Reviewed, UniProtKB/Swiss-Prot P07141 (CSF1_MOUSE)

Names and origin

Protein names

Recommended name:
    Macrophage colony-stimulating factor 1
      Short name=CSF-1
      Short name=MCSF
Cleaved into the following chain:
    1- Recommended name:
            Processed macrophage colony-stimulating factor 1

Gene names

Name:	Csf1
Synonyms:	Csfm

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	552 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	Granulocyte/macrophage colony-stimulating factors are cytokines that act in hematopoiesis by controlling the production, differentiation, and function of 2 related white cell populations of the blood, the granulocytes and the monocytes-macrophages. CSF-1 induces cells of the monocyte/macrophage lineage. It plays a role in immunological defenses, bone metabolism, lipoproteins clearance, fertility and pregnancy.
Subunit structure	Homodimer or heterodimer; disulfide-linked.
Subcellular location	Cell membrane; Single-pass membrane protein By similarity. Processed macrophage colony-stimulating factor 1: Secreted › extracellular space By similarity.
Post-translational modification	N-glycosylated. The predominant soluble form is a chondroitin sulfate-containing proteoglycan.
Involvement in disease	A defect in Csf1 is the cause of osteopetrosis. Osteopetrotic mice (op/op) are severely deficient in mature macrophages and osteoclasts, display failed tooth eruption, and have a restricted capacity for bone remodeling. Ref.11
Caution	The sequence reported in Ref.3 was thought to originate from rat, but was later shown (Ref.8 and Ref.9) to be derived from mouse.

Ontologies

Keywords
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing
Domain	Signal Transmembrane
Molecular function	Cytokine Growth factor
PTM	Disulfide bond Glycoprotein Proteoglycan
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	branching involved in mammary gland duct morphogenesis Inferred from mutant phenotype. Source: MGI homeostasis of number of cells within a tissue Inferred from mutant phenotype. Source: MGI mammary duct terminal end bud growth Inferred from mutant phenotype. Source: MGI mammary gland fat development Inferred from mutant phenotype. Source: MGI positive regulation of Ras protein signal transduction Inferred from direct assay. Source: MGI positive regulation of cell migration Inferred from genetic interaction. Source: MGI positive regulation of cell-matrix adhesion Inferred from genetic interaction. Source: MGI positive regulation of macrophage differentiation Inferred from mutant phenotype. Source: MGI positive regulation of monocyte differentiation Inferred from mutant phenotype. Source: MGI positive regulation of multicellular organism growth Inferred from mutant phenotype. Source: MGI positive regulation of odontogenesis of dentine-containing tooth Inferred from mutant phenotype. Source: MGI positive regulation of osteoclast differentiation Inferred from direct assay. Source: MGI positive regulation of protein kinase activity Inferred from genetic interaction. Source: MGI regulation of ossification Inferred from mutant phenotype. Source: MGI reproductive developmental process Inferred from mutant phenotype. Source: UniProtKB
Cellular component	extracellular space Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW receptor complex Inferred from direct assay. Source: UniProtKB
Molecular function	cytokine activity Inferred from electronic annotation. Source: UniProtKB-KW growth factor activity Inferred from electronic annotation. Source: UniProtKB-KW macrophage colony stimulating factor receptor binding Inferred from physical interaction. Source: UniProtKB protein homodimerization activity Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
0610011L14Rik	Q8C161	1	EBI-777188,EBI-777252
Cldn11	Q60771	1	EBI-777188,EBI-309095
Dync1h1	Q9JHU4	1	EBI-777188,EBI-645061
Src	P05480	2	EBI-777188,EBI-298680

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P07141-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P07141-2)

The sequence of this isoform differs from the canonical sequence as follows:
     182-476: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 32	32	Ref.6
	Chain	33 – 552	520	Macrophage colony-stimulating factor 1		PRO_0000005858
	Chain	33 – ?		Processed macrophage colony-stimulating factor 1		PRO_0000296232
Regions
	Topological domain	33 – 492	460	Extracellular Potential
	Transmembrane	493 – 515	23	Potential
	Topological domain	516 – 552	37	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	107	1	N-linked (GlcNAc...) Potential
	Glycosylation	154	1	N-linked (GlcNAc...) Potential
	Glycosylation	172	1	N-linked (GlcNAc...) Potential
	Disulfide bond	39 ↔ 122		By similarity
	Disulfide bond	63		Interchain By similarity
	Disulfide bond	80 ↔ 171		By similarity
	Disulfide bond	134 ↔ 178		By similarity
	Disulfide bond	189		Interchain By similarity
	Disulfide bond	191		Interchain By similarity
Natural variations
	Alternative sequence	182 – 476	295	Missing in isoform 2.		VSP_001189
	Natural variant	292	1	D → G
	Natural variant	345	1	S → P
Experimental info
	Sequence conflict	3	1	Missing Ref.5
	Sequence conflict	6	1	A → R Ref.5
	Sequence conflict	7 – 8	2	AG → PR Ref.5
	Sequence conflict	246	1	P → A in CAA28660. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 1, 1996. Version 2. Checksum: 3886D72D70E770AF	FASTA	552	60,649
	10 20 30 40 50 60 MTARGAAGRC PSSTWLGSRL LLVCLLMSRS IAKEVSEHCS HMIGNGHLKV LQQLIDSQME 70 80 90 100 110 120 TSCQIAFEFV DQEQLDDPVC YLKKAFFLVQ DIIDETMRFK DNTPNANATE RLQELSNNLN 130 140 150 160 170 180 SCFTKDYEEQ NKACVRTFHE TPLQLLEKIK NFFNETKNLL EKDWNIFTKN CNNSFAKCSS 190 200 210 220 230 240 RDVVTKPDCN CLYPKATPSS DPASASPHQP PAPSMAPLAG LAWDDSQRTE GSSLLPSELP 250 260 270 280 290 300 LRIEDPGSAK QRPPRSTCQT LESTEQPNHG DRLTEDSQPH PSAGGPVPGV EDILESSLGT 310 320 330 340 350 360 NWVLEEASGE ASEGFLTQEA KFSPSTPVGG SIQAETDRPR ALSASPFPKS TEDQKPVDIT 370 380 390 400 410 420 DRPLTEVNPM RPIGQTQNNT PEKTDGTSTL REDHQEPGSP HIATPNPQRV SNSATPVAQL 430 440 450 460 470 480 LLPKSHSWGI VLPLGELEGK RSTRDRRSPA ELEGGSASEG AARPVARFNS IPLTDTGHVE 490 500 510 520 530 540 QHEGSSDPQI PESVFHLLVP GIILVLLTVG GLLFYKWKWR SHRDPQTLDS SVGRPEDSSL 550 TQDEDRQVEL PV
	Isoform 2. Checksum: E1EF2A20C416E591	FASTA	257	29,353
	10 20 30 40 50 60 MTARGAAGRC PSSTWLGSRL LLVCLLMSRS IAKEVSEHCS HMIGNGHLKV LQQLIDSQME 70 80 90 100 110 120 TSCQIAFEFV DQEQLDDPVC YLKKAFFLVQ DIIDETMRFK DNTPNANATE RLQELSNNLN 130 140 150 160 170 180 SCFTKDYEEQ NKACVRTFHE TPLQLLEKIK NFFNETKNLL EKDWNIFTKN CNNSFAKCSS 190 200 210 220 230 240 RGHVEQHEGS SDPQIPESVF HLLVPGIILV LLTVGGLLFY KWKWRSHRDP QTLDSSVGRP 250 EDSSLTQDED RQVELPV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nucleotide sequence of a cDNA encoding murine CSF-1 (Macrophage-CSF)." Delamarter J.F., Hession C., Semon D., Gough N.M., Rothenbuhler R., Mermod J.-J. Nucleic Acids Res. 15:2389-2390(1987) [PubMed: 3494232] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"cDNA cloning and expression of murine macrophage colony-stimulating factor from L929 cells." Ladner M.B., Martin G.A., Noble J.A., Wittman V.P., Warren M.K., McGrogan M., Stanley E.R. Proc. Natl. Acad. Sci. U.S.A. 85:6706-6710(1988) [PubMed: 2457916] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Isolation and characterization of a cDNA clone encoding for rat CSF-1 gene. Post-transcriptional repression occurs in myogenic differentiation." Borycki A.G., Lenormund J., Guillier M., Leibovitch S.A. Biochim. Biophys. Acta 1174:143-152(1993) [PubMed: 8357831] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"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] (ISOFORMS 1 AND 2). Strain: C57BL/6J. Tissue: Embryonic germ cell and Neural stem cell.
[5]	"Cloning and tissue-specific expression of mouse macrophage colony-stimulating factor mRNA." Rajavashisth T.B., Eng R., Shadduck R.K., Waheed A., Ben-Avram C.M., Shively J.E., Lusis A.J. Proc. Natl. Acad. Sci. U.S.A. 84:1157-1161(1987) [PubMed: 3493488] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-100.
[6]	"Amino-terminal amino acid sequence of murine colony-stimulating factor 1." Ben-Avram C.M., Shively J.E., Shadduck R.K., Waheed A., Rajavashisth T.B., Lusis A.J. Proc. Natl. Acad. Sci. U.S.A. 82:4486-4489(1985) [PubMed: 3925458] [Abstract] Cited for: PROTEIN SEQUENCE OF 33-57.
[7]	"Cloning and characterization of the murine promoter for the colony-stimulating factor-1-encoding gene." Harrington M.A., Edenberg H.J., Saxman S.M., Pedigo L.M., Daub R., Broxmeyer H.E. Gene 102:165-170(1991) [PubMed: 1874443] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 1-13.
[8]	"Mutation of macrophage colony stimulating factor (Csf1) causes osteopetrosis in the tl rat." Dobbins D.E., Sood R., Hashiramoto A., Hansen C.T., Wilder R.L., Remmers E.F. Biochem. Biophys. Res. Commun. 294:1114-1120(2002) [PubMed: 12074592] [Abstract] Cited for: SHOWS THAT SEQUENCE DESCRIBED IN PUBMED:8357831 ORIGINATES FROM MOUSE.
[9]	"The osteopetrotic mutation toothless (tl) is a loss-of-function frameshift mutation in the rat Csf1 gene: evidence of a crucial role for CSF-1 in osteoclastogenesis and endochondral ossification." Van Wesenbeeck L., Odgren P.R., MacKay C.A., D'Angelo M., Safadi F.F., Popoff S.N., Van Hul W., Marks S.C. Jr. Proc. Natl. Acad. Sci. U.S.A. 99:14303-14308(2002) [PubMed: 12379742] [Abstract] Cited for: SHOWS THAT SEQUENCE DESCRIBED IN PUBMED:8357831 ORIGINATES FROM MOUSE.
[10]	"The predominant form of secreted colony stimulating factor-1 is a proteoglycan." Price L.K.H., Choi H.U., Rosenberg L., Stanley E.R. J. Biol. Chem. 267:2190-2199(1992) [PubMed: 1733926] [Abstract] Cited for: CHARACTERIZATION.
[11]	"The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene." Yoshida H., Hayashi S., Kunisada T., Ogawa M., Nishikawa S., Okamura H., Sudo T., Shultz L.D., Nishikawa S. Nature 345:442-444(1990) [PubMed: 2188141] [Abstract] Cited for: DISEASE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X05010 mRNA. Translation: CAA28660.1. M21952 mRNA. Translation: AAA37481.1. M21149 mRNA. Translation: AAA37482.1. M84361 mRNA. Translation: AAA03032.1. BC025593 mRNA. Translation: AAH25593.1. BC066187 mRNA. Translation: AAH66187.1. BC066200 mRNA. Translation: AAH66200.1. BC066205 mRNA. Translation: AAH66205.1. M15692 mRNA. Translation: AAA37480.1. M81316 Unassigned DNA. Translation: AAA19866.1.
IPI	IPI00125138. IPI00229812.
PIR	A31401.
RefSeq	NP_001107001.1. NP_001107002.1. NP_031804.3.
UniGene	Mm.795
3D structure databases
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-45278N.
IntAct	P07141. 41 interactions.
STRING	P07141.
PTM databases
PhosphoSite	P07141.
Proteomic databases
PRIDE	P07141.
Genome annotation databases
Ensembl	ENSMUST00000014743; ENSMUSP00000014743; ENSMUSG00000014599; Mus musculus. [Genome view] ENSMUST00000120243; ENSMUSP00000113617; ENSMUSG00000014599; Mus musculus. [Genome view]
GeneID	12977.
KEGG	mmu:12977.
UCSC	uc008qxl.1. mouse. uc008qxm.1. mouse.
Organism-specific databases
CTD	12977.
MGI	MGI:1339753. Csf1.
Phylogenomic databases
eggNOG	maNOG15476.
HOGENOM	HBG126175.
HOVERGEN	P07141.
InParanoid	P07141.
OMA	TRDRRSP.
OrthoDB	EOG9P2SNV.
PhylomeDB	P07141.
Gene expression databases
ArrayExpress	P07141.
Bgee	P07141.
CleanEx	MM_CSF1.
Genevestigator	P07141.
GermOnline	ENSMUSG00000014599. Mus musculus.
Family and domain databases
InterPro	IPR009079. 4_helix_cytokine-like_core. IPR008001. MCSF-1. [Graphical view]
PANTHER	PTHR10058. MCSF-1. 1 hit.
Pfam	PF05337. CSF-1. 2 hits. [Graphical view]
PIRSF	PIRSF001948. MCSF-1. 1 hit.
ProtoNet	Search...
Other Resources
NextBio	282746.
SOURCE	Search...

Entry information

Entry name

CSF1_MOUSE

Accession

Primary (citable) accession number: P07141
Secondary accession number(s): Q8R3C8

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1988
Last sequence update:	February 1, 1996
Last modified:	January 19, 2010
This is version 103 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)