EPHA8_HUMAN
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 03-AUG-2022, entry version 219.
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; 33.
DR IntAct; P29322; 11.
DR MINT; P29322; -.
DR STRING; 9606.ENSP00000166244; -.
DR BindingDB; P29322; -.
DR ChEMBL; CHEMBL4134; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; P29322; -.
DR GuidetoPHARMACOLOGY; 1828; -.
DR GlyGen; P29322; 3 sites.
DR iPTMnet; P29322; -.
DR PhosphoSitePlus; P29322; -.
DR BioMuta; EPHA8; -.
DR DMDM; 19857975; -.
DR EPD; P29322; -.
DR jPOST; P29322; -.
DR MassIVE; P29322; -.
DR MaxQB; P29322; -.
DR PaxDb; P29322; -.
DR PeptideAtlas; P29322; -.
DR PRIDE; P29322; -.
DR ProteomicsDB; 54538; -. [P29322-1]
DR ProteomicsDB; 54539; -. [P29322-2]
DR Antibodypedia; 4046; 172 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 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; 933071at2759; -.
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; 10 hits in 1102 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 46 other tissues.
DR Genevisible; P29322; HS.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0043005; C:neuron projection; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
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: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; 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:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISS:UniProtKB.
DR GO; GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; ISS:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; 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 GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
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; IPR001090; Ephrin_rcpt_lig-bd_dom.
DR InterPro; IPR020691; EphrinA_rcpt8.
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; PTHR24416:SF339; PTHR24416:SF339; 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; 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 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; 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
