Q00495
uniprot
Q00495
canonical
activity_regulation
ACTIVITY 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 (By similarity). {ECO:0000250}.
uniprot
proteins
amino_acid_sequence
MELGPPLVLLLATVWHGQGAPVIEPSGPELVVEPGETVTLRCVSNGSVEWDGPISPYWTLDPESPGSTLTTRNATFKNTGTYRCTELEDPMAGSTTIHLYVKDPAHSWNLLAQEVTVVEGQEAVLPCLITDPALKDSVSLMREGGRQVLRKTVYFFSAWRGFIIRKAKVLDSNTYVCKTMVNGRESTSTGIWLKVNRVHPEPPQIKLEPSKLVRIRGEAAQIVCSATNAEVGFNVILKRGDTKLEIPLNSDFQDNYYKKVRALSLNAVDFQDAGIYSCVASNDVGTRTATMNFQVVESAYLNLTSEQSLLQEVSVGDSLILTVHADAYPSIQHYNWTYLGPFFEDQRKLEFITQRAIYRYTFKLFLNRVKASEAGQYFLMAQNKAGWNNLTFELTLRYPPEVSVTWMPVNGSDVLFCDVSGYPQPSVTWMECRGHTDRCDEAQALQVWNDTHPEVLSQKPFDKVIIQSQLPIGTLKHNMTYFCKTHNSVGNSSQYFRAVSLGQSKQLPDESLFTPVVVACMSVMSLLVLLLLLLLYKYKQKPKYQVRWKIIERYEGNSYTFIDPTQLPYNEKWEFPRNNLQFGKTLGAGAFGKVVEATAFGLGKEDAVLKVAVKMLKSTAHADEKEALMSELKIMSHLGQHENIVNLLGACTHGGPVLVITEYCCYGDLLNFLRRKAEAMLGPSLSPGQDSEGDSSYKNIHLEKKYVRRDSGFSSQGVDTYVEMRPVSTSSSDSFFKQDLDKEPSRPLELWDLLHFSSQVAQGMAFLASKNCIHRDVAARNVLLTSGHVAKIGDFGLARDIMNDSNYVVKGNARLPVKWMAPESILYCVYTVQSDVWSYGILLWEIFSLGLNPYPGILVNNKFYKLVKDGYQMAQPVFAPKNIYSIMQSCWDLEPTRRPTFQQICFLLQEQARLERRDQDYANLPSSGGSSGSDSGGGSSGGSSSEPEEESSSEHLACCEPGDIAQPLLQPNNYQFAC
uniprot
proteins
ec_number
2.7.10.1
uniprot
proteins
function
FUNCTION: Tyrosine-protein kinase that acts as a 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 pro-inflammatory 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, including the ERK1/2 and the JNK pathway (By similarity). 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 (By similarity). In the central nervous system, may play a role in the development of microglia macrophages (By similarity). {ECO:0000250|UniProtKB:P07333, ECO:0000269|PubMed:17121910}.
uniprot
proteins
mass_dalton
109264
uniprot
proteins
post_translational_modification
PTM: Autophosphorylated in response to CSF1 or IL34 binding. Phosphorylation at Tyr-559 is important for normal down-regulation of signaling by ubiquitination, internalization and degradation. Phosphorylation at Tyr-559 and Tyr-807 is important for interaction with SRC family members, including FYN, YES1 and SRC, and for subsequent activation of these protein kinases. Phosphorylation at Tyr-697 and Tyr-921 is important for interaction with GRB2. Phosphorylation at Tyr-721 is important for interaction with PIK3R1. Phosphorylation at Tyr-721 and Tyr-807 is important for interaction with PLCG2. Phosphorylation at Tyr-974 is important for interaction with CBL. Dephosphorylation by PTPN2 negatively regulates downstream signaling and macrophage differentiation (By similarity). {ECO:0000250}.; PTM: Ubiquitinated. Becomes rapidly polyubiquitinated after autophosphorylation, leading to its degradation (By similarity). {ECO:0000250}.
uniprot
proteins
protein_family
CSF-1/PDGF receptor subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
Tyr protein kinase family
uniprot
proteins
pubmed
1389227
uniprot
proteins
pubmed
17121910
uniprot
proteins
sequence_length
978
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Note=The autophosphorylated receptor is ubiquitinated and internalized, leading to its degradation. {ECO:0000250}.
uniprot
proteins
transmembrane_region
TRANSMEM 516..536; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins