P04141 (CSF2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	144 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 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 component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Cytokine Growth factor
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Pharmaceutical Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to lipopolysaccharide Inferred from electronic annotation. Source: Compara dendritic cell differentiation Inferred from direct assay PubMed 21149635. Source: DFLAT embryonic placenta development Inferred from electronic annotation. Source: Compara epithelial fluid transport Inferred from electronic annotation. Source: Compara immune response Inferred from electronic annotation. Source: InterPro macrophage activation Inferred from electronic annotation. Source: Compara myeloid dendritic cell differentiation Inferred from electronic annotation. Source: Compara negative regulation of apoptotic process Inferred from direct assay PubMed 10666185. Source: BHF-UCL negative regulation of cytolysis 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: Compara 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_component	extracellular region Traceable author statement. Source: Reactome extracellular space Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	granulocyte macrophage colony-stimulating factor receptor binding Traceable author statement PubMed 2999978. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CSF2RB	P32927	2	EBI-1809826,EBI-1809771

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 17

17

Chain

18 – 144

127

Granulocyte-macrophage colony-stimulating factor

PRO_0000005865

Amino acid modifications

Glycosylation

22

1

O-linked (GalNAc...) Ref.10

Glycosylation

24

1

O-linked (GalNAc...) Ref.10

Glycosylation

26

1

O-linked (GalNAc...) Ref.10

Glycosylation

27

1

O-linked (GalNAc...); partial Ref.10

Glycosylation

44

1

N-linked (GlcNAc...)

Glycosylation

54

1

N-linked (GlcNAc...)

Disulfide bond

71 ↔ 113

Ref.13

Disulfide bond

105 ↔ 138

Ref.13

Natural variations

Natural variant

115

1

T → I. Ref.6
Corresponds to variant rs2069640 [ dbSNP | Ensembl ].

VAR_013089

Natural variant

117

1

I → T. Ref.6 Ref.8 Ref.9
Corresponds to variant rs25882 [ dbSNP | Ensembl ].

VAR_001975

Experimental info

Sequence conflict

96

1

M → K in AAM44054. Ref.9

Sequence conflict

123

1

F → L in AAM44054. Ref.9

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

144

Helix Strand Turn

Details...

Turn

25 – 27

3

Helix

30 – 45

16

Helix

50 – 53

4

Beta strand

56 – 62

7

Beta strand

66 – 68

3

Helix

72 – 81

10

Helix

85 – 90

6

Helix

91 – 104

14

Beta strand

115 – 119

5

Helix

120 – 131

12

Sequences

	Sequence		Length	Mass (Da)
	P04141 [UniParc]. Last modified November 1, 1986. Version 1. Checksum: 75D1E50506BCA7A8	FASTA	144	16,295
	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

References

	« Hide 'large scale' referencesShow '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. , 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.

IPI

IPI00022270.

PIR

FQHUGM. C24636.

RefSeq

NP_000749.2. NM_000758.3.

UniGene

Hs.1349.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]

ProteinModelPortal

P04141.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-386N.

IntAct

P04141. 2 interactions.

STRING

9606.ENSP00000296871.

PTM databases

PhosphoSite

P04141.

Polymorphism databases

DMDM

117561.

Proteomic databases

PaxDb

P04141.

PRIDE

P04141.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000296871; ENSP00000296871; ENSG00000164400.

GeneID

1437.

KEGG

hsa:1437.

UCSC

uc003kwf.3. human.

Organism-specific databases

CTD

1437.

GeneCards

GC05P131409.

HGNC

HGNC:2434. CSF2.

MIM

138960. gene.

neXtProt

NX_P04141.

PharmGKB

PA26937.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG42131.

HOGENOM

HOG000037940.

HOVERGEN

HBG000532.

InParanoid

P04141.

KO

K05427.

OMA

TCLQTRL.

OrthoDB

EOG4255V3.

PhylomeDB

P04141.

Enzyme and pathway databases

Pathway_Interaction_DB

nfat_tfpathway. Calcineurin-regulated NFAT-dependent transcription in lymphocytes.
tcrcalciumpathway. Calcium signaling in the CD4+ TCR pathway.
syndecan_2_pathway. Syndecan-2-mediated signaling events.

Reactome

REACT_6900. Immune System.

Gene expression databases

Bgee

P04141.

CleanEx

HS_CSF2.

Genevestigator

P04141.

GermOnline

ENSG00000164400. Homo sapiens.

Family and domain databases

Gene3D

1.20.1250.10. 1 hit.

InterPro

IPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR000773. GM_colony-stim-fac.
[Graphical view]

PANTHER

PTHR10059. PTHR10059. 1 hit.

Pfam

PF01109. GM_CSF. 1 hit.
[Graphical view]

PRINTS

PR00693. GMCSFACTOR.

ProDom

PD007349. GM_colony-stim-fac. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00040. CSF2. 1 hit.
[Graphical view]

SUPFAM

SSF47266. 4_helix_cytokine. 1 hit.

PROSITE

PS00702. GM_CSF. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB00020. Sargramostim.

EvolutionaryTrace

P04141.

GenomeRNAi

1437.

NextBio

5871.

PMAP-CutDB

P04141.

SOURCE

Search...

Entry information

Entry name

CSF2_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 140 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.