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P04141

- CSF2_HUMAN

UniProt

P04141 - CSF2_HUMAN

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Protein

Granulocyte-macrophage colony-stimulating factor

Gene

CSF2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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

GO - Molecular functioni

  1. granulocyte macrophage colony-stimulating factor receptor binding Source: ProtInc

GO - Biological processi

  1. cellular response to lipopolysaccharide Source: Ensembl
  2. dendritic cell differentiation Source: DFLAT
  3. embryonic placenta development Source: Ensembl
  4. epithelial fluid transport Source: Ensembl
  5. immune response Source: InterPro
  6. macrophage activation Source: Ensembl
  7. myeloid dendritic cell differentiation Source: Ensembl
  8. negative regulation of cytolysis Source: BHF-UCL
  9. negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: BHF-UCL
  10. positive regulation of cell proliferation Source: Ensembl
  11. positive regulation of DNA replication Source: BHF-UCL
  12. positive regulation of gene expression Source: BHF-UCL
  13. positive regulation of interleukin-23 production Source: BHF-UCL
  14. positive regulation of macrophage derived foam cell differentiation Source: BHF-UCL
  15. positive regulation of podosome assembly Source: BHF-UCL
  16. positive regulation of tyrosine phosphorylation of Stat5 protein Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Cytokine, Growth factor

Enzyme and pathway databases

ReactomeiREACT_1695. GPVI-mediated activation cascade.
REACT_19290. G beta:gamma signalling through PI3Kgamma.
REACT_23837. Interleukin-3, 5 and GM-CSF signaling.
REACT_23891. Interleukin receptor SHC signaling.
SignaLinkiP04141.

Names & Taxonomyi

Protein namesi
Recommended name:
Granulocyte-macrophage colony-stimulating factor
Short name:
GM-CSF
Alternative name(s):
Colony-stimulating factor
Short name:
CSF
Molgramostin
Sargramostim
Gene namesi
Name:CSF2
Synonyms:GMCSF
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 5

Organism-specific databases

HGNCiHGNC:2434. CSF2.

Subcellular locationi

GO - Cellular componenti

  1. extracellular region Source: Reactome
  2. extracellular space Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Pharmaceutical usei

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.

Organism-specific databases

PharmGKBiPA26937.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1717Add
BLAST
Chaini18 – 144127Granulocyte-macrophage colony-stimulating factorPRO_0000005865Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi22 – 221O-linked (GalNAc...)1 Publication
Glycosylationi24 – 241O-linked (GalNAc...)1 Publication
Glycosylationi26 – 261O-linked (GalNAc...)1 Publication
Glycosylationi27 – 271O-linked (GalNAc...); partial1 Publication
Glycosylationi44 – 441N-linked (GlcNAc...)
Glycosylationi54 – 541N-linked (GlcNAc...)
Disulfide bondi71 ↔ 1131 Publication
Disulfide bondi105 ↔ 1381 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP04141.
PRIDEiP04141.

PTM databases

PhosphoSiteiP04141.

Miscellaneous databases

PMAP-CutDBP04141.

Expressioni

Gene expression databases

BgeeiP04141.
CleanExiHS_CSF2.
GenevestigatoriP04141.

Interactioni

Subunit structurei

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.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
CSF2RBP329272EBI-1809826,EBI-1809771

Protein-protein interaction databases

BioGridi107824. 10 interactions.
DIPiDIP-386N.
IntActiP04141. 2 interactions.
STRINGi9606.ENSP00000296871.

Structurei

Secondary structure

1
144
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni25 – 273Combined sources
Helixi30 – 4516Combined sources
Helixi50 – 534Combined sources
Beta strandi56 – 627Combined sources
Beta strandi66 – 683Combined sources
Helixi72 – 8110Combined sources
Helixi85 – 906Combined sources
Helixi91 – 10414Combined sources
Beta strandi115 – 1195Combined sources
Helixi120 – 13112Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1CSGX-ray2.70A/B18-144[»]
2GMFX-ray2.40A/B18-144[»]
3CXEX-ray3.30B18-144[»]
ProteinModelPortaliP04141.
SMRiP04141. Positions 21-141.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP04141.

Family & Domainsi

Sequence similaritiesi

Belongs to the GM-CSF family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG42131.
GeneTreeiENSGT00390000013425.
HOGENOMiHOG000037940.
HOVERGENiHBG000532.
InParanoidiP04141.
KOiK05427.
OMAiTCLQTRL.
OrthoDBiEOG7J9VRQ.
PhylomeDBiP04141.
TreeFamiTF338611.

Family and domain databases

Gene3Di1.20.1250.10. 1 hit.
InterProiIPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR000773. GM_colony-stim-fac.
[Graphical view]
PANTHERiPTHR10059. PTHR10059. 1 hit.
PfamiPF01109. GM_CSF. 1 hit.
[Graphical view]
PRINTSiPR00693. GMCSFACTOR.
ProDomiPD007349. GM_colony-stim-fac. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTiSM00040. CSF2. 1 hit.
[Graphical view]
SUPFAMiSSF47266. SSF47266. 1 hit.
PROSITEiPS00702. GM_CSF. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

P04141-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MWLQSLLLLG TVACSISAPA RSPSPSTQPW EHVNAIQEAR RLLNLSRDTA
60 70 80 90 100
AEMNETVEVI SEMFDLQEPT CLQTRLELYK QGLRGSLTKL KGPLTMMASH
110 120 130 140
YKQHCPPTPE TSCATQIITF ESFKENLKDF LLVIPFDCWE PVQE
Length:144
Mass (Da):16,295
Last modified:November 1, 1986 - v1
Checksum:i75D1E50506BCA7A8
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti96 – 961M → K in AAM44054. 1 PublicationCurated
Sequence conflicti123 – 1231F → L in AAM44054. 1 PublicationCurated

Polymorphismi

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

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti115 – 1151T → I.1 Publication
Corresponds to variant rs2069640 [ dbSNP | Ensembl ].
VAR_013089
Natural varianti117 – 1171I → T.3 Publications
Corresponds to variant rs25882 [ dbSNP | Ensembl ].
VAR_001975

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS4150.1.
PIRiC24636. FQHUGM.
RefSeqiNP_000749.2. NM_000758.3.
UniGeneiHs.1349.

Genome annotation databases

EnsembliENST00000296871; ENSP00000296871; ENSG00000164400.
GeneIDi1437.
KEGGihsa:1437.
UCSCiuc003kwf.4. human.

Polymorphism databases

DMDMi117561.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Leukine

Clinical information on Leukine

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 .
CCDSi CCDS4150.1.
PIRi C24636. FQHUGM.
RefSeqi NP_000749.2. NM_000758.3.
UniGenei Hs.1349.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1CSG X-ray 2.70 A/B 18-144 [» ]
2GMF X-ray 2.40 A/B 18-144 [» ]
3CXE X-ray 3.30 B 18-144 [» ]
ProteinModelPortali P04141.
SMRi P04141. Positions 21-141.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 107824. 10 interactions.
DIPi DIP-386N.
IntActi P04141. 2 interactions.
STRINGi 9606.ENSP00000296871.

PTM databases

PhosphoSitei P04141.

Polymorphism databases

DMDMi 117561.

Proteomic databases

PaxDbi P04141.
PRIDEi P04141.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000296871 ; ENSP00000296871 ; ENSG00000164400 .
GeneIDi 1437.
KEGGi hsa:1437.
UCSCi uc003kwf.4. human.

Organism-specific databases

CTDi 1437.
GeneCardsi GC05P131409.
HGNCi HGNC:2434. CSF2.
MIMi 138960. gene.
neXtProti NX_P04141.
PharmGKBi PA26937.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG42131.
GeneTreei ENSGT00390000013425.
HOGENOMi HOG000037940.
HOVERGENi HBG000532.
InParanoidi P04141.
KOi K05427.
OMAi TCLQTRL.
OrthoDBi EOG7J9VRQ.
PhylomeDBi P04141.
TreeFami TF338611.

Enzyme and pathway databases

Reactomei REACT_1695. GPVI-mediated activation cascade.
REACT_19290. G beta:gamma signalling through PI3Kgamma.
REACT_23837. Interleukin-3, 5 and GM-CSF signaling.
REACT_23891. Interleukin receptor SHC signaling.
SignaLinki P04141.

Miscellaneous databases

EvolutionaryTracei P04141.
GeneWikii Granulocyte_macrophage_colony-stimulating_factor.
GenomeRNAii 1437.
NextBioi 5871.
PMAP-CutDB P04141.
PROi P04141.
SOURCEi Search...

Gene expression databases

Bgeei P04141.
CleanExi HS_CSF2.
Genevestigatori P04141.

Family and domain databases

Gene3Di 1.20.1250.10. 1 hit.
InterProi IPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR000773. GM_colony-stim-fac.
[Graphical view ]
PANTHERi PTHR10059. PTHR10059. 1 hit.
Pfami PF01109. GM_CSF. 1 hit.
[Graphical view ]
PRINTSi PR00693. GMCSFACTOR.
ProDomi PD007349. GM_colony-stim-fac. 1 hit.
[Graphical view ] [Entries sharing at least one domain ]
SMARTi SM00040. CSF2. 1 hit.
[Graphical view ]
SUPFAMi SSF47266. SSF47266. 1 hit.
PROSITEi PS00702. GM_CSF. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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.
    , 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.

Entry informationi

Entry nameiCSF2_HUMAN
AccessioniPrimary (citable) accession number: P04141
Secondary accession number(s): Q14CE8, Q2VPI8, Q8NFI6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1986
Last sequence update: November 1, 1986
Last modified: November 26, 2014
This is version 155 of the entry and version 1 of the sequence. [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, Pharmaceutical, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: 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
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3