Csf1r
entrez
12978
canonical
uniprot
P09581
canonical
ensembl
ENSMUSG00000024621
resolver
ensp
ENSMUSP00000025523
resolver
ensp
ENSMUSP00000110923
resolver
enst
ENSMUST00000025523
resolver
enst
ENSMUST00000115268
resolver
genesymbol
Csf1r
resolver
genesymbol_syn
Csfmr
resolver
genesymbol_syn
Fms
resolver
uniprot
Q0P635
resolver
uniprot
Q3U3P1
resolver
uniprot
Q3UKC6
resolver
uniprot
Q6NXV8
resolver
uniprot
Q9DBH9
resolver
uniprot_entry
CSF1R_MOUSE
resolver
uniprot_entry
Q0P635_MOUSE
resolver
uniprot_entry
Q3UKC6_MOUSE
resolver
uniprot_entry
Q6NXV8_MOUSE
resolver
uniprot_sec
Q3U3P1
resolver
uniprot_sec
Q9DBH9
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:15297464, ECO:0000269|PubMed:18814279}.
uniprot
proteins
amino_acid_sequence
MELGPPLVLLLATVWHGQGAPVIEPSGPELVVEPGETVTLRCVSNGSVEWDGPISPYWTLDPESPGSTLTTRNATFKNTGTYRCTELEDPMAGSTTIHLYVKDPAHSWNLLAQEVTVVEGQEAVLPCLITDPALKDSVSLMREGGRQVLRKTVYFFSPWRGFIIRKAKVLDSNTYVCKTMVNGRESTSTGIWLKVNRVHPEPPQIKLEPSKLVRIRGEAAQIVCSATNAEVGFNVILKRGDTKLEIPLNSDFQDNYYKKVRALSLNAVDFQDAGIYSCVASNDVGTRTATMNFQVVESAYLNLTSEQSLLQEVSVGDSLILTVHADAYPSIQHYNWTYLGPFFEDQRKLEFITQRAIYRYTFKLFLNRVKASEAGQYFLMAQNKAGWNNLTFELTLRYPPEVSVTWMPVNGSDVLFCDVSGYPQPSVTWMECRGHTDRCDEAQALQVWNDTHPEVLSQKPFDKVIIQSQLPIGTLKHNMTYFCKTHNSVGNSSQYFRAVSLGQSKQLPDESLFTPVVVACMSVMSLLVLLLLLLLYKYKQKPKYQVRWKIIERYEGNSYTFIDPTQLPYNEKWEFPRNNLQFGKTLGAGAFGKVVEATAFGLGKEDAVLKVAVKMLKSTAHADEKEALMSELKIMSHLGQHENIVNLLGACTHGGPVLVITEYCCYGDLLNFLRRKAEAMLGPSLSPGQDSEGDSSYKNIHLEKKYVRRDSGFSSQGVDTYVEMRPVSTSSSDSFFKQDLDKEASRPLELWDLLHFSSQVAQGMAFLASKNCIHRDVAARNVLLTSGHVAKIGDFGLARDIMNDSNYVVKGNARLPVKWMAPESIFDCVYTVQSDVWSYGILLWEIFSLGLNPYPGILVNNKFYKLVKDGYQMAQPVFAPKNIYSIMQSCWDLEPTRRPTFQQICFLLQEQARLERRDQDYANLPSSGGSSGSDSGGGSSGGSSSEPEEESSSEHLACCEPGDIAQPLLQPNNYQFC
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. In the central nervous system, may play a role in the development of microglia macrophages (By similarity). {ECO:0000250|UniProtKB:P07333, ECO:0000269|PubMed:10958675, ECO:0000269|PubMed:11756160, ECO:0000269|PubMed:1652061, ECO:0000269|PubMed:16950670, ECO:0000269|PubMed:17353186, ECO:0000269|PubMed:17420255, ECO:0000269|PubMed:17420256, ECO:0000269|PubMed:17972959, ECO:0000269|PubMed:18814279, ECO:0000269|PubMed:20181277, ECO:0000269|PubMed:20504948, ECO:0000269|PubMed:21610095, ECO:0000269|PubMed:21727904, ECO:0000269|PubMed:8007983, ECO:0000269|PubMed:8262059, ECO:0000269|PubMed:9312046}.
uniprot
proteins
mass_dalton
109179
uniprot
proteins
mutagenesis
MUTAGEN 544; /note="Y->F: No effect on binding to THOC5."; /evidence="ECO:0000269|PubMed:10597251"; MUTAGEN 559; /note="Y->F: Reduced interaction with CBL. Prolonged signaling, due to reduced internalization and degradation. Reduced interaction with FYN. Promotes cell proliferation. Reduced autophosphorylation at Tyr-807."; /evidence="ECO:0000269|PubMed:15297464, ECO:0000269|PubMed:17420255, ECO:0000269|PubMed:8007983"; MUTAGEN 614; /note="K->A: Loss of kinase activity."; /evidence="ECO:0000269|PubMed:10597251, ECO:0000269|PubMed:8262059, ECO:0000269|PubMed:9312046"; MUTAGEN 614; /note="K->M: Loss of kinase activity. Abolishes binding to THOC5."; /evidence="ECO:0000269|PubMed:10597251, ECO:0000269|PubMed:8262059, ECO:0000269|PubMed:9312046"; MUTAGEN 697; /note="Y->F: Abolishes interaction with GRB2."; /evidence="ECO:0000269|PubMed:8262059, ECO:0000269|PubMed:9312046"; MUTAGEN 706; /note="Y->F: No effect on binding to THOC5. Slightly reduced enhancement of cell proliferation."; /evidence="ECO:0000269|PubMed:10597251, ECO:0000269|PubMed:1652061"; MUTAGEN 706; /note="Y->G: Slightly impaired signaling."; /evidence="ECO:0000269|PubMed:10597251, ECO:0000269|PubMed:1652061"; MUTAGEN 721; /note="Y->F: Abolishes interaction with PIK3R1. Strongly reduced phosphorylation of PLCG2. No effect on binding to THOC5."; /evidence="ECO:0000269|PubMed:10597251, ECO:0000269|PubMed:21610095, ECO:0000269|PubMed:8262059, ECO:0000269|PubMed:9312046"; MUTAGEN 807; /note="Y->F: Reduced kinase activity. Strongly reduced phosphorylation of PLCG2. Diminishes binding to THOC5."; /evidence="ECO:0000269|PubMed:10597251, ECO:0000269|PubMed:1652061, ECO:0000269|PubMed:9312046"; MUTAGEN 807; /note="Y->G: May alter protein folding or stability. Loss of kinase activity. No effect on interaction with PIK3R1."; /evidence="ECO:0000269|PubMed:10597251, ECO:0000269|PubMed:1652061, ECO:0000269|PubMed:9312046
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. {ECO:0000269|PubMed:11850825, ECO:0000269|PubMed:15297464, ECO:0000269|PubMed:1652061, ECO:0000269|PubMed:17420255, ECO:0000269|PubMed:20504948, ECO:0000269|PubMed:2160591, ECO:0000269|PubMed:21610095, ECO:0000269|PubMed:8007983, ECO:0000269|PubMed:8262059}.; PTM: Ubiquitinated. Becomes rapidly polyubiquitinated after autophosphorylation, leading to its degradation.
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
10597251
uniprot
proteins
pubmed
10958675
uniprot
proteins
pubmed
11756160
uniprot
proteins
pubmed
11850825
uniprot
proteins
pubmed
15297464
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15557176
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
1652061
uniprot
proteins
pubmed
16705167
uniprot
proteins
pubmed
16944957
uniprot
proteins
pubmed
16950670
uniprot
proteins
pubmed
17353186
uniprot
proteins
pubmed
17420255
uniprot
proteins
pubmed
17420256
uniprot
proteins
pubmed
17972959
uniprot
proteins
pubmed
18814279
uniprot
proteins
pubmed
19017797
uniprot
proteins
pubmed
19144319
uniprot
proteins
pubmed
20181277
uniprot
proteins
pubmed
20504948
uniprot
proteins
pubmed
21041311
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
2160591
uniprot
proteins
pubmed
21610095
uniprot
proteins
pubmed
21727904
uniprot
proteins
pubmed
2966922
uniprot
proteins
pubmed
8007983
uniprot
proteins
pubmed
8262059
uniprot
proteins
pubmed
8441691
uniprot
proteins
pubmed
8497248
uniprot
proteins
pubmed
9312046
uniprot
proteins
sequence_length
977
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17353186, ECO:0000269|PubMed:8007983}; Single-pass type I membrane protein {ECO:0000269|PubMed:17353186, ECO:0000269|PubMed:8007983}. Note=The autophosphorylated receptor is ubiquitinated and internalized, leading to its degradation.
uniprot
proteins
transmembrane_region
TRANSMEM 516..536; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins