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MGP000685

UniProt Annotations

Entry Information

Gene Name	v-crk avian sarcoma virus CT10 oncogene homolog
Protein Entry	CRK_HUMAN
UniProt ID	P46108
Species	Human

Comments

Comment type	Description
Alternative Products	Event=Alternative splicing; Named isoforms=2; Name=Crk-II; IsoId=P46108-1; Sequence=Displayed; Name=Crk-I; IsoId=P46108-2; Sequence=VSP_041153, VSP_041154; Note=Contains a phosphoserine at position 194.;
Domain	The C-terminal SH3 domain function as a negative modulator for transformation and the N-terminal SH3 domain appears to function as a positive regulator for transformation. {ECO:0000250}.
Domain	The SH2 domain mediates interaction with tyrosine phosphorylated proteins. Mediates interaction with SHB.
Function	The Crk-I and Crk-II forms differ in their biological activities. Crk-II has less transforming activity than Crk-I. Crk- II mediates attachment-induced MAPK8 activation, membrane ruffling and cell motility in a Rac-dependent manner. Involved in phagocytosis of apoptotic cells and cell motility via its interaction with DOCK1 and DOCK4. May regulate the EFNA5-EPHA3 signaling. {ECO:0000269\|PubMed:11870224, ECO:0000269\|PubMed:1630456, ECO:0000269\|PubMed:17515907}.
Interaction	P00519:ABL1; NbExp=2; IntAct=EBI-886, EBI-375543; P42684:ABL2; NbExp=5; IntAct=EBI-886, EBI-1102694; O15085:ARHGEF11; NbExp=2; IntAct=EBI-886, EBI-311099; Q9ULH1:ASAP1; NbExp=2; IntAct=EBI-886, EBI-346622; P54253:ATXN1; NbExp=3; IntAct=EBI-886, EBI-930964; P56945:BCAR1; NbExp=5; IntAct=EBI-886, EBI-702093; P22681:CBL; NbExp=6; IntAct=EBI-886, EBI-518228; P00533:EGFR; NbExp=3; IntAct=EBI-287556, EBI-297353; P21860:ERBB3; NbExp=2; IntAct=EBI-886, EBI-720706; P11362:FGFR1; NbExp=2; IntAct=EBI-886, EBI-1028277; P21333:FLNA; NbExp=3; IntAct=EBI-886, EBI-350432; Q14315:FLNC; NbExp=2; IntAct=EBI-886, EBI-489954; Q13480:GAB1; NbExp=2; IntAct=EBI-886, EBI-517684; O14654:IRS4; NbExp=8; IntAct=EBI-886, EBI-356594; P35968:KDR; NbExp=2; IntAct=EBI-886, EBI-1005487; P10721:KIT; NbExp=4; IntAct=EBI-886, EBI-1379503; Q92918:MAP4K1; NbExp=3; IntAct=EBI-886, EBI-881; Q9Y4K4:MAP4K5; NbExp=5; IntAct=EBI-886, EBI-1279; P45983:MAPK8; NbExp=2; IntAct=EBI-886, EBI-286483; P20774:OGN; NbExp=2; IntAct=EBI-886, EBI-1753690; P16234:PDGFRA; NbExp=4; IntAct=EBI-886, EBI-2861522; P27986:PIK3R1; NbExp=2; IntAct=EBI-886, EBI-79464; P29074:PTPN4; NbExp=3; IntAct=EBI-886, EBI-710431; Q13905:RAPGEF1; NbExp=3; IntAct=EBI-886, EBI-976876; Q9UPX8:SHANK2; NbExp=2; IntAct=EBI-886, EBI-1570571; P29353:SHC1; NbExp=3; IntAct=EBI-886, EBI-78835; O60493:SNX3; NbExp=2; IntAct=EBI-886, EBI-727209; Q07889:SOS1; NbExp=3; IntAct=EBI-886, EBI-297487; Q07890:SOS2; NbExp=2; IntAct=EBI-886, EBI-298181;
Ptm	Phosphorylated on Tyr-221 upon cell adhesion. Results in the negative regulation of the association with SH2- and SH3-binding partners, possibly by the formation of an intramolecular interaction of phosphorylated Tyr-221 with the SH2 domain. This leads finally to the down-regulation of the Crk signaling pathway. {ECO:0000269\|PubMed:17515907}.
Ptm	Phosphorylation of Crk-II (40 kDa) gives rise to a 42 kDa form. Isoform Crk-II is phosphorylated by KIT.
Ptm	Proline isomerization at Pro-237 by PPIA acts as a switch between two conformations: an autoinhibitory conformation in the cis form, where the tandem SH3 domains interact intramolecularly, and an activated conformation in the trans form. {ECO:0000250}.
Similarity	Belongs to the CRK family. {ECO:0000305}.
Similarity	Contains 1 SH2 domain. {ECO:0000255\|PROSITE- ProRule:PRU00191}.
Similarity	Contains 2 SH3 domains. {ECO:0000255\|PROSITE- ProRule:PRU00192}.
Subcellular Location	Cytoplasm {ECO:0000250}. Cell membrane {ECO:0000250}. Note=Translocated to the plasma membrane upon cell adhesion. {ECO:0000250}.
Subunit	Interacts with ABL1, C3G, DOCK3, MAP4K1, MAPK8 and SOS via its first SH3 domain. Interacts (via SH2 domain) with BCAR1, CBL, CBLB, PXN, IRS4 and GAB1 upon stimulus-induced tyrosine phosphorylation. Interacts (via SH2 domain) with several tyrosine- phosphorylated growth factor receptors such as EGFR and INSR. Interacts with FLT1 (tyrosine-phosphorylated). Interacts with DOCK1 and DOCK4. Interacts with SHB. Interacts with PEAK1. Interacts with FASLG. Isoform Crk-II interacts with KIT. Interacts with EPHA3; upon activation of EPHA3 by the ligand EFNA5 and EPHA3 tyrosine kinase activity-dependent. Interacts with EPHA3 (phosphorylated); mediates EFNA5-EPHA3 signaling through RHOA GTPase activation. Interacts with FLT4 (tyrosine-phosphorylated). Isoform Crk-II (via SH2 domain) interacts with PDGFRA (tyrosine phosphorylated) and PDGFRB (tyrosine phosphorylated). Part of a collagen stimulated complex involved in cell migration composed of CDC42, CRK, TNK2 and p130cas/BCAR1. Interacts (via SH2 domain) with the 'Tyr-9' phosphorylated form of PDPK1. Interacts with CBLC. Found in a complex with ABL1, ABL2, CRK and UNC119; leading to the inhibition of CRK phosphorylation by ABL kinases. {ECO:0000269\|PubMed:10362357, ECO:0000269\|PubMed:10733900, ECO:0000269\|PubMed:10964504, ECO:0000269\|PubMed:11870224, ECO:0000269\|PubMed:12384576, ECO:0000269\|PubMed:12628187, ECO:0000269\|PubMed:12878163, ECO:0000269\|PubMed:16076871, ECO:0000269\|PubMed:17038317, ECO:0000269\|PubMed:18024423, ECO:0000269\|PubMed:19381274, ECO:0000269\|PubMed:19807924, ECO:0000269\|PubMed:20534451, ECO:0000269\|PubMed:8657152, ECO:0000269\|PubMed:8662907, ECO:0000269\|PubMed:9614078}.
Web Resource	Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/CRKID40149ch17p13.html";