FGR - Tyrosine-protein kinase Fgr - human protein (Function)
 
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FGR »  Tyrosine-protein kinase Fgr   [ EC 2.7.10.2 ]
 
Protein also known as:  Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog.
Gene name:  FGR
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
Non-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.  
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  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
Fc-gamma receptor I complex bindingdefinition[GO:0034988]  
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  • IDAUniProtKB
Immunoglobulin receptor bindingdefinition[GO:0034987]  
  • ISSOrtholog Curator
Non-membrane spanning protein tyrosine kinase activitydefinition[GO:0004715]  
1
  • IDAUniProtKB
Phosphotyrosine bindingdefinition[GO:0001784]  
  • ISSOrtholog Curator
Protein bindingdefinition[GO:0005515]  
2
  • IPIIntAct
Protein kinase bindingdefinition[GO:0019901]  
  • ISSOrtholog Curator
Protein tyrosine kinase activitydefinition[GO:0004713]  
1
  • IDAUniProtKB
GO biological process 
Defense response to Gram-positive bacteriumdefinition[GO:0050830]  
  • ISSOrtholog Curator
Immune response-regulating cell surface receptor signaling pathwaydefinition[GO:0002768]  
1
  • TASUniProtKB
Integrin-mediated signaling pathwaydefinition[GO:0007229]  
2
  • IMPUniProtKB
  • ISSOrtholog Curator
Peptidyl-tyrosine phosphorylationdefinition[GO:0018108]  
2
  • IDAUniProtKB
Positive regulation of cell migrationdefinition[GO:0030335]  
  • ISSOrtholog Curator
Positive regulation of cytokine secretiondefinition[GO:0050715]  
  • ISSOrtholog Curator
Positive regulation of mast cell degranulationdefinition[GO:0043306]  
  • ISSOrtholog Curator
Positive regulation of phosphatidylinositol 3-kinase activitydefinition[GO:0043552]  
1
  • IMPUniProtKB
Positive regulation of phosphatidylinositol 3-kinase signalingdefinition[GO:0014068]  
1
  • IMPUniProtKB
Protein autophosphorylationdefinition[GO:0046777]  
2
  • IDAUniProtKB
Protein phosphorylationdefinition[GO:0006468]  
1
  • TASPINC
Regulation of cell shapedefinition[GO:0008360]  
  • ISSOrtholog Curator
Regulation of innate immune responsedefinition[GO:0045088]  
  • ISSOrtholog Curator
Regulation of phagocytosisdefinition[GO:0050764]  
  • ISSOrtholog Curator
Regulation of protein kinase activitydefinition[GO:0045859]  
  • ISSOrtholog Curator
Response to virusdefinition[GO:0009615]  
1
  • TASPINC
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.10.2: ATP + a [protein]-L-tyrosine ADP + a [protein]-L-tyrosine phosphate.  
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  • CuratedUniProtKB
It is regulated in the following manner
Activated 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.  
3
  • CuratedUniProtKB
Pathways 
According to KEGG, this protein belongs to the following pathway:
Chemokine signaling pathway  hsa04062+2268  
According to Reactome, this protein belongs to the following pathways:
Hemostasis  REACT_604  
Immune System  REACT_6900  
 

Keywords

Biological process 
Immunity  definition   [KW-0391]
Innate immunity  definition   [KW-0399]
Molecular function 
Kinase  definition   [KW-0418]
Transferase  definition   [KW-0808]
Tyrosine-protein kinase  definition   [KW-0829]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: FGR_(gene)
GenomeRNAi: 2268
PRO: PR:P09769
Chemistry
GuidetoPHARMACOLOGY: 2024