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Protein

Macrophage colony-stimulating factor 1

Gene

CSF1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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.4 Publications

GO - Molecular functioni

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

Keywordsi

Molecular functionCytokine, Growth factor
Biological processImmunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

ReactomeiR-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-449836 Other interleukin signaling
R-HSA-6783783 Interleukin-10 signaling
R-HSA-8957275 Post-translational protein phosphorylation
SignaLinkiP09603
SIGNORiP09603

Names & Taxonomyi

Protein namesi
Recommended name:
Macrophage colony-stimulating factor 1
Short name:
CSF-1
Short name:
M-CSF
Short name:
MCSF
Alternative name(s):
Lanimostim
Cleaved into the following chain:
Gene namesi
Name:CSF1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000184371.13
HGNCiHGNC:2432 CSF1
MIMi120420 gene
neXtProtiNX_P09603

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini33 – 496LumenalSequence analysisAdd BLAST464
Transmembranei497 – 517HelicalSequence analysisAdd BLAST21
Topological domaini518 – 554CytoplasmicSequence analysisAdd BLAST37

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

Aberrant expression of CSF1 or CSF1R can promote cancer cell proliferation, invasion and formation of metastases. Overexpression of CSF1 or CSF1R is observed in a significant percentage of breast, ovarian, prostate, and endometrial cancers.
Aberrant expression of CSF1 or CSF1R may play a role in inflammatory diseases, such as rheumatoid arthritis, glomerulonephritis, atherosclerosis, and allograft rejection.

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi489 – 554Missing : Produces biologically active protein which is secreted. 1 PublicationAdd BLAST66

Organism-specific databases

DisGeNETi1435
OpenTargetsiENSG00000184371
PharmGKBiPA26935

Chemistry databases

ChEMBLiCHEMBL3989382

Polymorphism and mutation databases

BioMutaiCSF1
DMDMi311033367

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 321 PublicationAdd BLAST32
ChainiPRO_000000585733 – 554Macrophage colony-stimulating factor 1Add BLAST522
ChainiPRO_000029623133 – 450Processed macrophage colony-stimulating factor 1By similarityAdd BLAST418

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi39 ↔ 1221 Publication
Disulfide bondi63Interchain1 Publication
Disulfide bondi80 ↔ 1711 Publication
Disulfide bondi134 ↔ 1781 Publication
Glycosylationi154N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi172N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi189Interchain1 Publication
Disulfide bondi191Interchain1 Publication
Modified residuei266Phosphothreonine; by FAM20C1 Publication1
Glycosylationi363O-linked (GalNAc...) threonine1 Publication1
Glycosylationi365O-linked (GalNAc...) threonine1 Publication1

Post-translational modificationi

N- and O-glycosylated. Glycosylation and proteolytic cleavage yield different soluble forms. One high molecular weight soluble form is a proteoglycan containing chondroitin sulfate. O-glycosylated with core 1 or possibly core 8 glycans. Isoform 1 is N- and O-glycosylated. Isoform 3 is only N-glycosylated.4 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Proteoglycan

Proteomic databases

EPDiP09603
MaxQBiP09603
PaxDbiP09603
PeptideAtlasiP09603
PRIDEiP09603
ProteomicsDBi52250
52251 [P09603-2]
52252 [P09603-3]

PTM databases

iPTMnetiP09603
PhosphoSitePlusiP09603

Miscellaneous databases

PMAP-CutDBiP09603

Expressioni

Gene expression databases

BgeeiENSG00000184371
CleanExiHS_CSF1
ExpressionAtlasiP09603 baseline and differential
GenevisibleiP09603 HS

Interactioni

Subunit structurei

Homodimer or heterodimer; disulfide-linked. Interacts with CSF1R.4 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi107822, 8 interactors
DIPiDIP-41860N
IntActiP09603, 14 interactors
STRINGi9606.ENSP00000327513

Structurei

Secondary structure

1554
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi37 – 41Combined sources5
Helixi45 – 56Combined sources12
Beta strandi65 – 70Combined sources6
Turni72 – 74Combined sources3
Helixi78 – 95Combined sources18
Helixi104 – 119Combined sources16
Helixi120 – 122Combined sources3
Helixi128 – 130Combined sources3
Beta strandi135 – 140Combined sources6
Helixi142 – 162Combined sources21
Helixi166 – 168Combined sources3
Helixi172 – 176Combined sources5

3D structure databases

ProteinModelPortaliP09603
SMRiP09603
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP09603

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni406 – 426O-glycosylated at one siteAdd BLAST21

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410II8R Eukaryota
ENOG410Z5Q9 LUCA
GeneTreeiENSGT00390000015805
HOVERGENiHBG005410
InParanoidiP09603
KOiK05453
OMAiDTGHERQ
OrthoDBiEOG091G0TMC
PhylomeDBiP09603
TreeFamiTF337718

Family and domain databases

InterProiView protein in InterPro
IPR009079 4_helix_cytokine-like_core
IPR008001 MCSF-1
PANTHERiPTHR10058 PTHR10058, 1 hit
PfamiView protein in Pfam
PF05337 CSF-1, 1 hit
PIRSFiPIRSF001948 MCSF-1, 1 hit
SUPFAMiSSF47266 SSF47266, 1 hit

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P09603-1) [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
MTAPGAAGRC PPTTWLGSLL LLVCLLASRS ITEEVSEYCS HMIGSGHLQS
60 70 80 90 100
LQRLIDSQME TSCQITFEFV DQEQLKDPVC YLKKAFLLVQ DIMEDTMRFR
110 120 130 140 150
DNTPNAIAIV QLQELSLRLK SCFTKDYEEH DKACVRTFYE TPLQLLEKVK
160 170 180 190 200
NVFNETKNLL DKDWNIFSKN CNNSFAECSS QDVVTKPDCN CLYPKAIPSS
210 220 230 240 250
DPASVSPHQP LAPSMAPVAG LTWEDSEGTE GSSLLPGEQP LHTVDPGSAK
260 270 280 290 300
QRPPRSTCQS FEPPETPVVK DSTIGGSPQP RPSVGAFNPG MEDILDSAMG
310 320 330 340 350
TNWVPEEASG EASEIPVPQG TELSPSRPGG GSMQTEPARP SNFLSASSPL
360 370 380 390 400
PASAKGQQPA DVTGTALPRV GPVRPTGQDW NHTPQKTDHP SALLRDPPEP
410 420 430 440 450
GSPRISSLRP QGLSNPSTLS AQPQLSRSHS SGSVLPLGEL EGRRSTRDRR
460 470 480 490 500
SPAEPEGGPA SEGAARPLPR FNSVPLTDTG HERQSEGSFS PQLQESVFHL
510 520 530 540 550
LVPSVILVLL AVGGLLFYRW RRRSHQEPQR ADSPLEQPEG SPLTQDDRQV

ELPV
Length:554
Mass (Da):60,179
Last modified:November 2, 2010 - v2
Checksum:i656B0894F9255AED
GO
Isoform 2 (identifier: P09603-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     365-480: Missing.

Show »
Length:438
Mass (Da):47,903
Checksum:i1B6A3CDBE1C06775
GO
Isoform 3 (identifier: P09603-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     182-479: Missing.

Show »
Length:256
Mass (Da):29,215
Checksum:i0656D858DE1A4086
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti69F → S AA sequence (PubMed:3498652).Curated1
Sequence conflicti91D → Y in AAB59527 (PubMed:2996129).Curated1
Sequence conflicti91D → Y in AAA59572 (PubMed:2460758).Curated1
Sequence conflicti91D → Y in AAA64849 (PubMed:2460758).Curated1
Sequence conflicti91D → Y in AAA52120 (PubMed:1791839).Curated1
Sequence conflicti104 – 106PNA → ANP in AAA52117 (PubMed:3493529).Curated3
Sequence conflicti364G → A in AAA52117 (PubMed:3493529).Curated1
Sequence conflicti374R → M in AAA52117 (PubMed:3493529).Curated1
Sequence conflicti412G → A in AAA52117 (PubMed:3493529).Curated1
Sequence conflicti450R → T in AAA52117 (PubMed:3493529).Curated1
Sequence conflicti457 – 458GG → AA in AAA52117 (PubMed:3493529).Curated2
Sequence conflicti480Missing in AAA59573 (PubMed:2660794).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_048810341S → N. Corresponds to variant dbSNP:rs12565736Ensembl.1
Natural variantiVAR_020454408L → P1 PublicationCorresponds to variant dbSNP:rs1058885Ensembl.1
Natural variantiVAR_029320438G → R. Corresponds to variant dbSNP:rs2229165Ensembl.1
Natural variantiVAR_048811489F → S9 PublicationsCorresponds to variant dbSNP:rs333971Ensembl.1
Natural variantiVAR_020455496S → F. Corresponds to variant dbSNP:rs12721516Ensembl.1
Natural variantiVAR_022146531A → V. Corresponds to variant dbSNP:rs2229167Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_001187182 – 479Missing in isoform 3. 1 PublicationAdd BLAST298
Alternative sequenceiVSP_001188365 – 480Missing in isoform 2. CuratedAdd BLAST116

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M11296, M11038, M11295 Genomic DNA Translation: AAB59527.1
M37435 mRNA Translation: AAA52117.1
M64592 mRNA Translation: AAA59572.1
U22386 mRNA Translation: AAA64849.1
M27087 mRNA Translation: AAA59573.1
AK291660 mRNA Translation: BAF84349.1
AL450468 Genomic DNA No translation available.
CH471122 Genomic DNA Translation: EAW56416.1
BC021117 mRNA Translation: AAH21117.1
X05825 mRNA Translation: CAA29265.1
X06106 Genomic DNA Translation: CAA29479.1
M76453 mRNA Translation: AAA52120.2
CCDSiCCDS30797.1 [P09603-3]
CCDS816.1 [P09603-1]
CCDS817.1 [P09603-2]
PIRiA47583 FQHUMP
RefSeqiNP_000748.3, NM_000757.5
NP_757349.1, NM_172210.2
NP_757350.1, NM_172211.3
NP_757351.1, NM_172212.2
UniGeneiHs.173894

Genome annotation databases

EnsembliENST00000329608; ENSP00000327513; ENSG00000184371 [P09603-1]
ENST00000369801; ENSP00000358816; ENSG00000184371 [P09603-2]
ENST00000369802; ENSP00000358817; ENSG00000184371 [P09603-1]
ENST00000420111; ENSP00000407317; ENSG00000184371 [P09603-3]
GeneIDi1435
KEGGihsa:1435
UCSCiuc001dyt.3 human [P09603-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiCSF1_HUMAN
AccessioniPrimary (citable) accession number: P09603
Secondary accession number(s): A8K6J5
, Q13130, Q14086, Q14806, Q5VVF3, Q5VVF4, Q9UQR8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: November 2, 2010
Last modified: July 18, 2018
This is version 194 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

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

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

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