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Granulocyte colony-stimulating factor (G-CSF) (Pluripoietin) (Filgrastim) (Lenograstim)

 CSF3_HUMAN              Reviewed;         207 AA.
P09919; A8MXR7;
01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
01-JUL-1989, sequence version 1.
10-OCT-2018, entry version 197.
RecName: Full=Granulocyte colony-stimulating factor;
Short=G-CSF;
AltName: Full=Pluripoietin;
AltName: INN=Filgrastim;
AltName: INN=Lenograstim;
Flags: Precursor;
Name=CSF3; Synonyms=C17orf33, GCSF;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
PubMed=3484805; DOI=10.1038/319415a0;
Nagata S., Tsuchiya M., Asano S., Kaziro Y., Yamazaki T., Yamamoto O.,
Hirata Y., Kubota N., Oheda M., Nomura H., Ono M.;
"Molecular cloning and expression of cDNA for human granulocyte
colony-stimulating factor.";
Nature 319:415-418(1986).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM SHORT), AND
ALTERNATIVE SPLICING.
PubMed=2423327;
Nagata S., Tsuchiya M., Asano S., Yamamoto O., Hirata Y., Kubota N.,
Oheda M., Nomura H., Yamazaki T.;
"The chromosomal gene structure and two mRNAs for human granulocyte
colony-stimulating factor.";
EMBO J. 5:575-581(1986).
[3]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
PubMed=3494801;
Devlin J.J., Devlin P.E., Myambo K., Lilly M.B., Rado T.A.,
Warren M.K.;
"Expression of granulocyte colony-stimulating factor by human cell
lines.";
J. Leukoc. Biol. 41:302-306(1987).
[4]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS MET-157 AND THR-174.
SeattleSNPs variation discovery resource;
Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
PubMed=15028279; DOI=10.1016/j.ygeno.2003.09.023;
Jin P., Fu G.K., Wilson A.D., Yang J., Chien D., Hawkins P.R.,
Au-Young J., Stuve L.L.;
"PCR isolation and cloning of novel splice variant mRNAs from known
drug target genes.";
Genomics 83:566-571(2004).
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=16625196; DOI=10.1038/nature04689;
Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R.,
Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N.,
Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B.,
Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J.,
Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E.,
Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J.,
Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C.,
Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
"DNA sequence of human chromosome 17 and analysis of rearrangement in
the human lineage.";
Nature 440:1045-1049(2006).
[7]
NUCLEOTIDE SEQUENCE [MRNA] OF 19-207 (ISOFORM SHORT).
PubMed=2420009; DOI=10.1126/science.2420009;
Souza L.M., Boone T.C., Gabrilove J., Lai P.H., Zsebo K.M.,
Murdock D.C., Chazin V.R., Bruszewski J., Lu H., Chen K.K.,
Barendt J., Platzer E., Moore M.A.S., Mertelsmann R., Welte K.;
"Recombinant human granulocyte colony-stimulating factor: effects on
normal and leukemic myeloid cells.";
Science 232:61-66(1986).
[8]
PROTEIN SEQUENCE OF 30-46.
PubMed=8554326; DOI=10.1006/abbi.1995.0047;
Haniu M., Horan T., Arakawa T., Le J., Katta V., Rohde M.F.;
"Extracellular domain of granulocyte-colony stimulating factor
receptor. Interaction with its ligand and identification of a domain
in close proximity of ligand-binding region.";
Arch. Biochem. Biophys. 324:344-356(1995).
[9]
GLYCOSYLATION AT THR-166.
PubMed=7685769; DOI=10.1016/0021-9673(93)83098-D;
Clogston C.L., Hu S., Boone T.C., Lu H.S.;
"Glycosidase digestion, electrophoresis and chromatographic analysis
of recombinant human granulocyte colony-stimulating factor glycoforms
produced in Chinese hamster ovary cells.";
J. Chromatogr. A 637:55-62(1993).
[10]
STRUCTURE BY NMR.
PubMed=1281794; DOI=10.1016/0014-5793(92)81521-M;
Zink T., Ross A., Ambrosius D., Rudolph R., Holak T.A.;
"Secondary structure of human granulocyte colony-stimulating factor
derived from NMR spectroscopy.";
FEBS Lett. 314:435-439(1992).
[11]
STRUCTURE BY NMR.
PubMed=7518249; DOI=10.1021/bi00194a009;
Zink T., Ross A., Luers K., Cieslar C., Rudolph R., Holak T.A.;
"Structure and dynamics of the human granulocyte colony-stimulating
factor determined by NMR spectroscopy. Loop mobility in a four-helix-
bundle protein.";
Biochemistry 33:8453-8463(1994).
[12]
X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
PubMed=7685117; DOI=10.1073/pnas.90.11.5167;
Hill C.P., Osslund T.D., Eisenberg D.;
"The structure of granulocyte-colony-stimulating factor and its
relationship to other growth factors.";
Proc. Natl. Acad. Sci. U.S.A. 90:5167-5171(1993).
[13]
X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 31-207 IN COMPLEX WITH CSF3R.
PubMed=10537111; DOI=10.1038/44394;
Aritomi M., Kunishima N., Okamoto T., Kuroki R., Ota Y., Morikawa K.;
"Atomic structure of the GCSF-receptor complex showing a new cytokine-
receptor recognition scheme.";
Nature 401:713-717(1999).
[14]
X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 31-207 IN COMPLEX WITH CSF3R.
PubMed=16492764; DOI=10.1073/pnas.0511264103;
Tamada T., Honjo E., Maeda Y., Okamoto T., Ishibashi M., Tokunaga M.,
Kuroki R.;
"Homodimeric cross-over structure of the human granulocyte colony-
stimulating factor (GCSF) receptor signaling complex.";
Proc. Natl. Acad. Sci. U.S.A. 103:3135-3140(2006).
-!- FUNCTION: Granulocyte/macrophage colony-stimulating factors are
cytokines that act in hematopoiesis by controlling the production,
differentiation, and function of 2 related white cell populations
of the blood, the granulocytes and the monocytes-macrophages. This
CSF induces granulocytes.
-!- SUBUNIT: Monomer. {ECO:0000269|PubMed:10537111,
ECO:0000269|PubMed:16492764}.
-!- SUBCELLULAR LOCATION: Secreted.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=3;
Name=Long;
IsoId=P09919-1; Sequence=Displayed;
Name=Short;
IsoId=P09919-2; Sequence=VSP_002673;
Name=3;
IsoId=P09919-3; Sequence=VSP_045246;
Note=No experimental confirmation available.;
-!- PTM: O-glycan consists of Gal-GalNAc disaccharide which can be
modified with up to two sialic acid residues (done in
recombinantly expressed G-CSF from CHO cells).
-!- PHARMACEUTICAL: Available under the names Neupogen or Granulokine
(Amgen/Roche) and Granocyte (Rhone-Poulenc). Used to treat
neutropenia (a disorder characterized by an extremely low number
of neutrophils in blood).
-!- SIMILARITY: Belongs to the IL-6 superfamily. {ECO:0000305}.
-!- CAUTION: PubMed:2420009 misquotes the gene name as "CSF1".
{ECO:0000305}.
-!- WEB RESOURCE: Name=Neupogen/Granulokine; Note=Clinical information
on Neupogen/Granulokine;
URL="https://www.neupogen.com";
-!- WEB RESOURCE: Name=SeattleSNPs;
URL="http://pga.gs.washington.edu/data/csf3/";
-----------------------------------------------------------------------
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EMBL; X03438; CAA27168.1; -; mRNA.
EMBL; X03656; CAA27291.1; -; Genomic_DNA.
EMBL; X03655; CAA27290.1; -; mRNA.
EMBL; M17706; AAA35882.1; -; mRNA.
EMBL; AF388025; AAK62469.1; -; Genomic_DNA.
EMBL; CD013926; -; NOT_ANNOTATED_CDS; mRNA.
EMBL; AC090844; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; M13008; AAA03056.1; -; mRNA.
CCDS; CCDS11357.1; -. [P09919-1]
CCDS; CCDS11358.2; -. [P09919-3]
CCDS; CCDS42314.1; -. [P09919-2]
PIR; A24573; A24573.
PIR; A25093; FQHUGL.
RefSeq; NP_000750.1; NM_000759.3. [P09919-1]
RefSeq; NP_001171618.1; NM_001178147.1.
RefSeq; NP_757373.1; NM_172219.2. [P09919-2]
RefSeq; NP_757374.2; NM_172220.2. [P09919-3]
UniGene; Hs.2233; -.
PDB; 1CD9; X-ray; 2.80 A; A/C=31-207.
PDB; 1GNC; NMR; -; A=31-207.
PDB; 1PGR; X-ray; 3.50 A; A/C/E/G=31-207.
PDB; 1RHG; X-ray; 2.20 A; A/B/C=31-207.
PDB; 2D9Q; X-ray; 2.80 A; A=31-207.
PDB; 5GW9; X-ray; 1.65 A; A/B/C/D=40-205.
PDBsum; 1CD9; -.
PDBsum; 1GNC; -.
PDBsum; 1PGR; -.
PDBsum; 1RHG; -.
PDBsum; 2D9Q; -.
PDBsum; 5GW9; -.
ProteinModelPortal; P09919; -.
SMR; P09919; -.
BioGrid; 107827; 10.
DIP; DIP-61120N; -.
IntAct; P09919; 2.
STRING; 9606.ENSP00000225474; -.
Allergome; 8367; Hom s G-CSF.
iPTMnet; P09919; -.
PhosphoSitePlus; P09919; -.
BioMuta; CSF3; -.
DMDM; 117564; -.
PaxDb; P09919; -.
PeptideAtlas; P09919; -.
PRIDE; P09919; -.
ProteomicsDB; 52279; -.
ProteomicsDB; 52280; -. [P09919-2]
DNASU; 1440; -.
Ensembl; ENST00000225474; ENSP00000225474; ENSG00000108342. [P09919-1]
Ensembl; ENST00000394148; ENSP00000377704; ENSG00000108342. [P09919-3]
Ensembl; ENST00000394149; ENSP00000377705; ENSG00000108342. [P09919-2]
GeneID; 1440; -.
KEGG; hsa:1440; -.
UCSC; uc002htp.4; human. [P09919-1]
CTD; 1440; -.
DisGeNET; 1440; -.
EuPathDB; HostDB:ENSG00000108342.12; -.
GeneCards; CSF3; -.
HGNC; HGNC:2438; CSF3.
MIM; 138970; gene.
neXtProt; NX_P09919; -.
OpenTargets; ENSG00000108342; -.
PharmGKB; PA26941; -.
eggNOG; ENOG410IIM2; Eukaryota.
eggNOG; ENOG4111DA4; LUCA.
GeneTree; ENSGT00390000017328; -.
HOGENOM; HOG000015371; -.
HOVERGEN; HBG005411; -.
InParanoid; P09919; -.
KO; K05423; -.
OMA; KLCHPEE; -.
OrthoDB; EOG091G0NDU; -.
PhylomeDB; P09919; -.
TreeFam; TF337698; -.
Reactome; R-HSA-449836; Other interleukin signaling.
Reactome; R-HSA-6783783; Interleukin-10 signaling.
SignaLink; P09919; -.
SIGNOR; P09919; -.
ChiTaRS; CSF3; human.
EvolutionaryTrace; P09919; -.
GeneWiki; Granulocyte_colony-stimulating_factor; -.
GenomeRNAi; 1440; -.
PRO; PR:P09919; -.
Proteomes; UP000005640; Chromosome 17.
Bgee; ENSG00000108342; Expressed in 128 organ(s), highest expression level in smooth muscle tissue.
CleanEx; HS_CSF3; -.
ExpressionAtlas; P09919; baseline and differential.
Genevisible; P09919; HS.
GO; GO:0005576; C:extracellular region; TAS:Reactome.
GO; GO:0005615; C:extracellular space; IBA:GO_Central.
GO; GO:0005125; F:cytokine activity; IDA:BHF-UCL.
GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
GO; GO:0005130; F:granulocyte colony-stimulating factor receptor binding; IBA:GO_Central.
GO; GO:0008083; F:growth factor activity; IBA:GO_Central.
GO; GO:0071345; P:cellular response to cytokine stimulus; IDA:BHF-UCL.
GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl.
GO; GO:0019221; P:cytokine-mediated signaling pathway; TAS:Reactome.
GO; GO:0030851; P:granulocyte differentiation; NAS:UniProtKB.
GO; GO:0006955; P:immune response; IEA:InterPro.
GO; GO:0030225; P:macrophage differentiation; IBA:GO_Central.
GO; GO:0007275; P:multicellular organism development; TAS:ProtInc.
GO; GO:0061515; P:myeloid cell development; IBA:GO_Central.
GO; GO:1901215; P:negative regulation of neuron death; IEA:Ensembl.
GO; GO:0030223; P:neutrophil differentiation; IBA:GO_Central.
GO; GO:2000251; P:positive regulation of actin cytoskeleton reorganization; IDA:BHF-UCL.
GO; GO:0030838; P:positive regulation of actin filament polymerization; IDA:BHF-UCL.
GO; GO:0008284; P:positive regulation of cell proliferation; IBA:GO_Central.
GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IDA:BHF-UCL.
GO; GO:0045639; P:positive regulation of myeloid cell differentiation; IBA:GO_Central.
GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:BHF-UCL.
GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:BHF-UCL.
GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IDA:BHF-UCL.
GO; GO:0032092; P:positive regulation of protein binding; IDA:BHF-UCL.
GO; GO:0051897; P:positive regulation of protein kinase B signaling; IDA:BHF-UCL.
GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
InterPro; IPR009079; 4_helix_cytokine-like_core.
InterPro; IPR030474; IL-6/GCSF/MGF.
InterPro; IPR030473; IL6/GCSF/MGF_CS.
Pfam; PF16647; GCSF; 1.
PIRSF; PIRSF001935; IL6_MGF_GCSF; 1.
PRINTS; PR00433; IL6GCSFMGF.
SMART; SM00126; IL6; 1.
SUPFAM; SSF47266; SSF47266; 1.
PROSITE; PS00254; INTERLEUKIN_6; 1.
1: Evidence at protein level;
3D-structure; Alternative splicing; Complete proteome; Cytokine;
Direct protein sequencing; Disulfide bond; Glycoprotein;
Growth factor; Pharmaceutical; Polymorphism; Reference proteome;
Secreted; Signal.
SIGNAL 1 29 {ECO:0000305|PubMed:8554326}.
CHAIN 30 207 Granulocyte colony-stimulating factor.
/FTId=PRO_0000015570.
CARBOHYD 166 166 O-linked (GalNAc...) threonine.
{ECO:0000250}.
DISULFID 69 75
DISULFID 97 107
VAR_SEQ 66 68 Missing (in isoform Short).
{ECO:0000303|PubMed:2420009,
ECO:0000303|PubMed:2423327,
ECO:0000303|PubMed:3494801}.
/FTId=VSP_002673.
VAR_SEQ 69 104 Missing (in isoform 3).
{ECO:0000303|PubMed:15028279}.
/FTId=VSP_045246.
VARIANT 157 157 L -> M (in dbSNP:rs2227329).
{ECO:0000269|Ref.4}.
/FTId=VAR_013073.
VARIANT 174 174 A -> T (in dbSNP:rs2227330).
{ECO:0000269|Ref.4}.
/FTId=VAR_013074.
CONFLICT 30 30 A -> M (in Ref. 8; AA sequence).
{ECO:0000305}.
STRAND 37 39 {ECO:0000244|PDB:1CD9}.
HELIX 41 65 {ECO:0000244|PDB:5GW9}.
HELIX 69 72 {ECO:0000244|PDB:5GW9}.
HELIX 77 87 {ECO:0000244|PDB:5GW9}.
STRAND 99 101 {ECO:0000244|PDB:5GW9}.
HELIX 104 124 {ECO:0000244|PDB:5GW9}.
TURN 125 127 {ECO:0000244|PDB:5GW9}.
TURN 130 132 {ECO:0000244|PDB:5GW9}.
HELIX 133 157 {ECO:0000244|PDB:5GW9}.
STRAND 166 168 {ECO:0000244|PDB:1GNC}.
HELIX 176 201 {ECO:0000244|PDB:5GW9}.
TURN 203 205 {ECO:0000244|PDB:2D9Q}.
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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