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MGP001079

UniProt Annotations

Entry Information
Gene NameFGR proto-oncogene, Src family tyrosine kinase
Protein EntryFGR_HUMAN
UniProt IDP09769
SpeciesHuman
Comments
Comment typeDescription
Catalytic ActivityATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. {ECO:0000255|PROSITE- ProRule:PRU10028, ECO:0000269|PubMed:1737799, ECO:0000269|PubMed:2181286, ECO:0000269|PubMed:8327512}.
DiseaseNote=Mutations that cause aberrant kinase activation can confer oncogene activity and promote aberrant cell proliferation.
Enzyme RegulationActivated by autophosphorylation. Prior phosphorylation at Tyr-523 by SRC inhibits ulterior autophosphorylation at Tyr-412. Activated by phorbol myristate acetate, phosphatidic acid and poly-Lys. Binding (via SH2 domain) of HCLS1 that is already phosphorylated by SYK strongly increases kinase activity. {ECO:0000269|PubMed:11078731, ECO:0000269|PubMed:8327512, ECO:0000269|PubMed:8603737}.
FunctionNon-receptor tyrosine-protein kinase that transmits signals from cell surface receptors devoid of kinase activity and contributes to the regulation of immune responses, including neutrophil, monocyte, macrophage and mast cell functions, cytoskeleton remodeling in response to extracellular stimuli, phagocytosis, cell adhesion and migration. Promotes mast cell degranulation, release of inflammatory cytokines and IgE-mediated anaphylaxis. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as MS4A2/FCER1B, FCGR2A and/or FCGR2B. Acts downstream of ITGB1 and ITGB2, and regulates actin cytoskeleton reorganization, cell spreading and adhesion. Depending on the context, activates or inhibits cellular responses. Functions as negative regulator of ITGB2 signaling, phagocytosis and SYK activity in monocytes. Required for normal ITGB1 and ITGB2 signaling, normal cell spreading and adhesion in neutrophils and macrophages. Functions as positive regulator of cell migration and regulates cytoskeleton reorganization via RAC1 activation. Phosphorylates SYK (in vitro) and promotes SYK- dependent activation of AKT1 and MAP kinase signaling. Phosphorylates PLD2 in antigen-stimulated mast cells, leading to PLD2 activation and the production of the signaling molecules lysophosphatidic acid and diacylglycerol. Promotes activation of PIK3R1. Phosphorylates FASLG, and thereby regulates its ubiquitination and subsequent internalization. Phosphorylates ABL1. Promotes phosphorylation of CBL, CTTN, PIK3R1, PTK2/FAK1, PTK2B/PYK2 and VAV2. Phosphorylates HCLS1 that has already been phosphorylated by SYK, but not unphosphorylated HCLS1. {ECO:0000269|PubMed:10739672, ECO:0000269|PubMed:17164290, ECO:0000269|PubMed:1737799, ECO:0000269|PubMed:7519620}.
InteractionP09917:ALOX5; NbExp=2; IntAct=EBI-1383732, EBI-79934; P10275:AR; NbExp=3; IntAct=EBI-1383732, EBI-608057; P00533:EGFR; NbExp=2; IntAct=EBI-1383732, EBI-297353; P04626:ERBB2; NbExp=3; IntAct=EBI-1383732, EBI-641062; P08238:HSP90AB1; NbExp=2; IntAct=EBI-1383732, EBI-352572; P10721:KIT; NbExp=2; IntAct=EBI-1383732, EBI-1379503; P08581:MET; NbExp=2; IntAct=EBI-1383732, EBI-1039152;
PtmPhosphorylated. Autophosphorylated on tyrosine residues. Becomes phosphorylated in response to FCGR2A and/or FCGR2B engagement, cell adhesion and signaling by ITGB2. Prior phosphorylation at Tyr-523 by SRC inhibits ulterior autophosphorylation at Tyr-412. {ECO:0000269|PubMed:10739672, ECO:0000269|PubMed:19369195, ECO:0000269|PubMed:7519620}.
PtmUbiquitinated. Becomes ubiquitinated in response to ITGB2 signaling; this does not lead to degradation. {ECO:0000269|PubMed:12435267}.
SimilarityBelongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily. {ECO:0000255|PROSITE- ProRule:PRU00159}.
SimilarityContains 1 protein kinase domain. {ECO:0000255|PROSITE-ProRule:PRU00159}.
SimilarityContains 1 SH2 domain. {ECO:0000255|PROSITE- ProRule:PRU00191}.
SimilarityContains 1 SH3 domain. {ECO:0000255|PROSITE- ProRule:PRU00192}.
Subcellular LocationCell membrane {ECO:0000305}; Lipid-anchor {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Cell projection, ruffle membrane. Cytoplasm, cytosol. Cytoplasm, cytoskeleton. Mitochondrion inner membrane {ECO:0000250}. Mitochondrion intermembrane space {ECO:0000250}. Note=Detected in mitochondrial intermembrane space and at inner membranes (By similarity). Colocalizes with actin fibers at membrane ruffles. Detected at plasma membrane lipid rafts. {ECO:0000250}.
SubunitInteracts with ITGB1, ITGB2, MS4A2/FCER1B, FCER1G, FCGR2A and/or FCGR2B. Interacts (via SH2 domain) with SYK (tyrosine phosphorylated). Interacts (via SH2 domain) with FLT3 (tyrosine phosphorylated). Interacts with PTK2/FAK1. Interacts (via SH2 domain) with HCLS1 (tyrosine phosphorylated by SYK). Interacts with SIRPA and PTPNS1. Interacts (not phosphorylated on tyrosine residues) with CBL; FGR tyrosine phosphorylation promotes dissociation. Interacts with PIK3R1 and FASLG (By similarity). {ECO:0000250}.
Tissue SpecificityDetected in neutrophils, monocytes and natural killer cells (at protein level). Detected in monocytes and large lymphocytes. {ECO:0000269|PubMed:11078731, ECO:0000269|PubMed:2181286, ECO:0000269|PubMed:8327512}.
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