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P09919

- CSF3_HUMAN

UniProt

P09919 - CSF3_HUMAN

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Protein
Granulocyte colony-stimulating factor
Gene
CSF3, C17orf33, GCSF
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.

GO - Molecular functioni

  1. cytokine activity Source: UniProtKB
  2. enzyme binding Source: UniProtKB
  3. granulocyte colony-stimulating factor receptor binding Source: ProtInc

GO - Biological processi

  1. cellular response to cytokine stimulus Source: BHF-UCL
  2. cellular response to lipopolysaccharide Source: Ensembl
  3. cytokine-mediated signaling pathway Source: UniProtKB
  4. granulocyte differentiation Source: UniProtKB
  5. immune response Source: InterPro
  6. multicellular organismal development Source: ProtInc
  7. negative regulation of neuron death Source: Ensembl
  8. positive regulation of actin cytoskeleton reorganization Source: BHF-UCL
  9. positive regulation of actin filament polymerization Source: BHF-UCL
  10. positive regulation of cell proliferation Source: ProtInc
  11. positive regulation of peptidyl-serine phosphorylation Source: BHF-UCL
  12. positive regulation of peptidyl-tyrosine phosphorylation Source: BHF-UCL
  13. positive regulation of phosphatidylinositol 3-kinase signaling Source: BHF-UCL
  14. positive regulation of protein binding Source: BHF-UCL
  15. positive regulation of protein kinase B signaling Source: BHF-UCL
  16. positive regulation of transcription factor import into nucleus Source: BHF-UCL
  17. positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Cytokine, Growth factor

Enzyme and pathway databases

SignaLinkiP09919.

Names & Taxonomyi

Protein namesi
Recommended name:
Granulocyte colony-stimulating factor
Short name:
G-CSF
Alternative name(s):
Pluripoietin
INN: Filgrastim
INN: Lenograstim
Gene namesi
Name:CSF3
Synonyms:C17orf33, GCSF
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 17

Organism-specific databases

HGNCiHGNC:2438. CSF3.

Subcellular locationi

GO - Cellular componenti

  1. extracellular space Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Pharmaceutical usei

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).

Organism-specific databases

PharmGKBiPA26941.

Protein family/group databases

Allergomei8367. Hom s G-CSF.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2929 Inferred
Add
BLAST
Chaini30 – 207178Granulocyte colony-stimulating factor
PRO_0000015570Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi69 ↔ 75
Disulfide bondi97 ↔ 107
Glycosylationi166 – 1661O-linked (GalNAc...) By similarity

Post-translational modificationi

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).

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP09919.
PRIDEiP09919.

PTM databases

PhosphoSiteiP09919.

Expressioni

Gene expression databases

ArrayExpressiP09919.
BgeeiP09919.
CleanExiHS_CSF3.
GenevestigatoriP09919.

Organism-specific databases

HPAiCAB016131.
HPA001412.

Interactioni

Subunit structurei

Monomer.

Protein-protein interaction databases

STRINGi9606.ENSP00000225474.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi37 – 393
Helixi41 – 6525
Helixi69 – 713
Helixi77 – 804
Helixi81 – 866
Beta strandi96 – 1005
Helixi105 – 12420
Turni125 – 1273
Turni130 – 1323
Helixi133 – 15624
Beta strandi166 – 1683
Helixi176 – 20429

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1CD9X-ray2.80A/C31-207[»]
1GNCNMR-A31-207[»]
1PGRX-ray3.50A/C/E/G31-207[»]
1RHGX-ray2.20A/B/C31-207[»]
2D9QX-ray2.80A31-207[»]
ProteinModelPortaliP09919.
SMRiP09919. Positions 34-207.

Miscellaneous databases

EvolutionaryTraceiP09919.

Family & Domainsi

Sequence similaritiesi

Belongs to the IL-6 superfamily.

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG47652.
HOGENOMiHOG000015371.
HOVERGENiHBG005411.
InParanoidiP09919.
KOiK05423.
OMAiKLCHPEE.
PhylomeDBiP09919.
TreeFamiTF337698.

Family and domain databases

Gene3Di1.20.1250.10. 1 hit.
InterProiIPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR003573. IL-6/IL-23/GCSF/MGF.
[Graphical view]
PfamiPF00489. IL6. 1 hit.
[Graphical view]
PIRSFiPIRSF001935. IL6_MGF_GCSF. 1 hit.
PRINTSiPR00433. IL6GCSFMGF.
SMARTiSM00126. IL6. 1 hit.
[Graphical view]
SUPFAMiSSF47266. SSF47266. 1 hit.
PROSITEiPS00254. INTERLEUKIN_6. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. Align

Isoform Long (identifier: P09919-1) [UniParc]FASTAAdd to Basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

MAGPATQSPM KLMALQLLLW HSALWTVQEA TPLGPASSLP QSFLLKCLEQ    50
VRKIQGDGAA LQEKLVSECA TYKLCHPEEL VLLGHSLGIP WAPLSSCPSQ 100
ALQLAGCLSQ LHSGLFLYQG LLQALEGISP ELGPTLDTLQ LDVADFATTI 150
WQQMEELGMA PALQPTQGAM PAFASAFQRR AGGVLVASHL QSFLEVSYRV 200
LRHLAQP 207
Length:207
Mass (Da):22,293
Last modified:July 1, 1989 - v1
Checksum:i421F635ECC776996
GO
Isoform Short (identifier: P09919-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     66-68: Missing.

Show »
Length:204
Mass (Da):21,978
Checksum:i5F07C52F13D6A6D3
GO
Isoform 3 (identifier: P09919-3) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     69-104: Missing.

Note: No experimental confirmation available.

Show »
Length:171
Mass (Da):18,434
Checksum:iC62B366732AD7664
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti157 – 1571L → M.1 Publication
Corresponds to variant rs2227329 [ dbSNP | Ensembl ].
VAR_013073
Natural varianti174 – 1741A → T.1 Publication
Corresponds to variant rs2227330 [ dbSNP | Ensembl ].
VAR_013074

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei66 – 683Missing in isoform Short.
VSP_002673
Alternative sequencei69 – 10436Missing in isoform 3.
VSP_045246Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti30 – 301A → M AA sequence 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X03438 mRNA. Translation: CAA27168.1.
X03656 Genomic DNA. Translation: CAA27291.1.
X03655 mRNA. Translation: CAA27290.1.
M17706 mRNA. Translation: AAA35882.1.
AF388025 Genomic DNA. Translation: AAK62469.1.
CD013926 mRNA. No translation available.
AC090844 Genomic DNA. No translation available.
M13008 mRNA. Translation: AAA03056.1.
CCDSiCCDS11357.1. [P09919-1]
CCDS11358.2. [P09919-3]
CCDS42314.1. [P09919-2]
PIRiA24573.
A25093. FQHUGL.
RefSeqiNP_000750.1. NM_000759.3. [P09919-1]
NP_001171618.1. NM_001178147.1.
NP_757373.1. NM_172219.2. [P09919-2]
NP_757374.2. NM_172220.2. [P09919-3]
UniGeneiHs.2233.

Genome annotation databases

EnsembliENST00000225474; ENSP00000225474; ENSG00000108342. [P09919-1]
ENST00000394148; ENSP00000377704; ENSG00000108342. [P09919-3]
ENST00000394149; ENSP00000377705; ENSG00000108342. [P09919-2]
GeneIDi1440.
KEGGihsa:1440.
UCSCiuc002htp.3. human. [P09919-1]

Polymorphism databases

DMDMi117564.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Neupogen/Granulokine

Clinical information on Neupogen/Granulokine

SeattleSNPs

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X03438 mRNA. Translation: CAA27168.1 .
X03656 Genomic DNA. Translation: CAA27291.1 .
X03655 mRNA. Translation: CAA27290.1 .
M17706 mRNA. Translation: AAA35882.1 .
AF388025 Genomic DNA. Translation: AAK62469.1 .
CD013926 mRNA. No translation available.
AC090844 Genomic DNA. No translation available.
M13008 mRNA. Translation: AAA03056.1 .
CCDSi CCDS11357.1. [P09919-1 ]
CCDS11358.2. [P09919-3 ]
CCDS42314.1. [P09919-2 ]
PIRi A24573.
A25093. FQHUGL.
RefSeqi NP_000750.1. NM_000759.3. [P09919-1 ]
NP_001171618.1. NM_001178147.1.
NP_757373.1. NM_172219.2. [P09919-2 ]
NP_757374.2. NM_172220.2. [P09919-3 ]
UniGenei Hs.2233.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1CD9 X-ray 2.80 A/C 31-207 [» ]
1GNC NMR - A 31-207 [» ]
1PGR X-ray 3.50 A/C/E/G 31-207 [» ]
1RHG X-ray 2.20 A/B/C 31-207 [» ]
2D9Q X-ray 2.80 A 31-207 [» ]
ProteinModelPortali P09919.
SMRi P09919. Positions 34-207.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 9606.ENSP00000225474.

Chemistry

DrugBanki DB00099. Filgrastim.
DB00019. Pegfilgrastim.

Protein family/group databases

Allergomei 8367. Hom s G-CSF.

PTM databases

PhosphoSitei P09919.

Polymorphism databases

DMDMi 117564.

Proteomic databases

PaxDbi P09919.
PRIDEi P09919.

Protocols and materials databases

DNASUi 1440.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000225474 ; ENSP00000225474 ; ENSG00000108342 . [P09919-1 ]
ENST00000394148 ; ENSP00000377704 ; ENSG00000108342 . [P09919-3 ]
ENST00000394149 ; ENSP00000377705 ; ENSG00000108342 . [P09919-2 ]
GeneIDi 1440.
KEGGi hsa:1440.
UCSCi uc002htp.3. human. [P09919-1 ]

Organism-specific databases

CTDi 1440.
GeneCardsi GC17P038171.
HGNCi HGNC:2438. CSF3.
HPAi CAB016131.
HPA001412.
MIMi 138970. gene.
neXtProti NX_P09919.
PharmGKBi PA26941.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG47652.
HOGENOMi HOG000015371.
HOVERGENi HBG005411.
InParanoidi P09919.
KOi K05423.
OMAi KLCHPEE.
PhylomeDBi P09919.
TreeFami TF337698.

Enzyme and pathway databases

SignaLinki P09919.

Miscellaneous databases

EvolutionaryTracei P09919.
GeneWikii Granulocyte_colony-stimulating_factor.
GenomeRNAii 1440.
NextBioi 5893.
PROi P09919.
SOURCEi Search...

Gene expression databases

ArrayExpressi P09919.
Bgeei P09919.
CleanExi HS_CSF3.
Genevestigatori P09919.

Family and domain databases

Gene3Di 1.20.1250.10. 1 hit.
InterProi IPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR003573. IL-6/IL-23/GCSF/MGF.
[Graphical view ]
Pfami PF00489. IL6. 1 hit.
[Graphical view ]
PIRSFi PIRSF001935. IL6_MGF_GCSF. 1 hit.
PRINTSi PR00433. IL6GCSFMGF.
SMARTi SM00126. IL6. 1 hit.
[Graphical view ]
SUPFAMi SSF47266. SSF47266. 1 hit.
PROSITEi PS00254. INTERLEUKIN_6. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning and expression of cDNA for human granulocyte colony-stimulating factor."
    Nagata S., Tsuchiya M., Asano S., Kaziro Y., Yamazaki T., Yamamoto O., Hirata Y., Kubota N., Oheda M., Nomura H., Ono M.
    Nature 319:415-418(1986) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
  2. "The chromosomal gene structure and two mRNAs for human granulocyte colony-stimulating factor."
    Nagata S., Tsuchiya M., Asano S., Yamamoto O., Hirata Y., Kubota N., Oheda M., Nomura H., Yamazaki T.
    EMBO J. 5:575-581(1986) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM SHORT), ALTERNATIVE SPLICING.
  3. "Expression of granulocyte colony-stimulating factor by human cell lines."
    Devlin J.J., Devlin P.E., Myambo K., Lilly M.B., Rado T.A., Warren M.K.
    J. Leukoc. Biol. 41:302-306(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
  4. SeattleSNPs variation discovery resource
    Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS MET-157 AND THR-174.
  5. "PCR isolation and cloning of novel splice variant mRNAs from known drug target genes."
    Jin P., Fu G.K., Wilson A.D., Yang J., Chien D., Hawkins P.R., Au-Young J., Stuve L.L.
    Genomics 83:566-571(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
  6. "DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
    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.
    Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. "Recombinant human granulocyte colony-stimulating factor: effects on normal and leukemic myeloid cells."
    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.
    Science 232:61-66(1986) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 19-207 (ISOFORM SHORT).
  8. "Extracellular domain of granulocyte-colony stimulating factor receptor. Interaction with its ligand and identification of a domain in close proximity of ligand-binding region."
    Haniu M., Horan T., Arakawa T., Le J., Katta V., Rohde M.F.
    Arch. Biochem. Biophys. 324:344-356(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 30-46.
  9. "Glycosidase digestion, electrophoresis and chromatographic analysis of recombinant human granulocyte colony-stimulating factor glycoforms produced in Chinese hamster ovary cells."
    Clogston C.L., Hu S., Boone T.C., Lu H.S.
    J. Chromatogr. A 637:55-62(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION AT THR-166.
  10. "Secondary structure of human granulocyte colony-stimulating factor derived from NMR spectroscopy."
    Zink T., Ross A., Ambrosius D., Rudolph R., Holak T.A.
    FEBS Lett. 314:435-439(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR.
  11. "Structure and dynamics of the human granulocyte colony-stimulating factor determined by NMR spectroscopy. Loop mobility in a four-helix-bundle protein."
    Zink T., Ross A., Luers K., Cieslar C., Rudolph R., Holak T.A.
    Biochemistry 33:8453-8463(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR.
  12. "The structure of granulocyte-colony-stimulating factor and its relationship to other growth factors."
    Hill C.P., Osslund T.D., Eisenberg D.
    Proc. Natl. Acad. Sci. U.S.A. 90:5167-5171(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
  13. "Atomic structure of the GCSF-receptor complex showing a new cytokine-receptor recognition scheme."
    Aritomi M., Kunishima N., Okamoto T., Kuroki R., Ota Y., Morikawa K.
    Nature 401:713-717(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 31-207 IN COMPLEX WITH CSF3R.
  14. "Homodimeric cross-over structure of the human granulocyte colony-stimulating factor (GCSF) receptor signaling complex."
    Tamada T., Honjo E., Maeda Y., Okamoto T., Ishibashi M., Tokunaga M., Kuroki R.
    Proc. Natl. Acad. Sci. U.S.A. 103:3135-3140(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 31-207 IN COMPLEX WITH CSF3R.

Entry informationi

Entry nameiCSF3_HUMAN
AccessioniPrimary (citable) accession number: P09919
Secondary accession number(s): A8MXR7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: July 9, 2014
This is version 162 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Pharmaceutical, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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