTAGENESIS OF TYR-596; TYR-602; TYR-742 AND RP SER-768. RX PubMed=18547520; DOI=10.1016/j.str.2008.03.008; RA Davis T.L., Walker J.R., Loppnau P., Butler-Cole C., Allali-Hassani A., RA Dhe-Paganon S.; RT "Autoregulation by the juxtamembrane region of the human ephrin receptor RT tyrosine kinase A3 (EphA3)."; RL Structure 16:873-884(2008). RN [13] RP VARIANTS [LARGE SCALE ANALYSIS] LYS-37; SER-85; LEU-621 AND ASN-806. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [14] RP VARIANTS LYS-660 AND MET-933. RX PubMed=16941478; DOI=10.1002/humu.9452; RA Wood L.D., Calhoun E.S., Silliman N., Ptak J., Szabo S., Powell S.M., RA Riggins G.J., Wang T.L., Yan H., Gazdar A., Kern S.E., Pennacchio L., RA Kinzler K.W., Vogelstein B., Velculescu V.E.; RT "Somatic mutations of GUCY2F, EPHA3, and NTRK3 in human cancers."; RL Hum. Mutat. 27:1060-1061(2006). RN [15] RP VARIANTS [LARGE SCALE ANALYSIS] TYR-229; PHE-449; LEU-518; VAL-564; RP SER-568; PRO-590; GLU-766; GLY-777; HIS-914 AND ARG-924. 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 [16] RP VARIANT ASN-207. RX PubMed=20838624; DOI=10.1371/journal.pone.0012653; RA Corbo V., Ritelli R., Barbi S., Funel N., Campani D., Bardelli A., RA Scarpa A.; RT "Mutational profiling of kinases in human tumours of pancreatic origin RT identifies candidate cancer genes in ductal and ampulla of vater RT carcinomas."; RL PLoS ONE 5:E12653-E12653(2010). CC -!- FUNCTION: Receptor tyrosine kinase which binds promiscuously membrane- CC bound ephrin 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 (PubMed:11870224, PubMed:12794130). CC Highly promiscuous for ephrin-A ligands it binds preferentially EFNA5 CC (By similarity). Upon activation by EFNA5 regulates cell-cell adhesion, CC cytoskeletal organization and cell migration (PubMed:11870224). Also CC activated by EFNA1, inhibiting epithelial-to-mesenchymal transition of CC cardiac cells and playing a role in heart development CC (PubMed:12794130). Involved in the retinotectal mapping of neurons. May CC also control the segregation but not the guidance of motor and sensory CC axons during neuromuscular circuit development (By similarity). CC {ECO:0000250|UniProtKB:P29319, ECO:0000269|PubMed:11870224, CC ECO:0000269|PubMed:12794130}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + CC ADP + H(+); Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- CC COMP:20101, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, CC ChEBI:CHEBI:61978, ChEBI:CHEBI:456216; EC=2.7.10.1; CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028}; CC -!- SUBUNIT: Heterotetramer upon binding of the ligand. The heterotetramer CC is composed of an ephrin dimer and a receptor dimer. Oligomerization is CC probably required to induce biological responses. Forms a ternary CC EFNA5-EPHA3-ADAM10 complex mediating EFNA5 extracellular domain CC shedding by ADAM10 which regulates the EFNA5-EPHA3 complex CC internalization and function. Interacts with NCK1 (via SH2 domain); CC mediates EFNA5-EPHA3 signaling (By similarity). Interacts CC (phosphorylated) with PTPN1; dephosphorylates EPHA3 and may regulate CC its trafficking and function. Interacts (phosphorylated) with CRK; CC mediates EFNA5-EPHA3 signaling through RHOA GTPase activation. CC {ECO:0000250, ECO:0000269|PubMed:11870224, ECO:0000269|PubMed:14660665, CC ECO:0000269|PubMed:16239146, ECO:0000269|PubMed:18547520, CC ECO:0000269|PubMed:21135139}. CC -!- INTERACTION: CC P29320; P29317: EPHA2; NbExp=3; IntAct=EBI-1641575, EBI-702104; CC P29320; Q15375: EPHA7; NbExp=4; IntAct=EBI-1641575, EBI-1383428; CC P29320; Q13485: SMAD4; NbExp=6; IntAct=EBI-1641575, EBI-347263; CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane CC {ECO:0000269|PubMed:11870224}; Single-pass type I membrane protein CC {ECO:0000255}. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Secreted CC {ECO:0000269|PubMed:21135139}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P29320-1; Sequence=Displayed; CC Name=2; CC IsoId=P29320-2; Sequence=VSP_002995, VSP_002996; CC -!- TISSUE SPECIFICITY: Widely expressed. Highest level in placenta. CC -!- PTM: Autophosphorylates upon activation by EFNA5. Phosphorylation on CC Tyr-602 mediates interaction with NCK1. Dephosphorylated by PTPN1. CC {ECO:0000269|PubMed:11870224, ECO:0000269|PubMed:18547520, CC ECO:0000269|PubMed:21135139}. CC -!- DISEASE: Colorectal cancer (CRC) [MIM:114500]: A complex disease CC characterized by malignant lesions arising from the inner wall of the CC large intestine (the colon) and the rectum. Genetic alterations are CC often associated with progression from premalignant lesion (adenoma) to CC invasive adenocarcinoma. Risk factors for cancer of the colon and CC rectum include colon polyps, long-standing ulcerative colitis, and CC genetic family history. {ECO:0000269|PubMed:12738854}. Note=The gene CC represented in this entry may be involved in disease pathogenesis. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. Ephrin receptor subfamily. {ECO:0000255|PROSITE- CC ProRule:PRU00159}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/40463/EPHA3"; 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; M83941; AAA58633.1; -; mRNA. DR EMBL; AF213459; AAG43576.1; -; mRNA. DR EMBL; AF213460; AAG43577.1; -; mRNA. DR CCDS; CCDS2922.1; -. [P29320-1] DR CCDS; CCDS46875.1; -. [P29320-2] DR PIR; A38224; A38224. DR RefSeq; NP_005224.2; NM_005233.6. [P29320-1] DR RefSeq; NP_872585.1; NM_182644.3. [P29320-2] DR PDB; 2GSF; X-ray; 1.77 A; A=577-947. DR PDB; 2QO2; X-ray; 1.60 A; A=577-947. DR PDB; 2QO7; X-ray; 1.60 A; A=577-947. DR PDB; 2QO9; X-ray; 1.55 A; A=577-947. DR PDB; 2QOB; X-ray; 1.65 A; A=606-947. DR PDB; 2QOC; X-ray; 1.25 A; A=606-947. DR PDB; 2QOD; X-ray; 1.15 A; A=577-947. DR PDB; 2QOF; X-ray; 1.20 A; A=577-947. DR PDB; 2QOI; X-ray; 1.25 A; A=577-947. DR PDB; 2QOK; X-ray; 1.20 A; A=577-947. DR PDB; 2QOL; X-ray; 1.07 A; A=577-947. DR PDB; 2QON; X-ray; 1.79 A; A=577-947. DR PDB; 2QOO; X-ray; 1.25 A; A=577-947. DR PDB; 2QOQ; X-ray; 1.60 A; A=577-947. DR PDB; 3DZQ; X-ray; 1.75 A; A=606-947. DR PDB; 3FXX; X-ray; 1.70 A; A=577-947. DR PDB; 3FY2; X-ray; 1.80 A; A=577-947. DR PDB; 4G2F; X-ray; 1.70 A; A=606-947. DR PDB; 4GK2; X-ray; 2.19 A; A=606-947. DR PDB; 4GK3; X-ray; 1.90 A; A=606-947. DR PDB; 4GK4; X-ray; 2.10 A; A=606-947. DR PDB; 4L0P; X-ray; 2.26 A; A=29-201. DR PDB; 4P4C; X-ray; 1.60 A; A=606-947. DR PDB; 4P5Q; X-ray; 1.35 A; A=606-947. DR PDB; 4P5Z; X-ray; 2.00 A; A=606-947. DR PDB; 4TWN; X-ray; 1.71 A; A=609-947. DR PDB; 4TWO; X-ray; 2.05 A; A=609-947. DR PDB; 6IN0; X-ray; 1.50 A; A=613-904. DR AlphaFoldDB; P29320; -. DR MDRepo; P29320; -. DR SMR; P29320; -. DR BioGRID; 108356; 117. DR DIP; DIP-40307N; -. DR FunCoup; P29320; 1027. DR IntAct; P29320; 85. DR MINT; P29320; -. DR NDEx; IQUERY-CP-EPHA3; 7 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000337451; -. DR BindingDB; P29320; -. DR ChEMBL; CHEMBL4954; -. DR DrugBank; DB12010; Fostamatinib. DR DrugCentral; P29320; -. DR GuidetoPHARMACOLOGY; 1823; -. DR GlyCosmos; P29320; 5 sites, No reported glycans. DR GlyGen; P29320; 7 sites, 3 N-linked glycans (3 sites). DR iPTMnet; P29320; -. DR MetOSite; P29320; -. DR PhosphoSitePlus; P29320; -. DR SwissPalm; P29320; -. DR BioMuta; EPHA3; -. DR DMDM; 116241351; -. DR CPTAC; CPTAC-1774; -. DR CPTAC; CPTAC-3202; -. DR CPTAC; CPTAC-3203; -. DR jPOST; P29320; -. DR MassIVE; P29320; -. DR PaxDb; 9606-ENSP00000337451; -. DR PeptideAtlas; P29320; -. DR ProteomicsDB; 54536; -. [P29320-1] DR ProteomicsDB; 54537; -. [P29320-2] DR ABCD; P29320; 1 sequenced antibody. DR Antibodypedia; 4182; 573 antibodies from 43 providers. DR DNASU; 2042; -. DR Ensembl; ENST00000336596.7; ENSP00000337451.2; ENSG00000044524.12. [P29320-1] DR Ensembl; ENST00000452448.6; ENSP00000399926.2; ENSG00000044524.12. [P29320-2] DR GeneID; 2042; -. DR KEGG; hsa:2042; -. DR MANE-Select; ENST00000336596.7; ENSP00000337451.2; NM_005233.6; NP_005224.2. DR UCSC; uc003dqx.2; human. [P29320-1] DR AGR; HGNC:3387; -. DR ClinPGx; PA27819; -. DR CTD; 2042; -. DR DisGeNET; 2042; -. DR GeneCards; EPHA3; -. DR HGNC; HGNC:3387; EPHA3. DR HPA; ENSG00000044524; Tissue enhanced (prostate). DR MalaCards; EPHA3; -. DR MIM; 114500; phenotype. DR MIM; 179611; gene. DR OpenTargets; ENSG00000044524; -. DR VEuPathDB; HostDB:ENSG00000044524; -. DR eggNOG; KOG0196; Eukaryota. DR GeneTree; ENSGT00940000157088; -. DR HOGENOM; CLU_000288_141_3_1; -. DR InParanoid; P29320; -. DR OMA; GNTKCAK; -. DR OrthoDB; 4062651at2759; -. DR PAN-GO; P29320; 5 GO annotations based on evolutionary models. DR PhylomeDB; P29320; -. DR BRENDA; 2.7.10.1; 2681. DR PathwayCommons; P29320; -. DR Reactome; R-HSA-2682334; EPH-Ephrin signaling. DR Reactome; R-HSA-3928663; EPHA-mediated growth cone collapse. DR Reactome; R-HSA-3928665; EPH-ephrin mediated repulsion of cells. DR SignaLink; P29320; -. DR SIGNOR; P29320; -. DR Agora; ENSG00000044524; -. DR BioGRID-ORCS; 2042; 12 hits in 1194 CRISPR screens. DR ChiTaRS; EPHA3; human. DR EvolutionaryTrace; P29320; -. DR GeneWiki; EPH_receptor_A3; -. DR GenomeRNAi; 2042; -. DR Pharos; P29320; Tchem. DR PRO; PR:P29320; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; P29320; protein. DR Bgee; ENSG00000044524; Expressed in ganglionic eminence and 159 other cell types or tissues. DR ExpressionAtlas; P29320; baseline and differential. DR GO; GO:0030425; C:dendrite; IBA:GO_Central. DR GO; GO:0005769; C:early endosome; IDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; EXP:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:InterPro. DR GO; GO:0005003; F:ephrin receptor activity; IDA:ARUK-UCL. DR GO; GO:0005004; F:GPI-linked ephrin receptor activity; IDA:UniProtKB. DR GO; GO:0005005; F:transmembrane-ephrin receptor activity; IBA:GO_Central. DR GO; GO:0007411; P:axon guidance; IBA:GO_Central. DR GO; GO:0016477; P:cell migration; ISS:UniProtKB. DR GO; GO:0071300; P:cellular response to retinoic acid; IMP:BHF-UCL. DR GO; GO:0048013; P:ephrin receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0097156; P:fasciculation of motor neuron axon; ISS:UniProtKB. DR GO; GO:0097155; P:fasciculation of sensory neuron axon; ISS:UniProtKB. DR GO; GO:0045806; P:negative regulation of endocytosis; IDA:UniProtKB. DR GO; GO:0010719; P:negative regulation of epithelial to mesenchymal transition; ISS:UniProt. DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB. DR GO; GO:0010976; P:positive regulation of neuron projection development; IMP:BHF-UCL. DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; IDA:UniProtKB. DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IDA:UniProtKB. DR GO; GO:0022407; P:regulation of cell-cell adhesion; IDA:UniProt. DR GO; GO:0010717; P:regulation of epithelial to mesenchymal transition; ISS:UniProtKB. DR GO; GO:0051893; P:regulation of focal adhesion assembly; IDA:UniProtKB. DR GO; GO:0070507; P:regulation of microtubule cytoskeleton organization; IDA:UniProtKB. DR CDD; cd10481; EphR_LBD_A3; 1. DR CDD; cd00063; FN3; 2. DR CDD; cd05066; PTKc_EphR_A; 1. DR FunFam; 1.10.150.50:FF:000046; ephrin type-A receptor 3; 1. DR FunFam; 2.60.40.10:FF:000041; ephrin type-A receptor 3; 1. DR FunFam; 1.10.510.10:FF:000019; Ephrin type-A receptor 5; 1. DR FunFam; 2.10.50.10:FF:000001; Ephrin type-A receptor 5; 1. DR FunFam; 2.60.40.10:FF:000045; Ephrin type-A receptor 5; 1. DR FunFam; 2.60.40.1770:FF:000001; Ephrin type-A receptor 5; 1. DR FunFam; 3.30.200.20:FF:000001; Ephrin type-A receptor 5; 1. DR FunFam; 2.60.120.260:FF:000001; Ephrin type-A receptor 7; 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; 3.30.200.20; Phosphorylase Kinase, domain 1; 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; IPR016257; EPH. DR InterPro; IPR061283; EPH_CRD. DR InterPro; IPR001090; EPH_LBD. DR InterPro; IPR027936; EPH_TM. DR InterPro; IPR034266; EphA3_rcpt_lig-bd. DR InterPro; IPR050449; Ephrin_rcpt_TKs. 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; 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; PF25599; Ephrin_CRD; 1. DR Pfam; PF01404; Ephrin_lbd; 1. DR Pfam; PF07699; Ephrin_rec_like; 1. DR Pfam; PF00041; fn3; 2. DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1. DR Pfam; PF07647; SAM_2; 1. DR PIRSF; PIRSF000666; TyrPK_ephrin_receptor; 1. DR PRINTS; PR00014; FNTYPEIII. 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 PDBsum; 2GSF; -. DR PDBsum; 2QO2; -. DR PDBsum; 2QO7; -. DR PDBsum; 2QO9; -. DR PDBsum; 2QOB; -. DR PDBsum; 2QOC; -. DR PDBsum; 2QOD; -. DR PDBsum; 2QOF; -. DR PDBsum; 2QOI; -. DR PDBsum; 2QOK; -. DR PDBsum; 2QOL; -. DR PDBsum; 2QON; -. DR PDBsum; 2QOO; -. DR PDBsum; 2QOQ; -. DR PDBsum; 3DZQ; -. DR PDBsum; 3FXX; -. DR PDBsum; 3FY2; -. DR PDBsum; 4G2F; -. DR PDBsum; 4GK2; -. DR PDBsum; 4GK3; -. DR PDBsum; 4GK4; -. DR PDBsum; 4L0P; -. DR PDBsum; 4P4C; -. DR PDBsum; 4P5Q; -. DR PDBsum; 4P5Z; -. DR PDBsum; 4TWN; -. DR PDBsum; 4TWO; -. DR PDBsum; 6IN0; -. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Cell adhesion; KW Cell membrane; Direct protein sequencing; Glycoprotein; Kinase; Membrane; KW Nucleotide-binding; Phosphoprotein; Proteomics identification; Receptor; KW Reference proteome; Repeat; Secreted; Signal; Transferase; Transmembrane; KW Transmembrane helix; Tyrosine-protein kinase. FT SIGNAL 1..20 FT /evidence="ECO:0000269|PubMed:1737782" FT CHAIN 21..983 FT /note="Ephrin type-A receptor 3" FT /id="PRO_0000016802" FT TOPO_DOM 21..541 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 542..565 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 566..983 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 29..207 FT /note="Eph LBD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00883" FT DOMAIN 325..435 FT /note="Fibronectin type-III 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 436..531 FT /note="Fibronectin type-III 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 621..882 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT DOMAIN 911..975 FT /note="SAM" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184" FT MOTIF 981..983 FT /note="PDZ-binding" FT /evidence="ECO:0000255" FT ACT_SITE 746 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10028" FT BINDING 628..633 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT BINDING 653 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT BINDING 700..706 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT BINDING 750..751 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT MOD_RES 596 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:11870224, FT ECO:0000269|PubMed:18547520" FT MOD_RES 602 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:11870224, FT ECO:0000269|PubMed:18547520" FT MOD_RES 701 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:18547520" FT MOD_RES 779 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:11870224" FT MOD_RES 937 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P29319" FT CARBOHYD 232 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 337 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 391 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 404 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 493 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VAR_SEQ 532..539 FT /note="SFSISGES -> CMYYFNAV (in isoform 2)" FT /evidence="ECO:0000303|PubMed:10987298" FT /id="VSP_002995" FT VAR_SEQ 540..983 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:10987298" FT /id="VSP_002996" FT VARIANT 37 FT /note="T -> K (in a colorectal cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036086" FT VARIANT 85 FT /note="N -> S (in a colorectal cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036087" FT VARIANT 207 FT /note="K -> N (in a pancreatic ductal adenocarcinoma FT sample; somatic mutation; dbSNP:rs200567888)" FT /evidence="ECO:0000269|PubMed:20838624" FT /id="VAR_068853" FT VARIANT 229 FT /note="S -> Y (in a lung large cell carcinoma sample; FT somatic mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042126" FT VARIANT 449 FT /note="S -> F (in a lung neuroendocrine carcinoma sample; FT somatic mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042127" FT VARIANT 518 FT /note="G -> L (in a lung squamous cell carcinoma sample; FT somatic mutation; requires 2 nucleotide substitutions)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042128" FT VARIANT 564 FT /note="I -> V (in dbSNP:rs55712516)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042129" FT VARIANT 568 FT /note="C -> S (in dbSNP:rs56077781)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042130" FT VARIANT 590 FT /note="L -> P (in dbSNP:rs56081642)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042131" FT VARIANT 621 FT /note="I -> L (in a colorectal cancer sample; somatic FT mutation; dbSNP:rs1414714315)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036088" FT VARIANT 660 FT /note="T -> K (in a lung carcinoma sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16941478" FT /id="VAR_065831" FT VARIANT 766 FT /note="G -> E (in a lung adenocarcinoma sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042132" FT VARIANT 777 FT /note="A -> G (in dbSNP:rs34437982)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042133" FT VARIANT 806 FT /note="D -> N (in a colorectal cancer sample; somatic FT mutation; dbSNP:rs2107553474)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036089" FT VARIANT 914 FT /note="R -> H (in dbSNP:rs17801309)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_027919" FT VARIANT 924 FT /note="W -> R (in dbSNP:rs35124509)" FT /evidence="ECO:0000269|PubMed:1311845, FT ECO:0000269|PubMed:17344846" FT /id="VAR_042134" FT VARIANT 933 FT /note="T -> M (in a lung carcinoma sample; somatic FT mutation; dbSNP:rs372594677)" FT /evidence="ECO:0000269|PubMed:16941478" FT /id="VAR_065832" FT MUTAGEN 133 FT /note="V->E: Loss of EFNA5-binding ability and function." FT /evidence="ECO:0000269|PubMed:14660665" FT MUTAGEN 152 FT /note="F->L: Loss of EFNA5-binding ability and function." FT /evidence="ECO:0000269|PubMed:14660665" FT MUTAGEN 596 FT /note="Y->F: 10-fold suppression of kinase activity; when FT associated with F-602. Full kinase activity; when FT associated with F-602 and F-742. Full kinase activity; when FT associated with F-602 and A-768." FT /evidence="ECO:0000269|PubMed:18547520" FT MUTAGEN 602 FT /note="Y->F: 10-fold suppression of kinase activity; when FT associated with F-596. Full kinase activity; when FT associated with F-596 and F-742. Full kinase activity; when FT associated with F-596 and A-768." FT /evidence="ECO:0000269|PubMed:18547520" FT MUTAGEN 742 FT /note="Y->F: Full kinase activity; when associated with FT F-596 and F-602." FT /evidence="ECO:0000269|PubMed:18547520" FT MUTAGEN 768 FT /note="S->A: Full kinase activity; when associated with FT F-596 and F-602." FT /evidence="ECO:0000269|PubMed:18547520" FT CONFLICT 911 FT /note="T -> S (in Ref. 1; AAA58633)" FT /evidence="ECO:0000305" FT STRAND 29..34 FT /evidence="ECO:0007829|PDB:4L0P" FT TURN 38..41 FT /evidence="ECO:0007829|PDB:4L0P" FT STRAND 45..48 FT /evidence="ECO:0007829|PDB:4L0P" FT STRAND 51..58 FT /evidence="ECO:0007829|PDB:4L0P" FT STRAND 64..71 FT /evidence="ECO:0007829|PDB:4L0P" FT STRAND 75..77 FT /evidence="ECO:0007829|PDB:4L0P" FT STRAND 80..83 FT /evidence="ECO:0007829|PDB:4L0P" FT STRAND 96..104 FT /evidence="ECO:0007829|PDB:4L0P" FT HELIX 106..108 FT /evidence="ECO:0007829|PDB:4L0P" FT STRAND 117..128 FT /evidence="ECO:0007829|PDB:4L0P" FT STRAND 130..132 FT /evidence="ECO:0007829|PDB:4L0P" FT HELIX 137..139 FT /evidence="ECO:0007829|PDB:4L0P" FT STRAND 141..147 FT /evidence="ECO:0007829|PDB:4L0P" FT HELIX 154..159 FT /evidence="ECO:0007829|PDB:4L0P" FT STRAND 165..170 FT /evidence="ECO:0007829|PDB:4L0P" FT STRAND 176..200 FT /evidence="ECO:0007829|PDB:4L0P" FT TURN 610..612 FT /evidence="ECO:0007829|PDB:2QOL" FT HELIX 618..620 FT /evidence="ECO:0007829|PDB:2QOL" FT STRAND 621..629 FT /evidence="ECO:0007829|PDB:2QOL" FT STRAND 631..641 FT /evidence="ECO:0007829|PDB:2QOL" FT STRAND 647..654 FT /evidence="ECO:0007829|PDB:2QOL" FT HELIX 661..674 FT /evidence="ECO:0007829|PDB:2QOL" FT STRAND 685..689 FT /evidence="ECO:0007829|PDB:2QOL" FT STRAND 691..694 FT /evidence="ECO:0007829|PDB:2QOL" FT STRAND 696..700 FT /evidence="ECO:0007829|PDB:2QOL" FT HELIX 707..712 FT /evidence="ECO:0007829|PDB:2QOL" FT TURN 713..716 FT /evidence="ECO:0007829|PDB:2QOL" FT HELIX 720..739 FT /evidence="ECO:0007829|PDB:2QOL" FT HELIX 749..751 FT /evidence="ECO:0007829|PDB:2QOL" FT STRAND 752..754 FT /evidence="ECO:0007829|PDB:2QOL" FT STRAND 760..762 FT /evidence="ECO:0007829|PDB:2QOL" FT HELIX 765..768 FT /evidence="ECO:0007829|PDB:4TWN" FT HELIX 788..790 FT /evidence="ECO:0007829|PDB:2QOD" FT HELIX 793..798 FT /evidence="ECO:0007829|PDB:2QOL" FT HELIX 803..818 FT /evidence="ECO:0007829|PDB:2QOL" FT TURN 819..821 FT /evidence="ECO:0007829|PDB:2QOL" FT TURN 824..827 FT /evidence="ECO:0007829|PDB:2QOL" FT HELIX 830..838 FT /evidence="ECO:0007829|PDB:2QOL" FT HELIX 843..846 FT /evidence="ECO:0007829|PDB:2QOL" FT HELIX 851..860 FT /evidence="ECO:0007829|PDB:2QOL" FT HELIX 865..867 FT /evidence="ECO:0007829|PDB:2QOL" FT HELIX 871..883 FT /evidence="ECO:0007829|PDB:2QOL" FT HELIX 885..889 FT /evidence="ECO:0007829|PDB:2QOL" FT STRAND 898..903 FT /evidence="ECO:0007829|PDB:2QOC" SQ SEQUENCE 983 AA; 110131 MW; BE04DBF958245424 CRC64; MDCQLSILLL LSCSVLDSFG ELIPQPSNEV NLLDSKTIQG ELGWISYPSH GWEEISGVDE HYTPIRTYQV CNVMDHSQNN WLRTNWVPRN SAQKIYVELK FTLRDCNSIP LVLGTCKETF NLYYMESDDD HGVKFREHQF TKIDTIAADE SFTQMDLGDR ILKLNTEIRE VGPVNKKGFY LAFQDVGACV ALVSVRVYFK KCPFTVKNLA MFPDTVPMDS QSLVEVRGSC VNNSKEEDPP RMYCSTEGEW LVPIGKCSCN AGYEERGFMC QACRPGFYKA LDGNMKCAKC PPHSSTQEDG SMNCRCENNY FRADKDPPSM ACTRPPSSPR NVISNINETS VILDWSWPLD TGGRKDVTFN IICKKCGWNI KQCEPCSPNV RFLPRQFGLT NTTVTVTDLL AHTNYTFEID AVNGVSELSS PPRQFAAVSI TTNQAAPSPV LTIKKDRTSR NSISLSWQEP EHPNGIILDY EVKYYEKQEQ ETSYTILRAR GTNVTISSLK PDTIYVFQIR ARTAAGYGTN SRKFEFETSP DSFSISGESS QVVMIAISAA VAIILLTVVI YVLIGRFCGY KSKHGADEKR LHFGNGHLKL PGLRTYVDPH TYEDPTQAVH EFAKELDATN ISIDKVVGAG EFGEVCSGRL KLPSKKEISV AIKTLKVGYT EKQRRDFLGE ASIMGQFDHP NIIRLEGVVT KSKPVMIVTE YMENGSLDSF LRKHDAQFTV IQLVGMLRGI ASGMKYLSDM GYVHRDLAAR NILINSNLVC KVSDFGLSRV LEDDPEAAYT TRGGKIPIRW TSPEAIAYRK FTSASDVWSY GIVLWEVMSY GERPYWEMSN QDVIKAVDEG YRLPPPMDCP AALYQLMLDC WQKDRNNRPK FEQIVSILDK LIRNPGSLKI ITSAAARPSN LLLDQSNVDI TTFRTTGDWL NGVWTAHCKE IFTGVEYSSC DTIAKISTDD MKKVGVTVVG PQKKIISSIK ALETQSKNGP VPV //