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P04141 (CSF2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 149. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Granulocyte-macrophage colony-stimulating factor

Short name=GM-CSF
Alternative name(s):
Colony-stimulating factor
Short name=CSF
Molgramostin
Sargramostim
Gene names
Name:CSF2
Synonyms:GMCSF
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length144 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Cytokine that stimulates the growth and differentiation of hematopoietic precursor cells from various lineages, including granulocytes, macrophages, eosinophils and erythrocytes.

Subunit structure

Monomer. The signaling GM-CSF receptor complex is a dodecamer of two head-to-head hexamers of two alpha, two beta, and two ligand subunits. Ref.13

Subcellular location

Secreted.

Polymorphism

Variant Ile-117 may be a risk factor for atopic asthma.

Pharmaceutical use

Available under the names Leukine (Immunex) and Leucomax (Novartis). Used in myeloid reconstitution following bone marrow transplant, bone marrow transplant engraftment failure or delay, mobilization and following transplantation of autologous peripheral blood progenitor cells, and following induction chemotherapy in older adults with acute myelogenous leukemia.

Sequence similarities

Belongs to the GM-CSF family.

Ontologies

Keywords
   Cellular componentSecreted
   Coding sequence diversityPolymorphism
   DomainSignal
   Molecular functionCytokine
Growth factor
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Pharmaceutical
Reference proteome
Gene Ontology (GO)
   Biological_processcellular response to lipopolysaccharide

Inferred from electronic annotation. Source: Ensembl

dendritic cell differentiation

Inferred from direct assay PubMed 21149635. Source: DFLAT

embryonic placenta development

Inferred from electronic annotation. Source: Ensembl

epithelial fluid transport

Inferred from electronic annotation. Source: Ensembl

immune response

Inferred from electronic annotation. Source: InterPro

macrophage activation

Inferred from electronic annotation. Source: Ensembl

myeloid dendritic cell differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of cytolysis

Inferred from direct assay PubMed 10666185. Source: BHF-UCL

negative regulation of extrinsic apoptotic signaling pathway in absence of ligand

Inferred from direct assay PubMed 10666185. Source: BHF-UCL

positive regulation of DNA replication

Inferred from direct assay PubMed 9722506. Source: BHF-UCL

positive regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of gene expression

Inferred from direct assay PubMed 10666185. Source: BHF-UCL

positive regulation of interleukin-23 production

Inferred from direct assay PubMed 20027291. Source: BHF-UCL

positive regulation of macrophage derived foam cell differentiation

Inferred from direct assay PubMed 19032770. Source: BHF-UCL

positive regulation of podosome assembly

Inferred from direct assay PubMed 15220135. Source: BHF-UCL

positive regulation of tyrosine phosphorylation of Stat5 protein

Inferred from direct assay PubMed 9722506. Source: BHF-UCL

   Cellular_componentextracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_functiongranulocyte macrophage colony-stimulating factor receptor binding

Traceable author statement PubMed 2999978. Source: ProtInc

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CSF2RBP329272EBI-1809826,EBI-1809771

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1717
Chain18 – 144127Granulocyte-macrophage colony-stimulating factor
PRO_0000005865

Amino acid modifications

Glycosylation221O-linked (GalNAc...) Ref.10
Glycosylation241O-linked (GalNAc...) Ref.10
Glycosylation261O-linked (GalNAc...) Ref.10
Glycosylation271O-linked (GalNAc...); partial Ref.10
Glycosylation441N-linked (GlcNAc...)
Glycosylation541N-linked (GlcNAc...)
Disulfide bond71 ↔ 113 Ref.13
Disulfide bond105 ↔ 138 Ref.13

Natural variations

Natural variant1151T → I. Ref.6
Corresponds to variant rs2069640 [ dbSNP | Ensembl ].
VAR_013089
Natural variant1171I → T. Ref.6 Ref.8 Ref.9
Corresponds to variant rs25882 [ dbSNP | Ensembl ].
VAR_001975

Experimental info

Sequence conflict961M → K in AAM44054. Ref.9
Sequence conflict1231F → L in AAM44054. Ref.9

Secondary structure

................... 144
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P04141 [UniParc].

Last modified November 1, 1986. Version 1.
Checksum: 75D1E50506BCA7A8

FASTA14416,295
        10         20         30         40         50         60 
MWLQSLLLLG TVACSISAPA RSPSPSTQPW EHVNAIQEAR RLLNLSRDTA AEMNETVEVI 

        70         80         90        100        110        120 
SEMFDLQEPT CLQTRLELYK QGLRGSLTKL KGPLTMMASH YKQHCPPTPE TSCATQIITF 

       130        140 
ESFKENLKDF LLVIPFDCWE PVQE 

« Hide

References

« Hide 'large scale' references
[1]"Isolation of cDNA for a human granulocyte-macrophage colony-stimulating factor by functional expression in mammalian cells."
Lee F., Yokota T., Otsuka T., Gemmell L., Larson N., Luh J., Arai K., Rennick D.
Proc. Natl. Acad. Sci. U.S.A. 82:4360-4364(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Genomic cloning, characterization, and multilineage growth-promoting activity of human granulocyte-macrophage colony-stimulating factor."
Kaushansky K., O'Hara P.J., Berkner K., Segal G.M., Hagen F.S., Adamson J.W.
Proc. Natl. Acad. Sci. U.S.A. 83:3101-3105(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Cloning, sequence, and expression of a human granulocyte/macrophage colony-stimulating factor."
Cantrell M.A., Anderson D., Cerretti D.P., Price V., McKereghan K., Tushinski R.J., Mochizuki D.Y., Larsen A., Grabstein S., Gillis S., Cosman D.
Proc. Natl. Acad. Sci. U.S.A. 82:6250-6254(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"Human GM-CSF: molecular cloning of the complementary DNA and purification of the natural and recombinant proteins."
Wong G.G., Witek J.S., Temple P.A., Wilkens K.M., Leary A.C., Luxenberg D.P., Jones S.S., Brown E.L., Kay R.M., Orr E.C., Shoemaker C., Golde D.W., Kaufman R.J., Hewick R.M., Wang E.A., Clark S.C.
Science 228:810-815(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]"Structure of the chromosomal gene for granulocyte-macrophage colony stimulating factor: comparison of the mouse and human genes."
Miyatake S., Otsuka T., Yokota T., Lee F., Arai K.
EMBO J. 4:2561-2568(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]SeattleSNPs variation discovery resource
Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ILE-115 AND THR-117.
[7]"The DNA sequence and comparative analysis of human chromosome 5."
Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. expand/collapse author list , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"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], VARIANT THR-117.
[9]Bhattacharya P., Pandey G., Mukherjee K.J.
Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 18-144, VARIANT THR-117.
Tissue: Peripheral blood.
[10]"Role of carbohydrate modification in the production and secretion of human granulocyte macrophage colony-stimulating factor in genetically engineered and normal mesenchymal cells."
Kaushansky K., Lopez J.A., Brown C.B.
Biochemistry 31:1881-1886(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT SER-22; SER-24; SER-26 AND THR-27.
[11]"Novel fold and putative receptor binding site of granulocyte-macrophage colony-stimulating factor."
Diederichs K., Boone T., Karplus P.A.
Science 254:1779-1782(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
[12]"Three-dimensional structure of recombinant human granulocyte-macrophage colony-stimulating factor."
Walter M.R., Cook W.J., Ealick S.E., Nagabhushan T.L., Trotta P.P., Bugg C.E.
J. Mol. Biol. 224:1075-1085(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
[13]"The structure of the GM-CSF receptor complex reveals a distinct mode of cytokine receptor activation."
Hansen G., Hercus T.R., McClure B.J., Stomski F.C., Dottore M., Powell J., Ramshaw H., Woodcock J.M., Xu Y., Guthridge M., McKinstry W.J., Lopez A.F., Parker M.W.
Cell 134:496-507(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF 18-144 IN COMPLEX WITH CSF2RA AND CSF2RB, SUBUNIT, DISULFIDE BOND.
+Additional computationally mapped references.

Web resources

Leukine

Clinical information on Leukine

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M13207 Genomic DNA. Translation: AAA98768.1.
M11734 mRNA. Translation: AAA52122.1.
M11220 mRNA. Translation: AAA52578.1.
X03021 Genomic DNA. Translation: CAA26822.1.
M10663 mRNA. Translation: AAA52121.1.
AF373868 Genomic DNA. Translation: AAK51563.1.
AC004511 Genomic DNA. Translation: AAC08707.1.
BC108724 mRNA. Translation: AAI08725.1.
BC113924 mRNA. Translation: AAI13925.1.
BC113999 mRNA. Translation: AAI14000.1.
AF510855 mRNA. Translation: AAM44054.1.
PIRFQHUGM. C24636.
RefSeqNP_000749.2. NM_000758.3.
UniGeneHs.1349.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1CSGX-ray2.70A/B18-144[»]
2GMFX-ray2.40A/B18-144[»]
3CXEX-ray3.30B18-144[»]
ProteinModelPortalP04141.
SMRP04141. Positions 21-141.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107824. 10 interactions.
DIPDIP-386N.
IntActP04141. 2 interactions.
STRING9606.ENSP00000296871.

Chemistry

DrugBankDB00020. Sargramostim.

PTM databases

PhosphoSiteP04141.

Polymorphism databases

DMDM117561.

Proteomic databases

PaxDbP04141.
PRIDEP04141.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000296871; ENSP00000296871; ENSG00000164400.
GeneID1437.
KEGGhsa:1437.
UCSCuc003kwf.4. human.

Organism-specific databases

CTD1437.
GeneCardsGC05P131409.
HGNCHGNC:2434. CSF2.
MIM138960. gene.
neXtProtNX_P04141.
PharmGKBPA26937.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG42131.
HOGENOMHOG000037940.
HOVERGENHBG000532.
InParanoidP04141.
KOK05427.
OMATCLQTRL.
OrthoDBEOG7J9VRQ.
PhylomeDBP04141.
TreeFamTF338611.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.
SignaLinkP04141.

Gene expression databases

BgeeP04141.
CleanExHS_CSF2.
GenevestigatorP04141.

Family and domain databases

Gene3D1.20.1250.10. 1 hit.
InterProIPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR000773. GM_colony-stim-fac.
[Graphical view]
PANTHERPTHR10059. PTHR10059. 1 hit.
PfamPF01109. GM_CSF. 1 hit.
[Graphical view]
PRINTSPR00693. GMCSFACTOR.
ProDomPD007349. GM_colony-stim-fac. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00040. CSF2. 1 hit.
[Graphical view]
SUPFAMSSF47266. SSF47266. 1 hit.
PROSITEPS00702. GM_CSF. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP04141.
GeneWikiGranulocyte_macrophage_colony-stimulating_factor.
GenomeRNAi1437.
NextBio5871.
PMAP-CutDBP04141.
PROP04141.
SOURCESearch...

Entry information

Entry nameCSF2_HUMAN
AccessionPrimary (citable) accession number: P04141
Secondary accession number(s): Q14CE8, Q2VPI8, Q8NFI6
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1986
Last sequence update: November 1, 1986
Last modified: February 19, 2014
This is version 149 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM