Tyrosine-protein kinase Fgr

UniProt P09769 Organism Homo sapiens Gene FGR, SRC2 EC 2.7.10.2

Also known as: FGR, SRC2

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 a 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 a 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. Together with CLNK, it acts as a negative regulator of natural killer cell-activating receptors and inhibits interferon-gamma production (By similarity).

Classification

Family (Pfam): PF07714 PK_Tyr_Ser-Thr, PF00017 SH2, PF00018 SH3_1
InterPro: Fgr_SH2, Kinase-like_dom_sf, Non-receptor_tyrosine_kinases, Prot_kinase_dom, Protein_kinase_ATP_BS, Ser-Thr/Tyr_kinase_cat_dom, SH2, SH2_dom_sf, SH3-like_dom_sf, SH3_domain, Tyr_kinase_AS, Tyr_kinase_cat_dom
Functional cluster: Serine/Threonine Protein Kinases

Experimental structures · PDB · 3

7JT9 X-ray 1.93A
7UY0 X-ray 2.55A
7UY3 X-ray 2.99A

A predicted model is available from AlphaFold.

Gene Ontology · 38

Drugs targeting this protein · 5

DASATINIB ANHYDROUS inhibitor
ILORASERTIB inhibitor
XL-228 inhibitor
TG100-801 inhibitor
ENMD-981693 inhibitor

Related proteins · sequence + function similarity

Tyrosine-protein kinase Fgr 0.99
Tyrosine-protein kinase Fgr 0.98
Proto-oncogene tyrosine-protein kinase Yrk 0.98
Tyrosine-protein kinase Src-1 0.96
Tyrosine-protein kinase fyna 0.96
Tyrosine-protein kinase Src-2 0.96
Tyrosine-protein kinase Fyn 0.96
Proto-oncogene tyrosine-protein kinase LCK 0.96
Proto-oncogene tyrosine-protein kinase Src 0.96
Tyrosine-protein kinase Fyn 0.96
Tyrosine-protein kinase Lck 0.95
Tyrosine-protein kinase transforming protein Src 0.95

Co-cited proteins · studied together in the literature

Tumor necrosis factor ligand superfamily member 6 1 shared papers
Low affinity immunoglobulin gamma Fc region receptor II-a 1 shared papers
Low affinity immunoglobulin gamma Fc region receptor II-b 1 shared papers
E3 ubiquitin-protein ligase CBL 1 shared papers
Phosphatidylinositol 3-kinase regulatory subunit alpha 1 shared papers

Literature · 19 cited papers

Large-scale proteomics analysis of the human kinome. Mol. Cell. Proteomics · 2009
Patterns of somatic mutation in human cancer genomes. Nature · 2007
Sorting of Fas ligand to secretory lysosomes is regulated by mono-ubiquitylation and phosphorylation. J. Cell Sci. · 2007
The DNA sequence and biological annotation of human chromosome 1. Nature · 2006
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
Fgr but not Syk tyrosine kinase is a target for beta 2 integrin-induced c-Cbl-mediated ubiquitination in adherent human neutrophils. Biochem. J. · 2003
Phosphatidic acid regulates tyrosine phosphorylating activity in human neutrophils: enhancement of Fgr activity. J. Biol. Chem. · 2001
Clustering of beta(2)-integrins on human neutrophils activates dual signaling pathways to PtdIns 3-kinase. Exp. Cell Res. · 2000
Activation of SRC family kinases in human neutrophils. Evidence that p58C-FGR and p53/56LYN redistributed to a Triton X-100-insoluble cytoskeletal fraction, also enriched in the caveolar protein caveolin, display an enhanced kinase activity. FEBS Lett. · 1996
Association of immunoglobulin G Fc receptor II with Src-like protein-tyrosine kinase Fgr in neutrophils. Proc. Natl. Acad. Sci. U.S.A. · 1993
Beta 2 integrin-dependent protein tyrosine phosphorylation and activation of the FGR protein tyrosine kinase in human neutrophils. J. Cell Biol. · 1994
Isolation and sequencing of cDNA clones homologous to the v-fgr oncogene from a human B lymphocyte cell line, IM-9. Oncogene · 1987
… and 7 more in the literature graph

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