Reviewed, UniProtKB/Swiss-Prot P07333 (CSF1R_HUMAN)

Names and origin

Protein names

Recommended name:
    Macrophage colony-stimulating factor 1 receptor
      Short name=CSF-1-R
    EC=2.7.10.1
Alternative name(s):
    Fms 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	Protein tyrosine-kinase transmembrane receptor for CSF1 and IL34. Ref.11
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure	Interacts with INPPL1/SHIP2 and THOC5 By similarity.
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	Expressed in bone marrow and in differentiated blood mononuclear cells.
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
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Proto-oncogene
Domain	Immunoglobulin domain Repeat Signal Transmembrane
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	cell proliferation Traceable author statement. Source: ProtInc multicellular organismal development Traceable author statement. Source: ProtInc protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro transmembrane receptor protein tyrosine kinase signaling pathway Inferred from electronic annotation. Source: InterPro
Cellular component	integral to plasma membrane Ref.2 Traceable author statement. Source: ProtInc receptor complex Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW cytokine binding Inferred from sequence or structural similarity. Source: UniProtKB macrophage colony stimulating factor receptor activity Traceable author statement. Source: ProtInc protein homodimerization activity Inferred from sequence or structural similarity. 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 – 972

953

Macrophage colony-stimulating factor 1 receptor

PRO_0000016765

Regions

Topological domain

20 – 512

493

Extracellular Potential

Transmembrane

513 – 537

25

Potential

Topological domain

538 – 972

435

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

Sites

Active site

778

1

Proton acceptor By similarity

Binding site

616

1

ATP By similarity

Amino acid modifications

Modified residue

555

1

Phosphoserine Ref.10

Modified residue

556

1

Phosphotyrosine Ref.10

Modified residue

562

1

Phosphothreonine Ref.10

Modified residue

567

1

Phosphothreonine Ref.10

Modified residue

699

1

Phosphotyrosine; by autocatalysis By similarity

Modified residue

708

1

Phosphotyrosine; by autocatalysis By similarity

Modified residue

716

1

Phosphoserine By similarity

Modified residue

809

1

Phosphotyrosine; by autocatalysis By similarity

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.9

Glycosylation

335

1

N-linked (GlcNAc...) Potential

Glycosylation

353

1

N-linked (GlcNAc...) Ref.9

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

Potential

Disulfide bond

127 ↔ 177

Potential

Disulfide bond

224 ↔ 278

Potential

Disulfide bond

419 ↔ 485

Potential

Natural variations

Natural variant

32

1

V → G Ref.12

VAR_042038

Natural variant

279

1

V → M: dbSNP rs3829986.

VAR_049718

Natural variant

362

1

H → R: dbSNP rs10079250. Ref.12

VAR_042039

Natural variant

413

1

G → S Ref.12

VAR_042040

Natural variant

536

1

L → V Ref.12

VAR_042041

Natural variant

693

1

P → H in a lung squamous cell carcinoma sample; somatic mutation. Ref.12

VAR_042042

Natural variant

920

1

E → D: dbSNP rs34030164. Ref.12

VAR_042043

Natural variant

921

1

R → Q Ref.12

VAR_042044

Natural variant

969

1

Y → C: dbSNP rs1801271.

VAR_011953

Experimental info

Sequence conflict

54

1

P → A in CAA27300. Ref.2

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)
	P07333-1 [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]	"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.
[5]	"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.
[6]	"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.
[7]	"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.
[8]	"'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.
[9]	"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.
[10]	"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.
[11]	"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.
[12]	"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

EMBLGenBankDDBJ

X03663 mRNA. Translation: CAA27300.1.
U63963 Genomic DNA. Translation: AAB51696.1.
M25786 mRNA. Translation: AAA58421.1.
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.

UniGene

Hs.586219
Hs.654394

3D structure databases

PDBPDBe

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	[»]

ModBase

Search...

PTM databases

PhosphoSite

P07333.

Proteomic databases

PeptideAtlas

P07333.

PRIDE

P07333.

Genome annotation databases

Ensembl

ENSG00000182578. Homo sapiens. [Contig view]

GeneID

1436.

KEGG

hsa:1436.

Organism-specific databases

GeneCards

GC05M149413.

HGNC

HGNC:2433. CSF1R.

HPA

CAB008970.
HPA012323.

MIM

164770. gene.

PharmGKB

PA26936.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P07333.

HOVERGEN

P07333.

OMA

P07333. KEDAVLK.

Enzyme and pathway databases

BRENDA

2.7.10.1. 247.

Pathway_Interaction_DB

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

Gene expression databases

Bgee

P07333.

CleanEx

HS_CSF1R.

GermOnline

ENSG00000182578. Homo sapiens.

Family and domain databases

InterPro

IPR013151. Ig.
IPR007110. Ig-like.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR013106. Ig_V-set.
IPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_BS.
IPR001824. Recept_tyr_kinase-III_CS.
IPR001245. Tyr_pkinase.
IPR008266. Tyr_pkinase_AS.
IPR016243. TyrPK_CSF1-R.
[Graphical view]

Gene3D

G3DSA:2.60.40.10. Ig-like_fold. 3 hits.

Pfam

PF00047. ig. 2 hits.
PF07714. Pkinase_Tyr. 1 hit.
PF07686. V-set. 1 hit.
[Graphical view]

PIRSF

PIRSF000615. TyrPK_CSF1-R. 1 hit.

ProDom

PD000001. Prot_kinase. 2 hits.
[Graphical view] [Entries sharing at least one domain]

SMART

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

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 Resources

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): Q6LDW5, Q6LDY4

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1988
Last sequence update:	June 1, 1994
Last modified:	June 16, 2009
This is version 118 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)