P07141 (CSF1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

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. Processed macrophage colony-stimulating factor 1

Gene names

Name:	Csf1
Synonyms:	Csfm

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	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	Cytokine that 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, 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 development. Required for normal male and female fertility. Promotes reorganization of the actin cytoskeleton, regulates formation of membrane ruffles, cell adhesion and cell migration. Plays a role in lipoprotein clearance.
Subunit structure	Homodimer or heterodimer; disulfide-linked. Interacts with CSF1R. Ref.14
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.13
Caution	The sequence reported in Ref.3 was thought to originate from rat, but was later shown (Ref.10 and Ref.11) to be derived from mouse.

Ontologies

Keywords
Biological process	Immunity Inflammatory response Innate immunity
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing
Domain	Signal Transmembrane Transmembrane helix
Molecular function	Cytokine Growth factor
PTM	Disulfide bond Glycoprotein Proteoglycan
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	branching involved in mammary gland duct morphogenesis Inferred from mutant phenotype PubMed 10804170. Source: MGI cell proliferation Inferred from electronic annotation. Source: Compara developmental process involved in reproduction Inferred from mutant phenotype PubMed 16237150. Source: BHF-UCL homeostasis of number of cells within a tissue Inferred from mutant phenotype PubMed 9215625. Source: MGI inflammatory response Inferred from electronic annotation. Source: UniProtKB-KW innate immune response Inferred from electronic annotation. Source: UniProtKB-KW macrophage differentiation Inferred from electronic annotation. Source: Compara mammary duct terminal end bud growth Inferred from mutant phenotype PubMed 10804170. Source: MGI mammary gland fat development Inferred from mutant phenotype PubMed 10804170. Source: MGI odontogenesis Inferred from electronic annotation. Source: Compara ossification Inferred from electronic annotation. Source: Compara osteoclast differentiation Inferred from electronic annotation. Source: Compara positive regulation of Ras protein signal transduction Inferred from direct assay PubMed 17053831. Source: MGI positive regulation of cell migration Inferred from genetic interaction PubMed 17053831. Source: MGI positive regulation of cell-matrix adhesion Inferred from genetic interaction PubMed 17053831. Source: MGI positive regulation of gene expression Inferred from electronic annotation. Source: Compara positive regulation of macrophage derived foam cell differentiation Inferred from electronic annotation. Source: Compara positive regulation of macrophage differentiation Inferred from mutant phenotype PubMed 9215625. Source: MGI positive regulation of monocyte differentiation Inferred from mutant phenotype PubMed 9215625. Source: MGI positive regulation of mononuclear cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of multicellular organism growth Inferred from mutant phenotype PubMed 12865350. Source: MGI positive regulation of odontogenesis of dentin-containing tooth Inferred from mutant phenotype PubMed 12865350. Source: MGI positive regulation of osteoclast differentiation Inferred from direct assay PubMed 15657444. Source: MGI positive regulation of protein kinase activity Inferred from genetic interaction PubMed 17053831. Source: MGI regulation of ossification Inferred from mutant phenotype PubMed 12865350. Source: MGI
Cellular_component	extracellular space Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW perinuclear region of cytoplasm Inferred from electronic annotation. Source: Compara plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell receptor complex Inferred from direct assay Ref.14. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Aar2	Q8C161	2	EBI-777188,EBI-777252
Cldn11	Q60771	2	EBI-777188,EBI-309095
Dync1h1	Q9JHU4	2	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.8

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

Helical; 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

Ref.14

Disulfide bond

63

Interchain Ref.14

Disulfide bond

80 ↔ 171

Ref.14

Disulfide bond

134 ↔ 178

Ref.14

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 in AAA37480. Ref.7

Sequence conflict

6

1

A → R in AAA37480. Ref.7

Sequence conflict

7 – 8

2

AG → PR in AAA37480. Ref.7

Sequence conflict

246

1

P → A in CAA28660. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

552

Helix Strand Turn

Details...

Helix

37 – 41

5

Helix

45 – 55

11

Beta strand

65 – 70

6

Turn

72 – 74

3

Helix

78 – 95

18

Helix

104 – 118

15

Helix

119 – 122

4

Turn

131 – 134

4

Beta strand

135 – 140

6

Helix

142 – 162

21

Turn

164 – 167

4

Helix

172 – 177

6

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 [UniParc]. 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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: Head and Spinal cord.
[5]	Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] (ISOFORMS 1 AND 2). Strain: C57BL/6J. Tissue: Embryonic germ cell and Neural stem cell.
[7]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-100.
[8]	"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] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 33-57.
[9]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 1-13.
[10]	"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] [Europe PMC] [Abstract] Cited for: SHOWS THAT SEQUENCE DESCRIBED IN PUBMED:8357831 ORIGINATES FROM MOUSE.
[11]	"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] [Europe PMC] [Abstract] Cited for: SHOWS THAT SEQUENCE DESCRIBED IN PUBMED:8357831 ORIGINATES FROM MOUSE.
[12]	"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] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[13]	"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] [Europe PMC] [Abstract] Cited for: DISEASE.
[14]	"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 (2.40 ANGSTROMS) OF 36-180 IN COMPLEX WITH CSF1R, SUBUNIT, DISULFIDE BONDS.
+	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.
AK138489 mRNA. Translation: BAE23681.1.
AK154872 mRNA. Translation: BAE32893.1.
AK160995 mRNA. Translation: BAE36140.1.
CH466607 Genomic DNA. Translation: EDL01916.1.
CH466607 Genomic DNA. Translation: EDL01919.1.
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. NM_001113529.1.
NP_001107002.1. NM_001113530.1.
NP_031804.3. NM_007778.4.

UniGene

Mm.795.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3EJJ	X-ray	2.40	A/B	36-180	[»]
3UF5	X-ray	2.80	A/B	33-181	[»]
4ADQ	X-ray	4.50	E/F/G/H	33-181	[»]

ProteinModelPortal

P07141.

SMR

P07141. Positions 36-180.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-45278N.

IntAct

P07141. 41 interactions.

PTM databases

PhosphoSite

P07141.

Proteomic databases

PaxDb

P07141.

PRIDE

P07141.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000014743; ENSMUSP00000014743; ENSMUSG00000014599.
ENSMUST00000118593; ENSMUSP00000113136; ENSMUSG00000014599.
ENSMUST00000120243; ENSMUSP00000113617; ENSMUSG00000014599.

GeneID

12977.

KEGG

mmu:12977.

UCSC

uc008qxl.2. mouse.

Organism-specific databases

CTD

1435.

MGI

MGI:1339753. Csf1.

Phylogenomic databases

eggNOG

NOG43822.

GeneTree

ENSGT00390000015805.

HOGENOM

HOG000112010.

HOVERGEN

HBG005410.

InParanoid

Q3U395.

KO

K05453.

OMA

DTGHERQ.

OrthoDB

EOG4RR6H2.

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. PTHR10058. 1 hit.

Pfam

PF05337. CSF-1. 2 hits.
[Graphical view]

PIRSF

PIRSF001948. MCSF-1. 1 hit.

SUPFAM

SSF47266. 4_helix_cytokine. 1 hit.

ProtoNet

Search...

Other

EvolutionaryTrace

P07141.

NextBio

282746.

SOURCE

Search...

Entry information

Entry name

CSF1_MOUSE

Accession

Primary (citable) accession number: P07141
Secondary accession number(s): Q3U395, Q8R3C8

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1988
Last sequence update:	February 1, 1996
Last modified:	April 3, 2013
This is version 128 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program