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 27-MAR-2024, entry version 215. 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/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 14. 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 GlyCosmos; P04141; 6 sites, No reported glycans. DR GlyGen; P04141; 8 sites, 1 O-linked glycan (1 site). DR iPTMnet; P04141; -. DR PhosphoSitePlus; P04141; -. DR BioMuta; CSF2; -. DR DMDM; 117561; -. DR MassIVE; P04141; -. DR PaxDb; 9606-ENSP00000296871; -. DR PeptideAtlas; P04141; -. DR ProteomicsDB; 51656; -. DR ABCD; P04141; 51 sequenced antibodies. DR Antibodypedia; 14363; 2040 antibodies from 50 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 AGR; HGNC:2434; -. 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; LTMIASH; -. DR OrthoDB; 5263930at2759; -. 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 1146 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 cell types or tissues. 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; NAS: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: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:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; IDA:BHF-UCL. DR GO; GO:0030223; P:neutrophil differentiation; IEA:Ensembl. DR GO; GO:0030335; P:positive regulation of cell migration; 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: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:SF0; GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR; 1. DR PANTHER; PTHR10059; GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR GM-CSF; 1. DR Pfam; PF01109; GM_CSF; 1. DR PRINTS; PR00693; GMCSFACTOR. DR SMART; SM00040; CSF2; 1. DR SUPFAM; SSF47266; 4-helical cytokines; 1. DR PROSITE; PS00702; GM_CSF; 1. DR Genevisible; P04141; HS. 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 //