ID CSF3_HUMAN Reviewed; 207 AA. AC P09919; A8MXR7; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1989, sequence version 1. DT 27-MAR-2024, entry version 230. DE RecName: Full=Granulocyte colony-stimulating factor; DE Short=G-CSF; DE AltName: Full=Pluripoietin; DE AltName: INN=Filgrastim; DE AltName: INN=Lenograstim; DE Flags: Precursor; GN Name=CSF3; Synonyms=C17orf33, GCSF; 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] (ISOFORM LONG). RX PubMed=3484805; DOI=10.1038/319415a0; RA Nagata S., Tsuchiya M., Asano S., Kaziro Y., Yamazaki T., Yamamoto O., RA Hirata Y., Kubota N., Oheda M., Nomura H., Ono M.; RT "Molecular cloning and expression of cDNA for human granulocyte colony- RT stimulating factor."; RL Nature 319:415-418(1986). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM SHORT), AND ALTERNATIVE RP SPLICING. RX PubMed=2423327; DOI=10.1002/j.1460-2075.1986.tb04249.x; RA Nagata S., Tsuchiya M., Asano S., Yamamoto O., Hirata Y., Kubota N., RA Oheda M., Nomura H., Yamazaki T.; RT "The chromosomal gene structure and two mRNAs for human granulocyte colony- RT stimulating factor."; RL EMBO J. 5:575-581(1986). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT). RX PubMed=3494801; DOI=10.1002/jlb.41.4.302; RA Devlin J.J., Devlin P.E., Myambo K., Lilly M.B., Rado T.A., Warren M.K.; RT "Expression of granulocyte colony-stimulating factor by human cell lines."; RL J. Leukoc. Biol. 41:302-306(1987). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS MET-157 AND THR-174. RG SeattleSNPs variation discovery resource; RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RX PubMed=15028279; DOI=10.1016/j.ygeno.2003.09.023; RA Jin P., Fu G.K., Wilson A.D., Yang J., Chien D., Hawkins P.R., Au-Young J., RA Stuve L.L.; RT "PCR isolation and cloning of novel splice variant mRNAs from known drug RT target genes."; RL Genomics 83:566-571(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the RT human lineage."; RL Nature 440:1045-1049(2006). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 19-207 (ISOFORM SHORT). RX PubMed=2420009; DOI=10.1126/science.2420009; RA Souza L.M., Boone T.C., Gabrilove J., Lai P.H., Zsebo K.M., Murdock D.C., RA Chazin V.R., Bruszewski J., Lu H., Chen K.K., Barendt J., Platzer E., RA Moore M.A.S., Mertelsmann R., Welte K.; RT "Recombinant human granulocyte colony-stimulating factor: effects on normal RT and leukemic myeloid cells."; RL Science 232:61-66(1986). RN [8] RP PROTEIN SEQUENCE OF 31-46. RX PubMed=8554326; DOI=10.1006/abbi.1995.0047; RA Haniu M., Horan T., Arakawa T., Le J., Katta V., Rohde M.F.; RT "Extracellular domain of granulocyte-colony stimulating factor receptor. RT Interaction with its ligand and identification of a domain in close RT proximity of ligand-binding region."; RL Arch. Biochem. Biophys. 324:344-356(1995). RN [9] RP GLYCOSYLATION AT THR-166. RX PubMed=7685769; DOI=10.1016/0021-9673(93)83098-d; RA Clogston C.L., Hu S., Boone T.C., Lu H.S.; RT "Glycosidase digestion, electrophoresis and chromatographic analysis of RT recombinant human granulocyte colony-stimulating factor glycoforms produced RT in Chinese hamster ovary cells."; RL J. Chromatogr. A 637:55-62(1993). RN [10] RP STRUCTURE BY NMR. RX PubMed=1281794; DOI=10.1016/0014-5793(92)81521-m; RA Zink T., Ross A., Ambrosius D., Rudolph R., Holak T.A.; RT "Secondary structure of human granulocyte colony-stimulating factor derived RT from NMR spectroscopy."; RL FEBS Lett. 314:435-439(1992). RN [11] RP STRUCTURE BY NMR. RX PubMed=7518249; DOI=10.1021/bi00194a009; RA Zink T., Ross A., Luers K., Cieslar C., Rudolph R., Holak T.A.; RT "Structure and dynamics of the human granulocyte colony-stimulating factor RT determined by NMR spectroscopy. Loop mobility in a four-helix-bundle RT protein."; RL Biochemistry 33:8453-8463(1994). RN [12] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS). RX PubMed=7685117; DOI=10.1073/pnas.90.11.5167; RA Hill C.P., Osslund T.D., Eisenberg D.; RT "The structure of granulocyte-colony-stimulating factor and its RT relationship to other growth factors."; RL Proc. Natl. Acad. Sci. U.S.A. 90:5167-5171(1993). RN [13] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 31-207 IN COMPLEX WITH CSF3R. RX PubMed=10537111; DOI=10.1038/44394; RA Aritomi M., Kunishima N., Okamoto T., Kuroki R., Ota Y., Morikawa K.; RT "Atomic structure of the GCSF-receptor complex showing a new cytokine- RT receptor recognition scheme."; RL Nature 401:713-717(1999). RN [14] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 31-207 IN COMPLEX WITH CSF3R. RX PubMed=16492764; DOI=10.1073/pnas.0511264103; RA Tamada T., Honjo E., Maeda Y., Okamoto T., Ishibashi M., Tokunaga M., RA Kuroki R.; RT "Homodimeric cross-over structure of the human granulocyte colony- RT stimulating factor (GCSF) receptor signaling complex."; RL Proc. Natl. Acad. Sci. U.S.A. 103:3135-3140(2006). CC -!- FUNCTION: Granulocyte/macrophage colony-stimulating factors are CC cytokines that act in hematopoiesis by controlling the production, CC differentiation, and function of 2 related white cell populations of CC the blood, the granulocytes and the monocytes-macrophages. This CSF CC induces granulocytes. CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:10537111, CC ECO:0000269|PubMed:16492764}. CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=Long; CC IsoId=P09919-1; Sequence=Displayed; CC Name=Short; CC IsoId=P09919-2; Sequence=VSP_002673; CC Name=3; CC IsoId=P09919-3; Sequence=VSP_045246; CC -!- PTM: O-glycan consists of Gal-GalNAc disaccharide which can be modified CC with up to two sialic acid residues (done in recombinantly expressed G- CC CSF from CHO cells). CC -!- PHARMACEUTICAL: Available under the names Neupogen or Granulokine CC (Amgen/Roche) and Granocyte (Rhone-Poulenc). Used to treat neutropenia CC (a disorder characterized by an extremely low number of neutrophils in CC blood). CC -!- SIMILARITY: Belongs to the IL-6 superfamily. {ECO:0000305}. CC -!- CAUTION: PubMed:2420009 misquotes the gene name as 'CSF1'. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=Neupogen/Granulokine; Note=Clinical information on CC Neupogen/Granulokine; CC URL="https://www.neupogen.com"; CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/csf3/"; 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; X03438; CAA27168.1; -; mRNA. DR EMBL; X03656; CAA27291.1; -; Genomic_DNA. DR EMBL; X03655; CAA27290.1; -; mRNA. DR EMBL; M17706; AAA35882.1; -; mRNA. DR EMBL; AF388025; AAK62469.1; -; Genomic_DNA. DR EMBL; CD013926; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AC090844; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; M13008; AAA03056.1; -; mRNA. DR CCDS; CCDS11357.1; -. [P09919-1] DR CCDS; CCDS11358.2; -. [P09919-3] DR CCDS; CCDS42314.1; -. [P09919-2] DR PIR; A24573; A24573. DR PIR; A25093; FQHUGL. DR RefSeq; NP_000750.1; NM_000759.3. [P09919-1] DR RefSeq; NP_001171618.1; NM_001178147.1. DR RefSeq; NP_757373.1; NM_172219.2. [P09919-2] DR RefSeq; NP_757374.2; NM_172220.2. [P09919-3] DR PDB; 1CD9; X-ray; 2.80 A; A/C=31-207. DR PDB; 1GNC; NMR; -; A=31-207. DR PDB; 1PGR; X-ray; 3.50 A; A/C/E/G=31-207. DR PDB; 1RHG; X-ray; 2.20 A; A/B/C=31-207. DR PDB; 2D9Q; X-ray; 2.80 A; A=31-207. DR PDB; 5GW9; X-ray; 1.65 A; A/B/C/D=40-205. DR PDB; 5ZO6; X-ray; 1.70 A; X=37-205. DR PDBsum; 1CD9; -. DR PDBsum; 1GNC; -. DR PDBsum; 1PGR; -. DR PDBsum; 1RHG; -. DR PDBsum; 2D9Q; -. DR PDBsum; 5GW9; -. DR PDBsum; 5ZO6; -. DR AlphaFoldDB; P09919; -. DR BMRB; P09919; -. DR SMR; P09919; -. DR BioGRID; 107827; 16. DR DIP; DIP-61120N; -. DR IntAct; P09919; 2. DR STRING; 9606.ENSP00000225474; -. DR Allergome; 8367; Hom s G-CSF. DR CarbonylDB; P09919; -. DR GlyCosmos; P09919; 1 site, No reported glycans. DR GlyGen; P09919; 1 site. DR iPTMnet; P09919; -. DR MetOSite; P09919; -. DR PhosphoSitePlus; P09919; -. DR BioMuta; CSF3; -. DR DMDM; 117564; -. DR MassIVE; P09919; -. DR PaxDb; 9606-ENSP00000225474; -. DR PeptideAtlas; P09919; -. DR ProteomicsDB; 2347; -. DR ProteomicsDB; 52279; -. [P09919-1] DR ProteomicsDB; 52280; -. [P09919-2] DR Antibodypedia; 799; 1455 antibodies from 40 providers. DR DNASU; 1440; -. DR Ensembl; ENST00000225474.6; ENSP00000225474.2; ENSG00000108342.13. [P09919-1] DR Ensembl; ENST00000394148.7; ENSP00000377704.3; ENSG00000108342.13. [P09919-3] DR Ensembl; ENST00000394149.8; ENSP00000377705.4; ENSG00000108342.13. [P09919-2] DR GeneID; 1440; -. DR KEGG; hsa:1440; -. DR MANE-Select; ENST00000394149.8; ENSP00000377705.4; NM_172219.3; NP_757373.1. [P09919-2] DR UCSC; uc002htp.4; human. [P09919-1] DR AGR; HGNC:2438; -. DR CTD; 1440; -. DR DisGeNET; 1440; -. DR GeneCards; CSF3; -. DR HGNC; HGNC:2438; CSF3. DR HPA; ENSG00000108342; Tissue enhanced (lung, urinary bladder). DR MIM; 138970; gene. DR neXtProt; NX_P09919; -. DR OpenTargets; ENSG00000108342; -. DR PharmGKB; PA26941; -. DR VEuPathDB; HostDB:ENSG00000108342; -. DR eggNOG; ENOG502SCNA; Eukaryota. DR GeneTree; ENSGT00390000017328; -. DR InParanoid; P09919; -. DR OMA; APLEQCH; -. DR OrthoDB; 4636828at2759; -. DR PhylomeDB; P09919; -. DR TreeFam; TF337698; -. DR PathwayCommons; P09919; -. DR Reactome; R-HSA-449836; Other interleukin signaling. DR Reactome; R-HSA-6783783; Interleukin-10 signaling. DR Reactome; R-HSA-9674555; Signaling by CSF3 (G-CSF). DR Reactome; R-HSA-9705462; Inactivation of CSF3 (G-CSF) signaling. DR SignaLink; P09919; -. DR SIGNOR; P09919; -. DR BioGRID-ORCS; 1440; 14 hits in 1145 CRISPR screens. DR ChiTaRS; CSF3; human. DR EvolutionaryTrace; P09919; -. DR GeneWiki; Granulocyte_colony-stimulating_factor; -. DR GenomeRNAi; 1440; -. DR Pharos; P09919; Tbio. DR PRO; PR:P09919; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; P09919; Protein. DR Bgee; ENSG00000108342; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 133 other cell types or tissues. DR ExpressionAtlas; P09919; baseline and differential. DR GO; GO:0071682; C:endocytic vesicle lumen; TAS:Reactome. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IBA:GO_Central. DR GO; GO:0043202; C:lysosomal lumen; TAS:Reactome. DR GO; GO:0005125; F:cytokine activity; IDA:BHF-UCL. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0005130; F:granulocyte colony-stimulating factor receptor binding; IBA:GO_Central. DR GO; GO:0008083; F:growth factor activity; IBA:GO_Central. DR GO; GO:0071345; P:cellular response to cytokine stimulus; IDA:BHF-UCL. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:0019221; P:cytokine-mediated signaling pathway; NAS:UniProtKB. DR GO; GO:0038158; P:granulocyte colony-stimulating factor signaling pathway; IDA:BHF-UCL. DR GO; GO:0030851; P:granulocyte differentiation; NAS:UniProtKB. DR GO; GO:0006955; P:immune response; IEA:InterPro. DR GO; GO:0030838; P:positive regulation of actin filament polymerization; IDA:BHF-UCL. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IBA:GO_Central. DR GO; GO:0045639; P:positive regulation of myeloid cell differentiation; IBA:GO_Central. DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:BHF-UCL. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IDA:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL. DR GO; GO:0110053; P:regulation of actin filament organization; IDA:BHF-UCL. DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl. DR Gene3D; 1.20.1250.10; -; 1. DR InterPro; IPR009079; 4_helix_cytokine-like_core. DR InterPro; IPR040117; GCSF/MGF. DR InterPro; IPR030474; IL-6/GCSF/MGF. DR InterPro; IPR030473; IL6/GCSF/MGF_CS. DR PANTHER; PTHR10511; GRANULOCYTE COLONY-STIMULATING FACTOR; 1. DR PANTHER; PTHR10511:SF2; GRANULOCYTE COLONY-STIMULATING FACTOR; 1. DR Pfam; PF16647; GCSF; 1. DR PIRSF; PIRSF001935; IL6_MGF_GCSF; 1. DR PRINTS; PR00433; IL6GCSFMGF. DR SMART; SM00126; IL6; 1. DR SUPFAM; SSF47266; 4-helical cytokines; 1. DR PROSITE; PS00254; INTERLEUKIN_6; 1. DR Genevisible; P09919; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytokine; Direct protein sequencing; KW Disulfide bond; Glycoprotein; Growth factor; Pharmaceutical; KW Reference proteome; Secreted; Signal. FT SIGNAL 1..30 FT /evidence="ECO:0000305|PubMed:8554326" FT CHAIN 31..207 FT /note="Granulocyte colony-stimulating factor" FT /id="PRO_0000015570" FT CARBOHYD 166 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000250" FT DISULFID 69..75 FT DISULFID 97..107 FT VAR_SEQ 66..68 FT /note="Missing (in isoform Short)" FT /evidence="ECO:0000303|PubMed:2420009, FT ECO:0000303|PubMed:2423327, ECO:0000303|PubMed:3494801" FT /id="VSP_002673" FT VAR_SEQ 69..104 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15028279" FT /id="VSP_045246" FT VARIANT 157 FT /note="L -> M (in dbSNP:rs2227329)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_013073" FT VARIANT 174 FT /note="A -> T (in dbSNP:rs2227330)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_013074" FT STRAND 37..39 FT /evidence="ECO:0007829|PDB:1CD9" FT HELIX 41..65 FT /evidence="ECO:0007829|PDB:5GW9" FT HELIX 69..72 FT /evidence="ECO:0007829|PDB:5GW9" FT HELIX 77..87 FT /evidence="ECO:0007829|PDB:5GW9" FT STRAND 99..101 FT /evidence="ECO:0007829|PDB:5GW9" FT HELIX 104..124 FT /evidence="ECO:0007829|PDB:5GW9" FT TURN 125..127 FT /evidence="ECO:0007829|PDB:5GW9" FT TURN 130..132 FT /evidence="ECO:0007829|PDB:5GW9" FT HELIX 133..157 FT /evidence="ECO:0007829|PDB:5GW9" FT STRAND 166..168 FT /evidence="ECO:0007829|PDB:1GNC" FT HELIX 176..201 FT /evidence="ECO:0007829|PDB:5GW9" FT TURN 203..205 FT /evidence="ECO:0007829|PDB:2D9Q" SQ SEQUENCE 207 AA; 22293 MW; 421F635ECC776996 CRC64; MAGPATQSPM KLMALQLLLW HSALWTVQEA TPLGPASSLP QSFLLKCLEQ VRKIQGDGAA LQEKLVSECA TYKLCHPEEL VLLGHSLGIP WAPLSSCPSQ ALQLAGCLSQ LHSGLFLYQG LLQALEGISP ELGPTLDTLQ LDVADFATTI WQQMEELGMA PALQPTQGAM PAFASAFQRR AGGVLVASHL QSFLEVSYRV LRHLAQP //