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O95750

- FGF19_HUMAN

UniProt

O95750 - FGF19_HUMAN

Protein

Fibroblast growth factor 19

Gene

FGF19

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 136 (01 Oct 2014)
      Sequence version 1 (01 May 1999)
      Previous versions | rss
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    Functioni

    Involved in the suppression of bile acid biosynthesis through down-regulation of CYP7A1 expression, following positive regulation of the JNK and ERK1/2 cascades. Stimulates glucose uptake in adipocytes. Activity requires the presence of KLB and FGFR4.4 Publications

    GO - Molecular functioni

    1. fibroblast growth factor receptor binding Source: UniProtKB
    2. protein binding Source: UniProtKB

    GO - Biological processi

    1. epidermal growth factor receptor signaling pathway Source: Reactome
    2. Fc-epsilon receptor signaling pathway Source: Reactome
    3. fibroblast growth factor receptor signaling pathway Source: MGI
    4. heart development Source: Ensembl
    5. innate immune response Source: Reactome
    6. insulin receptor signaling pathway Source: Reactome
    7. negative regulation of bile acid biosynthetic process Source: UniProtKB
    8. nervous system development Source: ProtInc
    9. neural crest cell migration Source: Ensembl
    10. neurotrophin TRK receptor signaling pathway Source: Reactome
    11. phosphatidylinositol-mediated signaling Source: Reactome
    12. positive regulation of cell proliferation Source: MGI
    13. positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
    14. positive regulation of glucose import Source: UniProtKB
    15. positive regulation of JNK cascade Source: UniProtKB

    Keywords - Molecular functioni

    Growth factor

    Enzyme and pathway databases

    ReactomeiREACT_111046. betaKlotho-mediated ligand binding.
    REACT_111184. Negative regulation of FGFR signaling.
    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_9452. FGFR4 ligand binding and activation.
    REACT_976. PI3K Cascade.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Fibroblast growth factor 19
    Short name:
    FGF-19
    Gene namesi
    Name:FGF19
    ORF Names:UNQ334/PRO533
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 11

    Organism-specific databases

    HGNCiHGNC:3675. FGF19.

    Subcellular locationi

    GO - Cellular componenti

    1. extracellular region Source: Reactome

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA28114.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 24241 PublicationAdd
    BLAST
    Chaini25 – 216192Fibroblast growth factor 19PRO_0000008993Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi58 ↔ 701 Publication
    Disulfide bondi102 ↔ 1201 Publication

    Keywords - PTMi

    Disulfide bond

    Proteomic databases

    PaxDbiO95750.
    PRIDEiO95750.

    PTM databases

    PhosphoSiteiO95750.

    Expressioni

    Tissue specificityi

    Expressed in fetal brain, cartilage, retina, and adult gall bladder.1 Publication

    Inductioni

    Induced by the bile acids receptor NR1H4 that binds and activates a NR1H4-responsive element within intron 2.1 Publication

    Gene expression databases

    BgeeiO95750.
    CleanExiHS_FGF19.
    GenevestigatoriO95750.

    Organism-specific databases

    HPAiHPA036082.

    Interactioni

    Subunit structurei

    Interacts with FGFR1, FGFR2, FGFR3 and FGFR4. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by KL, KLB and heparan sulfate glycosaminoglycans that function as coreceptors. Interacts with KL; this interaction is direct. Interacts with KLB; this interaction is direct. Interacts with FGFR4 in the presence of heparin, KL or KLB.5 Publications

    Protein-protein interaction databases

    BioGridi115290. 1 interaction.
    DIPiDIP-6039N.
    STRINGi9606.ENSP00000294312.

    Structurei

    Secondary structure

    1
    216
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi42 – 498
    Beta strandi58 – 625
    Beta strandi66 – 738
    Helixi76 – 783
    Beta strandi80 – 867
    Beta strandi89 – 946
    Turni95 – 973
    Beta strandi100 – 1034
    Helixi105 – 1073
    Beta strandi109 – 1146
    Helixi117 – 1204
    Beta strandi121 – 1266
    Beta strandi132 – 1365
    Turni137 – 1404
    Helixi150 – 1523
    Helixi153 – 1564
    Beta strandi165 – 1684

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1PWAX-ray1.30A39-196[»]
    2P23X-ray1.80A/B23-216[»]
    ProteinModelPortaliO95750.
    SMRiO95750. Positions 40-175.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiO95750.

    Family & Domainsi

    Sequence similaritiesi

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiNOG294039.
    HOGENOMiHOG000112572.
    HOVERGENiHBG051611.
    InParanoidiO95750.
    KOiK04358.
    OMAiQYSAGDC.
    OrthoDBiEOG7BS4C1.
    PhylomeDBiO95750.
    TreeFamiTF335872.

    Family and domain databases

    InterProiIPR008996. Cytokine_IL1-like.
    IPR028303. FGF15/FGF19.
    IPR002209. Fibroblast_GF_fam.
    IPR028142. IL-1_fam/FGF_fam.
    [Graphical view]
    PANTHERiPTHR11486. PTHR11486. 1 hit.
    PTHR11486:SF74. PTHR11486:SF74. 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]

    Sequencei

    Sequence statusi: Complete.

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

    O95750-1 [UniParc]FASTAAdd to Basket

    « Hide

    MRSGCVVVHV WILAGLWLAV AGRPLAFSDA GPHVHYGWGD PIRLRHLYTS    50
    GPHGLSSCFL RIRADGVVDC ARGQSAHSLL EIKAVALRTV AIKGVHSVRY 100
    LCMGADGKMQ GLLQYSEEDC AFEEEIRPDG YNVYRSEKHR LPVSLSSAKQ 150
    RQLYKNRGFL PLSHFLPMLP MVPEEPEDLR GHLESDMFSS PLETDSMDPF 200
    GLVTGLEAVR SPSFEK 216
    Length:216
    Mass (Da):24,003
    Last modified:May 1, 1999 - v1
    Checksum:iE0BCBC9C220F9832
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB018122 mRNA. Translation: BAA75500.1.
    AF110400 mRNA. Translation: AAD45973.1.
    AY358302 mRNA. Translation: AAQ88669.1.
    BT006729 mRNA. Translation: AAP35375.1.
    BC017664 mRNA. Translation: AAH17664.1.
    CCDSiCCDS8193.1.
    RefSeqiNP_005108.1. NM_005117.2.
    UniGeneiHs.249200.

    Genome annotation databases

    EnsembliENST00000294312; ENSP00000294312; ENSG00000162344.
    GeneIDi9965.
    KEGGihsa:9965.
    UCSCiuc001opf.3. human.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB018122 mRNA. Translation: BAA75500.1 .
    AF110400 mRNA. Translation: AAD45973.1 .
    AY358302 mRNA. Translation: AAQ88669.1 .
    BT006729 mRNA. Translation: AAP35375.1 .
    BC017664 mRNA. Translation: AAH17664.1 .
    CCDSi CCDS8193.1.
    RefSeqi NP_005108.1. NM_005117.2.
    UniGenei Hs.249200.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1PWA X-ray 1.30 A 39-196 [» ]
    2P23 X-ray 1.80 A/B 23-216 [» ]
    ProteinModelPortali O95750.
    SMRi O95750. Positions 40-175.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 115290. 1 interaction.
    DIPi DIP-6039N.
    STRINGi 9606.ENSP00000294312.

    PTM databases

    PhosphoSitei O95750.

    Proteomic databases

    PaxDbi O95750.
    PRIDEi O95750.

    Protocols and materials databases

    DNASUi 9965.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000294312 ; ENSP00000294312 ; ENSG00000162344 .
    GeneIDi 9965.
    KEGGi hsa:9965.
    UCSCi uc001opf.3. human.

    Organism-specific databases

    CTDi 9965.
    GeneCardsi GC11M069513.
    HGNCi HGNC:3675. FGF19.
    HPAi HPA036082.
    MIMi 603891. gene.
    neXtProti NX_O95750.
    PharmGKBi PA28114.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG294039.
    HOGENOMi HOG000112572.
    HOVERGENi HBG051611.
    InParanoidi O95750.
    KOi K04358.
    OMAi QYSAGDC.
    OrthoDBi EOG7BS4C1.
    PhylomeDBi O95750.
    TreeFami TF335872.

    Enzyme and pathway databases

    Reactomei REACT_111046. betaKlotho-mediated ligand binding.
    REACT_111184. Negative regulation of FGFR signaling.
    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_9452. FGFR4 ligand binding and activation.
    REACT_976. PI3K Cascade.

    Miscellaneous databases

    EvolutionaryTracei O95750.
    GeneWikii FGF19.
    GenomeRNAii 9965.
    NextBioi 37606.
    PROi O95750.
    SOURCEi Search...

    Gene expression databases

    Bgeei O95750.
    CleanExi HS_FGF19.
    Genevestigatori O95750.

    Family and domain databases

    InterProi IPR008996. Cytokine_IL1-like.
    IPR028303. FGF15/FGF19.
    IPR002209. Fibroblast_GF_fam.
    IPR028142. IL-1_fam/FGF_fam.
    [Graphical view ]
    PANTHERi PTHR11486. PTHR11486. 1 hit.
    PTHR11486:SF74. PTHR11486:SF74. 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. "Structure and expression of a novel human FGF, FGF-19, expressed in the fetal brain."
      Nishimura T., Utsunomiya Y., Hoshikawa M., Ohuchi H., Itoh N.
      Biochim. Biophys. Acta 1444:148-151(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Brain.
    2. "FGF-19, a novel fibroblast growth factor with unique specificity for FGFR4."
      Xie M.-H., Holcomb I., Deuel B., Dowd P., Huang A., Vagts A., Foster J., Liang J., Brush J., Gu Q., Hillan K., Goddard A., Gurney A.L.
      Cytokine 11:729-735(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, INTERACTION WITH FGFR4, RECEPTOR SPECIFICITY.
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    4. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
      Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
      Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    5. "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].
      Tissue: Colon.
    6. "Signal peptide prediction based on analysis of experimentally verified cleavage sites."
      Zhang Z., Henzel W.J.
      Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 25-39.
    7. "Definition of a novel growth factor-dependent signal cascade for the suppression of bile acid biosynthesis."
      Holt J.A., Luo G., Billin A.N., Bisi J., McNeill Y.Y., Kozarsky K.F., Donahee M., Wang D.Y., Mansfield T.A., Kliewer S.A., Goodwin B., Jones S.A.
      Genes Dev. 17:1581-1591(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION BY NR1H4, FUNCTION.
    8. "Receptor specificity of the fibroblast growth factor family. The complete mammalian FGF family."
      Zhang X., Ibrahimi O.A., Olsen S.K., Umemori H., Mohammadi M., Ornitz D.M.
      J. Biol. Chem. 281:15694-15700(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH FGFR1; FGFR2; FGFR3 AND FGFR4, FUNCTION IN STIMULATION OF CELL PROLIFERATION.
    9. "Tissue-specific expression of betaKlotho and fibroblast growth factor (FGF) receptor isoforms determines metabolic activity of FGF19 and FGF21."
      Kurosu H., Choi M., Ogawa Y., Dickson A.S., Goetz R., Eliseenkova A.V., Mohammadi M., Rosenblatt K.P., Kliewer S.A., Kuro-o M.
      J. Biol. Chem. 282:26687-26695(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH FGFR4 AND KLB.
    10. "C-terminal tail of FGF19 determines its specificity toward Klotho co-receptors."
      Wu X., Lemon B., Li X., Gupte J., Weiszmann J., Stevens J., Hawkins N., Shen W., Lindberg R., Chen J.-L., Tian H., Li Y.
      J. Biol. Chem. 283:33304-33309(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH FGFR4; KL AND KLB.
    11. "Bile acids activate fibroblast growth factor 19 signaling in human hepatocytes to inhibit cholesterol 7alpha-hydroxylase gene expression."
      Song K.H., Li T., Owsley E., Strom S., Chiang J.Y.
      Hepatology 49:297-305(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    12. "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.
    13. "The crystal structure of fibroblast growth factor (FGF) 19 reveals novel features of the FGF family and offers a structural basis for its unusual receptor affinity."
      Harmer N.J., Pellegrini L., Chirgadze D., Fernandez-Recio J., Blundell T.L.
      Biochemistry 43:629-640(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) OF 39-196, DISULFIDE BONDS.
    14. Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 23-216, INTERACTION WITH KLB.

    Entry informationi

    Entry nameiFGF19_HUMAN
    AccessioniPrimary (citable) accession number: O95750
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 1, 2000
    Last sequence update: May 1, 1999
    Last modified: October 1, 2014
    This is version 136 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

    Miscellaneous

    Contrarily to other members of the family that can bind several FGF receptors FGF19 is specific for FGFR4.

    Keywords - Technical termi

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