EPHA3_HUMAN
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 03-AUG-2022, entry version 223.
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 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 [7]
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 [8]
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 [9]
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 [10]
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 [11]
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 [12]
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 [13]
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 [14]
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 [15]
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. Highly promiscuous for ephrin-A
CC ligands it binds preferentially EFNA5. Upon activation by EFNA5
CC regulates cell-cell adhesion, cytoskeletal organization and cell
CC migration. Plays a role in cardiac cells migration and differentiation
CC and regulates the formation of the atrioventricular canal and septum
CC during development probably through activation by EFNA1. Involved in
CC the retinotectal mapping of neurons. May also control the segregation
CC but not the guidance of motor and sensory axons during neuromuscular
CC circuit development. {ECO:0000269|PubMed:11870224}.
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: 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 -!- 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="http://atlasgeneticsoncology.org/Genes/EPHA3ID40463ch3p11.html";
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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_005233.5. [P29320-1]
DR RefSeq; NP_872585.1; NM_182644.2. [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=609-947.
DR PDB; 2QOC; X-ray; 1.25 A; A=609-947.
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=609-947.
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=609-947.
DR PDB; 4GK2; X-ray; 2.20 A; A=609-947.
DR PDB; 4GK3; X-ray; 1.90 A; A=609-947.
DR PDB; 4GK4; X-ray; 2.10 A; A=609-947.
DR PDB; 4L0P; X-ray; 2.26 A; A=29-201.
DR PDB; 4P4C; X-ray; 1.60 A; A=609-947.
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=612-904.
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; -.
DR AlphaFoldDB; P29320; -.
DR SMR; P29320; -.
DR BioGRID; 108356; 52.
DR DIP; DIP-40307N; -.
DR IntAct; P29320; 29.
DR MINT; P29320; -.
DR STRING; 9606.ENSP00000337451; -.
DR BindingDB; P29320; -.
DR ChEMBL; CHEMBL4954; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; P29320; -.
DR GuidetoPHARMACOLOGY; 1823; -.
DR GlyGen; P29320; 5 sites.
DR iPTMnet; P29320; -.
DR MetOSite; P29320; -.
DR PhosphoSitePlus; P29320; -.
DR BioMuta; EPHA3; -.
DR DMDM; 116241351; -.
DR CPTAC; CPTAC-1774; -.
DR jPOST; P29320; -.
DR MassIVE; P29320; -.
DR MaxQB; P29320; -.
DR PaxDb; P29320; -.
DR PeptideAtlas; P29320; -.
DR PRIDE; P29320; -.
DR ProteomicsDB; 54536; -. [P29320-1]
DR ProteomicsDB; 54537; -. [P29320-2]
DR ABCD; P29320; 1 sequenced antibody.
DR Antibodypedia; 4182; 521 antibodies from 37 providers.
DR DNASU; 2042; -.
DR Ensembl; ENST00000336596.7; ENSP00000337451.2; ENSG00000044524.11. [P29320-1]
DR Ensembl; ENST00000452448.6; ENSP00000399926.2; ENSG00000044524.11. [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 CTD; 2042; -.
DR DisGeNET; 2042; -.
DR GeneCards; EPHA3; -.
DR HGNC; HGNC:3387; EPHA3.
DR HPA; ENSG00000044524; Tissue enhanced (prostate).
DR MIM; 114500; phenotype.
DR MIM; 179611; gene.
DR neXtProt; NX_P29320; -.
DR OpenTargets; ENSG00000044524; -.
DR PharmGKB; PA27819; -.
DR VEuPathDB; HostDB:ENSG00000044524; -.
DR eggNOG; KOG0196; Eukaryota.
DR GeneTree; ENSGT00940000157088; -.
DR HOGENOM; CLU_000288_141_3_1; -.
DR InParanoid; P29320; -.
DR OMA; NCKCEKN; -.
DR PhylomeDB; P29320; -.
DR TreeFam; TF315608; -.
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 BioGRID-ORCS; 2042; 9 hits in 1108 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 158 other tissues.
DR ExpressionAtlas; P29320; baseline and differential.
DR Genevisible; P29320; HS.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:HPA.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
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:0031965; C:nuclear membrane; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
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:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
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:0007155; P:cell adhesion; IEA:UniProtKB-KW.
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:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
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: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:0043087; P:regulation of GTPase activity; IDA:UniProtKB.
DR GO; GO:0070507; P:regulation of microtubule cytoskeleton organization; IDA:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd10481; EphR_LBD_A3; 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; IPR034266; EphA3_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; 2.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF07647; SAM_2; 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; ATP-binding; Cell adhesion;
KW Cell membrane; Direct protein sequencing; Glycoprotein; Kinase; Membrane;
KW Nucleotide-binding; Phosphoprotein; Receptor; Reference proteome; Repeat;
KW Secreted; Signal; Transferase; Transmembrane; Transmembrane helix;
KW 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)"
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 F-
FT 596 and F-602."
FT /evidence="ECO:0000269|PubMed:18547520"
FT MUTAGEN 768
FT /note="S->A: Full kinase activity; when associated with F-
FT 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:2QO9"
FT TURN 824..827
FT /evidence="ECO:0007829|PDB:2QOL"
FT HELIX 830..838
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 890..892
FT /evidence="ECO:0007829|PDB:4G2F"
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
