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Protein

Macrophage colony-stimulating factor 1

Gene

Csf1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.

GO - Molecular functioni

  • cytokine activity Source: MGI
  • growth factor activity Source: MGI
  • macrophage colony-stimulating factor receptor binding Source: BHF-UCL
  • protein homodimerization activity Source: BHF-UCL

GO - Biological processi

  • branching involved in mammary gland duct morphogenesis Source: MGI
  • developmental process involved in reproduction Source: BHF-UCL
  • homeostasis of number of cells within a tissue Source: MGI
  • inflammatory response Source: UniProtKB-KW
  • innate immune response Source: UniProtKB-KW
  • macrophage colony-stimulating factor signaling pathway Source: BHF-UCL
  • mammary duct terminal end bud growth Source: MGI
  • mammary gland fat development Source: MGI
  • osteoclast differentiation Source: MGI
  • osteoclast proliferation Source: MGI
  • positive regulation of cell-matrix adhesion Source: MGI
  • positive regulation of cell migration Source: MGI
  • positive regulation of cell proliferation Source: MGI
  • positive regulation of cellular protein metabolic process Source: MGI
  • positive regulation of gene expression Source: MGI
  • positive regulation of macrophage chemotaxis Source: MGI
  • positive regulation of macrophage colony-stimulating factor signaling pathway Source: MGI
  • positive regulation of macrophage derived foam cell differentiation Source: MGI
  • positive regulation of macrophage differentiation Source: MGI
  • positive regulation of microglial cell migration Source: MGI
  • positive regulation of monocyte differentiation Source: MGI
  • positive regulation of mononuclear cell proliferation Source: MGI
  • positive regulation of multicellular organism growth Source: MGI
  • positive regulation of odontogenesis of dentin-containing tooth Source: MGI
  • positive regulation of osteoclast differentiation Source: MGI
  • positive regulation of protein kinase activity Source: MGI
  • positive regulation of Ras protein signal transduction Source: MGI
  • regulation of ossification Source: MGI
  • transmembrane receptor protein tyrosine kinase signaling pathway Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Cytokine, Growth factor

Keywords - Biological processi

Immunity, Inflammatory response, Innate immunity

Names & Taxonomyi

Protein namesi
Recommended name:
Macrophage colony-stimulating factor 1
Short name:
CSF-1
Short name:
MCSF
Cleaved into the following chain:
Gene namesi
Name:Csf1
Synonyms:Csfm
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:1339753. Csf1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini33 – 492ExtracellularSequence analysisAdd BLAST460
Transmembranei493 – 515HelicalSequence analysisAdd BLAST23
Topological domaini516 – 552CytoplasmicSequence analysisAdd BLAST37

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

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.

Chemistry databases

ChEMBLiCHEMBL3638330.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 321 PublicationAdd BLAST32
ChainiPRO_000000585833 – 552Macrophage colony-stimulating factor 1Add BLAST520
ChainiPRO_000029623233 – 447Processed macrophage colony-stimulating factor 1By similarityAdd BLAST415

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi39 ↔ 1221 Publication
Disulfide bondi63Interchain1 Publication
Disulfide bondi80 ↔ 1711 Publication
Glycosylationi107N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi134 ↔ 1781 Publication
Glycosylationi154N-linked (GlcNAc...)Sequence analysis1
Glycosylationi172N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi189InterchainBy similarity
Disulfide bondi191InterchainBy similarity

Post-translational modificationi

N-glycosylated. The predominant soluble form is a chondroitin sulfate-containing proteoglycan.

Keywords - PTMi

Disulfide bond, Glycoprotein, Proteoglycan

Proteomic databases

PaxDbiP07141.
PeptideAtlasiP07141.
PRIDEiP07141.

PTM databases

iPTMnetiP07141.
PhosphoSitePlusiP07141.
SwissPalmiP07141.

Expressioni

Gene expression databases

BgeeiENSMUSG00000014599.
CleanExiMM_CSF1.
ExpressionAtlasiP07141. baseline and differential.
GenevisibleiP07141. MM.

Interactioni

Subunit structurei

Homodimer or heterodimer; disulfide-linked. Interacts with CSF1R.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
Aar2Q8C1612EBI-777188,EBI-777252
Cldn11Q607712EBI-777188,EBI-309095
Csf1rP095814EBI-777188,EBI-6305373
Dync1h1Q9JHU42EBI-777188,EBI-645061
SrcP054802EBI-777188,EBI-298680

GO - Molecular functioni

  • cytokine activity Source: MGI
  • growth factor activity Source: MGI
  • macrophage colony-stimulating factor receptor binding Source: BHF-UCL
  • protein homodimerization activity Source: BHF-UCL

Protein-protein interaction databases

DIPiDIP-45278N.
IntActiP07141. 42 interactors.
STRINGi10090.ENSMUSP00000014743.

Chemistry databases

BindingDBiP07141.

Structurei

Secondary structure

1552
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi37 – 41Combined sources5
Helixi45 – 55Combined sources11
Beta strandi65 – 70Combined sources6
Turni72 – 74Combined sources3
Helixi78 – 95Combined sources18
Helixi104 – 118Combined sources15
Helixi119 – 122Combined sources4
Turni131 – 134Combined sources4
Beta strandi135 – 140Combined sources6
Helixi142 – 162Combined sources21
Turni164 – 167Combined sources4
Helixi172 – 177Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3EJJX-ray2.40A/B36-180[»]
3UF5X-ray2.80A/B33-181[»]
4ADQX-ray4.50E/F/G/H33-181[»]
ProteinModelPortaliP07141.
SMRiP07141.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP07141.

Family & Domainsi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410II8R. Eukaryota.
ENOG410Z5Q9. LUCA.
GeneTreeiENSGT00390000015805.
HOGENOMiHOG000112010.
HOVERGENiHBG005410.
InParanoidiP07141.
KOiK05453.
OMAiDTGHERQ.
OrthoDBiEOG091G0TMC.
PhylomeDBiP07141.
TreeFamiTF337718.

Family and domain databases

InterProiIPR009079. 4_helix_cytokine-like_core.
IPR008001. MCSF-1.
[Graphical view]
PANTHERiPTHR10058. PTHR10058. 1 hit.
PfamiPF05337. CSF-1. 1 hit.
[Graphical view]
PIRSFiPIRSF001948. MCSF-1. 1 hit.
SUPFAMiSSF47266. SSF47266. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P07141-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MTARGAAGRC PSSTWLGSRL LLVCLLMSRS IAKEVSEHCS HMIGNGHLKV
60 70 80 90 100
LQQLIDSQME TSCQIAFEFV DQEQLDDPVC YLKKAFFLVQ DIIDETMRFK
110 120 130 140 150
DNTPNANATE RLQELSNNLN SCFTKDYEEQ NKACVRTFHE TPLQLLEKIK
160 170 180 190 200
NFFNETKNLL EKDWNIFTKN CNNSFAKCSS RDVVTKPDCN CLYPKATPSS
210 220 230 240 250
DPASASPHQP PAPSMAPLAG LAWDDSQRTE GSSLLPSELP LRIEDPGSAK
260 270 280 290 300
QRPPRSTCQT LESTEQPNHG DRLTEDSQPH PSAGGPVPGV EDILESSLGT
310 320 330 340 350
NWVLEEASGE ASEGFLTQEA KFSPSTPVGG SIQAETDRPR ALSASPFPKS
360 370 380 390 400
TEDQKPVDIT DRPLTEVNPM RPIGQTQNNT PEKTDGTSTL REDHQEPGSP
410 420 430 440 450
HIATPNPQRV SNSATPVAQL LLPKSHSWGI VLPLGELEGK RSTRDRRSPA
460 470 480 490 500
ELEGGSASEG AARPVARFNS IPLTDTGHVE QHEGSSDPQI PESVFHLLVP
510 520 530 540 550
GIILVLLTVG GLLFYKWKWR SHRDPQTLDS SVGRPEDSSL TQDEDRQVEL

PV
Length:552
Mass (Da):60,649
Last modified:February 1, 1996 - v2
Checksum:i3886D72D70E770AF
GO
Isoform 2 (identifier: P07141-2) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.
Show »
Length:257
Mass (Da):29,353
Checksum:iE1EF2A20C416E591
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti3Missing in AAA37480 (PubMed:3493488).Curated1
Sequence conflicti6A → R in AAA37480 (PubMed:3493488).Curated1
Sequence conflicti7 – 8AG → PR in AAA37480 (PubMed:3493488).Curated2
Sequence conflicti246P → A in CAA28660 (PubMed:3494232).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti292D → G.1
Natural varianti345S → P.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_001189182 – 476Missing in isoform 2. 1 PublicationAdd BLAST295

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS17740.1. [P07141-1]
CCDS51044.1. [P07141-2]
PIRiA31401.
RefSeqiNP_001107001.1. NM_001113529.1. [P07141-2]
NP_001107002.1. NM_001113530.1. [P07141-1]
NP_031804.3. NM_007778.4. [P07141-1]
UniGeneiMm.795.

Genome annotation databases

EnsembliENSMUST00000014743; ENSMUSP00000014743; ENSMUSG00000014599. [P07141-1]
ENSMUST00000118593; ENSMUSP00000113136; ENSMUSG00000014599. [P07141-2]
ENSMUST00000120243; ENSMUSP00000113617; ENSMUSG00000014599. [P07141-1]
GeneIDi12977.
KEGGimmu:12977.
UCSCiuc008qxk.2. mouse. [P07141-1]
uc008qxl.2. mouse. [P07141-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS17740.1. [P07141-1]
CCDS51044.1. [P07141-2]
PIRiA31401.
RefSeqiNP_001107001.1. NM_001113529.1. [P07141-2]
NP_001107002.1. NM_001113530.1. [P07141-1]
NP_031804.3. NM_007778.4. [P07141-1]
UniGeneiMm.795.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3EJJX-ray2.40A/B36-180[»]
3UF5X-ray2.80A/B33-181[»]
4ADQX-ray4.50E/F/G/H33-181[»]
ProteinModelPortaliP07141.
SMRiP07141.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-45278N.
IntActiP07141. 42 interactors.
STRINGi10090.ENSMUSP00000014743.

Chemistry databases

BindingDBiP07141.
ChEMBLiCHEMBL3638330.

PTM databases

iPTMnetiP07141.
PhosphoSitePlusiP07141.
SwissPalmiP07141.

Proteomic databases

PaxDbiP07141.
PeptideAtlasiP07141.
PRIDEiP07141.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000014743; ENSMUSP00000014743; ENSMUSG00000014599. [P07141-1]
ENSMUST00000118593; ENSMUSP00000113136; ENSMUSG00000014599. [P07141-2]
ENSMUST00000120243; ENSMUSP00000113617; ENSMUSG00000014599. [P07141-1]
GeneIDi12977.
KEGGimmu:12977.
UCSCiuc008qxk.2. mouse. [P07141-1]
uc008qxl.2. mouse. [P07141-2]

Organism-specific databases

CTDi1435.
MGIiMGI:1339753. Csf1.

Phylogenomic databases

eggNOGiENOG410II8R. Eukaryota.
ENOG410Z5Q9. LUCA.
GeneTreeiENSGT00390000015805.
HOGENOMiHOG000112010.
HOVERGENiHBG005410.
InParanoidiP07141.
KOiK05453.
OMAiDTGHERQ.
OrthoDBiEOG091G0TMC.
PhylomeDBiP07141.
TreeFamiTF337718.

Miscellaneous databases

EvolutionaryTraceiP07141.
PROiP07141.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000014599.
CleanExiMM_CSF1.
ExpressionAtlasiP07141. baseline and differential.
GenevisibleiP07141. MM.

Family and domain databases

InterProiIPR009079. 4_helix_cytokine-like_core.
IPR008001. MCSF-1.
[Graphical view]
PANTHERiPTHR10058. PTHR10058. 1 hit.
PfamiPF05337. CSF-1. 1 hit.
[Graphical view]
PIRSFiPIRSF001948. MCSF-1. 1 hit.
SUPFAMiSSF47266. SSF47266. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiCSF1_MOUSE
AccessioniPrimary (citable) accession number: P07141
Secondary accession number(s): Q3U395, Q8R3C8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1988
Last sequence update: February 1, 1996
Last modified: November 30, 2016
This is version 159 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

The sequence reported in PubMed:8357831 was thought to originate from rat, but was later shown (PubMed:12074592 and PubMed:12379742) to be derived from mouse.Curated

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.