CSF2_HUMAN
ID CSF2_HUMAN Reviewed; 144 AA.
AC P04141; Q14CE8; Q2VPI8; Q8NFI6;
DT 01-NOV-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1986, sequence version 1.
DT 03-AUG-2022, entry version 206.
DE RecName: Full=Granulocyte-macrophage colony-stimulating factor;
DE Short=GM-CSF;
DE AltName: Full=Colony-stimulating factor;
DE Short=CSF;
DE AltName: Full=Molgramostin;
DE AltName: Full=Sargramostim;
DE Flags: Precursor;
GN Name=CSF2; Synonyms=GMCSF;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=3925454; DOI=10.1073/pnas.82.13.4360;
RA Lee F., Yokota T., Otsuka T., Gemmell L., Larson N., Luh J., Arai K.,
RA Rennick D.;
RT "Isolation of cDNA for a human granulocyte-macrophage colony-stimulating
RT factor by functional expression in mammalian cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 82:4360-4364(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3486413; DOI=10.1073/pnas.83.10.3101;
RA Kaushansky K., O'Hara P.J., Berkner K., Segal G.M., Hagen F.S.,
RA Adamson J.W.;
RT "Genomic cloning, characterization, and multilineage growth-promoting
RT activity of human granulocyte-macrophage colony-stimulating factor.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:3101-3105(1986).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3898082; DOI=10.1073/pnas.82.18.6250;
RA Cantrell M.A., Anderson D., Cerretti D.P., Price V., McKereghan K.,
RA Tushinski R.J., Mochizuki D.Y., Larsen A., Grabstein S., Gillis S.,
RA Cosman D.;
RT "Cloning, sequence, and expression of a human granulocyte/macrophage
RT colony-stimulating factor.";
RL Proc. Natl. Acad. Sci. U.S.A. 82:6250-6254(1985).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3923623; DOI=10.1126/science.3923623;
RA Wong G.G., Witek J.S., Temple P.A., Wilkens K.M., Leary A.C.,
RA Luxenberg D.P., Jones S.S., Brown E.L., Kay R.M., Orr E.C., Shoemaker C.,
RA Golde D.W., Kaufman R.J., Hewick R.M., Wang E.A., Clark S.C.;
RT "Human GM-CSF: molecular cloning of the complementary DNA and purification
RT of the natural and recombinant proteins.";
RL Science 228:810-815(1985).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3876930; DOI=10.1002/j.1460-2075.1985.tb03971.x;
RA Miyatake S., Otsuka T., Yokota T., Lee F., Arai K.;
RT "Structure of the chromosomal gene for granulocyte-macrophage colony
RT stimulating factor: comparison of the mouse and human genes.";
RL EMBO J. 4:2561-2568(1985).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ILE-115 AND THR-117.
RG SeattleSNPs variation discovery resource;
RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT THR-117.
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 18-144, AND VARIANT THR-117.
RC TISSUE=Peripheral blood;
RA Bhattacharya P., Pandey G., Mukherjee K.J.;
RL Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP GLYCOSYLATION AT SER-22; SER-24; SER-26 AND THR-27, AND SUBCELLULAR
RP LOCATION.
RX PubMed=1737041; DOI=10.1021/bi00121a042;
RA Kaushansky K., Lopez J.A., Brown C.B.;
RT "Role of carbohydrate modification in the production and secretion of human
RT granulocyte macrophage colony-stimulating factor in genetically engineered
RT and normal mesenchymal cells.";
RL Biochemistry 31:1881-1886(1992).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
RX PubMed=1837174; DOI=10.1126/science.1837174;
RA Diederichs K., Boone T., Karplus P.A.;
RT "Novel fold and putative receptor binding site of granulocyte-macrophage
RT colony-stimulating factor.";
RL Science 254:1779-1782(1991).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 18-144, AND DISULFIDE BONDS.
RX PubMed=1569568; DOI=10.1016/0022-2836(92)90470-5;
RA Walter M.R., Cook W.J., Ealick S.E., Nagabhushan T.L., Trotta P.P.,
RA Bugg C.E.;
RT "Three-dimensional structure of recombinant human granulocyte-macrophage
RT colony-stimulating factor.";
RL J. Mol. Biol. 224:1075-1085(1992).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF 18-144 IN COMPLEX WITH CSF2RA AND
RP CSF2RB, SUBUNIT, AND DISULFIDE BOND.
RX PubMed=18692472; DOI=10.1016/j.cell.2008.05.053;
RA Hansen G., Hercus T.R., McClure B.J., Stomski F.C., Dottore M., Powell J.,
RA Ramshaw H., Woodcock J.M., Xu Y., Guthridge M., McKinstry W.J., Lopez A.F.,
RA Parker M.W.;
RT "The structure of the GM-CSF receptor complex reveals a distinct mode of
RT cytokine receptor activation.";
RL Cell 134:496-507(2008).
CC -!- FUNCTION: Cytokine that stimulates the growth and differentiation of
CC hematopoietic precursor cells from various lineages, including
CC granulocytes, macrophages, eosinophils and erythrocytes.
CC {ECO:0000269|PubMed:3925454}.
CC -!- SUBUNIT: Monomer. The signaling GM-CSF receptor complex is a dodecamer
CC of two head-to-head hexamers of two alpha, two beta, and two ligand
CC subunits. {ECO:0000269|PubMed:18692472}.
CC -!- INTERACTION:
CC P04141; P01023: A2M; NbExp=3; IntAct=EBI-1809826, EBI-640741;
CC P04141; P32927: CSF2RB; NbExp=2; IntAct=EBI-1809826, EBI-1809771;
CC P04141; P50570-2: DNM2; NbExp=3; IntAct=EBI-1809826, EBI-10968534;
CC P04141; P42858: HTT; NbExp=15; IntAct=EBI-1809826, EBI-466029;
CC P04141; P50222: MEOX2; NbExp=6; IntAct=EBI-1809826, EBI-748397;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:1737041,
CC ECO:0000269|PubMed:3925454}.
CC -!- POLYMORPHISM: Variant Ile-117 may be a risk factor for atopic asthma.
CC -!- PHARMACEUTICAL: Available under the names Leukine (Immunex) and
CC Leucomax (Novartis). Used in myeloid reconstitution following bone
CC marrow transplant, bone marrow transplant engraftment failure or delay,
CC mobilization and following transplantation of autologous peripheral
CC blood progenitor cells, and following induction chemotherapy in older
CC adults with acute myelogenous leukemia.
CC -!- SIMILARITY: Belongs to the GM-CSF family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Leukine; Note=Clinical information on Leukine;
CC URL="https://www.leukine.com/";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/csf2/";
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DR EMBL; M13207; AAA98768.1; -; Genomic_DNA.
DR EMBL; M11734; AAA52122.1; -; mRNA.
DR EMBL; M11220; AAA52578.1; -; mRNA.
DR EMBL; X03021; CAA26822.1; -; Genomic_DNA.
DR EMBL; M10663; AAA52121.1; -; mRNA.
DR EMBL; AF373868; AAK51563.1; -; Genomic_DNA.
DR EMBL; AC004511; AAC08707.1; -; Genomic_DNA.
DR EMBL; BC108724; AAI08725.1; -; mRNA.
DR EMBL; BC113924; AAI13925.1; -; mRNA.
DR EMBL; BC113999; AAI14000.1; -; mRNA.
DR EMBL; AF510855; AAM44054.1; -; mRNA.
DR CCDS; CCDS4150.1; -.
DR PIR; C24636; FQHUGM.
DR RefSeq; NP_000749.2; NM_000758.3.
DR PDB; 1CSG; X-ray; 2.70 A; A/B=18-144.
DR PDB; 2GMF; X-ray; 2.40 A; A/B=18-144.
DR PDB; 4NKQ; X-ray; 3.30 A; C=18-144.
DR PDB; 4RS1; X-ray; 2.68 A; A=31-142.
DR PDB; 5C7X; X-ray; 2.95 A; A/B=18-144.
DR PDB; 5D70; X-ray; 2.06 A; A=18-144.
DR PDB; 5D71; X-ray; 2.25 A; A=1-127.
DR PDB; 5D72; X-ray; 2.60 A; A/B=1-127.
DR PDB; 6BFQ; X-ray; 2.60 A; G/I/J/K=18-144.
DR PDB; 6BFS; X-ray; 2.00 A; C=18-144.
DR PDBsum; 1CSG; -.
DR PDBsum; 2GMF; -.
DR PDBsum; 4NKQ; -.
DR PDBsum; 4RS1; -.
DR PDBsum; 5C7X; -.
DR PDBsum; 5D70; -.
DR PDBsum; 5D71; -.
DR PDBsum; 5D72; -.
DR PDBsum; 6BFQ; -.
DR PDBsum; 6BFS; -.
DR AlphaFoldDB; P04141; -.
DR BMRB; P04141; -.
DR SMR; P04141; -.
DR BioGRID; 107824; 12.
DR ComplexPortal; CPX-512; Granulocyte-macrophage colony-stimulating factor-receptor complex.
DR CORUM; P04141; -.
DR DIP; DIP-386N; -.
DR IntAct; P04141; 6.
DR STRING; 9606.ENSP00000296871; -.
DR BindingDB; P04141; -.
DR ChEMBL; CHEMBL3712955; -.
DR DrugBank; DB05194; KB002.
DR GlyGen; P04141; 6 sites.
DR iPTMnet; P04141; -.
DR PhosphoSitePlus; P04141; -.
DR BioMuta; CSF2; -.
DR DMDM; 117561; -.
DR MassIVE; P04141; -.
DR PaxDb; P04141; -.
DR PeptideAtlas; P04141; -.
DR PRIDE; P04141; -.
DR ProteomicsDB; 51656; -.
DR ABCD; P04141; 51 sequenced antibodies.
DR Antibodypedia; 14363; 1838 antibodies from 49 providers.
DR DNASU; 1437; -.
DR Ensembl; ENST00000296871.4; ENSP00000296871.2; ENSG00000164400.6.
DR GeneID; 1437; -.
DR KEGG; hsa:1437; -.
DR MANE-Select; ENST00000296871.4; ENSP00000296871.2; NM_000758.4; NP_000749.2.
DR UCSC; uc003kwf.5; human.
DR CTD; 1437; -.
DR DisGeNET; 1437; -.
DR GeneCards; CSF2; -.
DR HGNC; HGNC:2434; CSF2.
DR HPA; ENSG00000164400; Tissue enhanced (lung).
DR MIM; 138960; gene.
DR neXtProt; NX_P04141; -.
DR OpenTargets; ENSG00000164400; -.
DR PharmGKB; PA26937; -.
DR VEuPathDB; HostDB:ENSG00000164400; -.
DR eggNOG; ENOG502TDUI; Eukaryota.
DR GeneTree; ENSGT00390000013425; -.
DR HOGENOM; CLU_152286_0_0_1; -.
DR InParanoid; P04141; -.
DR OMA; VTRPWKH; -.
DR OrthoDB; 1412355at2759; -.
DR PhylomeDB; P04141; -.
DR TreeFam; TF338611; -.
DR PathwayCommons; P04141; -.
DR Reactome; R-HSA-512988; Interleukin-3, Interleukin-5 and GM-CSF signaling.
DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade.
DR Reactome; R-HSA-6783783; Interleukin-10 signaling.
DR Reactome; R-HSA-8939246; RUNX1 regulates transcription of genes involved in differentiation of myeloid cells.
DR Reactome; R-HSA-912526; Interleukin receptor SHC signaling.
DR SignaLink; P04141; -.
DR SIGNOR; P04141; -.
DR BioGRID-ORCS; 1437; 23 hits in 1068 CRISPR screens.
DR ChiTaRS; CSF2; human.
DR EvolutionaryTrace; P04141; -.
DR GeneWiki; Granulocyte_macrophage_colony-stimulating_factor; -.
DR GenomeRNAi; 1437; -.
DR Pharos; P04141; Tbio.
DR PRO; PR:P04141; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; P04141; protein.
DR Bgee; ENSG00000164400; Expressed in cartilage tissue and 62 other tissues.
DR Genevisible; P04141; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0030526; C:granulocyte macrophage colony-stimulating factor receptor complex; IDA:ComplexPortal.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; EXP:ComplexPortal.
DR GO; GO:0005125; F:cytokine activity; IDA:UniProtKB.
DR GO; GO:0005129; F:granulocyte macrophage colony-stimulating factor receptor binding; TAS:ProtInc.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0008283; P:cell population proliferation; IEA:Ensembl.
DR GO; GO:0097011; P:cellular response to granulocyte macrophage colony-stimulating factor stimulus; IDA:CAFA.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0097028; P:dendritic cell differentiation; IDA:DFLAT.
DR GO; GO:0001892; P:embryonic placenta development; IEA:Ensembl.
DR GO; GO:0042045; P:epithelial fluid transport; IEA:Ensembl.
DR GO; GO:0038157; P:granulocyte-macrophage colony-stimulating factor signaling pathway; IDA:ComplexPortal.
DR GO; GO:0001821; P:histamine secretion; IEA:Ensembl.
DR GO; GO:0006955; P:immune response; IEA:InterPro.
DR GO; GO:0042116; P:macrophage activation; IEA:Ensembl.
DR GO; GO:0030225; P:macrophage differentiation; IDA:ARUK-UCL.
DR GO; GO:0030224; P:monocyte differentiation; IEA:Ensembl.
DR GO; GO:0030099; P:myeloid cell differentiation; IBA:GO_Central.
DR GO; GO:0043011; P:myeloid dendritic cell differentiation; IDA:UniProtKB.
DR GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; IDA:BHF-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0030223; P:neutrophil differentiation; IEA:Ensembl.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:BHF-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:BHF-UCL.
DR GO; GO:0032747; P:positive regulation of interleukin-23 production; IDA:BHF-UCL.
DR GO; GO:0070665; P:positive regulation of leukocyte proliferation; IDA:ComplexPortal.
DR GO; GO:0010744; P:positive regulation of macrophage derived foam cell differentiation; IDA:BHF-UCL.
DR GO; GO:0071803; P:positive regulation of podosome assembly; IDA:BHF-UCL.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IDA:BHF-UCL.
DR GO; GO:0006468; P:protein phosphorylation; IDA:ComplexPortal.
DR GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; IDA:ComplexPortal.
DR GO; GO:0045187; P:regulation of circadian sleep/wake cycle, sleep; IEA:Ensembl.
DR GO; GO:0034405; P:response to fluid shear stress; IEA:Ensembl.
DR GO; GO:0034021; P:response to silicon dioxide; IEA:Ensembl.
DR CDD; cd00040; CSF2; 1.
DR Gene3D; 1.20.1250.10; -; 1.
DR InterPro; IPR009079; 4_helix_cytokine-like_core.
DR InterPro; IPR000773; GM_colony-stim-fac.
DR PANTHER; PTHR10059; PTHR10059; 1.
DR Pfam; PF01109; GM_CSF; 1.
DR PRINTS; PR00693; GMCSFACTOR.
DR SMART; SM00040; CSF2; 1.
DR SUPFAM; SSF47266; SSF47266; 1.
DR PROSITE; PS00702; GM_CSF; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytokine; Disulfide bond; Glycoprotein; Growth factor;
KW Pharmaceutical; Reference proteome; Secreted; Signal.
FT SIGNAL 1..17
FT CHAIN 18..144
FT /note="Granulocyte-macrophage colony-stimulating factor"
FT /id="PRO_0000005865"
FT CARBOHYD 22
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000269|PubMed:1737041"
FT CARBOHYD 24
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000269|PubMed:1737041"
FT CARBOHYD 26
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000269|PubMed:1737041"
FT CARBOHYD 27
FT /note="O-linked (GalNAc...) threonine; partial"
FT /evidence="ECO:0000269|PubMed:1737041"
FT CARBOHYD 44
FT /note="N-linked (GlcNAc...) asparagine"
FT CARBOHYD 54
FT /note="N-linked (GlcNAc...) asparagine"
FT DISULFID 71..113
FT /evidence="ECO:0000269|PubMed:1569568,
FT ECO:0000269|PubMed:18692472, ECO:0007744|PDB:1CSG,
FT ECO:0007744|PDB:2GMF, ECO:0007744|PDB:4RS1,
FT ECO:0007744|PDB:5C7X, ECO:0007744|PDB:5D70"
FT DISULFID 105..138
FT /evidence="ECO:0000269|PubMed:1569568,
FT ECO:0000269|PubMed:18692472, ECO:0007744|PDB:1CSG,
FT ECO:0007744|PDB:2GMF, ECO:0007744|PDB:4RS1,
FT ECO:0007744|PDB:5C7X, ECO:0007744|PDB:5D70"
FT VARIANT 115
FT /note="T -> I (in dbSNP:rs2069640)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_013089"
FT VARIANT 117
FT /note="I -> T (in dbSNP:rs25882)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.6,
FT ECO:0000269|Ref.9"
FT /id="VAR_001975"
FT CONFLICT 96
FT /note="M -> K (in Ref. 9; AAM44054)"
FT /evidence="ECO:0000305"
FT CONFLICT 123
FT /note="F -> L (in Ref. 9; AAM44054)"
FT /evidence="ECO:0000305"
FT TURN 25..27
FT /evidence="ECO:0007829|PDB:2GMF"
FT TURN 29..31
FT /evidence="ECO:0007829|PDB:5D70"
FT HELIX 32..45
FT /evidence="ECO:0007829|PDB:6BFS"
FT TURN 50..52
FT /evidence="ECO:0007829|PDB:6BFS"
FT STRAND 56..62
FT /evidence="ECO:0007829|PDB:6BFS"
FT STRAND 66..68
FT /evidence="ECO:0007829|PDB:5D70"
FT HELIX 72..82
FT /evidence="ECO:0007829|PDB:6BFS"
FT HELIX 85..90
FT /evidence="ECO:0007829|PDB:6BFS"
FT HELIX 91..104
FT /evidence="ECO:0007829|PDB:6BFS"
FT STRAND 115..119
FT /evidence="ECO:0007829|PDB:6BFS"
FT HELIX 120..133
FT /evidence="ECO:0007829|PDB:6BFS"
SQ SEQUENCE 144 AA; 16295 MW; 75D1E50506BCA7A8 CRC64;
MWLQSLLLLG TVACSISAPA RSPSPSTQPW EHVNAIQEAR RLLNLSRDTA AEMNETVEVI
SEMFDLQEPT CLQTRLELYK QGLRGSLTKL KGPLTMMASH YKQHCPPTPE TSCATQIITF
ESFKENLKDF LLVIPFDCWE PVQE
