CSF3_HUMAN
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 03-AUG-2022, entry version 221.
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/";
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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; 14.
DR DIP; DIP-61120N; -.
DR IntAct; P09919; 2.
DR STRING; 9606.ENSP00000225474; -.
DR Allergome; 8367; Hom s G-CSF.
DR CarbonylDB; P09919; -.
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; P09919; -.
DR PeptideAtlas; P09919; -.
DR PRIDE; P09919; -.
DR ProteomicsDB; 2347; -.
DR ProteomicsDB; 52279; -. [P09919-1]
DR ProteomicsDB; 52280; -. [P09919-2]
DR Antibodypedia; 799; 1313 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 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; HHQVGGF; -.
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; 10 hits in 1067 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 olfactory segment of nasal mucosa and 132 other tissues.
DR ExpressionAtlas; P09919; baseline and differential.
DR Genevisible; P09919; HS.
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:0030851; P:granulocyte differentiation; NAS:UniProtKB.
DR GO; GO:0006955; P:immune response; IEA:InterPro.
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 population proliferation; IBA:GO_Central.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IDA:BHF-UCL.
DR GO; GO:0045639; P:positive regulation of myeloid cell differentiation; IBA:GO_Central.
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:0045944; P:positive regulation of transcription by RNA polymerase II; 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; PTHR10511; 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; SSF47266; 1.
DR PROSITE; PS00254; INTERLEUKIN_6; 1.
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
