ID   EPHA8_HUMAN             Reviewed;        1005 AA.
AC   P29322; Q6IN80; Q8IUX6; Q9NUA9; Q9P269;
DT   01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT   18-OCT-2001, sequence version 2.
DT   24-JAN-2024, entry version 227.
DE   RecName: Full=Ephrin type-A receptor 8;
DE            EC=2.7.10.1;
DE   AltName: Full=EPH- and ELK-related kinase;
DE   AltName: Full=EPH-like kinase 3;
DE            Short=EK3;
DE            Short=hEK3;
DE   AltName: Full=Tyrosine-protein kinase receptor EEK;
DE   Flags: Precursor;
GN   Name=EPHA8; Synonyms=EEK, HEK3, KIAA1459;
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 [LARGE SCALE GENOMIC DNA].
RX   PubMed=16710414; DOI=10.1038/nature04727;
RA   Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA   Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA   Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA   Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA   Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA   Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA   Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA   Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA   Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA   Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA   Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA   Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA   Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA   Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA   Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA   Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA   Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA   Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA   McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA   Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA   Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA   Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA   Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA   Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA   White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA   Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA   Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA   Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT   "The DNA sequence and biological annotation of human chromosome 1.";
RL   Nature 441:315-321(2006).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Brain, and Eye;
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 153-1005 (ISOFORM 1), AND VARIANT
RP   GLN-612.
RC   TISSUE=Brain;
RX   PubMed=10819331; DOI=10.1093/dnares/7.2.143;
RA   Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. XVII. The
RT   complete sequences of 100 new cDNA clones from brain which code for large
RT   proteins in vitro.";
RL   DNA Res. 7:143-150(2000).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 706-726.
RX   PubMed=1648701;
RA   Chan J., Watt V.M.;
RT   "eek and erk, new members of the eph subclass of receptor protein-tyrosine
RT   kinases.";
RL   Oncogene 6:1057-1061(1991).
RN   [5]
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   [6]
RP   INTERACTION WITH FYN.
RX   PubMed=10498895; DOI=10.1038/sj.onc.1202917;
RA   Choi S., Park S.;
RT   "Phosphorylation at Tyr-838 in the kinase domain of EphA8 modulates Fyn
RT   binding to the Tyr-615 site by enhancing tyrosine kinase activity.";
RL   Oncogene 18:5413-5422(1999).
RN   [7]
RP   INTERACTION WITH PIK3CG.
RX   PubMed=11416136; DOI=10.1128/mcb.21.14.4579-4597.2001;
RA   Gu C., Park S.;
RT   "The EphA8 receptor regulates integrin activity through p110gamma
RT   phosphatidylinositol-3 kinase in a tyrosine kinase activity-independent
RT   manner.";
RL   Mol. Cell. Biol. 21:4579-4597(2001).
RN   [8]
RP   INTERACTION WITH ANKS1B.
RX   PubMed=17875921; DOI=10.1128/mcb.00794-07;
RA   Shin J., Gu C., Park E., Park S.;
RT   "Identification of phosphotyrosine binding domain-containing proteins as
RT   novel downstream targets of the EphA8 signaling function.";
RL   Mol. Cell. Biol. 27:8113-8126(2007).
RN   [9]
RP   INTERACTION WITH TIAM1.
RX   PubMed=20496116; DOI=10.1007/s10059-010-0075-2;
RA   Yoo S., Shin J., Park S.;
RT   "EphA8-ephrinA5 signaling and clathrin-mediated endocytosis is regulated by
RT   Tiam-1, a Rac-specific guanine nucleotide exchange factor.";
RL   Mol. Cells 29:603-609(2010).
RN   [10]
RP   STRUCTURE BY NMR OF 437-534 AND 932-1000.
RG   RIKEN structural genomics initiative (RSGI);
RT   "Solution structure of the second FN3 domain and of sterile alpha motif
RT   (SAM) domain of EPH receptor A8 protein.";
RL   Submitted (NOV-2005) to the PDB data bank.
RN   [11]
RP   VARIANTS [LARGE SCALE ANALYSIS] SER-45; LEU-60; LYS-123; CYS-179; LEU-198
RP   AND LEU-860.
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).
CC   -!- FUNCTION: Receptor tyrosine kinase which binds promiscuously GPI-
CC       anchored 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. The GPI-anchored ephrin-A EFNA2,
CC       EFNA3, and EFNA5 are able to activate EPHA8 through phosphorylation.
CC       With EFNA5 may regulate integrin-mediated cell adhesion and migration
CC       on fibronectin substrate but also neurite outgrowth. During development
CC       of the nervous system also plays a role in axon guidance. Downstream
CC       effectors of the EPHA8 signaling pathway include FYN which promotes
CC       cell adhesion upon activation by EPHA8 and the MAP kinases in the
CC       stimulation of neurite outgrowth (By similarity). {ECO:0000250}.
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. May also form
CC       heterodimers with other ephrin receptors (By similarity). Interacts
CC       with FYN; possible downstream effector of EPHA8 in regulation of cell
CC       adhesion. Interacts with PIK3CG; regulates integrin-mediated cell
CC       adhesion to substrate. Interacts with TIAM1; regulates clathrin-
CC       mediated endocytosis of EPHA8. Interacts with ANKS1A and ANKS1B; EPHA8
CC       kinase activity-independent but stimulated by EPHA8 ubiquitination.
CC       {ECO:0000250, ECO:0000269|PubMed:10498895, ECO:0000269|PubMed:11416136,
CC       ECO:0000269|PubMed:17875921, ECO:0000269|PubMed:20496116}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:O09127};
CC       Single-pass type I membrane protein {ECO:0000255}. Cell projection
CC       {ECO:0000250|UniProtKB:O09127}. Early endosome membrane
CC       {ECO:0000250|UniProtKB:O09127}. Note=Undergoes clathrin-mediated
CC       endocytosis upon EFNA5-binding and is targeted to early endosomes.
CC       {ECO:0000250|UniProtKB:O09127}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=P29322-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P29322-2; Sequence=VSP_041946, VSP_041947;
CC   -!- PTM: Phosphorylated. Phosphorylation is stimulated upon binding of its
CC       ligands including EFNA2, EFNA3 and EFNA5. Autophosphorylation on Tyr-
CC       616 is critical for association with FYN. Autophosphorylation on Tyr-
CC       839 modulates tyrosine kinase activity (By similarity). {ECO:0000250}.
CC   -!- PTM: Ubiquitinated. Ubiquitination by CBL regulates the receptor
CC       stability and activity through proteasomal degradation. ANKS1A prevents
CC       ubiquitination and degradation (By similarity). {ECO:0000250}.
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=CAA41980.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; AL035703; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC038796; AAH38796.1; -; mRNA.
DR   EMBL; BC072417; AAH72417.2; -; mRNA.
DR   EMBL; AB040892; BAA95983.1; -; mRNA.
DR   EMBL; X59291; CAA41980.1; ALT_INIT; Genomic_DNA.
DR   CCDS; CCDS225.1; -. [P29322-1]
DR   CCDS; CCDS30626.1; -. [P29322-2]
DR   PIR; S23361; S23361.
DR   RefSeq; NP_001006944.1; NM_001006943.2. [P29322-2]
DR   RefSeq; NP_065387.1; NM_020526.4. [P29322-1]
DR   PDB; 1UCV; NMR; -; A=933-1000.
DR   PDB; 1X5L; NMR; -; A=437-534.
DR   PDB; 3KUL; X-ray; 2.15 A; A/B=602-909.
DR   PDBsum; 1UCV; -.
DR   PDBsum; 1X5L; -.
DR   PDBsum; 3KUL; -.
DR   AlphaFoldDB; P29322; -.
DR   BMRB; P29322; -.
DR   SMR; P29322; -.
DR   BioGRID; 108360; 162.
DR   IntAct; P29322; 140.
DR   MINT; P29322; -.
DR   STRING; 9606.ENSP00000166244; -.
DR   BindingDB; P29322; -.
DR   ChEMBL; CHEMBL4134; -.
DR   DrugBank; DB12010; Fostamatinib.
DR   DrugCentral; P29322; -.
DR   GuidetoPHARMACOLOGY; 1828; -.
DR   GlyCosmos; P29322; 3 sites, No reported glycans.
DR   GlyGen; P29322; 3 sites.
DR   iPTMnet; P29322; -.
DR   PhosphoSitePlus; P29322; -.
DR   BioMuta; EPHA8; -.
DR   DMDM; 19857975; -.
DR   CPTAC; CPTAC-2820; -.
DR   CPTAC; CPTAC-3204; -.
DR   EPD; P29322; -.
DR   jPOST; P29322; -.
DR   MassIVE; P29322; -.
DR   MaxQB; P29322; -.
DR   PaxDb; 9606-ENSP00000166244; -.
DR   PeptideAtlas; P29322; -.
DR   ProteomicsDB; 54538; -. [P29322-1]
DR   ProteomicsDB; 54539; -. [P29322-2]
DR   Antibodypedia; 4046; 217 antibodies from 33 providers.
DR   DNASU; 2046; -.
DR   Ensembl; ENST00000166244.8; ENSP00000166244.3; ENSG00000070886.12. [P29322-1]
DR   Ensembl; ENST00000374644.8; ENSP00000363775.4; ENSG00000070886.12. [P29322-2]
DR   GeneID; 2046; -.
DR   KEGG; hsa:2046; -.
DR   MANE-Select; ENST00000166244.8; ENSP00000166244.3; NM_020526.5; NP_065387.1.
DR   UCSC; uc001bfw.4; human. [P29322-1]
DR   AGR; HGNC:3391; -.
DR   CTD; 2046; -.
DR   DisGeNET; 2046; -.
DR   GeneCards; EPHA8; -.
DR   HGNC; HGNC:3391; EPHA8.
DR   HPA; ENSG00000070886; Tissue enriched (choroid).
DR   MIM; 176945; gene.
DR   neXtProt; NX_P29322; -.
DR   OpenTargets; ENSG00000070886; -.
DR   PharmGKB; PA27823; -.
DR   VEuPathDB; HostDB:ENSG00000070886; -.
DR   eggNOG; KOG0196; Eukaryota.
DR   GeneTree; ENSGT00940000160469; -.
DR   HOGENOM; CLU_000288_141_3_1; -.
DR   InParanoid; P29322; -.
DR   OMA; MRMNIDD; -.
DR   OrthoDB; 1614410at2759; -.
DR   PhylomeDB; P29322; -.
DR   TreeFam; TF315608; -.
DR   BRENDA; 2.7.10.1; 2681.
DR   PathwayCommons; P29322; -.
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; P29322; -.
DR   SIGNOR; P29322; -.
DR   BioGRID-ORCS; 2046; 11 hits in 1180 CRISPR screens.
DR   ChiTaRS; EPHA8; human.
DR   EvolutionaryTrace; P29322; -.
DR   GeneWiki; EPHA8; -.
DR   GenomeRNAi; 2046; -.
DR   Pharos; P29322; Tchem.
DR   PRO; PR:P29322; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   RNAct; P29322; Protein.
DR   Bgee; ENSG00000070886; Expressed in endothelial cell and 47 other cell types or tissues.
DR   GO; GO:0030425; C:dendrite; IBA:GO_Central.
DR   GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0043005; C:neuron projection; ISS:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0005003; F:ephrin receptor activity; ISS:UniProtKB.
DR   GO; GO:0005004; F:GPI-linked ephrin receptor activity; ISS:UniProtKB.
DR   GO; GO:0019838; F:growth factor binding; IEA:Ensembl.
DR   GO; GO:0005005; F:transmembrane-ephrin receptor activity; IBA:GO_Central.
DR   GO; GO:0007411; P:axon guidance; ISS:UniProtKB.
DR   GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR   GO; GO:0071372; P:cellular response to follicle-stimulating hormone stimulus; IEA:Ensembl.
DR   GO; GO:0048013; P:ephrin receptor signaling pathway; ISS:UniProtKB.
DR   GO; GO:0031175; P:neuron projection development; ISS:UniProtKB.
DR   GO; GO:0016322; P:neuron remodeling; ISS:UniProtKB.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   GO; GO:0043410; P:positive regulation of MAPK cascade; ISS:UniProtKB.
DR   GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISS:UniProtKB.
DR   GO; GO:0030155; P:regulation of cell adhesion; ISS:UniProtKB.
DR   GO; GO:0033628; P:regulation of cell adhesion mediated by integrin; ISS:UniProtKB.
DR   GO; GO:0006929; P:substrate-dependent cell migration; ISS:UniProtKB.
DR   CDD; cd00063; FN3; 2.
DR   CDD; cd05066; PTKc_EphR_A; 1.
DR   CDD; cd09550; SAM_EPH-A8; 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; 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; IPR013783; Ig-like_fold.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR017441; Protein_kinase_ATP_BS.
DR   InterPro; IPR001660; SAM.
DR   InterPro; IPR013761; SAM/pointed_sf.
DR   InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR   InterPro; IPR008266; Tyr_kinase_AS.
DR   InterPro; IPR020635; Tyr_kinase_cat_dom.
DR   InterPro; IPR016257; Tyr_kinase_ephrin_rcpt.
DR   InterPro; IPR001426; Tyr_kinase_rcpt_V_CS.
DR   PANTHER; PTHR46877; EPH RECEPTOR A5; 1.
DR   PANTHER; PTHR46877:SF7; EPHRIN TYPE-A RECEPTOR 8; 1.
DR   Pfam; PF14575; EphA2_TM; 1.
DR   Pfam; PF01404; Ephrin_lbd; 1.
DR   Pfam; PF00041; fn3; 2.
DR   Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR   Pfam; PF00536; SAM_1; 1.
DR   PIRSF; PIRSF000666; TyrPK_ephrin_receptor; 1.
DR   PRINTS; 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; 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; P29322; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; ATP-binding; Cell adhesion;
KW   Cell membrane; Cell projection; Developmental protein; Endosome;
KW   Glycoprotein; Kinase; Membrane; Neurogenesis; Nucleotide-binding;
KW   Phosphoprotein; Receptor; Reference proteome; Repeat; Signal; Transferase;
KW   Transmembrane; Transmembrane helix; Tyrosine-protein kinase;
KW   Ubl conjugation.
FT   SIGNAL          1..27
FT                   /evidence="ECO:0000255"
FT   CHAIN           28..1005
FT                   /note="Ephrin type-A receptor 8"
FT                   /id="PRO_0000016822"
FT   TOPO_DOM        28..542
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        543..563
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        564..1005
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          31..209
FT                   /note="Eph LBD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00883"
FT   DOMAIN          328..438
FT                   /note="Fibronectin type-III 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT   DOMAIN          439..534
FT                   /note="Fibronectin type-III 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT   DOMAIN          635..896
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   DOMAIN          930..994
FT                   /note="SAM"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT   REGION          564..570
FT                   /note="Mediates interaction with ANKS1A and ANKS1B"
FT                   /evidence="ECO:0000250"
FT   REGION          589..644
FT                   /note="Mediates interaction with PIK3CG and required for
FT                   endocytosis"
FT                   /evidence="ECO:0000250"
FT   MOTIF           1003..1005
FT                   /note="PDZ-binding"
FT                   /evidence="ECO:0000255"
FT   ACT_SITE        760
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000255|PROSITE-ProRule:PRU10028"
FT   BINDING         641..649
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         667
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   MOD_RES         616
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000250|UniProtKB:O09127"
FT   MOD_RES         839
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000250|UniProtKB:O09127"
FT   CARBOHYD        340
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        407
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        432
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         439..495
FT                   /note="APSQVVVIRQERAGQTSVSLLWQEPEQPNGIILEYEIKYYEKDKEMQSYSTL
FT                   KAVTT -> GRRRNSVPQRPGPPASPASDPSRDQSSAGDVLWAFRQVPLWPCAPHQDPE
FT                   LEALHCL (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_041946"
FT   VAR_SEQ         496..1005
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_041947"
FT   VARIANT         45
FT                   /note="G -> S (in dbSNP:rs45498698)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_042153"
FT   VARIANT         60
FT                   /note="V -> L (in dbSNP:rs56402644)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_042154"
FT   VARIANT         123
FT                   /note="N -> K (in a breast infiltrating ductal carcinoma
FT                   sample; somatic mutation)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_042155"
FT   VARIANT         179
FT                   /note="R -> C (in a gastric adenocarcinoma sample; somatic
FT                   mutation; dbSNP:rs1557556639)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_042156"
FT   VARIANT         198
FT                   /note="R -> L (in a lung adenocarcinoma sample; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_042157"
FT   VARIANT         321
FT                   /note="P -> L (in dbSNP:rs56656925)"
FT                   /id="VAR_061292"
FT   VARIANT         444
FT                   /note="V -> M (in dbSNP:rs2295021)"
FT                   /id="VAR_022107"
FT   VARIANT         612
FT                   /note="E -> Q (in dbSNP:rs999765)"
FT                   /evidence="ECO:0000269|PubMed:10819331"
FT                   /id="VAR_024514"
FT   VARIANT         860
FT                   /note="P -> L (in a metastatic melanoma sample; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_042158"
FT   CONFLICT        237
FT                   /note="S -> L (in Ref. 3; BAA95983)"
FT                   /evidence="ECO:0000305"
FT   STRAND          456..460
FT                   /evidence="ECO:0007829|PDB:1X5L"
FT   STRAND          472..482
FT                   /evidence="ECO:0007829|PDB:1X5L"
FT   STRAND          488..499
FT                   /evidence="ECO:0007829|PDB:1X5L"
FT   STRAND          507..510
FT                   /evidence="ECO:0007829|PDB:1X5L"
FT   STRAND          512..516
FT                   /evidence="ECO:0007829|PDB:1X5L"
FT   STRAND          527..530
FT                   /evidence="ECO:0007829|PDB:1X5L"
FT   HELIX           632..634
FT                   /evidence="ECO:0007829|PDB:3KUL"
FT   STRAND          635..643
FT                   /evidence="ECO:0007829|PDB:3KUL"
FT   TURN            644..646
FT                   /evidence="ECO:0007829|PDB:3KUL"
FT   STRAND          647..654
FT                   /evidence="ECO:0007829|PDB:3KUL"
FT   STRAND          662..669
FT                   /evidence="ECO:0007829|PDB:3KUL"
FT   HELIX           675..688
FT                   /evidence="ECO:0007829|PDB:3KUL"
FT   STRAND          699..703
FT                   /evidence="ECO:0007829|PDB:3KUL"
FT   HELIX           705..707
FT                   /evidence="ECO:0007829|PDB:3KUL"
FT   STRAND          710..714
FT                   /evidence="ECO:0007829|PDB:3KUL"
FT   HELIX           721..726
FT                   /evidence="ECO:0007829|PDB:3KUL"
FT   TURN            727..730
FT                   /evidence="ECO:0007829|PDB:3KUL"
FT   HELIX           734..753
FT                   /evidence="ECO:0007829|PDB:3KUL"
FT   HELIX           763..765
FT                   /evidence="ECO:0007829|PDB:3KUL"
FT   STRAND          766..768
FT                   /evidence="ECO:0007829|PDB:3KUL"
FT   STRAND          774..776
FT                   /evidence="ECO:0007829|PDB:3KUL"
FT   HELIX           802..804
FT                   /evidence="ECO:0007829|PDB:3KUL"
FT   HELIX           807..812
FT                   /evidence="ECO:0007829|PDB:3KUL"
FT   HELIX           817..832
FT                   /evidence="ECO:0007829|PDB:3KUL"
FT   TURN            833..835
FT                   /evidence="ECO:0007829|PDB:3KUL"
FT   TURN            838..841
FT                   /evidence="ECO:0007829|PDB:3KUL"
FT   HELIX           844..852
FT                   /evidence="ECO:0007829|PDB:3KUL"
FT   HELIX           865..874
FT                   /evidence="ECO:0007829|PDB:3KUL"
FT   HELIX           879..881
FT                   /evidence="ECO:0007829|PDB:3KUL"
FT   HELIX           885..897
FT                   /evidence="ECO:0007829|PDB:3KUL"
FT   HELIX           935..941
FT                   /evidence="ECO:0007829|PDB:1UCV"
FT   HELIX           945..947
FT                   /evidence="ECO:0007829|PDB:1UCV"
FT   HELIX           948..953
FT                   /evidence="ECO:0007829|PDB:1UCV"
FT   HELIX           959..962
FT                   /evidence="ECO:0007829|PDB:1UCV"
FT   HELIX           967..973
FT                   /evidence="ECO:0007829|PDB:1UCV"
FT   HELIX           978..995
FT                   /evidence="ECO:0007829|PDB:1UCV"
SQ   SEQUENCE   1005 AA;  111003 MW;  6FBF85535E4212B3 CRC64;
     MAPARGRLPP ALWVVTAAAA AATCVSAARG EVNLLDTSTI HGDWGWLTYP AHGWDSINEV
     DESFQPIHTY QVCNVMSPNQ NNWLRTSWVP RDGARRVYAE IKFTLRDCNS MPGVLGTCKE
     TFNLYYLESD RDLGASTQES QFLKIDTIAA DESFTGADLG VRRLKLNTEV RSVGPLSKRG
     FYLAFQDIGA CLAILSLRIY YKKCPAMVRN LAAFSEAVTG ADSSSLVEVR GQCVRHSEER
     DTPKMYCSAE GEWLVPIGKC VCSAGYEERR DACVACELGF YKSAPGDQLC ARCPPHSHSA
     APAAQACHCD LSYYRAALDP PSSACTRPPS APVNLISSVN GTSVTLEWAP PLDPGGRSDI
     TYNAVCRRCP WALSRCEACG SGTRFVPQQT SLVQASLLVA NLLAHMNYSF WIEAVNGVSD
     LSPEPRRAAV VNITTNQAAP SQVVVIRQER AGQTSVSLLW QEPEQPNGII LEYEIKYYEK
     DKEMQSYSTL KAVTTRATVS GLKPGTRYVF QVRARTSAGC GRFSQAMEVE TGKPRPRYDT
     RTIVWICLTL ITGLVVLLLL LICKKRHCGY SKAFQDSDEE KMHYQNGQAP PPVFLPLHHP
     PGKLPEPQFY AEPHTYEEPG RAGRSFTREI EASRIHIEKI IGSGDSGEVC YGRLRVPGQR
     DVPVAIKALK AGYTERQRRD FLSEASIMGQ FDHPNIIRLE GVVTRGRLAM IVTEYMENGS
     LDTFLRTHDG QFTIMQLVGM LRGVGAGMRY LSDLGYVHRD LAARNVLVDS NLVCKVSDFG
     LSRVLEDDPD AAYTTTGGKI PIRWTAPEAI AFRTFSSASD VWSFGVVMWE VLAYGERPYW
     NMTNRDVISS VEEGYRLPAP MGCPHALHQL MLDCWHKDRA QRPRFSQIVS VLDALIRSPE
     SLRATATVSR CPPPAFVRSC FDLRGGSGGG GGLTVGDWLD SIRMGRYRDH FAAGGYSSLG
     MVLRMNAQDV RALGITLMGH QKKILGSIQT MRAQLTSTQG PRRHL
//