P09581 (CSF1R_MOUSE) 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:	Csfmr, Fms

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	977 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.8 Ref.9 Ref.10 Ref.11 Ref.13 Ref.14 Ref.18 Ref.20 Ref.21 Ref.22 Ref.23 Ref.25 Ref.26 Ref.27 Ref.28 Ref.30
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.25
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.20 Ref.30 Ref.31
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.20
Tissue specificity	Widely expressed. Ref.27
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. Ref.7 Ref.8 Ref.9 Ref.10 Ref.15 Ref.16 Ref.27 Ref.30 Ubiquitinated. Becomes rapidly polyubiquitinated after autophosphorylation, leading to its degradation. Ref.10 Ref.20 Ref.29
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 process	Immunity Inflammatory response Innate immunity
Cellular component	Cell membrane Membrane
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 electronic annotation. Source: Compara cell-cell junction maintenance Inferred from electronic annotation. Source: Compara inflammatory response Inferred from electronic annotation. Source: UniProtKB-KW innate immune response Inferred from electronic annotation. Source: UniProtKB-KW osteoclast differentiation Inferred from mutant phenotype PubMed 17121910Ref.25Ref.27. Source: UniProtKB peptidyl-tyrosine phosphorylation Inferred from direct assay Ref.10. Source: UniProtKB phosphatidylinositol metabolic process Inferred from mutant phenotype Ref.30. Source: UniProtKB phosphatidylinositol-mediated signaling Inferred from mutant phenotype Ref.30. 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.30. 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: Compara positive regulation of protein serine/threonine kinase activity Inferred from mutant phenotype Ref.30. Source: UniProtKB positive regulation of protein tyrosine kinase activity Inferred from electronic annotation. Source: Compara positive regulation of tyrosine phosphorylation of Stat3 protein Inferred from mutant phenotype Ref.10. Source: UniProtKB protein autophosphorylation Inferred from direct assay Ref.27Ref.10. Source: UniProtKB regulation of actin cytoskeleton reorganization Inferred from mutant phenotype Ref.30. Source: UniProtKB regulation of bone resorption Inferred from sequence or structural similarity. Source: UniProtKB regulation of cell shape Inferred from mutant phenotype Ref.30. Source: UniProtKB ruffle organization Inferred from mutant phenotype Ref.30. Source: UniProtKB transmembrane receptor protein tyrosine kinase signaling pathway Inferred from mutant phenotype Ref.9. Source: UniProtKB
Cellular_component	cell surface Inferred from direct assay Ref.10. Source: UniProtKB integral to 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.31. Source: BHF-UCL
Molecular_function	ATP 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
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 – 977

958

Macrophage colony-stimulating factor 1 receptor

PRO_0000016766

Regions

Topological domain

20 – 515

496

Extracellular Potential

Transmembrane

516 – 536

21

Helical; Potential

Topological domain

537 – 977

441

Cytoplasmic Potential

Domain

24 – 104

81

Ig-like C2-type 1

Domain

107 – 197

91

Ig-like C2-type 2

Domain

204 – 298

95

Ig-like C2-type 3

Domain

299 – 397

99

Ig-like C2-type 4

Domain

398 – 503

106

Ig-like C2-type 5

Domain

580 – 913

334

Protein kinase

Nucleotide binding

586 – 594

9

ATP By similarity

Region

540 – 572

33

Regulatory juxtamembrane domain By similarity

Region

794 – 816

23

Activation loop By similarity

Sites

Active site

776

1

Proton acceptor By similarity

Binding site

614

1

ATP Probable

Amino acid modifications

Modified residue

544

1

Phosphotyrosine; by autocatalysis By similarity

Modified residue

559

1

Phosphotyrosine; by autocatalysis Ref.10 Ref.16 Ref.27

Modified residue

697

1

Phosphotyrosine; by autocatalysis Ref.9

Modified residue

706

1

Phosphotyrosine; by autocatalysis Ref.7 Ref.8 Ref.9 Ref.30

Modified residue

711

1

Phosphoserine By similarity

Modified residue

714

1

Phosphoserine Ref.24

Modified residue

721

1

Phosphotyrosine; by autocatalysis Ref.9 Ref.27 Ref.30

Modified residue

807

1

Phosphotyrosine; by autocatalysis Ref.7 Ref.8 Ref.9 Ref.10 Ref.27

Modified residue

921

1

Phosphotyrosine; by autocatalysis

Modified residue

974

1

Phosphotyrosine; by autocatalysis Ref.15

Glycosylation

45

1

N-linked (GlcNAc...) Ref.31

Glycosylation

73

1

N-linked (GlcNAc...) Ref.31

Glycosylation

302

1

N-linked (GlcNAc...) Potential

Glycosylation

335

1

N-linked (GlcNAc...) Potential

Glycosylation

389

1

N-linked (GlcNAc...) Potential

Glycosylation

410

1

N-linked (GlcNAc...) Potential

Glycosylation

449

1

N-linked (GlcNAc...) Potential

Glycosylation

478

1

N-linked (GlcNAc...) Potential

Glycosylation

491

1

N-linked (GlcNAc...) Ref.19

Disulfide bond

42 ↔ 84

Ref.31

Disulfide bond

127 ↔ 177

Ref.31

Disulfide bond

224 ↔ 278

Ref.31

Disulfide bond

417 ↔ 483

By similarity

Experimental info

Mutagenesis

544

1

Y → F: No effect on binding to THOC5. Ref.12

Mutagenesis

559

1

Y → F: Reduced interaction with CBL. Prolonged signaling, due to reduced internalization and degradation. Reduced interaction with FYN. Promotes cell proliferation. Reduced autophosphorylation at Tyr-807. Ref.10 Ref.16 Ref.21

Mutagenesis

614

1

K → A: Loss of kinase activity. Ref.9 Ref.11 Ref.12

Mutagenesis

614

1

K → M: Loss of kinase activity. Abolishes binding to THOC5. Ref.9 Ref.11 Ref.12

Mutagenesis

697

1

Y → F: Abolishes interaction with GRB2. Ref.9 Ref.11

Mutagenesis

706

1

Y → F: No effect on binding to THOC5. Slightly reduced enhancement of cell proliferation. Ref.8 Ref.12

Mutagenesis

706

1

Y → G: Slightly impaired signaling. Ref.8 Ref.12

Mutagenesis

721

1

Y → F: Abolishes interaction with PIK3R1. Strongly reduced phosphorylation of PLCG2. No effect on binding to THOC5. Ref.9 Ref.11 Ref.12 Ref.30

Mutagenesis

807

1

Y → F: Reduced kinase activity. Strongly reduced phosphorylation of PLCG2. Diminishes binding to THOC5. Ref.8 Ref.11 Ref.12

Mutagenesis

807

1

Y → G: May alter protein folding or stability. Loss of kinase activity. No effect on interaction with PIK3R1. Ref.8 Ref.11 Ref.12

Sequence conflict

57

1

Y → I in CAA29666. Ref.1

Sequence conflict

72

1

R → S in CAA29666. Ref.1

Sequence conflict

162

1

F → S in CAA29666. Ref.1

Sequence conflict

446 – 447

2

QV → HL in CAA29666. Ref.1

Sequence conflict

474

1

T → P in CAA29666. Ref.1

Sequence conflict

660

1

I → Y in CAA29666. Ref.1

Sequence conflict

669

1

L → H in CAA29666. Ref.1

Sequence conflict

744

1

A → H in CAA29666. Ref.1

Sequence conflict

814

1

Missing in CAA29666. Ref.1

Sequence conflict

830

1

Y → I in CAA29666. Ref.1

Sequence conflict

858

1

L → H in CAA29666. Ref.1

Secondary structure

1

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977

Helix Strand Turn

Details...

Beta strand

22 – 25

4

Beta strand

27 – 32

6

Beta strand

38 – 43

6

Beta strand

49 – 51

3

Beta strand

55 – 60

6

Beta strand

64 – 66

3

Beta strand

68 – 73

6

Helix

76 – 78

3

Beta strand

80 – 85

6

Beta strand

95 – 101

7

Beta strand

107 – 111

5

Beta strand

113 – 118

6

Beta strand

123 – 125

3

Beta strand

127 – 130

4

Helix

132 – 136

5

Beta strand

137 – 142

6

Helix

143 – 145

3

Beta strand

154 – 157

4

Turn

158 – 160

3

Beta strand

161 – 166

6

Helix

169 – 171

3

Beta strand

173 – 181

9

Beta strand

184 – 187

4

Beta strand

191 – 198

8

Beta strand

204 – 213

10

Beta strand

216 – 218

3

Beta strand

220 – 231

12

Beta strand

234 – 239

6

Beta strand

248 – 252

5

Beta strand

254 – 267

14

Beta strand

270 – 272

3

Beta strand

274 – 281

8

Beta strand

286 – 294

9

Sequences

	Sequence		Length	Mass (Da)
	P09581 [UniParc]. Last modified May 10, 2002. Version 3. Checksum: 7EDF8310CCF98906	FASTA	977	109,179
	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

References

	« Hide 'large scale' referencesShow '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. , 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, MASS SPECTROMETRY. Strain: C57BL/6. Tissue: Plasma.
[20]	"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.
[21]	"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.
[22]	"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.
[23]	"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.
[24]	"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-714, MASS SPECTROMETRY. Tissue: Macrophage.
[25]	"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.
[26]	"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.
[27]	"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.
[28]	"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.
[29]	"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.
[30]	"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.
[31]	"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.

IPI

IPI00108003.

PIR

TVMSMD. S01880.

RefSeq

NP_001032948.2. NM_001037859.2.

UniGene

Mm.22574.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3EJJ	X-ray	2.40	X	20-296	[»]
4EXP	X-ray	2.80	X	20-298	[»]

ProteinModelPortal

P09581.

SMR

P09581. Positions 20-496, 541-916.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-46415N.

IntAct

P09581. 1 interaction.

MINT

MINT-8013693.

PTM databases

PhosphoSite

P09581.

Proteomic databases

PaxDb

P09581.

PRIDE

P09581.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000025523; ENSMUSP00000025523; ENSMUSG00000024621.
ENSMUST00000115268; ENSMUSP00000110923; ENSMUSG00000024621.

GeneID

12978.

KEGG

mmu:12978.

UCSC

uc008fbn.1. mouse.

Organism-specific databases

CTD

1436.

MGI

MGI:1339758. Csf1r.

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000112008.

HOVERGEN

HBG004335.

InParanoid

P09581.

KO

K05090.

OMA

SPGQDPE.

OrthoDB

EOG4BP1B0.

Enzyme and pathway databases

BRENDA

2.7.10.1. 3474.

Gene expression databases

ArrayExpress

P09581.

Bgee

P09581.

CleanEx

MM_CSF1R.

Genevestigator

P09581.

GermOnline

ENSMUSG00000024621. Mus musculus.

Family and domain databases

Gene3D

2.60.40.10. 5 hits.

InterPro

IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_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]

Pfam

PF07679. I-set. 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. 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]

ProtoNet

Search...

Other

ChEMBL

CHEMBL5570.

ChiTaRS

CSF1R. mouse.

EvolutionaryTrace

P09581.

NextBio

282750.

SOURCE

Search...

Entry information

Entry name

CSF1R_MOUSE

Accession

Primary (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:	May 29, 2013
This is version 164 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program