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Protein

Macrophage colony-stimulating factor 1 receptor

Gene

Csf1r

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 (By similarity).By similarity1 Publication

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

Enzyme regulationi

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).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei614 – 6141ATPPROSITE-ProRule annotation
Active sitei776 – 7761Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi586 – 5949ATPPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Immunity, Inflammatory response, Innate immunity

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1. 5301.

Names & Taxonomyi

Protein namesi
Recommended name:
Macrophage colony-stimulating factor 1 receptor
Alternative name(s):
CSF-1 receptor (EC:2.7.10.1)
Short name:
CSF-1-R
Short name:
CSF-1R
Short name:
M-CSF-R
Proto-oncogene c-Fms
CD_antigen: CD115
Gene namesi
Name:Csf1r
Synonyms:Csfmr, Fms
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi2425. Csf1r.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini20 – 515496ExtracellularSequence analysisAdd
BLAST
Transmembranei516 – 53621HelicalSequence analysisAdd
BLAST
Topological domaini537 – 978442CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1919By similarityAdd
BLAST
Chaini20 – 978959Macrophage colony-stimulating factor 1 receptorPRO_0000016767Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi42 ↔ 84PROSITE-ProRule annotation
Glycosylationi45 – 451N-linked (GlcNAc...)Sequence analysis
Glycosylationi73 – 731N-linked (GlcNAc...)Sequence analysis
Disulfide bondi127 ↔ 177PROSITE-ProRule annotation
Disulfide bondi224 ↔ 278PROSITE-ProRule annotation
Glycosylationi302 – 3021N-linked (GlcNAc...)Sequence analysis
Glycosylationi335 – 3351N-linked (GlcNAc...)Sequence analysis
Glycosylationi389 – 3891N-linked (GlcNAc...)Sequence analysis
Glycosylationi410 – 4101N-linked (GlcNAc...)Sequence analysis
Disulfide bondi417 ↔ 483PROSITE-ProRule annotation
Glycosylationi449 – 4491N-linked (GlcNAc...)Sequence analysis
Glycosylationi478 – 4781N-linked (GlcNAc...)Sequence analysis
Glycosylationi491 – 4911N-linked (GlcNAc...)Sequence analysis
Modified residuei544 – 5441Phosphotyrosine; by autocatalysisBy similarity
Modified residuei559 – 5591Phosphotyrosine; by autocatalysisBy similarity
Modified residuei697 – 6971Phosphotyrosine; by autocatalysisBy similarity
Modified residuei706 – 7061Phosphotyrosine; by autocatalysisBy similarity
Modified residuei711 – 7111PhosphoserineBy similarity
Modified residuei721 – 7211Phosphotyrosine; by autocatalysisBy similarity
Modified residuei807 – 8071Phosphotyrosine; by autocatalysisBy similarity
Modified residuei921 – 9211Phosphotyrosine; by autocatalysisBy similarity
Modified residuei974 – 9741Phosphotyrosine; by autocatalysisBy similarity

Post-translational modificationi

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).By similarity
Ubiquitinated. Becomes rapidly polyubiquitinated after autophosphorylation, leading to its degradation (By similarity).By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

PRIDEiQ00495.

PTM databases

iPTMnetiQ00495.
PhosphoSiteiQ00495.

Interactioni

Subunit structurei

Monomer. Homodimer. Interacts with CSF1 and IL34. Interaction with dimeric CSF1 or IL34 leads to receptor homodimerization. Interacts with INPPL1/SHIP2 and THOC5. Interacts (tyrosine phosphorylated) with PLCG2 (via SH2 domain). Interacts (tyrosine phosphorylated) with PIK3R1 (via SH2 domain). Interacts (tyrosine phosphorylated) with FYN, YES1 and SRC (via SH2 domain). Interacts (tyrosine phosphorylated) with CBL, GRB2 and SLA2 (By similarity).By similarity

GO - Molecular functioni

Structurei

3D structure databases

ProteinModelPortaliQ00495.
SMRiQ00495. Positions 541-916.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini24 – 10481Ig-like C2-type 1Add
BLAST
Domaini107 – 19791Ig-like C2-type 2Add
BLAST
Domaini204 – 29895Ig-like C2-type 3Add
BLAST
Domaini299 – 39799Ig-like C2-type 4Add
BLAST
Domaini398 – 503106Ig-like C2-type 5Add
BLAST
Domaini580 – 914335Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni540 – 57233Regulatory juxtamembrane domainBy similarityAdd
BLAST
Regioni794 – 81623Activation loopBy similarityAdd
BLAST

Domaini

The juxtamembrane domain functions as autoinhibitory region. Phosphorylation of tyrosine residues in this region leads to a conformation change and activation of the kinase (By similarity).By similarity
The activation loop plays an important role in the regulation of kinase activity. Phosphorylation of tyrosine residues in this region leads to a conformation change and activation of the kinase (By similarity).By similarity

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

HOVERGENiHBG004335.
InParanoidiQ00495.
PhylomeDBiQ00495.

Family and domain databases

Gene3Di2.60.40.10. 5 hits.
InterProiIPR030658. CSF-1_receptor.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR013151. Immunoglobulin.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR016243. Tyr_kinase_CSF1/PDGF_rcpt.
IPR001824. Tyr_kinase_rcpt_3_CS.
[Graphical view]
PANTHERiPTHR24416:SF47. PTHR24416:SF47. 3 hits.
PfamiPF00047. ig. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PIRSFiPIRSF500947. CSF-1_receptor. 1 hit.
PIRSF000615. TyrPK_CSF1-R. 1 hit.
SMARTiSM00409. IG. 5 hits.
SM00408. IGc2. 2 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 5 hits.
SSF56112. SSF56112. 2 hits.
PROSITEiPS50835. IG_LIKE. 4 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS00240. RECEPTOR_TYR_KIN_III. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q00495-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MELGPPLVLL LATVWHGQGA PVIEPSGPEL VVEPGETVTL RCVSNGSVEW
60 70 80 90 100
DGPISPYWTL DPESPGSTLT TRNATFKNTG TYRCTELEDP MAGSTTIHLY
110 120 130 140 150
VKDPAHSWNL LAQEVTVVEG QEAVLPCLIT DPALKDSVSL MREGGRQVLR
160 170 180 190 200
KTVYFFSAWR GFIIRKAKVL DSNTYVCKTM VNGRESTSTG IWLKVNRVHP
210 220 230 240 250
EPPQIKLEPS KLVRIRGEAA QIVCSATNAE VGFNVILKRG DTKLEIPLNS
260 270 280 290 300
DFQDNYYKKV RALSLNAVDF QDAGIYSCVA SNDVGTRTAT MNFQVVESAY
310 320 330 340 350
LNLTSEQSLL QEVSVGDSLI LTVHADAYPS IQHYNWTYLG PFFEDQRKLE
360 370 380 390 400
FITQRAIYRY TFKLFLNRVK ASEAGQYFLM AQNKAGWNNL TFELTLRYPP
410 420 430 440 450
EVSVTWMPVN GSDVLFCDVS GYPQPSVTWM ECRGHTDRCD EAQALQVWND
460 470 480 490 500
THPEVLSQKP FDKVIIQSQL PIGTLKHNMT YFCKTHNSVG NSSQYFRAVS
510 520 530 540 550
LGQSKQLPDE SLFTPVVVAC MSVMSLLVLL LLLLLYKYKQ KPKYQVRWKI
560 570 580 590 600
IERYEGNSYT FIDPTQLPYN EKWEFPRNNL QFGKTLGAGA FGKVVEATAF
610 620 630 640 650
GLGKEDAVLK VAVKMLKSTA HADEKEALMS ELKIMSHLGQ HENIVNLLGA
660 670 680 690 700
CTHGGPVLVI TEYCCYGDLL NFLRRKAEAM LGPSLSPGQD SEGDSSYKNI
710 720 730 740 750
HLEKKYVRRD SGFSSQGVDT YVEMRPVSTS SSDSFFKQDL DKEPSRPLEL
760 770 780 790 800
WDLLHFSSQV AQGMAFLASK NCIHRDVAAR NVLLTSGHVA KIGDFGLARD
810 820 830 840 850
IMNDSNYVVK GNARLPVKWM APESILYCVY TVQSDVWSYG ILLWEIFSLG
860 870 880 890 900
LNPYPGILVN NKFYKLVKDG YQMAQPVFAP KNIYSIMQSC WDLEPTRRPT
910 920 930 940 950
FQQICFLLQE QARLERRDQD YANLPSSGGS SGSDSGGGSS GGSSSEPEEE
960 970
SSSEHLACCE PGDIAQPLLQ PNNYQFAC
Length:978
Mass (Da):109,264
Last modified:April 1, 1993 - v1
Checksum:i0A68456EF56BC7E3
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X61479 mRNA. Translation: CAA43706.1.
PIRiI60321. S16385.
UniGeneiRn.72599.

Genome annotation databases

UCSCiRGD:2425. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X61479 mRNA. Translation: CAA43706.1.
PIRiI60321. S16385.
UniGeneiRn.72599.

3D structure databases

ProteinModelPortaliQ00495.
SMRiQ00495. Positions 541-916.
ModBaseiSearch...
MobiDBiSearch...

PTM databases

iPTMnetiQ00495.
PhosphoSiteiQ00495.

Proteomic databases

PRIDEiQ00495.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

UCSCiRGD:2425. rat.

Organism-specific databases

RGDi2425. Csf1r.

Phylogenomic databases

HOVERGENiHBG004335.
InParanoidiQ00495.
PhylomeDBiQ00495.

Enzyme and pathway databases

BRENDAi2.7.10.1. 5301.

Miscellaneous databases

PROiQ00495.

Family and domain databases

Gene3Di2.60.40.10. 5 hits.
InterProiIPR030658. CSF-1_receptor.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR013151. Immunoglobulin.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR016243. Tyr_kinase_CSF1/PDGF_rcpt.
IPR001824. Tyr_kinase_rcpt_3_CS.
[Graphical view]
PANTHERiPTHR24416:SF47. PTHR24416:SF47. 3 hits.
PfamiPF00047. ig. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PIRSFiPIRSF500947. CSF-1_receptor. 1 hit.
PIRSF000615. TyrPK_CSF1-R. 1 hit.
SMARTiSM00409. IG. 5 hits.
SM00408. IGc2. 2 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 5 hits.
SSF56112. SSF56112. 2 hits.
PROSITEiPS50835. IG_LIKE. 4 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS00240. RECEPTOR_TYR_KIN_III. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCSF1R_RAT
AccessioniPrimary (citable) accession number: Q00495
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: April 1, 1993
Last modified: September 7, 2016
This is version 141 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.