InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: FGR

Summary

InnateDB Protein

IDBP-94941.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

FGR

Protein Name

Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog

Synonyms

c-fgr; c-src2; p55-Fgr; p55c-fgr; p58-Fgr; p58c-fgr; SRC2;

Species

Homo sapiens

Ensembl Protein

ENSP00000363116

InnateDB Gene

IDBG-94937 (FGR)

Protein Structure

UniProt Annotation

Function

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. {ECO:0000269PubMed:10739672, ECO:0000269PubMed:17164290, ECO:0000269PubMed:1737799, ECO:0000269PubMed:7519620}.

Subcellular Localization

Cell 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}.

Disease Associations

Note=Mutations that cause aberrant kinase activation can confer oncogene activity and promote aberrant cell proliferation.

Tissue Specificity

Detected in neutrophils, monocytes and natural killer cells (at protein level). Detected in monocytes and large lymphocytes. {ECO:0000269PubMed:11078731, ECO:0000269PubMed:2181286, ECO:0000269PubMed:8327512}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 31 experimentally validated interaction(s) in this database.
They are also associated with 5 interaction(s) predicted by orthology.

Experimentally validated
Total	31 [view]
Protein-Protein	31 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	5 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0001784	phosphotyrosine binding
GO:0004672	protein kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0004715	non-membrane spanning protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0019901	protein kinase binding
GO:0034987	immunoglobulin receptor binding
GO:0034988	Fc-gamma receptor I complex binding

Biological Process

GO:0002768	immune response-regulating cell surface receptor signaling pathway
GO:0006468	protein phosphorylation
GO:0007229	integrin-mediated signaling pathway
GO:0007596	blood coagulation
GO:0008360	regulation of cell shape
GO:0009615	response to virus
GO:0014068	positive regulation of phosphatidylinositol 3-kinase signaling
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0030335	positive regulation of cell migration
GO:0038096	Fc-gamma receptor signaling pathway involved in phagocytosis
GO:0043306	positive regulation of mast cell degranulation
GO:0043552	positive regulation of phosphatidylinositol 3-kinase activity
GO:0045087	innate immune response
GO:0045088	regulation of innate immune response
GO:0045859	regulation of protein kinase activity
GO:0046777	protein autophosphorylation
GO:0050715	positive regulation of cytokine secretion
GO:0050764	regulation of phagocytosis
GO:0050830	defense response to Gram-positive bacterium

Cellular Component

GO:0005743	mitochondrial inner membrane
GO:0005758	mitochondrial intermembrane space
GO:0005829	cytosol
GO:0005856	cytoskeleton
GO:0005886	plasma membrane
GO:0015629	actin cytoskeleton
GO:0032587	ruffle membrane
GO:0070062	extracellular vesicular exosome

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR000980 SH2 domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR001452 SH3 domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR011511 Variant SH3 domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM