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P09919

- CSF3_HUMAN

UniProt

P09919 - CSF3_HUMAN

Protein

Granulocyte colony-stimulating factor

Gene

CSF3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 163 (01 Oct 2014)
      Sequence version 1 (01 Jul 1989)
      Previous versions | rss
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    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

    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

    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 – 29291 PublicationAdd
    BLAST
    Chaini30 – 207178Granulocyte colony-stimulating factorPRO_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.2 Publications

    Protein-protein interaction databases

    STRINGi9606.ENSP00000225474.

    Structurei

    Secondary structure

    1
    207
    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.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP09919.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the IL-6 superfamily.Curated

    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

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti30 – 301A → M AA sequence (PubMed:8554326)Curated

    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. 3 PublicationsVSP_002673
    Alternative sequencei69 – 10436Missing in isoform 3. 1 PublicationVSP_045246Add
    BLAST

    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

    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: October 1, 2014
    This is version 163 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