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Database: UniProt
Entry: P09919
LinkDB: P09919
Original site: P09919 
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   29-SEP-2021, entry version 218.
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   BMRB; P09919; -.
DR   SMR; P09919; -.
DR   BioGRID; 107827; 12.
DR   DIP; DIP-61120N; -.
DR   IntAct; P09919; 2.
DR   STRING; 9606.ENSP00000225474; -.
DR   Allergome; 8367; Hom s G-CSF.
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; 1297 antibodies.
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.4; human. [P09919-1]
DR   CTD; 1440; -.
DR   DisGeNET; 1440; -.
DR   GeneCards; CSF3; -.
DR   HGNC; HGNC:2438; CSF3.
DR   HPA; ENSG00000108342; Tissue enhanced (cervix, uterine, lung).
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; TVWQQME; -.
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; 7 hits in 1007 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 smooth muscle tissue and 149 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:0007275; P:multicellular organism 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 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
//
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