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P04141

- CSF2_HUMAN

UniProt

P04141 - CSF2_HUMAN

Protein

Granulocyte-macrophage colony-stimulating factor

Gene

CSF2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
  1. Functioni

    Cytokine that stimulates the growth and differentiation of hematopoietic precursor cells from various lineages, including granulocytes, macrophages, eosinophils and erythrocytes.

    GO - Molecular functioni

    1. granulocyte macrophage colony-stimulating factor receptor binding Source: ProtInc
    2. protein binding Source: IntAct

    GO - Biological processi

    1. cellular response to lipopolysaccharide Source: Ensembl
    2. dendritic cell differentiation Source: DFLAT
    3. embryonic placenta development Source: Ensembl
    4. epithelial fluid transport Source: Ensembl
    5. immune response Source: InterPro
    6. macrophage activation Source: Ensembl
    7. myeloid dendritic cell differentiation Source: Ensembl
    8. negative regulation of cytolysis Source: BHF-UCL
    9. negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: BHF-UCL
    10. positive regulation of cell proliferation Source: Ensembl
    11. positive regulation of DNA replication Source: BHF-UCL
    12. positive regulation of gene expression Source: BHF-UCL
    13. positive regulation of interleukin-23 production Source: BHF-UCL
    14. positive regulation of macrophage derived foam cell differentiation Source: BHF-UCL
    15. positive regulation of podosome assembly Source: BHF-UCL
    16. positive regulation of tyrosine phosphorylation of Stat5 protein Source: BHF-UCL

    Keywords - Molecular functioni

    Cytokine, Growth factor

    Enzyme and pathway databases

    ReactomeiREACT_23837. Interleukin-3, 5 and GM-CSF signaling.
    REACT_23891. Interleukin receptor SHC signaling.
    SignaLinkiP04141.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Granulocyte-macrophage colony-stimulating factor
    Short name:
    GM-CSF
    Alternative name(s):
    Colony-stimulating factor
    Short name:
    CSF
    Molgramostin
    Sargramostim
    Gene namesi
    Name:CSF2
    Synonyms:GMCSF
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 5

    Organism-specific databases

    HGNCiHGNC:2434. CSF2.

    Subcellular locationi

    GO - Cellular componenti

    1. extracellular region Source: Reactome
    2. extracellular space Source: UniProtKB-KW

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Pharmaceutical usei

    Available under the names Leukine (Immunex) and Leucomax (Novartis). Used in myeloid reconstitution following bone marrow transplant, bone marrow transplant engraftment failure or delay, mobilization and following transplantation of autologous peripheral blood progenitor cells, and following induction chemotherapy in older adults with acute myelogenous leukemia.

    Organism-specific databases

    PharmGKBiPA26937.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 1717Add
    BLAST
    Chaini18 – 144127Granulocyte-macrophage colony-stimulating factorPRO_0000005865Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi22 – 221O-linked (GalNAc...)1 Publication
    Glycosylationi24 – 241O-linked (GalNAc...)1 Publication
    Glycosylationi26 – 261O-linked (GalNAc...)1 Publication
    Glycosylationi27 – 271O-linked (GalNAc...); partial1 Publication
    Glycosylationi44 – 441N-linked (GlcNAc...)
    Glycosylationi54 – 541N-linked (GlcNAc...)
    Disulfide bondi71 ↔ 1131 Publication
    Disulfide bondi105 ↔ 1381 Publication

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    PaxDbiP04141.
    PRIDEiP04141.

    PTM databases

    PhosphoSiteiP04141.

    Miscellaneous databases

    PMAP-CutDBP04141.

    Expressioni

    Gene expression databases

    BgeeiP04141.
    CleanExiHS_CSF2.
    GenevestigatoriP04141.

    Interactioni

    Subunit structurei

    Monomer. The signaling GM-CSF receptor complex is a dodecamer of two head-to-head hexamers of two alpha, two beta, and two ligand subunits.1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CSF2RBP329272EBI-1809826,EBI-1809771

    Protein-protein interaction databases

    BioGridi107824. 10 interactions.
    DIPiDIP-386N.
    IntActiP04141. 2 interactions.
    STRINGi9606.ENSP00000296871.

    Structurei

    Secondary structure

    1
    144
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Turni25 – 273
    Helixi30 – 4516
    Helixi50 – 534
    Beta strandi56 – 627
    Beta strandi66 – 683
    Helixi72 – 8110
    Helixi85 – 906
    Helixi91 – 10414
    Beta strandi115 – 1195
    Helixi120 – 13112

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1CSGX-ray2.70A/B18-144[»]
    2GMFX-ray2.40A/B18-144[»]
    3CXEX-ray3.30B18-144[»]
    ProteinModelPortaliP04141.
    SMRiP04141. Positions 21-141.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP04141.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the GM-CSF family.Curated

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiNOG42131.
    HOGENOMiHOG000037940.
    HOVERGENiHBG000532.
    InParanoidiP04141.
    KOiK05427.
    OMAiTCLQTRL.
    OrthoDBiEOG7J9VRQ.
    PhylomeDBiP04141.
    TreeFamiTF338611.

    Family and domain databases

    Gene3Di1.20.1250.10. 1 hit.
    InterProiIPR009079. 4_helix_cytokine-like_core.
    IPR012351. 4_helix_cytokine_core.
    IPR000773. GM_colony-stim-fac.
    [Graphical view]
    PANTHERiPTHR10059. PTHR10059. 1 hit.
    PfamiPF01109. GM_CSF. 1 hit.
    [Graphical view]
    PRINTSiPR00693. GMCSFACTOR.
    ProDomiPD007349. GM_colony-stim-fac. 1 hit.
    [Graphical view] [Entries sharing at least one domain]
    SMARTiSM00040. CSF2. 1 hit.
    [Graphical view]
    SUPFAMiSSF47266. SSF47266. 1 hit.
    PROSITEiPS00702. GM_CSF. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

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

    P04141-1 [UniParc]FASTAAdd to Basket

    « Hide

    MWLQSLLLLG TVACSISAPA RSPSPSTQPW EHVNAIQEAR RLLNLSRDTA    50
    AEMNETVEVI SEMFDLQEPT CLQTRLELYK QGLRGSLTKL KGPLTMMASH 100
    YKQHCPPTPE TSCATQIITF ESFKENLKDF LLVIPFDCWE PVQE 144
    Length:144
    Mass (Da):16,295
    Last modified:November 1, 1986 - v1
    Checksum:i75D1E50506BCA7A8
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti96 – 961M → K in AAM44054. 1 PublicationCurated
    Sequence conflicti123 – 1231F → L in AAM44054. 1 PublicationCurated

    Polymorphismi

    Variant Ile-117 may be a risk factor for atopic asthma.

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti115 – 1151T → I.1 Publication
    Corresponds to variant rs2069640 [ dbSNP | Ensembl ].
    VAR_013089
    Natural varianti117 – 1171I → T.3 Publications
    Corresponds to variant rs25882 [ dbSNP | Ensembl ].
    VAR_001975

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M13207 Genomic DNA. Translation: AAA98768.1.
    M11734 mRNA. Translation: AAA52122.1.
    M11220 mRNA. Translation: AAA52578.1.
    X03021 Genomic DNA. Translation: CAA26822.1.
    M10663 mRNA. Translation: AAA52121.1.
    AF373868 Genomic DNA. Translation: AAK51563.1.
    AC004511 Genomic DNA. Translation: AAC08707.1.
    BC108724 mRNA. Translation: AAI08725.1.
    BC113924 mRNA. Translation: AAI13925.1.
    BC113999 mRNA. Translation: AAI14000.1.
    AF510855 mRNA. Translation: AAM44054.1.
    CCDSiCCDS4150.1.
    PIRiC24636. FQHUGM.
    RefSeqiNP_000749.2. NM_000758.3.
    UniGeneiHs.1349.

    Genome annotation databases

    EnsembliENST00000296871; ENSP00000296871; ENSG00000164400.
    GeneIDi1437.
    KEGGihsa:1437.
    UCSCiuc003kwf.4. human.

    Polymorphism databases

    DMDMi117561.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    Leukine

    Clinical information on Leukine

    SeattleSNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M13207 Genomic DNA. Translation: AAA98768.1 .
    M11734 mRNA. Translation: AAA52122.1 .
    M11220 mRNA. Translation: AAA52578.1 .
    X03021 Genomic DNA. Translation: CAA26822.1 .
    M10663 mRNA. Translation: AAA52121.1 .
    AF373868 Genomic DNA. Translation: AAK51563.1 .
    AC004511 Genomic DNA. Translation: AAC08707.1 .
    BC108724 mRNA. Translation: AAI08725.1 .
    BC113924 mRNA. Translation: AAI13925.1 .
    BC113999 mRNA. Translation: AAI14000.1 .
    AF510855 mRNA. Translation: AAM44054.1 .
    CCDSi CCDS4150.1.
    PIRi C24636. FQHUGM.
    RefSeqi NP_000749.2. NM_000758.3.
    UniGenei Hs.1349.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1CSG X-ray 2.70 A/B 18-144 [» ]
    2GMF X-ray 2.40 A/B 18-144 [» ]
    3CXE X-ray 3.30 B 18-144 [» ]
    ProteinModelPortali P04141.
    SMRi P04141. Positions 21-141.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 107824. 10 interactions.
    DIPi DIP-386N.
    IntActi P04141. 2 interactions.
    STRINGi 9606.ENSP00000296871.

    Chemistry

    DrugBanki DB00020. Sargramostim.

    PTM databases

    PhosphoSitei P04141.

    Polymorphism databases

    DMDMi 117561.

    Proteomic databases

    PaxDbi P04141.
    PRIDEi P04141.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000296871 ; ENSP00000296871 ; ENSG00000164400 .
    GeneIDi 1437.
    KEGGi hsa:1437.
    UCSCi uc003kwf.4. human.

    Organism-specific databases

    CTDi 1437.
    GeneCardsi GC05P131409.
    HGNCi HGNC:2434. CSF2.
    MIMi 138960. gene.
    neXtProti NX_P04141.
    PharmGKBi PA26937.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG42131.
    HOGENOMi HOG000037940.
    HOVERGENi HBG000532.
    InParanoidi P04141.
    KOi K05427.
    OMAi TCLQTRL.
    OrthoDBi EOG7J9VRQ.
    PhylomeDBi P04141.
    TreeFami TF338611.

    Enzyme and pathway databases

    Reactomei REACT_23837. Interleukin-3, 5 and GM-CSF signaling.
    REACT_23891. Interleukin receptor SHC signaling.
    SignaLinki P04141.

    Miscellaneous databases

    EvolutionaryTracei P04141.
    GeneWikii Granulocyte_macrophage_colony-stimulating_factor.
    GenomeRNAii 1437.
    NextBioi 5871.
    PMAP-CutDB P04141.
    PROi P04141.
    SOURCEi Search...

    Gene expression databases

    Bgeei P04141.
    CleanExi HS_CSF2.
    Genevestigatori P04141.

    Family and domain databases

    Gene3Di 1.20.1250.10. 1 hit.
    InterProi IPR009079. 4_helix_cytokine-like_core.
    IPR012351. 4_helix_cytokine_core.
    IPR000773. GM_colony-stim-fac.
    [Graphical view ]
    PANTHERi PTHR10059. PTHR10059. 1 hit.
    Pfami PF01109. GM_CSF. 1 hit.
    [Graphical view ]
    PRINTSi PR00693. GMCSFACTOR.
    ProDomi PD007349. GM_colony-stim-fac. 1 hit.
    [Graphical view ] [Entries sharing at least one domain ]
    SMARTi SM00040. CSF2. 1 hit.
    [Graphical view ]
    SUPFAMi SSF47266. SSF47266. 1 hit.
    PROSITEi PS00702. GM_CSF. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Isolation of cDNA for a human granulocyte-macrophage colony-stimulating factor by functional expression in mammalian cells."
      Lee F., Yokota T., Otsuka T., Gemmell L., Larson N., Luh J., Arai K., Rennick D.
      Proc. Natl. Acad. Sci. U.S.A. 82:4360-4364(1985) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "Genomic cloning, characterization, and multilineage growth-promoting activity of human granulocyte-macrophage colony-stimulating factor."
      Kaushansky K., O'Hara P.J., Berkner K., Segal G.M., Hagen F.S., Adamson J.W.
      Proc. Natl. Acad. Sci. U.S.A. 83:3101-3105(1986) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    3. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    4. "Human GM-CSF: molecular cloning of the complementary DNA and purification of the natural and recombinant proteins."
      Wong G.G., Witek J.S., Temple P.A., Wilkens K.M., Leary A.C., Luxenberg D.P., Jones S.S., Brown E.L., Kay R.M., Orr E.C., Shoemaker C., Golde D.W., Kaufman R.J., Hewick R.M., Wang E.A., Clark S.C.
      Science 228:810-815(1985) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    5. "Structure of the chromosomal gene for granulocyte-macrophage colony stimulating factor: comparison of the mouse and human genes."
      Miyatake S., Otsuka T., Yokota T., Lee F., Arai K.
      EMBO J. 4:2561-2568(1985) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    6. SeattleSNPs variation discovery resource
      Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ILE-115 AND THR-117.
    7. "The DNA sequence and comparative analysis of human chromosome 5."
      Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.
      , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
      Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    8. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT THR-117.
    9. Bhattacharya P., Pandey G., Mukherjee K.J.
      Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 18-144, VARIANT THR-117.
      Tissue: Peripheral blood.
    10. "Role of carbohydrate modification in the production and secretion of human granulocyte macrophage colony-stimulating factor in genetically engineered and normal mesenchymal cells."
      Kaushansky K., Lopez J.A., Brown C.B.
      Biochemistry 31:1881-1886(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION AT SER-22; SER-24; SER-26 AND THR-27.
    11. "Novel fold and putative receptor binding site of granulocyte-macrophage colony-stimulating factor."
      Diederichs K., Boone T., Karplus P.A.
      Science 254:1779-1782(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
    12. "Three-dimensional structure of recombinant human granulocyte-macrophage colony-stimulating factor."
      Walter M.R., Cook W.J., Ealick S.E., Nagabhushan T.L., Trotta P.P., Bugg C.E.
      J. Mol. Biol. 224:1075-1085(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
    13. "The structure of the GM-CSF receptor complex reveals a distinct mode of cytokine receptor activation."
      Hansen G., Hercus T.R., McClure B.J., Stomski F.C., Dottore M., Powell J., Ramshaw H., Woodcock J.M., Xu Y., Guthridge M., McKinstry W.J., Lopez A.F., Parker M.W.
      Cell 134:496-507(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF 18-144 IN COMPLEX WITH CSF2RA AND CSF2RB, SUBUNIT, DISULFIDE BOND.

    Entry informationi

    Entry nameiCSF2_HUMAN
    AccessioniPrimary (citable) accession number: P04141
    Secondary accession number(s): Q14CE8, Q2VPI8, Q8NFI6
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1986
    Last sequence update: November 1, 1986
    Last modified: October 1, 2014
    This is version 153 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, Pharmaceutical, Reference proteome

    Documents

    1. Human chromosome 5
      Human chromosome 5: 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