CSF1R
entrez
1436
canonical
uniprot
P07333
canonical
ensembl
ENSG00000182578
resolver
ensp
ENSP00000286301
resolver
ensp
ENSP00000501699
resolver
ensp
ENSP00000581172
resolver
genesymbol
CSF1R
resolver
genesymbol_syn
FMS
resolver
hgnc
HGNC:2433
resolver
uniprot
B5A955
resolver
uniprot
D3DQG2
resolver
uniprot
Q6LDW5
resolver
uniprot
Q6LDY4
resolver
uniprot
Q86VW7
resolver
uniprot_entry
CSF1R_HUMAN
resolver
uniprot_sec
B5A955
resolver
uniprot_sec
D3DQG2
resolver
uniprot_sec
Q6LDW5
resolver
uniprot_sec
Q6LDY4
resolver
uniprot_sec
Q86VW7
resolver
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. 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. {ECO:0000269|PubMed:16170366, ECO:0000269|PubMed:16648572, ECO:0000269|PubMed:17121910, ECO:0000269|PubMed:18814279, ECO:0000269|PubMed:20137931, ECO:0000269|PubMed:20156689, ECO:0000269|PubMed:20489731}.
uniprot
proteins
amino_acid_sequence
MGPGVLLLLLVATAWHGQGIPVIEPSVPELVVKPGATVTLRCVGNGSVEWDGPPSPHWTLYSDGSSSILSTNNATFQNTGTYRCTEPGDPLGGSAAIHLYVKDPARPWNVLAQEVVVFEDQDALLPCLLTDPVLEAGVSLVRVRGRPLMRHTNYSFSPWHGFTIHRAKFIQSQDYQCSALMGGRKVMSISIRLKVQKVIPGPPALTLVPAELVRIRGEAAQIVCSASSVDVNFDVFLQHNNTKLAIPQQSDFHNNRYQKVLTLNLDQVDFQHAGNYSCVASNVQGKHSTSMFFRVVESAYLNLSSEQNLIQEVTVGEGLNLKVMVEAYPGLQGFNWTYLGPFSDHQPEPKLANATTKDTYRHTFTLSLPRLKPSEAGRYSFLARNPGGWRALTFELTLRYPPEVSVIWTFINGSGTLLCAASGYPQPNVTWLQCSGHTDRCDEAQVLQVWDDPYPEVLSQEPFHKVTVQSLLTVETLEHNQTYECRAHNSVGSGSWAFIPISAGAHTHPPDEFLFTPVVVACMSIMALLLLLLLLLLYKYKQKPKYQVRWKIIESYEGNSYTFIDPTQLPYNEKWEFPRNNLQFGKTLGAGAFGKVVEATAFGLGKEDAVLKVAVKMLKSTAHADEKEALMSELKIMSHLGQHENIVNLLGACTHGGPVLVITEYCCYGDLLNFLRRKAEAMLGPSLSPGQDPEGGVDYKNIHLEKKYVRRDSGFSSQGVDTYVEMRPVSTSSNDSFSEQDLDKEDGRPLELRDLLHFSSQVAQGMAFLASKNCIHRDVAARNVLLTNGHVAKIGDFGLARDIMNDSNYIVKGNARLPVKWMAPESIFDCVYTVQSDVWSYGILLWEIFSLGLNPYPGILVNSKFYKLVKDGYQMAQPAFAPKNIYSIMQACWALEPTHRPTFQQICSFLQEQAQEDRRERDYTNLPSSSRSGGSGSSSSELEEESSSEHLTCCEQGDIAQPLLQPNNYQFC
uniprot
proteins
disease_involvement
DISEASE: 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.; DISEASE: Note=Aberrant expression of CSF1 or CSF1R may play a role in inflammatory diseases, such as rheumatoid arthritis, glomerulonephritis, atherosclerosis, and allograft rejection.; DISEASE: Leukoencephalopathy, hereditary diffuse, with spheroids 1 (HDLS1) [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:0000269|PubMed:22197934, ECO:0000269|PubMed:23408870, ECO:0000269|PubMed:24336230, ECO:0000269|PubMed:24532199}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS) [MIM:618476]: An autosomal recessive disease with variable manifestations. Main features are brain malformations with calcifying leukoencephalopathy, progressive neurodegeneration, and bone sclerotic features. The age at onset ranges from infancy to early adulthood. Neurologic features include loss of previous motor and language skills, cognitive impairment, spasticity, and focal seizures. Brain imaging shows periventricular white matter abnormalities and calcifications, large cisterna magna or Dandy-Walker malformation, and sometimes agenesis of the corpus callosum. {ECO:0000269|PubMed:30982608, ECO:0000269|PubMed:30982609}. Note=The disease is caused by variants affecting the gene represented in this entry.
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 (PubMed:20504948, PubMed:30982609). 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. In the central nervous system, may play a role in the development of microglia macrophages (PubMed:30982608). {ECO:0000269|PubMed:12882960, ECO:0000269|PubMed:15117969, ECO:0000269|PubMed:16170366, ECO:0000269|PubMed:16337366, ECO:0000269|PubMed:16648572, ECO:0000269|PubMed:17121910, ECO:0000269|PubMed:18467591, ECO:0000269|PubMed:18814279, ECO:0000269|PubMed:19193011, ECO:0000269|PubMed:19934330, ECO:0000269|PubMed:20489731, ECO:0000269|PubMed:20504948, ECO:0000269|PubMed:20829061, ECO:0000269|PubMed:30982608, ECO:0000269|PubMed:30982609, ECO:0000269|PubMed:7683918}.
uniprot
proteins
mass_dalton
107984
uniprot
proteins
mutagenesis
MUTAGEN 301; /note="L->S: Constitutive kinase activity."; /evidence="ECO:0000269|PubMed:15117969"; MUTAGEN 708; /note="Y->F: Impairs degradation of activated CSF1R."; /evidence="ECO:0000269|PubMed:10340379"; MUTAGEN 802; /note="D->V: Constitutive kinase activity. Loss of inhibition by imatinib."; /evidence="ECO:0000269|PubMed:10340379, ECO:0000269|PubMed:16170366"; MUTAGEN 809; /note="Y->F: Reduced kinase activity. Reduced interaction with SRC, FYN and YES1."; /evidence="ECO:0000269|PubMed:7681396"; MUTAGEN 969; /note="Y->F: Abolishes down-regulation of activated CSF1R."; /evidence="ECO:0000269|PubMed:15117969
uniprot
proteins
post_translational_modification
PTM: Autophosphorylated in response to CSF1 or IL34 binding (PubMed:20489731, PubMed:23408870, PubMed:24336230). Phosphorylation at Tyr-561 is important for normal down-regulation of signaling by ubiquitination, internalization and degradation. Phosphorylation at Tyr-561 and Tyr-809 is important for interaction with SRC family members, including FYN, YES1 and SRC, and for subsequent activation of these protein kinases. Phosphorylation at Tyr-699 and Tyr-923 is important for interaction with GRB2. Phosphorylation at Tyr-723 is important for interaction with PIK3R1. Phosphorylation at Tyr-708 is important for normal receptor degradation. Phosphorylation at Tyr-723 and Tyr-809 is important for interaction with PLCG2. Phosphorylation at Tyr-969 is important for interaction with CBL. Dephosphorylation by PTPN2 negatively regulates downstream signaling and macrophage differentiation. {ECO:0000269|PubMed:16170366, ECO:0000269|PubMed:20489731, ECO:0000269|PubMed:23408870, ECO:0000269|PubMed:24336230}.; PTM: Ubiquitinated. Becomes rapidly polyubiquitinated after autophosphorylation, leading to its degradation. {ECO:0000269|PubMed:16170366}.
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
10340379
uniprot
proteins
pubmed
12882960
uniprot
proteins
pubmed
15117969
uniprot
proteins
pubmed
15372022
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15519852
uniprot
proteins
pubmed
16170366
uniprot
proteins
pubmed
16335952
uniprot
proteins
pubmed
16337366
uniprot
proteins
pubmed
16648572
uniprot
proteins
pubmed
17121910
uniprot
proteins
pubmed
17132624
uniprot
proteins
pubmed
17292918
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
18342505
uniprot
proteins
pubmed
18467591
uniprot
proteins
pubmed
18593464
uniprot
proteins
pubmed
18687298
uniprot
proteins
pubmed
18814279
uniprot
proteins
pubmed
19132917
uniprot
proteins
pubmed
19193011
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19934330
uniprot
proteins
pubmed
20137931
uniprot
proteins
pubmed
20156689
uniprot
proteins
pubmed
20489731
uniprot
proteins
pubmed
20504948
uniprot
proteins
pubmed
20829061
uniprot
proteins
pubmed
22197934
uniprot
proteins
pubmed
23408870
uniprot
proteins
pubmed
2421165
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24336230
uniprot
proteins
pubmed
24532199
uniprot
proteins
pubmed
2524025
uniprot
proteins
pubmed
2524648
uniprot
proteins
pubmed
30982608
uniprot
proteins
pubmed
30982609
uniprot
proteins
pubmed
3525854
uniprot
proteins
pubmed
3532121
uniprot
proteins
pubmed
4028159
uniprot
proteins
pubmed
7681396
uniprot
proteins
pubmed
7683918
uniprot
proteins
pubmed
7845678
uniprot
proteins
pubmed
9027509
uniprot
proteins
sequence_length
972
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein.
uniprot
proteins
transmembrane_region
TRANSMEM 518..538; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins