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 11-NOV-2015, entry version 174. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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 RT colony-stimulating factor."; RL Nature 319:415-418(1986). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM SHORT), AND RP ALTERNATIVE SPLICING. RX PubMed=2423327; 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 RT colony-stimulating factor."; RL EMBO J. 5:575-581(1986). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT). RX PubMed=3494801; RA Devlin J.J., Devlin P.E., Myambo K., Lilly M.B., Rado T.A., RA Warren M.K.; RT "Expression of granulocyte colony-stimulating factor by human cell RT 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., RA Au-Young J., Stuve L.L.; RT "PCR isolation and cloning of novel splice variant mRNAs from known RT drug 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., RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., RA 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 RT the 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., RA Murdock D.C., Chazin V.R., Bruszewski J., Lu H., Chen K.K., RA Barendt J., Platzer E., Moore M.A.S., Mertelsmann R., Welte K.; RT "Recombinant human granulocyte colony-stimulating factor: effects on RT normal and leukemic myeloid cells."; RL Science 232:61-66(1986). RN [8] RP PROTEIN SEQUENCE OF 30-46. 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 RT receptor. Interaction with its ligand and identification of a domain RT in close 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 RT of recombinant human granulocyte colony-stimulating factor glycoforms RT produced 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 RT derived 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 RT factor determined by NMR spectroscopy. Loop mobility in a four-helix- RT bundle 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 CC of the blood, the granulocytes and the monocytes-macrophages. This CC CSF 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 Note=No experimental confirmation available.; CC -!- PTM: O-glycan consists of Gal-GalNAc disaccharide which can be CC modified with up to two sialic acid residues (done in CC recombinantly expressed G-CSF from CHO cells). CC -!- PHARMACEUTICAL: Available under the names Neupogen or Granulokine CC (Amgen/Roche) and Granocyte (Rhone-Poulenc). Used to treat CC neutropenia (a disorder characterized by an extremely low number CC of neutrophils in 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 CC on Neupogen/Granulokine; CC URL="http://www.neupogen.com/pi.html"; 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 UniGene; Hs.2233; -. 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 PDBsum; 1CD9; -. DR PDBsum; 1GNC; -. DR PDBsum; 1PGR; -. DR PDBsum; 1RHG; -. DR PDBsum; 2D9Q; -. DR ProteinModelPortal; P09919; -. DR SMR; P09919; 34-207. DR DIP; DIP-61120N; -. DR STRING; 9606.ENSP00000225474; -. DR Allergome; 8367; Hom s G-CSF. DR PhosphoSite; P09919; -. DR BioMuta; CSF3; -. DR DMDM; 117564; -. DR PaxDb; P09919; -. DR PRIDE; P09919; -. DR DNASU; 1440; -. DR Ensembl; ENST00000225474; ENSP00000225474; ENSG00000108342. [P09919-1] DR Ensembl; ENST00000394148; ENSP00000377704; ENSG00000108342. [P09919-3] DR Ensembl; ENST00000394149; ENSP00000377705; ENSG00000108342. [P09919-2] DR GeneID; 1440; -. DR KEGG; hsa:1440; -. DR UCSC; uc002htp.3; human. [P09919-1] DR CTD; 1440; -. DR GeneCards; CSF3; -. DR HGNC; HGNC:2438; CSF3. DR HPA; CAB016131; -. DR HPA; HPA001412; -. DR MIM; 138970; gene. DR neXtProt; NX_P09919; -. DR PharmGKB; PA26941; -. DR eggNOG; ENOG410IIM2; Eukaryota. DR eggNOG; ENOG4111DA4; LUCA. DR GeneTree; ENSGT00390000017328; -. DR HOGENOM; HOG000015371; -. DR HOVERGEN; HBG005411; -. DR InParanoid; P09919; -. DR KO; K05423; -. DR OMA; LWHSALW; -. DR PhylomeDB; P09919; -. DR TreeFam; TF337698; -. DR SignaLink; P09919; -. DR EvolutionaryTrace; P09919; -. DR GeneWiki; Granulocyte_colony-stimulating_factor; -. DR GenomeRNAi; 1440; -. DR NextBio; 5893; -. DR PRO; PR:P09919; -. DR Proteomes; UP000005640; Chromosome 17. DR Bgee; P09919; -. DR CleanEx; HS_CSF3; -. DR ExpressionAtlas; P09919; baseline and differential. DR Genevisible; P09919; HS. DR GO; GO:0005615; C:extracellular space; TAS:ProtInc. DR GO; GO:0005125; F:cytokine activity; NAS:UniProtKB. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0005130; F:granulocyte colony-stimulating factor receptor binding; TAS:ProtInc. 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:0030851; P:granulocyte differentiation; NAS:UniProtKB. DR GO; GO:0006955; P:immune response; IEA:InterPro. DR GO; GO:0007275; P:multicellular organismal development; TAS:ProtInc. DR GO; GO:1901215; P:negative regulation of neuron death; IEA:Ensembl. DR GO; GO:2000251; P:positive regulation of actin cytoskeleton reorganization; IDA:BHF-UCL. DR GO; GO:0030838; P:positive regulation of actin filament polymerization; IDA:BHF-UCL. DR GO; GO:0008284; P:positive regulation of cell proliferation; TAS:ProtInc. DR GO; GO:0045639; P:positive regulation of myeloid cell differentiation; IEA:Ensembl. DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:BHF-UCL. DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:BHF-UCL. DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IDA:BHF-UCL. DR GO; GO:0032092; P:positive regulation of protein binding; IDA:BHF-UCL. DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IDA:BHF-UCL. DR GO; GO:0042993; P:positive regulation of transcription factor import into nucleus; IDA:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL. DR Gene3D; 1.20.1250.10; -; 1. DR InterPro; IPR009079; 4_helix_cytokine-like_core. DR InterPro; IPR012351; 4_helix_cytokine_core. DR InterPro; IPR030474; IL-6/GCSF/MGF. DR InterPro; IPR030473; IL6/GCSF/MGF_CS. DR Pfam; PF16647; GCSF; 1. DR PIRSF; PIRSF001935; IL6_MGF_GCSF; 1. DR PRINTS; PR00433; IL6GCSFMGF. DR SMART; SM00126; IL6; 1. DR SUPFAM; SSF47266; SSF47266; 1. DR PROSITE; PS00254; INTERLEUKIN_6; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Complete proteome; Cytokine; KW Direct protein sequencing; Disulfide bond; Glycoprotein; KW Growth factor; Pharmaceutical; Polymorphism; Reference proteome; KW Secreted; Signal. FT SIGNAL 1 29 {ECO:0000305|PubMed:8554326}. FT CHAIN 30 207 Granulocyte colony-stimulating factor. FT /FTId=PRO_0000015570. FT CARBOHYD 166 166 O-linked (GalNAc...). {ECO:0000250}. FT DISULFID 69 75 FT DISULFID 97 107 FT VAR_SEQ 66 68 Missing (in isoform Short). FT {ECO:0000303|PubMed:2420009, FT ECO:0000303|PubMed:2423327, FT ECO:0000303|PubMed:3494801}. FT /FTId=VSP_002673. FT VAR_SEQ 69 104 Missing (in isoform 3). FT {ECO:0000303|PubMed:15028279}. FT /FTId=VSP_045246. FT VARIANT 157 157 L -> M (in dbSNP:rs2227329). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_013073. FT VARIANT 174 174 A -> T (in dbSNP:rs2227330). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_013074. FT CONFLICT 30 30 A -> M (in Ref. 8; AA sequence). FT {ECO:0000305}. FT STRAND 37 39 {ECO:0000244|PDB:1CD9}. FT HELIX 41 65 {ECO:0000244|PDB:1RHG}. FT HELIX 69 71 {ECO:0000244|PDB:1RHG}. FT HELIX 77 80 {ECO:0000244|PDB:1RHG}. FT HELIX 81 86 {ECO:0000244|PDB:1RHG}. FT STRAND 96 100 {ECO:0000244|PDB:2D9Q}. FT HELIX 105 124 {ECO:0000244|PDB:1RHG}. FT TURN 125 127 {ECO:0000244|PDB:1RHG}. FT TURN 130 132 {ECO:0000244|PDB:1RHG}. FT HELIX 133 156 {ECO:0000244|PDB:1RHG}. FT STRAND 166 168 {ECO:0000244|PDB:1GNC}. FT HELIX 176 204 {ECO:0000244|PDB:1RHG}. 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 //