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P09581 (CSF1R_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 176. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Macrophage colony-stimulating factor 1 receptor
Alternative name(s):
CSF-1 receptor
Short name=CSF-1-R
Short name=CSF-1R
Short name=M-CSF-R
EC=2.7.10.1
Proto-oncogene c-Fms
CD_antigen=CD115
Gene names
Name:Csf1r
Synonyms:Csfmr, Fms
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length977 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.8 Ref.9 Ref.10 Ref.11 Ref.13 Ref.14 Ref.18 Ref.21 Ref.22 Ref.23 Ref.24 Ref.26 Ref.27 Ref.28 Ref.29 Ref.31

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.9 Ref.10 Ref.11

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. Ref.16 Ref.26

Subunit structure

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. Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.15 Ref.17 Ref.21 Ref.31 Ref.32

Subcellular location

Cell membrane; Single-pass type I membrane protein. Note: The autophosphorylated receptor is ubiquitinated and internalized, leading to its degradation. Ref.10 Ref.21

Tissue specificity

Widely expressed. Ref.28

Domain

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. Ref.16

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. Ref.16

Post-translational modification

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. Ref.7 Ref.8 Ref.9 Ref.10 Ref.15 Ref.16 Ref.20 Ref.22 Ref.28 Ref.31

Ubiquitinated. Becomes rapidly polyubiquitinated after autophosphorylation, leading to its degradation. Ref.10 Ref.21 Ref.30

Disruption phenotype

Mice are born at slightly less than the expected Mendelian rate, and the number of surviving mice is significantly reduced after three weeks. Mice are considerably smaller than wild-type littermates and suffer from general skeletal deformities with shortened limbs, increased bone density, and decreased volume of femoral bone marrow. Mice have decreased numbers of circulating monocytes and lymphocytes, decreased numbers of tissue macrophages, paired with an increase in the number of circulating granulocytes. In addition, mice are deaf and have reduced male and female fertility. In females, the duration of the diestrous period is increased, and in pregnant females the lactating mammary gland fails to develop normally. Males mate less frequently and give rise to fewer pregnant females. Ref.14

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.

Contains 5 Ig-like C2-type (immunoglobulin-like) domains.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processImmunity
Inflammatory response
Innate immunity
   Cellular componentCell membrane
Membrane
   DiseaseProto-oncogene
   DomainImmunoglobulin domain
Repeat
Signal
Transmembrane
Transmembrane helix
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Receptor
Transferase
Tyrosine-protein kinase
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell proliferation

Inferred from electronic annotation. Source: Ensembl

cell-cell junction maintenance

Inferred from electronic annotation. Source: Ensembl

cellular response to cytokine stimulus

Inferred from mutant phenotype Ref.28. Source: UniProtKB

cellular response to macrophage colony-stimulating factor stimulus

Inferred from mutant phenotype Ref.10. Source: UniProtKB

inflammatory response

Inferred from electronic annotation. Source: UniProtKB-KW

innate immune response

Inferred from electronic annotation. Source: UniProtKB-KW

macrophage colony-stimulating factor signaling pathway

Inferred from mutant phenotype Ref.10. Source: GOC

osteoclast differentiation

Inferred from mutant phenotype PubMed 17121910Ref.26Ref.28. Source: UniProtKB

peptidyl-tyrosine phosphorylation

Inferred from direct assay Ref.10. Source: UniProtKB

phosphatidylinositol metabolic process

Inferred from mutant phenotype Ref.31. Source: UniProtKB

phosphatidylinositol-mediated signaling

Inferred from mutant phenotype Ref.31. Source: UniProtKB

positive regulation of ERK1 and ERK2 cascade

Inferred from mutant phenotype Ref.10. Source: UniProtKB

positive regulation of cell migration

Inferred from mutant phenotype Ref.31. Source: UniProtKB

positive regulation of cell proliferation

Inferred from mutant phenotype Ref.10. Source: UniProtKB

positive regulation of chemokine secretion

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein serine/threonine kinase activity

Inferred from mutant phenotype Ref.31. Source: UniProtKB

positive regulation of protein tyrosine kinase activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of tyrosine phosphorylation of Stat3 protein

Inferred from mutant phenotype Ref.10. Source: UniProtKB

protein autophosphorylation

Inferred from direct assay Ref.28Ref.10. Source: UniProtKB

regulation of actin cytoskeleton reorganization

Inferred from mutant phenotype Ref.31. Source: UniProtKB

regulation of bone resorption

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of cell shape

Inferred from mutant phenotype Ref.31. Source: UniProtKB

ruffle organization

Inferred from mutant phenotype Ref.31. Source: UniProtKB

transmembrane receptor protein tyrosine kinase signaling pathway

Inferred from mutant phenotype Ref.9. Source: UniProtKB

   Cellular_componentcell surface

Inferred from direct assay Ref.10. Source: UniProtKB

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Inferred from direct assay PubMed 15860730PubMed 22451653. Source: MGI

receptor complex

Inferred from direct assay Ref.32. Source: BHF-UCL

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

cytokine binding

Inferred from direct assay Ref.10. Source: UniProtKB

macrophage colony-stimulating factor receptor activity

Inferred from mutant phenotype Ref.10. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.32. Source: IntAct

protein homodimerization activity

Inferred from physical interaction Ref.32. Source: BHF-UCL

protein phosphatase binding

Inferred from physical interaction Ref.20. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Csf1P071414EBI-6305373,EBI-777188

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1919 Potential
Chain20 – 977958Macrophage colony-stimulating factor 1 receptor
PRO_0000016766

Regions

Topological domain20 – 515496Extracellular Potential
Transmembrane516 – 53621Helical; Potential
Topological domain537 – 977441Cytoplasmic Potential
Domain24 – 10481Ig-like C2-type 1
Domain107 – 19791Ig-like C2-type 2
Domain204 – 29895Ig-like C2-type 3
Domain299 – 39799Ig-like C2-type 4
Domain398 – 503106Ig-like C2-type 5
Domain580 – 913334Protein kinase
Nucleotide binding586 – 5949ATP By similarity
Region540 – 57233Regulatory juxtamembrane domain By similarity
Region794 – 81623Activation loop By similarity

Sites

Active site7761Proton acceptor By similarity
Binding site6141ATP Probable

Amino acid modifications

Modified residue5441Phosphotyrosine; by autocatalysis By similarity
Modified residue5591Phosphotyrosine; by autocatalysis Ref.10 Ref.16 Ref.28
Modified residue6971Phosphotyrosine; by autocatalysis Ref.9
Modified residue7061Phosphotyrosine; by autocatalysis Ref.7 Ref.8 Ref.9 Ref.31
Modified residue7111Phosphoserine By similarity
Modified residue7211Phosphotyrosine; by autocatalysis Ref.9 Ref.28 Ref.31
Modified residue8071Phosphotyrosine; by autocatalysis Ref.7 Ref.8 Ref.9 Ref.10 Ref.28
Modified residue9211Phosphotyrosine; by autocatalysis Probable
Modified residue9741Phosphotyrosine; by autocatalysis Ref.15
Glycosylation451N-linked (GlcNAc...) Ref.32
Glycosylation731N-linked (GlcNAc...) Ref.32
Glycosylation3021N-linked (GlcNAc...) Potential
Glycosylation3351N-linked (GlcNAc...) Potential
Glycosylation3891N-linked (GlcNAc...) Potential
Glycosylation4101N-linked (GlcNAc...) Potential
Glycosylation4491N-linked (GlcNAc...) Potential
Glycosylation4781N-linked (GlcNAc...) Potential
Glycosylation4911N-linked (GlcNAc...) Ref.19
Disulfide bond42 ↔ 84 Ref.32
Disulfide bond127 ↔ 177 Ref.32
Disulfide bond224 ↔ 278 Ref.32
Disulfide bond417 ↔ 483 By similarity

Experimental info

Mutagenesis5441Y → F: No effect on binding to THOC5. Ref.12
Mutagenesis5591Y → 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. Ref.10 Ref.16 Ref.22
Mutagenesis6141K → A: Loss of kinase activity. Ref.9 Ref.11 Ref.12
Mutagenesis6141K → M: Loss of kinase activity. Abolishes binding to THOC5. Ref.9 Ref.11 Ref.12
Mutagenesis6971Y → F: Abolishes interaction with GRB2. Ref.9 Ref.11
Mutagenesis7061Y → F: No effect on binding to THOC5. Slightly reduced enhancement of cell proliferation. Ref.8 Ref.12
Mutagenesis7061Y → G: Slightly impaired signaling. Ref.8 Ref.12
Mutagenesis7211Y → F: Abolishes interaction with PIK3R1. Strongly reduced phosphorylation of PLCG2. No effect on binding to THOC5. Ref.9 Ref.11 Ref.12 Ref.31
Mutagenesis8071Y → F: Reduced kinase activity. Strongly reduced phosphorylation of PLCG2. Diminishes binding to THOC5. Ref.8 Ref.11 Ref.12
Mutagenesis8071Y → G: May alter protein folding or stability. Loss of kinase activity. No effect on interaction with PIK3R1. Ref.8 Ref.11 Ref.12
Sequence conflict571Y → I in CAA29666. Ref.1
Sequence conflict721R → S in CAA29666. Ref.1
Sequence conflict1621F → S in CAA29666. Ref.1
Sequence conflict446 – 4472QV → HL in CAA29666. Ref.1
Sequence conflict4741T → P in CAA29666. Ref.1
Sequence conflict6601I → Y in CAA29666. Ref.1
Sequence conflict6691L → H in CAA29666. Ref.1
Sequence conflict7441A → H in CAA29666. Ref.1
Sequence conflict8141Missing in CAA29666. Ref.1
Sequence conflict8301Y → I in CAA29666. Ref.1
Sequence conflict8581L → H in CAA29666. Ref.1

Secondary structure

............................................................... 977
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P09581 [UniParc].

Last modified May 10, 2002. Version 3.
Checksum: 7EDF8310CCF98906

FASTA977109,179
        10         20         30         40         50         60 
MELGPPLVLL LATVWHGQGA PVIEPSGPEL VVEPGETVTL RCVSNGSVEW DGPISPYWTL 

        70         80         90        100        110        120 
DPESPGSTLT TRNATFKNTG TYRCTELEDP MAGSTTIHLY VKDPAHSWNL LAQEVTVVEG 

       130        140        150        160        170        180 
QEAVLPCLIT DPALKDSVSL MREGGRQVLR KTVYFFSPWR GFIIRKAKVL DSNTYVCKTM 

       190        200        210        220        230        240 
VNGRESTSTG IWLKVNRVHP EPPQIKLEPS KLVRIRGEAA QIVCSATNAE VGFNVILKRG 

       250        260        270        280        290        300 
DTKLEIPLNS DFQDNYYKKV RALSLNAVDF QDAGIYSCVA SNDVGTRTAT MNFQVVESAY 

       310        320        330        340        350        360 
LNLTSEQSLL QEVSVGDSLI LTVHADAYPS IQHYNWTYLG PFFEDQRKLE FITQRAIYRY 

       370        380        390        400        410        420 
TFKLFLNRVK ASEAGQYFLM AQNKAGWNNL TFELTLRYPP EVSVTWMPVN GSDVLFCDVS 

       430        440        450        460        470        480 
GYPQPSVTWM ECRGHTDRCD EAQALQVWND THPEVLSQKP FDKVIIQSQL PIGTLKHNMT 

       490        500        510        520        530        540 
YFCKTHNSVG NSSQYFRAVS LGQSKQLPDE SLFTPVVVAC MSVMSLLVLL LLLLLYKYKQ 

       550        560        570        580        590        600 
KPKYQVRWKI IERYEGNSYT FIDPTQLPYN EKWEFPRNNL QFGKTLGAGA FGKVVEATAF 

       610        620        630        640        650        660 
GLGKEDAVLK VAVKMLKSTA HADEKEALMS ELKIMSHLGQ HENIVNLLGA CTHGGPVLVI 

       670        680        690        700        710        720 
TEYCCYGDLL NFLRRKAEAM LGPSLSPGQD SEGDSSYKNI HLEKKYVRRD SGFSSQGVDT 

       730        740        750        760        770        780 
YVEMRPVSTS SSDSFFKQDL DKEASRPLEL WDLLHFSSQV AQGMAFLASK NCIHRDVAAR 

       790        800        810        820        830        840 
NVLLTSGHVA KIGDFGLARD IMNDSNYVVK GNARLPVKWM APESIFDCVY TVQSDVWSYG 

       850        860        870        880        890        900 
ILLWEIFSLG LNPYPGILVN NKFYKLVKDG YQMAQPVFAP KNIYSIMQSC WDLEPTRRPT 

       910        920        930        940        950        960 
FQQICFLLQE QARLERRDQD YANLPSSGGS SGSDSGGGSS GGSSSEPEEE SSSEHLACCE 

       970 
PGDIAQPLLQ PNNYQFC 

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References

« Hide 'large scale' references
[1]"Murine c-fms cDNA: cloning, sequence analysis and retroviral expression."
Rothwell V.M., Rohrschneider L.R.
Oncogene Res. 1:311-324(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]Rothwell V.M.
Submitted (SEP-1988) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION.
[3]"Reassessment of the murine c-fms proto-oncogene sequence."
de Parseval N., Bordereaux D., Gisselbrecht S., Sola B.
Nucleic Acids Res. 21:750-750(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: SEQUENCE REVISION.
[4]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J and NOD.
Tissue: Liver and Urinary bladder.
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6.
Tissue: Brain.
[6]"Expression of mRNA encoding the macrophage colony-stimulating factor receptor (c-fms) is controlled by a constitutive promoter and tissue-specific transcription elongation."
Yue X., Favot P., Dunn T.L., Cassady A.I., Hume D.A.
Mol. Cell. Biol. 13:3191-3201(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-16.
[7]"Identification of tyrosine 706 in the kinase insert as the major colony-stimulating factor 1 (CSF-1)-stimulated autophosphorylation site in the CSF-1 receptor in a murine macrophage cell line."
van der Geer P., Hunter T.
Mol. Cell. Biol. 10:2991-3002(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-706 AND TYR-807.
[8]"Tyrosine 706 and 807 phosphorylation site mutants in the murine colony-stimulating factor-1 receptor are unaffected in their ability to bind or phosphorylate phosphatidylinositol-3 kinase but show differential defects in their ability to induce early response gene transcription."
van der Geer P., Hunter T.
Mol. Cell. Biol. 11:4698-4709(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CELL PROLIFERATION AND PHOSPHORYLATION OF PIK3R1, INTERACTION WITH PIK3R1, PHOSPHORYLATION AT TYR-706 AND TYR-807, MUTAGENESIS OF TYR-706 AND TYR-807.
[9]"Mutation of Tyr697, a GRB2-binding site, and Tyr721, a PI 3-kinase binding site, abrogates signal transduction by the murine CSF-1 receptor expressed in Rat-2 fibroblasts."
van der Geer P., Hunter T.
EMBO J. 12:5161-5172(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS CSF1 RECEPTOR, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, PHOSPHORYLATION AT TYR-697; TYR-706; TYR-721 AND TYR-807, MUTAGENESIS OF LYS-614; TYR-697 AND TYR-721, INTERACTION WITH GRB2.
[10]"Tyrosine 569 in the c-Fms juxtamembrane domain is essential for kinase activity and macrophage colony-stimulating factor-dependent internalization."
Myles G.M., Brandt C.S., Carlberg K., Rohrschneider L.R.
Mol. Cell. Biol. 14:4843-4854(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS CSF1 RECEPTOR IN CELL PROLIFERATION AND IN ACTIVATION OF AKT1; MAPK1/ERK2; MAPK3/ERK1; STAT3; STAT5A AND STAT5B, INTERACTION WITH CBL; YES1; FYN AND SRC, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, PHOSPHORYLATION AT TYR-559 AND TYR-807, UBIQUITINATION, MUTAGENESIS OF TYR-559.
[11]"Sequential activation of phoshatidylinositol 3-kinase and phospholipase C-gamma2 by the M-CSF receptor is necessary for differentiation signaling."
Bourette R.P., Myles G.M., Choi J.L., Rohrschneider L.R.
EMBO J. 16:5880-5893(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN MACROPHAGE PROLIFERATION; MACROPHAGE DIFFERENTIATION; PHOSPHORYLATION OF PLCG2; PHOSPHORYLATION OF PIK3R1 AND PHOSPHORYLATION OF GRB2, CATALYTIC ACTIVITY, INTERACTION WITH PIK3R1; GRB2; PLCG2 AND FYN, MUTAGENESIS OF LYS-614; TYR-697; TYR-721 AND TYR-807.
[12]"FMIP, a novel Fms-interacting protein, affects granulocyte/macrophage differentiation."
Tamura T., Mancini A., Joos H., Koch A., Hakim C., Dumanski J., Weidner K.M., Niemann H.
Oncogene 18:6488-6495(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH THOC5, MUTAGENESIS OF TYR-544; LYS-614; TYR-706; TYR-721 AND TYR-807.
[13]"Both src-dependent and -independent mechanisms mediate phosphatidylinositol 3-kinase regulation of colony-stimulating factor 1-activated mitogen-activated protein kinases in myeloid progenitors."
Lee A.W., States D.J.
Mol. Cell. Biol. 20:6779-6798(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[14]"Targeted disruption of the mouse colony-stimulating factor 1 receptor gene results in osteopetrosis, mononuclear phagocyte deficiency, increased primitive progenitor cell frequencies, and reproductive defects."
Dai X.M., Ryan G.R., Hapel A.J., Dominguez M.G., Russell R.G., Kapp S., Sylvestre V., Stanley E.R.
Blood 99:111-120(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION.
[15]"C-Cbl binds the CSF-1 receptor at tyrosine 973, a novel phosphorylation site in the receptor's carboxy-terminus."
Wilhelmsen K., Burkhalter S., van der Geer P.
Oncogene 21:1079-1089(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CBL, PHOSPHORYLATION AT TYR-974.
[16]"A juxtamembrane tyrosine in the colony stimulating factor-1 receptor regulates ligand-induced Src association, receptor kinase function, and down-regulation."
Rohde C.M., Schrum J., Lee A.W.
J. Biol. Chem. 279:43448-43461(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF TYR-559, PHOSPHORYLATION AT TYR-559, DOMAIN, ENZYME REGULATION.
[17]"SHIP2 is recruited to the cell membrane upon macrophage colony-stimulating factor (M-CSF) stimulation and regulates M-CSF-induced signaling."
Wang Y., Keogh R.J., Hunter M.G., Mitchell C.A., Frey R.S., Javaid K., Malik A.B., Schurmans S., Tridandapani S., Marsh C.B.
J. Immunol. 173:6820-6830(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH INPPL1.
[18]"Activated c-Fms recruits Vav and Rac during CSF-1-induced cytoskeletal remodeling and spreading in osteoclasts."
Sakai H., Chen Y., Itokawa T., Yu K.P., Zhu M.L., Insogna K.
Bone 39:1290-1301(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[19]"Proteome-wide characterization of N-glycosylation events by diagonal chromatography."
Ghesquiere B., Van Damme J., Martens L., Vandekerckhove J., Gevaert K.
J. Proteome Res. 5:2438-2447(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-491.
Strain: C57BL/6.
Tissue: Plasma.
[20]"T-cell protein tyrosine phosphatase (Tcptp) is a negative regulator of colony-stimulating factor 1 signaling and macrophage differentiation."
Simoncic P.D., Bourdeau A., Lee-Loy A., Rohrschneider L.R., Tremblay M.L., Stanley E.R., McGlade C.J.
Mol. Cell. Biol. 26:4149-4160(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION, DEPHOSPHORYLATION BY PTPN2.
[21]"The Src-like adaptor protein 2 regulates colony-stimulating factor-1 receptor signaling and down-regulation."
Pakuts B., Debonneville C., Liontos L.M., Loreto M.P., McGlade C.J.
J. Biol. Chem. 282:17953-17963(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF SLA2, INTERACTION WITH SLA2 AND CBL, SUBCELLULAR LOCATION, UBIQUITINATION.
[22]"c-Fms tyrosine 559 is a major mediator of M-CSF-induced proliferation of primary macrophages."
Takeshita S., Faccio R., Chappel J., Zheng L., Feng X., Weber J.D., Teitelbaum S.L., Ross F.P.
J. Biol. Chem. 282:18980-18990(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF TYR-559, PHOSPHORYLATION AT TYR-921.
[23]"M-CSF regulates the cytoskeleton via recruitment of a multimeric signaling complex to c-Fms Tyr-559/697/721."
Faccio R., Takeshita S., Colaianni G., Chappel J., Zallone A., Teitelbaum S.L., Ross F.P.
J. Biol. Chem. 282:18991-18999(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[24]"Src-family kinases play an essential role in differentiation signaling downstream of macrophage colony-stimulating factor receptors mediating persistent phosphorylation of phospholipase C-gamma2 and MAP kinases ERK1 and ERK2."
Bourgin-Hierle C., Gobert-Gosse S., Therier J., Grasset M.F., Mouchiroud G.
Leukemia 22:161-169(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SIGNALING PATHWAY.
[25]"The phagosomal proteome in interferon-gamma-activated macrophages."
Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[26]"Imatinib mesylate suppresses bone metastases of breast cancer by inhibiting osteoclasts through the blockade of c-Fms signals."
Hiraga T., Nakamura H.
Int. J. Cancer 124:215-222(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN OSTEOCLAST DIFFERENTIATION, ROLE IN DISEASE, ENZYME REGULATION.
[27]"c-Fms-mediated differentiation and priming of monocyte lineage cells play a central role in autoimmune arthritis."
Paniagua R.T., Chang A., Mariano M.M., Stein E.A., Wang Q., Lindstrom T.M., Sharpe O., Roscow C., Ho P.P., Lee D.M., Robinson W.H.
Arthritis Res. Ther. 12:R32-R32(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: ROLE IN DISEASE.
[28]"Functional overlap but differential expression of CSF-1 and IL-34 in their CSF-1 receptor-mediated regulation of myeloid cells."
Wei S., Nandi S., Chitu V., Yeung Y.G., Yu W., Huang M., Williams L.T., Lin H., Stanley E.R.
J. Leukoc. Biol. 88:495-505(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS IL34 AND CSF1 RECEPTOR, FUNCTION IN ACTIVATION OF MAPK1/ERK2 AND MAPK3/ERK1, PHOSPHORYLATION AT TYR-559; TYR-807 AND TYR-721, AUTOPHOSPHORYLATION, TISSUE SPECIFICITY.
[29]"Control of macrophage lineage populations by CSF-1 receptor and GM-CSF in homeostasis and inflammation."
Lenzo J.C., Turner A.L., Cook A.D., Vlahos R., Anderson G.P., Reynolds E.C., Hamilton J.A.
Immunol. Cell Biol. 90:429-440(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[30]"A CSF-1 receptor phosphotyrosine 559 signaling pathway regulates receptor ubiquitination and tyrosine phosphorylation."
Xiong Y., Song D., Cai Y., Yu W., Yeung Y.G., Stanley E.R.
J. Biol. Chem. 286:952-960(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION.
[31]"Phosphorylation of CSF-1R Y721 mediates its association with PI3K to regulate macrophage motility and enhancement of tumor cell invasion."
Sampaio N.G., Yu W., Cox D., Wyckoff J., Condeelis J., Stanley E.R., Pixley F.J.
J. Cell Sci. 124:2021-2031(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN REGULATION OF CELL MOTILITY; CELL SHAPE; ACTIN CYTOSKELETON REORGANIZATION; PHOSPHORYLATION OF AKT1 AND REGULATION OF PHOSPHATIDYLINOSITOL METABOLISM, INTERACTION WITH PIK3R1 AND PLCG2, PHOSPHORYLATION AT TYR-706 AND TYR-721, MUTAGENESIS OF TYR-721.
[32]"Structure of macrophage colony stimulating factor bound to FMS: diverse signaling assemblies of class III receptor tyrosine kinases."
Chen X., Liu H., Focia P.J., Shim A.H., He X.
Proc. Natl. Acad. Sci. U.S.A. 105:18267-18272(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 20-296 IN COMPLEX WITH CSF1, GLYCOSYLATION AT ASN-45 AND ASN-73, SUBUNIT, DISULFIDE BONDS.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X06368 mRNA. Translation: CAA29666.1.
AK004947 mRNA. Translation: BAB23691.1.
AK079247 mRNA. Translation: BAC37587.1.
AK143545 mRNA. Translation: BAE25430.1.
AK154653 mRNA. Translation: BAE32744.1.
BC043054 mRNA. Translation: AAH43054.1.
S62219 Genomic DNA. No translation available.
CCDSCCDS29280.1.
PIRTVMSMD. S01880.
RefSeqNP_001032948.2. NM_001037859.2.
XP_006525646.1. XM_006525583.1.
XP_006525647.1. XM_006525584.1.
XP_006525648.1. XM_006525585.1.
XP_006525649.1. XM_006525586.1.
UniGeneMm.22574.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3EJJX-ray2.40X20-296[»]
4EXPX-ray2.80X20-298[»]
ProteinModelPortalP09581.
SMRP09581. Positions 20-496, 541-916.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid198928. 15 interactions.
DIPDIP-46415N.
IntActP09581. 5 interactions.
MINTMINT-8013693.

Chemistry

ChEMBLCHEMBL5570.

PTM databases

PhosphoSiteP09581.

Proteomic databases

MaxQBP09581.
PaxDbP09581.
PRIDEP09581.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000025523; ENSMUSP00000025523; ENSMUSG00000024621.
ENSMUST00000115268; ENSMUSP00000110923; ENSMUSG00000024621.
GeneID12978.
KEGGmmu:12978.
UCSCuc008fbn.1. mouse.

Organism-specific databases

CTD1436.
MGIMGI:1339758. Csf1r.

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000112008.
HOVERGENHBG004335.
InParanoidP09581.
KOK05090.
OMAVECVAFN.
OrthoDBEOG7KSX7R.
PhylomeDBP09581.
TreeFamTF325768.

Enzyme and pathway databases

BRENDA2.7.10.1. 3474.

Gene expression databases

ArrayExpressP09581.
BgeeP09581.
CleanExMM_CSF1R.
GenevestigatorP09581.

Family and domain databases

Gene3D2.60.40.10. 5 hits.
InterProIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
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]
PfamPF07679. I-set. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PIRSFPIRSF500947. CSF-1_receptor. 1 hit.
PIRSF000615. TyrPK_CSF1-R. 1 hit.
SMARTSM00409. IG. 3 hits.
SM00408. IGc2. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 2 hits.
PROSITEPS50835. 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]
ProtoNetSearch...

Other

ChiTaRSCSF1R. mouse.
EvolutionaryTraceP09581.
NextBio282750.
PROP09581.
SOURCESearch...

Entry information

Entry nameCSF1R_MOUSE
AccessionPrimary (citable) accession number: P09581
Secondary accession number(s): Q3U3P1, Q9DBH9
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: May 10, 2002
Last modified: July 9, 2014
This is version 176 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot