InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: CSF1R

Summary

InnateDB Protein

IDBP-53270.6

Last Modified

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

Gene Symbol

CSF1R

Protein Name

colony stimulating factor 1 receptor

Synonyms

C-FMS; CD115; CSF-1R; CSFR; FIM2; FMS; HDLS; M-CSF-R;

Species

Homo sapiens

Ensembl Protein

ENSP00000286301

InnateDB Gene

IDBG-53268 (CSF1R)

Protein Structure

UniProt Annotation

Function

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. {ECO:0000269PubMed:12882960, ECO:0000269PubMed:15117969, ECO:0000269PubMed:16170366, ECO:0000269PubMed:16337366, ECO:0000269PubMed:16648572, ECO:0000269PubMed:17121910, ECO:0000269PubMed:18467591, ECO:0000269PubMed:18814279, ECO:0000269PubMed:19193011, ECO:0000269PubMed:19934330, ECO:0000269PubMed:20489731, ECO:0000269PubMed:20504948, ECO:0000269PubMed:20829061, ECO:0000269PubMed:7683918}.

Subcellular Localization

Cell membrane; Single-pass type I membrane protein.

Disease Associations

Note=Aberrant expression of CSF1 or CSF1R can promote cancer cell proliferation, invasion and formation of metastases. Overexpression of CSF1 or CSF1R is observed in a significant percentage of breast, ovarian, prostate, and endometrial cancers.Note=Aberrant expression of CSF1 or CSF1R may play a role in inflammatory diseases, such as rheumatoid arthritis, glomerulonephritis, atherosclerosis, and allograft rejection.Leukoencephalopathy, diffuse hereditary, with spheroids (HDLS) [MIM:221820]: An autosomal dominant adult-onset rapidly progressive neurodegenerative disorder characterized by variable behavioral, cognitive, and motor changes. Patients often die of dementia within 6 years of onset. Brain imaging shows patchy abnormalities in the cerebral white matter, predominantly affecting the frontal and parietal lobes. {ECO:0000269PubMed:22197934}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Expressed in bone marrow and in differentiated blood mononuclear cells.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 44 experimentally validated interaction(s) in this database.
They are also associated with 19 interaction(s) predicted by orthology.

Experimentally validated
Total	44 [view]
Protein-Protein	35 [view]
Protein-DNA	9 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	19 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0004714	transmembrane receptor protein tyrosine kinase activity
GO:0005011	macrophage colony-stimulating factor receptor activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0019903	protein phosphatase binding
GO:0019955	cytokine binding
GO:0042803	protein homodimerization activity

Biological Process

GO:0001934	positive regulation of protein phosphorylation
GO:0006468	protein phosphorylation
GO:0006954	inflammatory response
GO:0007165	signal transduction
GO:0007169	transmembrane receptor protein tyrosine kinase signaling pathway
GO:0007275	multicellular organismal development
GO:0008283	cell proliferation
GO:0008284	positive regulation of cell proliferation
GO:0008360	regulation of cell shape
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0019221	cytokine-mediated signaling pathway
GO:0030097	hemopoiesis
GO:0030224	monocyte differentiation
GO:0030225	macrophage differentiation
GO:0030316	osteoclast differentiation
GO:0030335	positive regulation of cell migration
GO:0031529	ruffle organization
GO:0036006	cellular response to macrophage colony-stimulating factor stimulus
GO:0038145	macrophage colony-stimulating factor signaling pathway
GO:0042517	positive regulation of tyrosine phosphorylation of Stat3 protein
GO:0045087	innate immune response
GO:0045124	regulation of bone resorption
GO:0045217	cell-cell junction maintenance
GO:0046488	phosphatidylinositol metabolic process
GO:0046777	protein autophosphorylation
GO:0048015	phosphatidylinositol-mediated signaling
GO:0060603	mammary gland duct morphogenesis
GO:0061098	positive regulation of protein tyrosine kinase activity
GO:0070374	positive regulation of ERK1 and ERK2 cascade
GO:0071345	cellular response to cytokine stimulus
GO:0071902	positive regulation of protein serine/threonine kinase activity
GO:0090197	positive regulation of chemokine secretion
GO:2000147	positive regulation of cell motility
GO:2000249	regulation of actin cytoskeleton reorganization

Cellular Component

GO:0005886	plasma membrane
GO:0005887	integral component of plasma membrane
GO:0009986	cell surface
GO:0016021	integral component of membrane
GO:0043235	receptor complex

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR003598 Immunoglobulin subtype 2
IPR003599 Immunoglobulin subtype
IPR007110 Immunoglobulin-like domain
IPR011009 Protein kinase-like domain
IPR013151 Immunoglobulin
IPR016243 Tyrosine-protein kinase, CSF-1/PDGF receptor
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714
PF00047

PRINTS

PR00109

PIRSF

PIRSF000615
PIRSF500947

SMART

SM00220
SM00408
SM00409
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References