Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

FGR (P09769) - Overview - Molecular Target Synopsis

Protein


FGR, Tyrosine-protein kinase Fgr
Enzyme Classification 2.7.10.2
UniProt P09769

Also Known as FGR_HUMAN, FGR, SRC2

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. Interacts 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.

Isoforms / Transcripts (Protein Coding)


Drugs


FGR is targeted by Approved Drugs Dasatinib, Vandetanib. (see details)
Dasatinib
Vandetanib

Sub-cellular localization


UniProt: FGR is active in the following subcellular-locations: cell membrane, cell projection, cytoplasm, cytoskeleton, cytosol, mitochondrion inner membrane, mitochondrion intermembrane space, ruffle membrane.
GO terms: FGR is active in the following subcellular-locations: actin cytoskeleton, aggresome, cytosol, extracellular exosome, extracellular region, extrinsic component of cytoplasmic side of plasma membrane, mitochondrial inner membrane, mitochondrial intermembrane space, plasma membrane, ruffle membrane, secretory granule lumen.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project FGR has gain in 1 cell-lines, loss in 1 cell-lines and no signal in 1003 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: HL_60, KM12, HOP_92

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: COR-L26, CCRF-SB, EB2

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: CD14-positive monocyte, GM12878, CD20-positive B cell

(see details)

RNA Interference


FGR was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: H460, AC216. (see details)

3D Structures


At greater than 75% identity similarity to FGR there are:
72 structures (141 chains) solved
66 are solved in complex with at least one small molecule ligand
10 are solved with an approved drug

FGR is solved in complex with the approved drug(s):

AMP/ADENOSINE PHOSPHATE (3DQX_A, 3DQX_B),
DB8/BOSUTINIB (4MXO_A, 4MXO_B, 4MXX_A, 4MXX_B, 4MXY_A, 4MXY_B, 4MXZ_A, 4MXZ_B),
RXT/RUXOLITINIB (4U5J_A, 4U5J_B),
STI/IMATINIB (2OIQ_A, 3OEZ_A, 3OEZ_B),
1N1/DASATINIB (3G5D_A, 3G5D_B, 3QLG_A, 3QLG_B).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


FGR has been screened with 760 compounds (1398 bioactivities), 37 compounds have bioactivities that show binding affinity of <= 500nM (54 bioactivities). (see details)