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

CSF1R (P07333) - Overview - Molecular Target Synopsis

Protein


CSF1R, Macrophage colony-stimulating factor 1 receptor
Enzyme Classification 2.7.10.1
UniProt P07333

Also Known as CSF1R_HUMAN, CSF1R, FMS

Tyrosine-protein kinase that acts as cell-surface receptor for CSF1 and IL34 and plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes, such as macrophages and monocytes. Promotes the release of proinflammatory chemokines in response to IL34 and CSF1, and thereby plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, the regulation of bone resorption, and is required for normal bone and tooth development. Required for normal male and female fertility, and for normal development of milk ducts and acinar structures in the mammary gland during pregnancy. Promotes reorganization of the actin cytoskeleton, regulates formation of membrane ruffles, cell adhesion and cell migration, and promotes cancer cell invasion. Activates several signaling pathways in response to ligand binding. Phosphorylates PIK3R1, PLCG2, GRB2, SLA2 and CBL. Activation of PLCG2 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, that then lead to the activation of protein kinase C family members, especially PRKCD. Phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leads to activation of the AKT1 signaling pathway. Activated CSF1R also mediates activation of the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1, and of the SRC family kinases SRC, FYN and YES1. Activated CSF1R transmits signals both via proteins that directly interact with phosphorylated tyrosine residues in its intracellular domain, or via adapter proteins, such as GRB2. Promotes activation of STAT family members STAT3, STAT5A and/or STAT5B. Promotes tyrosine phosphorylation of SHC1 and INPP5D/SHIP-1. Receptor signaling is down-regulated by protein phosphatases, such as INPP5D/SHIP-1, that dephosphorylate the receptor and its downstream effectors, and by rapid internalization of the activated receptor. Interacts with INPPL1/SHIP2 and THOC5 (By similarity). Monomer. Homodimer. Interacts with CSF1 and IL34. Interaction with dimeric CSF1 or IL34 leads to receptor homodimerization. Interacts (tyrosine phosphorylated) with PLCG2 (via SH2 domain). Interacts (tyrosine phosphorylated) with PIK3R1 (via SH2 domain). Interacts (tyrosine phosphorylated) with FYN, YES1 and SRC (via SH2 domain). Interacts (tyrosine phosphorylated) with CBL, GRB2 and SLA2.

4R7H
CRYSTAL STRUCTURE OF FMS KINASE DOMAIN WITH A SMALL MOLECULAR INHIBITOR, PLX3397
RCSB/PDB
Inspect Structure
See all 3D Structures for CSF1R

Isoforms / Transcripts (Protein Coding)


Drugs


CSF1R is targeted by Approved Drugs Pazopanib, Sunitinib. (see details)
Pazopanib
Sunitinib

Sub-cellular localization


UniProt: CSF1R is active in the following subcellular-locations: cell membrane.
GO terms: CSF1R is active in the following subcellular-locations: cell surface, CSF1-CSF1R complex, integral component of plasma membrane, intracellular membrane-bounded organelle, nucleoplasm, plasma membrane, receptor complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project CSF1R has gain in 1 cell-lines, loss in 1 cell-lines and no signal in 1002 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SR, HOP_92, SK_MEL_5

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: UKE-1, SKM-1, THP-1

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, SK-N-SH, NHLF

(see details)

RNA Interference


CSF1R was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: HCC202, HUO3N1. (see details)

3D Structures


For CSF1R there are:
17 structures (18 chains) solved
15 are solved in complex with at least one small molecule ligand
1 are solved with an approved drug

CSF1R is solved in complex with the approved drug(s):

STI/IMATINIB (4R7I_A).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


CSF1R has been screened with 1805 compounds (2628 bioactivities), 824 compounds have bioactivities that show binding affinity of <= 500nM (960 bioactivities). (see details)