P07333 (CSF1R_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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:	FMS

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	972 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.11 Ref.15 Ref.16 Ref.18 Ref.19 Ref.20 Ref.22 Ref.23 Ref.24 Ref.27 Ref.28 Ref.29 Ref.31 Ref.37
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.18 Ref.19 Ref.20 Ref.36 Ref.37 Ref.38
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.18 Ref.19 Ref.20 Ref.23 Ref.27 Ref.38
Subunit structure	Interacts with INPPL1/SHIP2 and THOC5 By similarity. Monomer. Homodimer. Interacts with CSF1 and IL34. Interaction with dimeric CSF1 or IL34 leads to receptor homodimerization. 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.12 Ref.27
Subcellular location	Cell membrane; Single-pass type I membrane protein.
Tissue specificity	Expressed in bone marrow and in differentiated blood mononuclear cells.
Induction	Up-regulated by glucocorticoids. Ref.13 Ref.16 Ref.18 Ref.19 Ref.20 Ref.23 Ref.27 Ref.38
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. Ref.34 Ref.35 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. Ref.34 Ref.35
Post-translational modification	Autophosphorylated in response to CSF1 or IL34 binding. 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. Ref.15 Ref.18 Ref.19 Ref.21 Ref.25 Ref.26 Ref.27 Ref.29 Ubiquitinated. Becomes rapidly polyubiquitinated after autophosphorylation, leading to its degradation. Ref.20
Involvement in 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. Ref.16 Ref.18 Ref.19 Ref.23 Ref.24 Ref.31 Ref.37 Note=Aberrant expression of CSF1 or CSF1R may play a role in inflammatory diseases, such as rheumatoid arthritis, glomerulonephritis, arteriosclerosis, and allograft rejection. Ref.16 Ref.18 Ref.19 Ref.23 Ref.24 Ref.31 Ref.37
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 process	Immunity Inflammatory response Innate immunity
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Disease	Proto-oncogene
Domain	Immunoglobulin domain Repeat Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Disulfide bond Glycoprotein Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cell proliferation Inferred from mutant phenotype Ref.11. Source: UniProtKB cell-cell junction maintenance Inferred from mutant phenotype Ref.16. Source: UniProtKB cellular response to macrophage colony-stimulating factor stimulus Inferred from mutant phenotype Ref.29Ref.11. Source: UniProtKB cytokine-mediated signaling pathway Inferred from mutant phenotype Ref.29. Source: UniProtKB inflammatory response Traceable author statement Ref.33. Source: UniProtKB macrophage differentiation Traceable author statement Ref.33. Source: UniProtKB mammary gland duct morphogenesis Traceable author statement Ref.16. Source: UniProtKB monocyte differentiation Traceable author statement Ref.33. Source: UniProtKB osteoclast differentiation Inferred from sequence or structural similarity. Source: UniProtKB peptidyl-tyrosine phosphorylation Inferred from direct assay Ref.29. Source: UniProtKB phosphatidylinositol metabolic process Inferred from sequence or structural similarity. Source: UniProtKB phosphatidylinositol-mediated signaling Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of ERK1 and ERK2 cascade Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of cell migration Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of cell proliferation Inferred from mutant phenotype Ref.16Ref.29. Source: UniProtKB positive regulation of chemokine secretion Inferred from mutant phenotype Ref.28. Source: UniProtKB positive regulation of protein serine/threonine kinase activity Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of protein tyrosine kinase activity Inferred from mutant phenotype Ref.12. Source: UniProtKB positive regulation of tyrosine phosphorylation of Stat3 protein Inferred from sequence or structural similarity. Source: UniProtKB protein autophosphorylation Inferred from direct assay Ref.29. Source: UniProtKB regulation of actin cytoskeleton reorganization Inferred from sequence or structural similarity. Source: UniProtKB regulation of bone resorption Inferred from sequence or structural similarity. Source: UniProtKB regulation of cell shape Inferred from mutant phenotype Ref.16. Source: UniProtKB ruffle organization Inferred from sequence or structural similarity. Source: UniProtKB transmembrane receptor protein tyrosine kinase signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	cell surface Inferred from sequence or structural similarity. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW integral to plasma membrane Traceable author statement. Source: ProtInc receptor complex Inferred from sequence or structural similarity. Source: BHF-UCL
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW cytokine binding Inferred from direct assay Ref.29. Source: UniProtKB macrophage colony-stimulating factor receptor activity Inferred from mutant phenotype Ref.29Ref.11. Source: UniProtKB protein homodimerization activity Inferred from sequence or structural similarity. Source: BHF-UCL transmembrane receptor protein tyrosine kinase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 19

19

Potential

Chain

20 – 972

953

Macrophage colony-stimulating factor 1 receptor

PRO_0000016765

Regions

Topological domain

20 – 517

498

Extracellular Potential

Transmembrane

518 – 538

21

Helical; Potential

Topological domain

539 – 972

434

Cytoplasmic Potential

Domain

21 – 104

84

Ig-like C2-type 1

Domain

107 – 197

91

Ig-like C2-type 2

Domain

203 – 290

88

Ig-like C2-type 3

Domain

299 – 399

101

Ig-like C2-type 4

Domain

402 – 502

101

Ig-like C2-type 5

Domain

582 – 910

329

Protein kinase

Nucleotide binding

588 – 596

9

ATP By similarity

Region

542 – 574

33

Regulatory juxtamembrane domain

Region

796 – 818

23

Activation loop

Sites

Active site

778

1

Proton acceptor By similarity

Binding site

616

1

ATP Probable

Amino acid modifications

Modified residue

546

1

Phosphotyrosine; by autocatalysis Ref.27

Modified residue

555

1

Phosphoserine Ref.21

Modified residue

556

1

Phosphotyrosine Ref.21

Modified residue

561

1

Phosphotyrosine; by autocatalysis

Modified residue

562

1

Phosphothreonine Ref.21

Modified residue

567

1

Phosphothreonine Ref.21

Modified residue

699

1

Phosphotyrosine; by autocatalysis Ref.25 Ref.27

Modified residue

708

1

Phosphotyrosine; by autocatalysis Ref.27

Modified residue

713

1

Phosphoserine Ref.25

Modified residue

716

1

Phosphoserine Ref.25

Modified residue

723

1

Phosphotyrosine; by autocatalysis Ref.27 Ref.29

Modified residue

809

1

Phosphotyrosine; by autocatalysis Ref.27

Modified residue

923

1

Phosphotyrosine; by autocatalysis

Modified residue

969

1

Phosphotyrosine; by autocatalysis

Glycosylation

45

1

N-linked (GlcNAc...) Potential

Glycosylation

73

1

N-linked (GlcNAc...) Potential

Glycosylation

153

1

N-linked (GlcNAc...) Potential

Glycosylation

240

1

N-linked (GlcNAc...) Potential

Glycosylation

275

1

N-linked (GlcNAc...) Potential

Glycosylation

302

1

N-linked (GlcNAc...) Ref.17

Glycosylation

335

1

N-linked (GlcNAc...) Potential

Glycosylation

353

1

N-linked (GlcNAc...) Ref.17

Glycosylation

412

1

N-linked (GlcNAc...) Potential

Glycosylation

428

1

N-linked (GlcNAc...) Potential

Glycosylation

480

1

N-linked (GlcNAc...) Potential

Disulfide bond

42 ↔ 84

By similarity

Disulfide bond

127 ↔ 177

By similarity

Disulfide bond

224 ↔ 278

By similarity

Disulfide bond

419 ↔ 485

By similarity

Natural variations

Natural variant

32

1

V → G. Ref.39
Corresponds to variant rs56048668 [ dbSNP | Ensembl ].

VAR_042038

Natural variant

245

1

A → S.
Corresponds to variant rs41338945 [ dbSNP | Ensembl ].

VAR_061290

Natural variant

279

1

V → M.
Corresponds to variant rs3829986 [ dbSNP | Ensembl ].

VAR_049718

Natural variant

362

1

H → R. Ref.39
Corresponds to variant rs10079250 [ dbSNP | Ensembl ].

VAR_042039

Natural variant

413

1

G → S. Ref.39
Corresponds to variant rs34951517 [ dbSNP | Ensembl ].

VAR_042040

Natural variant

536

1

L → V. Ref.39
Corresponds to variant rs55942044 [ dbSNP | Ensembl ].

VAR_042041

Natural variant

693

1

P → H in a lung squamous cell carcinoma sample; somatic mutation. Ref.39

VAR_042042

Natural variant

920

1

E → D. Ref.39
Corresponds to variant rs34030164 [ dbSNP | Ensembl ].

VAR_042043

Natural variant

921

1

R → Q. Ref.39
Corresponds to variant rs56059682 [ dbSNP | Ensembl ].

VAR_042044

Natural variant

969

1

Y → C.
Corresponds to variant rs1801271 [ dbSNP | Ensembl ].

VAR_011953

Experimental info

Mutagenesis

301

1

L → S: Constitutive kinase activity. Ref.16

Mutagenesis

708

1

Y → F: Impairs degradation of activated CSF1R. Ref.14

Mutagenesis

802

1

D → V: Constitutive kinase activity. Loss of inhibition by imatinib. Ref.14 Ref.20

Mutagenesis

809

1

Y → F: Reduced kinase activity. Reduced interaction with SRC, FYN and YES1. Ref.12

Mutagenesis

969

1

Y → F: Abolishes down-regulation of activated CSF1R. Ref.16

Sequence conflict

54

1

P → A in CAA27300. Ref.2

Sequence conflict

247

1

P → H in AAH47521. Ref.5

Sequence conflict

354

1

A → V in AAH47521. Ref.5

Sequence conflict

629

1

A → S in AAH47521. Ref.5

Secondary structure

1

.

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972

Helix Strand Turn

Details...

Helix

579 – 581

3

Beta strand

582 – 590

9

Beta strand

592 – 604

13

Turn

605 – 608

4

Beta strand

612 – 618

7

Helix

624 – 640

17

Beta strand

649 – 653

5

Beta strand

655 – 658

4

Beta strand

660 – 664

5

Helix

671 – 676

6

Helix

752 – 771

20

Helix

781 – 783

3

Beta strand

784 – 786

3

Helix

788 – 790

3

Beta strand

792 – 794

3

Helix

798 – 800

3

Beta strand

809 – 811

3

Helix

819 – 821

3

Helix

824 – 828

5

Helix

834 – 849

16

Helix

863 – 871

9

Helix

883 – 892

10

Helix

897 – 899

3

Helix

903 – 911

9

Helix

917 – 920

4

Sequences

	Sequence		Length	Mass (Da)
	P07333 [UniParc]. Last modified June 1, 1994. Version 2. Checksum: A8D99BE237573FE8	FASTA	972	107,984
	10 20 30 40 50 60 MGPGVLLLLL VATAWHGQGI PVIEPSVPEL VVKPGATVTL RCVGNGSVEW DGPPSPHWTL 70 80 90 100 110 120 YSDGSSSILS TNNATFQNTG TYRCTEPGDP LGGSAAIHLY VKDPARPWNV LAQEVVVFED 130 140 150 160 170 180 QDALLPCLLT DPVLEAGVSL VRVRGRPLMR HTNYSFSPWH GFTIHRAKFI QSQDYQCSAL 190 200 210 220 230 240 MGGRKVMSIS IRLKVQKVIP GPPALTLVPA ELVRIRGEAA QIVCSASSVD VNFDVFLQHN 250 260 270 280 290 300 NTKLAIPQQS DFHNNRYQKV LTLNLDQVDF QHAGNYSCVA SNVQGKHSTS MFFRVVESAY 310 320 330 340 350 360 LNLSSEQNLI QEVTVGEGLN LKVMVEAYPG LQGFNWTYLG PFSDHQPEPK LANATTKDTY 370 380 390 400 410 420 RHTFTLSLPR LKPSEAGRYS FLARNPGGWR ALTFELTLRY PPEVSVIWTF INGSGTLLCA 430 440 450 460 470 480 ASGYPQPNVT WLQCSGHTDR CDEAQVLQVW DDPYPEVLSQ EPFHKVTVQS LLTVETLEHN 490 500 510 520 530 540 QTYECRAHNS VGSGSWAFIP ISAGAHTHPP DEFLFTPVVV ACMSIMALLL LLLLLLLYKY 550 560 570 580 590 600 KQKPKYQVRW KIIESYEGNS YTFIDPTQLP YNEKWEFPRN NLQFGKTLGA GAFGKVVEAT 610 620 630 640 650 660 AFGLGKEDAV LKVAVKMLKS TAHADEKEAL MSELKIMSHL GQHENIVNLL GACTHGGPVL 670 680 690 700 710 720 VITEYCCYGD LLNFLRRKAE AMLGPSLSPG QDPEGGVDYK NIHLEKKYVR RDSGFSSQGV 730 740 750 760 770 780 DTYVEMRPVS TSSNDSFSEQ DLDKEDGRPL ELRDLLHFSS QVAQGMAFLA SKNCIHRDVA 790 800 810 820 830 840 ARNVLLTNGH VAKIGDFGLA RDIMNDSNYI VKGNARLPVK WMAPESIFDC VYTVQSDVWS 850 860 870 880 890 900 YGILLWEIFS LGLNPYPGIL VNSKFYKLVK DGYQMAQPAF APKNIYSIMQ ACWALEPTHR 910 920 930 940 950 960 PTFQQICSFL QEQAQEDRRE RDYTNLPSSS RSGGSGSSSS ELEEESSSEH LTCCEQGDIA 970 QPLLQPNNYQ FC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nucleotide sequence and structural organization of the human FMS proto-oncogene." Hampe A., Shamoon B.M., Gobet M., Sherr C.J., Galibert F. Oncogene Res. 4:9-17(1989) [PubMed: 2524025] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Structural alteration of viral homologue of receptor proto-oncogene fms at carboxyl terminus." Coussens L., van Beveren C., Smith D., Chen E., Mitchell R.L., Isacke C.M., Verma I.M., Ullrich A. Nature 320:277-280(1986) [PubMed: 2421165] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Sequence analysis of two genomic regions containing the KIT and the FMS receptor tyrosine kinase genes." Andre C., Hampe A., Lachaume P., Martin E., Wang X.P., Manus V., Hu W.X., Galibert F. Genomics 39:216-226(1997) [PubMed: 9027509] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Placenta.
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[6]	"Differential transcription of exon 1 of the human c-fms gene in placental trophoblasts and monocytes." Visvader J., Verma I.M. Mol. Cell. Biol. 9:1336-1341(1989) [PubMed: 2524648] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-16.
[7]	"The amino-terminal domain of the v-fms oncogene product includes a functional signal peptide that directs synthesis of a transforming glycoprotein in the absence of feline leukemia virus gag sequences." Wheeler E.F., Roussel M.F., Hampe A., Walker M.H., Fried V.A., Look A.T., Rettenmier C.W., Sherr C.J. J. Virol. 59:224-233(1986) [PubMed: 3525854] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-16.
[8]	"Expression of a novel exon in the 5' UTR of human c-fms transcripts." Flick M.B., Sapi E., Kacinski B.M. Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-16. Tissue: Placenta.
[9]	"Expression of the human c-fms proto-oncogene in hematopoietic cells and its deletion in the 5q- syndrome." Nienhuis A.W., Bunn H.F., Turner P.H., Gopal T.V., Nash W.G., O'Brien S.J., Sherr C.J. Cell 42:421-428(1985) [PubMed: 4028159] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 244-295.
[10]	"'Replacement' of COOH-terminal truncation of v-fms with c-fms sequences markedly reduces transformation potential." Browning P.J., Bunn H.F., Cline A., Shuman M., Nienhuis A.W. Proc. Natl. Acad. Sci. U.S.A. 83:7800-7804(1986) [PubMed: 3532121] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 874-972.
[11]	"Expression of human colony-stimulating factor-1 (CSF-1) receptor in murine pluripotent hematopoietic NFS-60 cells induces long-term proliferation in response to CSF-1 without loss of erythroid differentiation potential." Bourette R.P., Mouchiroud G., Ouazana R., Morle F., Godet J., Blanchet J.P. Blood 81:2511-2520(1993) [PubMed: 7683918] [Abstract] Cited for: FUNCTION IN CELL PROLIFERATION.
[12]	"Activation of Src family kinases by colony stimulating factor-1, and their association with its receptor." Courtneidge S.A., Dhand R., Pilat D., Twamley G.M., Waterfield M.D., Roussel M.F. EMBO J. 12:943-950(1993) [PubMed: 7681396] [Abstract] Cited for: INTERACTION WITH SRC; FYN AND YES1, MUTAGENESIS OF TYR-809.
[13]	"Transcriptional regulation of the c-fms (CSF-1R) proto-oncogene in human breast carcinoma cells by glucocorticoids." Sapi E., Flick M.B., Gilmore-Hebert M., Rodov S., Kacinski B.M. Oncogene 10:529-542(1995) [PubMed: 7845678] [Abstract] Cited for: INDUCTION BY GLUCOCORTICOIDS.
[14]	"Cell specific transformation by c-fms activating loop mutations is attributable to constitutive receptor degradation." Morley G.M., Uden M., Gullick W.J., Dibb N.J. Oncogene 18:3076-3084(1999) [PubMed: 10340379] [Abstract] Cited for: MUTAGENESIS OF TYR-708 AND ASP-802.
[15]	"The inositol 5'-phosphatase SHIP-1 and the Src kinase Lyn negatively regulate macrophage colony-stimulating factor-induced Akt activity." Baran C.P., Tridandapani S., Helgason C.D., Humphries R.K., Krystal G., Marsh C.B. J. Biol. Chem. 278:38628-38636(2003) [PubMed: 12882960] [Abstract] Cited for: FUNCTION IN CELLULAR SIGNALING; PHOSPHORYLATION OF INPP5D AND ACTIVATION OF AKT1.
[16]	"Autocrine CSF-1R activation promotes Src-dependent disruption of mammary epithelial architecture." Wrobel C.N., Debnath J., Lin E., Beausoleil S., Roussel M.F., Brugge J.S. J. Cell Biol. 165:263-273(2004) [PubMed: 15117969] [Abstract] Cited for: FUNCTION IN REGULATION OF CELL PROLIFERATION; CELL ADHESION; CELL SHAPE AND INTEGRITY OF CELL JUNCTIONS, MUTAGENESIS OF LEU-301 AND TYR-969, ROLE IN DISEASE.
[17]	"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry." Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D. J. Proteome Res. 4:2070-2080(2005) [PubMed: 16335952] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-302 AND ASN-353, MASS SPECTROMETRY. Tissue: Plasma.
[18]	"Inhibition of phosphorylation of the colony-stimulating factor-1 receptor (c-Fms) tyrosine kinase in transfected cells by ABT-869 and other tyrosine kinase inhibitors." Guo J., Marcotte P.A., McCall J.O., Dai Y., Pease L.J., Michaelides M.R., Davidsen S.K., Glaser K.B. Mol. Cancer Ther. 5:1007-1013(2006) [PubMed: 16648572] [Abstract] Cited for: FUNCTION AS CSF1 RECEPTOR, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, ROLE IN DISEASE, ENZYME REGULATION.
[19]	"A c-fms tyrosine kinase inhibitor, Ki20227, suppresses osteoclast differentiation and osteolytic bone destruction in a bone metastasis model." Ohno H., Kubo K., Murooka H., Kobayashi Y., Nishitoba T., Shibuya M., Yoneda T., Isoe T. Mol. Cancer Ther. 5:2634-2643(2006) [PubMed: 17121910] [Abstract] Cited for: FUNCTION IN CELL PROLIFERATION, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, ROLE IN DISEASE, ENZYME REGULATION.
[20]	"FMS receptor for M-CSF (CSF-1) is sensitive to the kinase inhibitor imatinib and mutation of Asp-802 to Val confers resistance." Taylor J.R., Brownlow N., Domin J., Dibb N.J. Oncogene 25:147-151(2006) [PubMed: 16170366] [Abstract] Cited for: FUNCTION IN REGULATION OF CELL PROLIFERATION AND CELL SHAPE, CATALYTIC ACTIVITY, UBIQUITINATION, ENZYME REGULATION, MUTAGENESIS OF ASP-802.
[21]	"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column." Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y. Anal. Sci. 24:161-166(2008) [PubMed: 18187866] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-555; TYR-556; THR-562 AND THR-567, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[22]	"Discovery of a cytokine and its receptor by functional screening of the extracellular proteome." Lin H., Lee E., Hestir K., Leo C., Huang M., Bosch E., Halenbeck R., Wu G., Zhou A., Behrens D., Hollenbaugh D., Linnemann T., Qin M., Wong J., Chu K., Doberstein S.K., Williams L.T. Science 320:807-811(2008) [PubMed: 18467591] [Abstract] Cited for: FUNCTION AS IL34 RECEPTOR.
[23]	"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: 18814279] [Abstract] Cited for: ROLE IN DISEASE, ENZYME REGULATION.
[24]	"Invasion of human breast cancer cells in vivo requires both paracrine and autocrine loops involving the colony-stimulating factor-1 receptor." Patsialou A., Wyckoff J., Wang Y., Goswami S., Stanley E.R., Condeelis J.S. Cancer Res. 69:9498-9506(2009) [PubMed: 19934330] [Abstract] Cited for: ROLE IN DISEASE.
[25]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-699; SER-713 AND SER-716, MASS SPECTROMETRY.
[26]	"Colony stimulating factor-1 receptor as a target for small molecule inhibitors." Mashkani B., Griffith R., Ashman L.K. Bioorg. Med. Chem. 18:1789-1797(2010) [PubMed: 20156689] [Abstract] Cited for: AUTOPHOSPHORYLATION, ENZYME REGULAITON.
[27]	"IL-34 and M-CSF share the receptor Fms but are not identical in biological activity and signal activation." Chihara T., Suzu S., Hassan R., Chutiwitoonchai N., Hiyoshi M., Motoyoshi K., Kimura F., Okada S. Cell Death Differ. 17:1917-1927(2010) [PubMed: 20489731] [Abstract] Cited for: FUNCTION AS RECEPTOR FOR IL34 AND CSF1, PHOSPHORYLATION AT TYR-546; TYR-699; TYR-708; TYR-723 AND TYR-809, AUTOPHOSPHORYLATION, ENZYME REGULATION, INTERACTION WITH IL34 AND CSF1.
[28]	"Macrophage-colony stimulating factor and interleukin-34 induce chemokines in human whole blood." Eda H., Zhang J., Keith R.H., Michener M., Beidler D.R., Monahan J.B. Cytokine 52:215-220(2010) [PubMed: 20829061] [Abstract] Cited for: FUNCTION IN RELEASE OF PROINFLAMMATORY CHEMOKINES.
[29]	"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: 20504948] [Abstract] Cited for: FUNCTION AS IL34 AND CSF1 RECEPTOR; ACTIVATION OF MAPK1/ERK2; MAPK3/ERK1; PHOSPHORYLATION AT TYR-723, AUTOPHOSPHORYLATION.
[30]	"CSF-1 regulation of the wandering macrophage: complexity in action." Pixley F.J., Stanley E.R. Trends Cell Biol. 14:628-638(2004) [PubMed: 15519852] [Abstract] Cited for: REVIEW ON FUNCTION; SIGNALING PATHWAYS AND PHOSPHORYLATION.
[31]	"Colony-stimulating factor-1 in immunity and inflammation." Chitu V., Stanley E.R. Curr. Opin. Immunol. 18:39-48(2006) [PubMed: 16337366] [Abstract] Cited for: REVIEW ON FUNCTION IN IMMUNITY AND INFLAMMATION, ROLE IN DISEASE.
[32]	"Macrophage colony stimulating factor: not just for macrophages anymore! A gateway into complex biologies." Douglass T.G., Driggers L., Zhang J.G., Hoa N., Delgado C., Williams C.C., Dan Q., Sanchez R., Jeffes E.W., Wepsic H.T., Myers M.P., Koths K., Jadus M.R. Int. Immunopharmacol. 8:1354-1376(2008) [PubMed: 18687298] [Abstract] Cited for: REVIEW ON FUNCTION; SIGNALING PATHWAYS AND PHOSPHORYLATION.
[33]	"Blood monocytes: development, heterogeneity, and relationship with dendritic cells." Auffray C., Sieweke M.H., Geissmann F. Annu. Rev. Immunol. 27:669-692(2009) [PubMed: 19132917] [Abstract] Cited for: REVIEW.
[34]	"Crystal structure of the tyrosine kinase domain of colony-stimulating factor-1 receptor (cFMS) in complex with two inhibitors." Schubert C., Schalk-Hihi C., Struble G.T., Ma H.C., Petrounia I.P., Brandt B., Deckman I.C., Patch R.J., Player M.R., Spurlino J.C., Springer B.A. J. Biol. Chem. 282:4094-4101(2007) [PubMed: 17132624] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 538-922 IN COMPLEXES WITH ARYLAMIDE AND QUINOLONE INHIBITORS, DOMAIN.
[35]	"The 2.7 A crystal structure of the autoinhibited human c-Fms kinase domain." Walter M., Lucet I.S., Patel O., Broughton S.E., Bamert R., Williams N.K., Fantino E., Wilks A.F., Rossjohn J. J. Mol. Biol. 367:839-847(2007) [PubMed: 17292918] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 543-918 IN AUTOINHIBITED CONFORMATION, DOMAIN.
[36]	"Design and synthesis of a pyrido[2,3-d]pyrimidin-5-one class of anti-inflammatory FMS inhibitors." Huang H., Hutta D.A., Hu H., DesJarlais R.L., Schubert C., Petrounia I.P., Chaikin M.A., Manthey C.L., Player M.R. Bioorg. Med. Chem. Lett. 18:2355-2361(2008) [PubMed: 18342505] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.02 ANGSTROMS) OF 538-922 IN COMPLEX WITH PYRIMIDINOPYRIDONE INHIBITOR, CATALYTIC ACTIVITY.
[37]	"Pyrido[2,3-d]pyrimidin-5-ones: a novel class of antiinflammatory macrophage colony-stimulating factor-1 receptor inhibitors." Huang H., Hutta D.A., Rinker J.M., Hu H., Parsons W.H., Schubert C., DesJarlais R.L., Crysler C.S., Chaikin M.A., Donatelli R.R., Chen Y., Cheng D., Zhou Z., Yurkow E., Manthey C.L., Player M.R. J. Med. Chem. 52:1081-1099(2009) [PubMed: 19193011] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 538-922 IN COMPLEX WITH INHIBITOR, CATALYTIC ACTIVITY, FUNCTION IN INFLAMMATION AND DISEASE.
[38]	"Structure-based drug design enables conversion of a DFG-in binding CSF-1R kinase inhibitor to a DFG-out binding mode." Meyers M.J., Pelc M., Kamtekar S., Day J., Poda G.I., Hall M.K., Michener M.L., Reitz B.A., Mathis K.J., Pierce B.S., Parikh M.D., Mischke D.A., Long S.A., Parlow J.J., Anderson D.R., Thorarensen A. Bioorg. Med. Chem. Lett. 20:1543-1547(2010) [PubMed: 20137931] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 538-922 IN COMPLEXES WITH INHIBITORS, CATALYTIC ACTIVITY, ENZYME REGULATION.
[39]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] GLY-32; ARG-362; SER-413; VAL-536; HIS-693; ASP-920 AND GLN-921.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X03663 mRNA. Translation: CAA27300.1.
U63963 Genomic DNA. Translation: AAB51696.1.
M25786 mRNA. Translation: AAA58421.1.
CH471062 Genomic DNA. Translation: EAW61749.1.
CH471062 Genomic DNA. Translation: EAW61750.1.
BC047521 mRNA. Translation: AAH47521.1.
M14002 Genomic DNA. Translation: AAA35849.1.
U78096 Genomic DNA. Translation: AAB51235.1.
M11067 Genomic DNA. Translation: AAA35848.1.
M14193 mRNA. Translation: AAA35834.1.

IPI

IPI00011218.

PIR

TVHUMD. S08123.

RefSeq

NP_005202.2. NM_005211.3.

UniGene

Hs.586219.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2I0V	X-ray	2.80	A	538-922	[»]
2I0Y	X-ray	1.90	A	538-922	[»]
2I1M	X-ray	1.80	A	538-922	[»]
2OGV	X-ray	2.70	A	543-918	[»]
3BEA	X-ray	2.02	A	538-922	[»]
3DPK	X-ray	1.95	A	538-922	[»]
3KRJ	X-ray	2.10	A	538-922	[»]
3KRL	X-ray	2.40	A	538-922	[»]
3LCD	X-ray	2.50	A	538-922	[»]
3LCO	X-ray	3.40	A	550-919	[»]

ProteinModelPortal

P07333.

SMR

P07333. Positions 19-500, 544-921.

ModBase

Search...

Protein-protein interaction databases

IntAct

P07333. 3 interactions.

STRING

P07333.

PTM databases

PhosphoSite

P07333.

Polymorphism databases

DMDM

547770.

Proteomic databases

PeptideAtlas

P07333.

PRIDE

P07333.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000286301; ENSP00000286301; ENSG00000182578.
ENST00000394307; ENSP00000377844; ENSG00000182578.

GeneID

1436.

KEGG

hsa:1436.

UCSC

uc003lrl.1. human.

Organism-specific databases

CTD

1436.

GeneCards

GC05M149413.

HGNC

HGNC:2433. CSF1R.

HPA

CAB008970.
HPA012323.

MIM

164770. gene.

neXtProt

NX_P07333.

PharmGKB

PA26936.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

HBG445154.

HOVERGEN

HBG004335.

InParanoid

P07333.

OMA

GACTYGG.

PhylomeDB

P07333.

Enzyme and pathway databases

BRENDA

2.7.10.1. 2681.

Pathway_Interaction_DB

avb3_integrin_pathway. Integrins in angiogenesis.
ptp1bpathway. Signaling events mediated by PTP1B.

Gene expression databases

ArrayExpress

P07333.

Bgee

P07333.

CleanEx

HS_CSF1R.

Genevestigator

P07333.

GermOnline

ENSG00000182578. Homo sapiens.

Family and domain databases

InterPro

IPR007110. Ig-like.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR013151. Immunoglobulin.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR016243. Tyr_kinase_CSF1/PDGF_rcpt.
IPR001824. Tyr_kinase_rcpt_3_CS.
[Graphical view]

Gene3D

G3DSA:2.60.40.10. Ig-like_fold. 5 hits.

KO

K05090.

Pfam

PF00047. ig. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]

PIRSF

PIRSF000615. TyrPK_CSF1-R. 1 hit.

SMART

SM00409. IG. 3 hits.
SM00408. IGc2. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

PS50835. IG_LIKE. 3 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]

ProtoNet

Search...

Other

DrugBank

DB00619. Imatinib.
DB01268. Sunitinib.

NextBio

5867.

SOURCE

Search...

Entry information

Entry name

CSF1R_HUMAN

Accession

Primary (citable) accession number: P07333
Secondary accession number(s): D3DQG2 , Q6LDW5, Q6LDY4, Q86VW7

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1988
Last sequence update:	June 1, 1994
Last modified:	January 25, 2012
This is version 146 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.