Colony stimulating factor 1 receptor

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Protein CSF1R PDB 2I0V.png
Available structures
PDB Ortholog search: PDBe RCSB
Aliases CSF1R, C-FMS, CD115, CSF-1R, CSFR, FIM2, FMS, HDLS, M-CSF-R, colony stimulating factor 1 receptor
External IDs MGI: 1339758 HomoloGene: 3817 GeneCards: CSF1R
EC number
Targeted by Drug
cediranib, crenolanib, linifanib, pazopanib[1]
RNA expression pattern
PBB GE CSF1R 203104 at fs.png
More reference expression data
Species Human Mouse
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC) Chr 5: 150.05 – 150.11 Mb Chr 18: 61.11 – 61.13 Mb
PubMed search [2] [3]
View/Edit Human View/Edit Mouse

Colony stimulating factor 1 receptor (CSF1R), also known as macrophage colony-stimulating factor receptor (M-CSFR), and CD115 (Cluster of Differentiation 115), is a cell-surface protein encoded, in humans, by the CSF1R gene (known also as c-FMS).[4][5] It is a receptor for a cytokine called colony stimulating factor 1.


The gene is located on long arm of chromosome 5 (5q32) on the Crick (minus) strand. It is 60.002 kilobases in length. The encoded protein has 972 amino acids and a predicted molecular weight of 107.984 kiloDaltons. The first intron of the CSF1R gene contains a transcriptionally inactive ribosomal protein L7 processed pseudogene, oriented in the opposite direction to the CSF1R gene.[4]


The encoded protein is a single pass type I membrane protein and acts as the receptor for colony stimulating factor 1, a cytokine which controls the production, differentiation, and function of macrophages. This receptor mediates most, if not all, of the biological effects of this cytokine. Ligand binding activates CSF1R through a process of oligomerization and trans-phosphorylation. The encoded protein is a tyrosine kinase transmembrane receptor and member of the CSF1/PDGF receptor family of tyrosine-protein kinases. A structure of the autophosphorylation complex of Y561 in the juxtamembrane region of CSF1R has been identified[6] in Protein Data Bank entry 3LCD.[7]

The structure of the autophosphorylation of a tyrosine residue in the N-terminal juxtamembrane region (Tyr561) has been identified in PDB entry 3LCD.[8]

Clinical significance[edit]

Mutations in CSF1R are associated with chronic myelomonocytic leukemia and type M4 acute myeloblastic leukemia.[9] Increased levels of CSF1R1 are found in microglia in Alzheimer's disease and after brain injuries. The increased receptor expression causes microglia to become more active.[10] Both CSF1R, and its ligand colony stimulating factor 1 play an important role in the development of the mammary gland and may be involved in the process of mammary gland carcinogenesis.[11][12][13] Mutations in the tyrosine kinase domain have been associated with hereditary diffuse leukoencephalopathy with spheroids.


Colony stimulating factor 1 receptor has been shown to interact with:

See also[edit]


  1. ^ "Drugs that physically interact with Colony stimulating factor 1 receptor view/edit references on wikidata". 
  2. ^ "Human PubMed Reference:". 
  3. ^ "Mouse PubMed Reference:". 
  4. ^ a b EntrezGene 1436
  5. ^ Galland F, Stefanova M, Lafage M, Birnbaum D (1992). "Localization of the 5' end of the MCF2 oncogene to human chromosome 15q15→q23". Cytogenet. Cell Genet. 60 (2): 114–6. doi:10.1159/000133316. PMID 1611909. 
  6. ^ Xu, Q.; Malecka, K. L.; Fink, L.; Jordan, E. J.; Duffy, E.; Kolander, S.; Peterson, J. R.; Dunbrack, R. L. (1 December 2015). "Identifying three-dimensional structures of autophosphorylation complexes in crystals of protein kinases". Science Signaling. 8 (405): rs13. doi:10.1126/scisignal.aaa6711. PMID 26628682. 
  7. ^ Meyers, Marvin J.; Pelc, Matthew; Kamtekar, Satwik; Day, Jacqueline; Poda, Gennadiy I.; Hall, Molly K.; Michener, Marshall L.; Reitz, Beverly A.; Mathis, Karl J.; Pierce, Betsy S.; Parikh, Mihir D.; Mischke, Deborah A.; Long, Scott A.; Parlow, John J.; Anderson, David R.; Thorarensen, Atli (March 2010). "Structure-based drug design enables conversion of a DFG-in binding CSF-1R kinase inhibitor to a DFG-out binding mode". Bioorganic & Medicinal Chemistry Letters. 20 (5): 1543–1547. doi:10.1016/j.bmcl.2010.01.078. PMID 20137931. 
  8. ^ Xu, Q; Malecka, KL; Fink, L; Jordan, EJ; Duffy, E; Kolander, S; Peterson, JR; Dunbrack RL, Jr (1 December 2015). "Identifying three-dimensional structures of autophosphorylation complexes in crystals of protein kinases.". Science signaling. 8 (405): rs13. doi:10.1126/scisignal.aaa6711. PMID 26628682. 
  9. ^ Ridge SA, Worwood M, Oscier D, Jacobs A, Padua RA (February 1990). "FMS mutations in myelodysplastic, leukemic, and normal subjects". Proc. Natl. Acad. Sci. U.S.A. 87 (4): 1377–80. doi:10.1073/pnas.87.4.1377. JSTOR 2353838. PMC 53478Freely accessible. PMID 2406720. 
  10. ^ Mitrasinovic OM, Grattan A, Robinson CC, Lapustea NB, Poon C, Ryan H, Phong C, Murphy GM (April 2005). "Microglia overexpressing the macrophage colony-stimulating factor receptor are neuroprotective in a microglial-hippocampal organotypic coculture system". J. Neurosci. 25 (17): 4442–51. doi:10.1523/JNEUROSCI.0514-05.2005. PMID 15858070. 
  11. ^ Tamimi RM, Brugge JS, Freedman ML, Miron A, Iglehart JD, Colditz GA, Hankinson SE (January 2008). "Circulating colony stimulating factor-1 and breast cancer risk". Cancer Res. 68 (1): 18–21. doi:10.1158/0008-5472.CAN-07-3234. PMC 2821592Freely accessible. PMID 18172291. 
  12. ^ Pollard JW, Hennighausen L (September 1994). "Colony stimulating factor 1 is required for mammary gland development during pregnancy". Proc. Natl. Acad. Sci. U.S.A. 91 (20): 9312–6. doi:10.1073/pnas.91.20.9312. PMC 44802Freely accessible. PMID 7937762. 
  13. ^ Sapi E (January 2004). "The role of CSF-1 in normal physiology of mammary gland and breast cancer: an update". Exp. Biol. Med. (Maywood). 229 (1): 1–11. PMID 14709771. 
  14. ^ Mancini A, Koch A, Wilms R, Tamura T (April 2002). "c-Cbl associates directly with the C-terminal tail of the receptor for the macrophage colony-stimulating factor, c-Fms, and down-modulates this receptor but not the viral oncogene v-Fms". J. Biol. Chem. 277 (17): 14635–40. doi:10.1074/jbc.M109214200. PMID 11847211. 
  15. ^ Courtneidge SA, Dhand R, Pilat D, Twamley GM, Waterfield MD, Roussel MF (March 1993). "Activation of Src family kinases by colony stimulating factor-1, and their association with its receptor". EMBO J. 12 (3): 943–50. PMC 413295Freely accessible. PMID 7681396. 
  16. ^ Mancini A, Niedenthal R, Joos H, Koch A, Trouliaris S, Niemann H, Tamura T (September 1997). "Identification of a second Grb2 binding site in the v-Fms tyrosine kinase". Oncogene. 15 (13): 1565–72. doi:10.1038/sj.onc.1201518. PMID 9380408. 
  17. ^ Bourette RP, De Sepulveda P, Arnaud S, Dubreuil P, Rottapel R, Mouchiroud G (June 2001). "Suppressor of cytokine signaling 1 interacts with the macrophage colony-stimulating factor receptor and negatively regulates its proliferation signal". J. Biol. Chem. 276 (25): 22133–9. doi:10.1074/jbc.M101878200. PMID 11297560. 

Further reading[edit]

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.