Drug Miner Browse

Names & Taxonomy

Uniprot ID:: P07333
Entry Name:: CSF1R_HUMAN
Status:: reviewed
Protein Names:: Macrophage colony-stimulating factor 1 receptor (CSF-1 receptor) (CSF-1-R) (CSF-1R) (M-CSF-R) (EC 2.7.10.1) (Proto-oncogene c-Fms) (CD antigen CD115)
Gene Names:: CSF1R FMS
Gene Names Primary:: CSF1R
Organism:: Homo sapiens (Human)

Structure

Length:: 972
Sequence:: MGPGVLLLLLVATAWHGQGIPVIEPSVPELVVKPGATVTLRCVGNGSVEWDGPPSPHWTLYSDGSSSILSTNNATFQNTGTYRCTEPGDPLGGSAAIHLYVKDPARPWNVLAQEVVVFEDQDALLPCLLTDPVLEAGVSLVRVRGRPLMRHTNYSFSPWHGFTIHRAKFIQSQDYQCSALMGGRKVMSISIRLKVQKVIPGPPALTLVPAELVRIRGEAAQIVCSASSVDVNFDVFLQHNNTKLAIPQQSDFHNNRYQKVLTLNLDQVDFQHAGNYSCVASNVQGKHSTSMFFRVVESAYLNLSSEQNLIQEVTVGEGLNLKVMVEAYPGLQGFNWTYLGPFSDHQPEPKLANATTKDTYRHTFTLSLPRLKPSEAGRYSFLARNPGGWRALTFELTLRYPPEVSVIWTFINGSGTLLCAASGYPQPNVTWLQCSGHTDRCDEAQVLQVWDDPYPEVLSQEPFHKVTVQSLLTVETLEHNQTYECRAHNSVGSGSWAFIPISAGAHTHPPDEFLFTPVVVACMSIMALLLLLLLLLLYKYKQKPKYQVRWKIIESYEGNSYTFIDPTQLPYNEKWEFPRNNLQFGKTLGAGAFGKVVEATAFGLGKEDAVLKVAVKMLKSTAHADEKEALMSELKIMSHLGQHENIVNLLGACTHGGPVLVITEYCCYGDLLNFLRRKAEAMLGPSLSPGQDPEGGVDYKNIHLEKKYVRRDSGFSSQGVDTYVEMRPVSTSSNDSFSEQDLDKEDGRPLELRDLLHFSSQVAQGMAFLASKNCIHRDVAARNVLLTNGHVAKIGDFGLARDIMNDSNYIVKGNARLPVKWMAPESIFDCVYTVQSDVWSYGILLWEIFSLGLNPYPGILVNSKFYKLVKDGYQMAQPAFAPKNIYSIMQACWALEPTHRPTFQQICSFLQEQAQEDRRERDYTNLPSSSRSGGSGSSSSELEEESSSEHLTCCEQGDIAQPLLQPNNYQFC
Proteomes:: UP000005640

Subcellular location

Subcellular Location:: Cell membrane; Single-pass type I membrane protein.

Function

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.
Catalytic Activity:: ATP + a -L-tyrosine = ADP + a -L-tyrosine phosphate.
Enzyme Regulation:: ENZYME REGULATION: Present in an inactive conformation in the absence of bound ligand. CSF1 or IL34 binding leads to dimerization and activation by autophosphorylation on tyrosine residues. Inhibited by imatinib/STI-571 (Gleevec), dasatinib, sunitinib/SU11248, lestaurtinib/CEP-701, midostaurin/PKC-412, Ki20227, linifanib/ABT-869, Axitinib/AG013736, sorafenib/BAY 43-9006 and GW2580.
Active Site:: ACT_SITE 778 778 Proton acceptor.
Cross Reference Drug Bank:: DB00619 DB01268
Gene Ontology Go:: cell surface
CSF1-CSF1R complex
integral component of plasma membrane
intracellular
plasma membrane
ATP binding
cytokine binding
macrophage colony-stimulating factor receptor activity
protein homodimerization activity
axon guidance
cell proliferation
cell-cell junction maintenance
cellular response to cytokine stimulus
cellular response to macrophage colony-stimulating factor stimulus
cytokine-mediated signaling pathway
forebrain neuron differentiation
hemopoiesis
inflammatory response
innate immune response
macrophage colony-stimulating factor signaling pathway
macrophage differentiation
mammary gland duct morphogenesis
monocyte differentiation
multicellular organism development
negative regulation of apoptotic process
negative regulation of cell proliferation
olfactory bulb development
osteoclast differentiation
peptidyl-tyrosine phosphorylation
phosphatidylinositol metabolic process
phosphatidylinositol-mediated signaling
positive regulation of cell migration
positive regulation of cell motility
positive regulation of cell proliferation
positive regulation of chemokine secretion
positive regulation of ERK1 and ERK2 cascade
positive regulation of osteoclast differentiation
positive regulation of protein phosphorylation
positive regulation of protein serine/threonine kinase activity
positive regulation of protein tyrosine kinase activity
positive regulation of tyrosine phosphorylation of Stat3 protein
protein autophosphorylation
regulation of actin cytoskeleton reorganization
regulation of bone resorption
regulation of cell shape
ruffle organization
signal transduction
skeletal muscle tissue development
transmembrane receptor protein tyrosine kinase signaling pathway
Gene Ontology Biological Process:: axon guidance
cell-cell junction maintenance
cell proliferation
cellular response to cytokine stimulus
cellular response to macrophage colony-stimulating factor stimulus
cytokine-mediated signaling pathway
forebrain neuron differentiation
hemopoiesis
inflammatory response
innate immune response
macrophage colony-stimulating factor signaling pathway
macrophage differentiation
mammary gland duct morphogenesis
monocyte differentiation
multicellular organism development
negative regulation of apoptotic process
negative regulation of cell proliferation
olfactory bulb development
osteoclast differentiation
peptidyl-tyrosine phosphorylation
phosphatidylinositol-mediated signaling
phosphatidylinositol metabolic process
positive regulation of cell migration
positive regulation of cell motility
positive regulation of cell proliferation
positive regulation of chemokine secretion
positive regulation of ERK1 and ERK2 cascade
positive regulation of osteoclast differentiation
positive regulation of protein phosphorylation
positive regulation of protein serine/threonine kinase activity
positive regulation of protein tyrosine kinase activity
positive regulation of tyrosine phosphorylation of Stat3 protein
protein autophosphorylation
regulation of actin cytoskeleton reorganization
regulation of bone resorption
regulation of cell shape
ruffle organization
signal transduction
skeletal muscle tissue development
transmembrane receptor protein tyrosine kinase signaling pathway
Gene Ontology Molecular Function:: ATP binding
cytokine binding
macrophage colony-stimulating factor receptor activity
protein homodimerization activity
Gene Ontology Cellular Component:: cell surface
CSF1-CSF1R complex
integral component of plasma membrane
intracellular
plasma membrane
Keywords:: 3D-structure
ATP-binding
Alternative splicing
Cell membrane
Complete proteome
Disease mutation
Disulfide bond
Glycoprotein
Immunity
Immunoglobulin domain
Inflammatory response
Innate immunity
Kinase
Membrane
Nucleotide-binding
Phosphoprotein
Polymorphism
Proto-oncogene
Receptor
Reference proteome
Repeat
Signal
Transferase
Transmembrane
Transmembrane helix
Tyrosine-protein kinase
Ubl conjugation

Names & Taxonomy

Structure

Subcellular location

Function

Publication