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P08620

- FGF4_HUMAN

UniProt

P08620 - FGF4_HUMAN

Protein

Fibroblast growth factor 4

Gene

FGF4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 143 (01 Oct 2014)
      Sequence version 1 (01 Aug 1988)
      Previous versions | rss
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    Functioni

    Plays an important role in the regulation of embryonic development, cell proliferation, and cell differentiation. Required for normal limb and cardiac valve development during embryogenesis.1 Publication

    GO - Molecular functioni

    1. growth factor activity Source: ProtInc
    2. heparin binding Source: UniProtKB-KW

    GO - Biological processi

    1. apoptotic process involved in morphogenesis Source: Ensembl
    2. cartilage condensation Source: Ensembl
    3. cell-cell signaling Source: ProtInc
    4. chondroblast differentiation Source: UniProtKB
    5. cranial suture morphogenesis Source: Ensembl
    6. embryonic hindlimb morphogenesis Source: Ensembl
    7. epidermal growth factor receptor signaling pathway Source: Reactome
    8. Fc-epsilon receptor signaling pathway Source: Reactome
    9. fibroblast growth factor receptor signaling pathway Source: MGI
    10. innate immune response Source: Reactome
    11. insulin receptor signaling pathway Source: Reactome
    12. mesenchymal cell proliferation Source: UniProtKB
    13. negative regulation of apoptotic process Source: Ensembl
    14. neurotrophin TRK receptor signaling pathway Source: Reactome
    15. odontogenesis of dentin-containing tooth Source: Ensembl
    16. phosphatidylinositol-mediated signaling Source: Reactome
    17. positive regulation of cell division Source: UniProtKB-KW
    18. positive regulation of cell proliferation Source: MGI
    19. positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
    20. positive regulation of protein phosphorylation Source: Ensembl
    21. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
    22. signal transduction Source: ProtInc
    23. stem cell maintenance Source: Ensembl

    Keywords - Molecular functioni

    Developmental protein, Growth factor, Mitogen

    Keywords - Biological processi

    Differentiation

    Keywords - Ligandi

    Heparin-binding

    Enzyme and pathway databases

    ReactomeiREACT_111184. Negative regulation of FGFR signaling.
    REACT_120863. Activated point mutants of FGFR2.
    REACT_121153. Signaling by activated point mutants of FGFR1.
    REACT_121249. Signaling by FGFR3 mutants.
    REACT_121337. Signaling by activated point mutants of FGFR3.
    REACT_121398. Signaling by FGFR mutants.
    REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_21247. FRS2-mediated cascade.
    REACT_21270. PI-3K cascade.
    REACT_21310. Phospholipase C-mediated cascade.
    REACT_21374. SHC-mediated cascade.
    REACT_75829. PIP3 activates AKT signaling.
    REACT_9413. FGFR2c ligand binding and activation.
    REACT_9452. FGFR4 ligand binding and activation.
    REACT_9510. FGFR3c ligand binding and activation.
    REACT_9515. FGFR1c ligand binding and activation.
    REACT_976. PI3K Cascade.
    SignaLinkiP08620.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Fibroblast growth factor 4
    Short name:
    FGF-4
    Alternative name(s):
    Heparin secretory-transforming protein 1
    Short name:
    HST
    Short name:
    HST-1
    Short name:
    HSTF-1
    Heparin-binding growth factor 4
    Short name:
    HBGF-4
    Transforming protein KS3
    Gene namesi
    Name:FGF4
    Synonyms:HST, HSTF1, KS3
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 11

    Organism-specific databases

    HGNCiHGNC:3682. FGF4.

    Subcellular locationi

    Secreted Curated

    GO - Cellular componenti

    1. cytosol Source: Ensembl
    2. extracellular region Source: Reactome
    3. nucleus Source: Ensembl

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Keywords - Diseasei

    Proto-oncogene

    Organism-specific databases

    PharmGKBiPA28121.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 3030Sequence AnalysisAdd
    BLAST
    Chaini31 – 206176Fibroblast growth factor 4PRO_0000008953Add
    BLAST

    Proteomic databases

    PaxDbiP08620.
    PRIDEiP08620.

    PTM databases

    PhosphoSiteiP08620.

    Expressioni

    Gene expression databases

    BgeeiP08620.
    CleanExiHS_FGF4.
    GenevestigatoriP08620.

    Organism-specific databases

    HPAiHPA011209.

    Interactioni

    Subunit structurei

    Interacts with FGFR1, FGFR2, FGFR3 and FGFR4. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by heparan sulfate glycosaminoglycans that function as coreceptors.1 Publication

    Protein-protein interaction databases

    DIPiDIP-4017N.
    STRINGi9606.ENSP00000168712.

    Structurei

    Secondary structure

    1
    206
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi82 – 887
    Beta strandi94 – 985
    Beta strandi104 – 1096
    Helixi112 – 1143
    Beta strandi116 – 1227
    Beta strandi125 – 1306
    Turni131 – 1344
    Beta strandi135 – 1395
    Beta strandi145 – 1506
    Beta strandi155 – 1617
    Helixi163 – 1653
    Beta strandi167 – 1748
    Beta strandi185 – 1873
    Helixi190 – 1923
    Helixi198 – 2003
    Beta strandi202 – 2054

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1IJTX-ray1.80A79-206[»]
    ProteinModelPortaliP08620.
    SMRiP08620. Positions 79-206.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP08620.

    Family & Domainsi

    Sequence similaritiesi

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiNOG290420.
    HOGENOMiHOG000236341.
    HOVERGENiHBG007580.
    InParanoidiP08620.
    KOiK04358.
    OMAiYNAYESH.
    OrthoDBiEOG7992S1.
    PhylomeDBiP08620.
    TreeFamiTF317805.

    Family and domain databases

    InterProiIPR008996. Cytokine_IL1-like.
    IPR028239. FGF4.
    IPR002209. Fibroblast_GF_fam.
    IPR028142. IL-1_fam/FGF_fam.
    [Graphical view]
    PANTHERiPTHR11486. PTHR11486. 1 hit.
    PTHR11486:SF31. PTHR11486:SF31. 1 hit.
    PfamiPF00167. FGF. 1 hit.
    [Graphical view]
    PRINTSiPR00263. HBGFFGF.
    PR00262. IL1HBGF.
    SMARTiSM00442. FGF. 1 hit.
    [Graphical view]
    SUPFAMiSSF50353. SSF50353. 1 hit.
    PROSITEiPS00247. HBGF_FGF. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

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

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P08620-1) [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

    MSGPGTAAVA LLPAVLLALL APWAGRGGAA APTAPNGTLE AELERRWESL    50
    VALSLARLPV AAQPKEAAVQ SGAGDYLLGI KRLRRLYCNV GIGFHLQALP 100
    DGRIGGAHAD TRDSLLELSP VERGVVSIFG VASRFFVAMS SKGKLYGSPF 150
    FTDECTFKEI LLPNNYNAYE SYKYPGMFIA LSKNGKTKKG NRVSPTMKVT 200
    HFLPRL 206
    Length:206
    Mass (Da):22,048
    Last modified:August 1, 1988 - v1
    Checksum:iC7FD54A0272A1569
    GO
    Isoform 2 (identifier: P08620-2) [UniParc]FASTAAdd to Basket

    Also known as: FGF4si

    The sequence of this isoform differs from the canonical sequence as follows:
         114-206: SLLELSPVER...MKVTHFLPRL → TLLHR

    Note: Antagonist of isoform 1, shutting down FGF4-induced Erk1/2 phosphorylation.

    Show »
    Length:118
    Mass (Da):12,237
    Checksum:iAAA97FBB8C667D7F
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei114 – 20693SLLEL…FLPRL → TLLHR in isoform 2. 1 PublicationVSP_053541Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    FJ456981 mRNA. Translation: ACJ68447.1.
    J02986 Genomic DNA. Translation: AAB59555.1.
    M17446 mRNA. Translation: AAA59473.1.
    CCDSiCCDS8194.1. [P08620-1]
    PIRiA28417. TVHUHS.
    RefSeqiNP_001998.1. NM_002007.2. [P08620-1]
    XP_005273904.1. XM_005273847.1. [P08620-2]
    XP_006718538.1. XM_006718475.1. [P08620-1]
    UniGeneiHs.1755.

    Genome annotation databases

    EnsembliENST00000168712; ENSP00000168712; ENSG00000075388. [P08620-1]
    GeneIDi2249.
    KEGGihsa:2249.
    UCSCiuc001opg.1. human. [P08620-1]

    Polymorphism databases

    DMDMi122750.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    FJ456981 mRNA. Translation: ACJ68447.1 .
    J02986 Genomic DNA. Translation: AAB59555.1 .
    M17446 mRNA. Translation: AAA59473.1 .
    CCDSi CCDS8194.1. [P08620-1 ]
    PIRi A28417. TVHUHS.
    RefSeqi NP_001998.1. NM_002007.2. [P08620-1 ]
    XP_005273904.1. XM_005273847.1. [P08620-2 ]
    XP_006718538.1. XM_006718475.1. [P08620-1 ]
    UniGenei Hs.1755.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1IJT X-ray 1.80 A 79-206 [» ]
    ProteinModelPortali P08620.
    SMRi P08620. Positions 79-206.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    DIPi DIP-4017N.
    STRINGi 9606.ENSP00000168712.

    Chemistry

    DrugBanki DB00686. Pentosan Polysulfate.

    PTM databases

    PhosphoSitei P08620.

    Polymorphism databases

    DMDMi 122750.

    Proteomic databases

    PaxDbi P08620.
    PRIDEi P08620.

    Protocols and materials databases

    DNASUi 2249.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000168712 ; ENSP00000168712 ; ENSG00000075388 . [P08620-1 ]
    GeneIDi 2249.
    KEGGi hsa:2249.
    UCSCi uc001opg.1. human. [P08620-1 ]

    Organism-specific databases

    CTDi 2249.
    GeneCardsi GC11M069588.
    HGNCi HGNC:3682. FGF4.
    HPAi HPA011209.
    MIMi 164980. gene.
    neXtProti NX_P08620.
    PharmGKBi PA28121.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG290420.
    HOGENOMi HOG000236341.
    HOVERGENi HBG007580.
    InParanoidi P08620.
    KOi K04358.
    OMAi YNAYESH.
    OrthoDBi EOG7992S1.
    PhylomeDBi P08620.
    TreeFami TF317805.

    Enzyme and pathway databases

    Reactomei REACT_111184. Negative regulation of FGFR signaling.
    REACT_120863. Activated point mutants of FGFR2.
    REACT_121153. Signaling by activated point mutants of FGFR1.
    REACT_121249. Signaling by FGFR3 mutants.
    REACT_121337. Signaling by activated point mutants of FGFR3.
    REACT_121398. Signaling by FGFR mutants.
    REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_21247. FRS2-mediated cascade.
    REACT_21270. PI-3K cascade.
    REACT_21310. Phospholipase C-mediated cascade.
    REACT_21374. SHC-mediated cascade.
    REACT_75829. PIP3 activates AKT signaling.
    REACT_9413. FGFR2c ligand binding and activation.
    REACT_9452. FGFR4 ligand binding and activation.
    REACT_9510. FGFR3c ligand binding and activation.
    REACT_9515. FGFR1c ligand binding and activation.
    REACT_976. PI3K Cascade.
    SignaLinki P08620.

    Miscellaneous databases

    EvolutionaryTracei P08620.
    GeneWikii FGF4.
    GenomeRNAii 2249.
    NextBioi 35478625.
    PROi P08620.
    SOURCEi Search...

    Gene expression databases

    Bgeei P08620.
    CleanExi HS_FGF4.
    Genevestigatori P08620.

    Family and domain databases

    InterProi IPR008996. Cytokine_IL1-like.
    IPR028239. FGF4.
    IPR002209. Fibroblast_GF_fam.
    IPR028142. IL-1_fam/FGF_fam.
    [Graphical view ]
    PANTHERi PTHR11486. PTHR11486. 1 hit.
    PTHR11486:SF31. PTHR11486:SF31. 1 hit.
    Pfami PF00167. FGF. 1 hit.
    [Graphical view ]
    PRINTSi PR00263. HBGFFGF.
    PR00262. IL1HBGF.
    SMARTi SM00442. FGF. 1 hit.
    [Graphical view ]
    SUPFAMi SSF50353. SSF50353. 1 hit.
    PROSITEi PS00247. HBGF_FGF. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Fibroblast growth factor 4 and its novel splice isoform have opposing effects on the maintenance of human embryonic stem cell self-renewal."
      Mayshar Y., Rom E., Chumakov I., Kronman A., Yayon A., Benvenisty N.
      Stem Cells 26:767-774(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING.
    2. "Genomic sequence of hst, a transforming gene encoding a protein homologous to fibroblast growth factors and the int-2-encoded protein."
      Yoshida T., Miyagawa K., Odagiri H., Sakamoto H., Little P.F.R., Terada M., Sugimura T.
      Proc. Natl. Acad. Sci. U.S.A. 84:7305-7309(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    3. "cDNA sequence of human transforming gene hst and identification of the coding sequence required for transforming activity."
      Taira M., Yoshida T., Miyagawa K., Sakamoto H., Terada M., Sugimura T.
      Proc. Natl. Acad. Sci. U.S.A. 84:2980-2984(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    4. "An oncogene isolated by transfection of Kaposi's sarcoma DNA encodes a growth factor that is a member of the FGF family."
      Delli-Bovi P., Curatola A.M., Kern F.G., Greco A., Ittmann M., Basilico C.
      Cell 50:729-737(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    5. Cited for: INTERACTION WITH FGFR1; FGFR2; FGFR3 AND FGFR4, FUNCTION IN CELL PROLIFERATION.
    6. "Fibroblast growth factor signalling: from development to cancer."
      Turner N., Grose R.
      Nat. Rev. Cancer 10:116-129(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    7. "Identification of receptor and heparin binding sites in fibroblast growth factor 4 by structure-based mutagenesis."
      Bellosta P., Iwahori A., Plotnikov A.N., Eliseenkova A.V., Basilico C., Mohammadi M.
      Mol. Cell. Biol. 21:5946-5957(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 79-206.

    Entry informationi

    Entry nameiFGF4_HUMAN
    AccessioniPrimary (citable) accession number: P08620
    Secondary accession number(s): B7U994
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1988
    Last sequence update: August 1, 1988
    Last modified: October 1, 2014
    This is version 143 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, Reference proteome

    Documents

    1. Human chromosome 11
      Human chromosome 11: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3