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Protein

Fibroblast growth factor 19

Gene

FGF19

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

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

  • fibroblast growth factor receptor binding Source: UniProtKB

GO - Biological processi

  • epidermal growth factor receptor signaling pathway Source: Reactome
  • Fc-epsilon receptor signaling pathway Source: Reactome
  • fibroblast growth factor receptor signaling pathway Source: MGI
  • heart development Source: Ensembl
  • innate immune response Source: Reactome
  • insulin receptor signaling pathway Source: Reactome
  • negative regulation of bile acid biosynthetic process Source: UniProtKB
  • negative regulation of gene expression Source: UniProtKB
  • nervous system development Source: ProtInc
  • neural crest cell migration Source: Ensembl
  • neurotrophin TRK receptor signaling pathway Source: Reactome
  • phosphatidylinositol-mediated signaling Source: Reactome
  • positive regulation of cell proliferation Source: MGI
  • positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
  • positive regulation of glucose import Source: UniProtKB
  • positive regulation of JNK cascade Source: UniProtKB
  • positive regulation of protein phosphorylation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Growth factor

Enzyme and pathway databases

ReactomeiREACT_111046. betaKlotho-mediated ligand binding.
REACT_147727. Constitutive Signaling by Aberrant PI3K in Cancer.
REACT_355159. SHC-mediated cascade:FGFR4.
REACT_355216. Phospholipase C-mediated cascade, FGFR4.
REACT_355304. PI-3K cascade:FGFR4.
REACT_355580. FRS2-mediated FGFR4 signaling.
REACT_355588. Negative regulation of FGFR4 signaling.
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 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:3675. FGF19.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA28114.

Polymorphism and mutation databases

BioMutaiFGF19.

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.
GenevisibleiO95750. HS.

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 – 498Combined sources
Beta strandi58 – 625Combined sources
Beta strandi66 – 738Combined sources
Helixi76 – 783Combined sources
Beta strandi80 – 867Combined sources
Beta strandi89 – 946Combined sources
Turni95 – 973Combined sources
Beta strandi100 – 1034Combined sources
Helixi105 – 1073Combined sources
Beta strandi109 – 1146Combined sources
Helixi117 – 1204Combined sources
Beta strandi121 – 1266Combined sources
Beta strandi132 – 1365Combined sources
Turni137 – 1404Combined sources
Helixi150 – 1523Combined sources
Helixi153 – 1564Combined sources
Beta strandi165 – 1684Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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.
GeneTreeiENSGT00530000063469.
HOGENOMiHOG000112572.
HOVERGENiHBG051611.
InParanoidiO95750.
KOiK04358.
OMAiSEEDCAF.
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.
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

        10         20         30         40         50
MRSGCVVVHV WILAGLWLAV AGRPLAFSDA GPHVHYGWGD PIRLRHLYTS
60 70 80 90 100
GPHGLSSCFL RIRADGVVDC ARGQSAHSLL EIKAVALRTV AIKGVHSVRY
110 120 130 140 150
LCMGADGKMQ GLLQYSEEDC AFEEEIRPDG YNVYRSEKHR LPVSLSSAKQ
160 170 180 190 200
RQLYKNRGFL PLSHFLPMLP MVPEEPEDLR GHLESDMFSS PLETDSMDPF
210
GLVTGLEAVR SPSFEK
Length:216
Mass (Da):24,003
Last modified:May 1, 1999 - v1
Checksum:iE0BCBC9C220F9832
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

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

Protein-protein interaction databases

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

PTM databases

PhosphoSiteiO95750.

Polymorphism and mutation databases

BioMutaiFGF19.

Proteomic databases

PaxDbiO95750.
PRIDEiO95750.

Protocols and materials databases

DNASUi9965.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi9965.
GeneCardsiGC11M069513.
HGNCiHGNC:3675. FGF19.
HPAiHPA036082.
MIMi603891. gene.
neXtProtiNX_O95750.
PharmGKBiPA28114.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG294039.
GeneTreeiENSGT00530000063469.
HOGENOMiHOG000112572.
HOVERGENiHBG051611.
InParanoidiO95750.
KOiK04358.
OMAiSEEDCAF.
OrthoDBiEOG7BS4C1.
PhylomeDBiO95750.
TreeFamiTF335872.

Enzyme and pathway databases

ReactomeiREACT_111046. betaKlotho-mediated ligand binding.
REACT_147727. Constitutive Signaling by Aberrant PI3K in Cancer.
REACT_355159. SHC-mediated cascade:FGFR4.
REACT_355216. Phospholipase C-mediated cascade, FGFR4.
REACT_355304. PI-3K cascade:FGFR4.
REACT_355580. FRS2-mediated FGFR4 signaling.
REACT_355588. Negative regulation of FGFR4 signaling.
REACT_75829. PIP3 activates AKT signaling.
REACT_9452. FGFR4 ligand binding and activation.
REACT_976. PI3K Cascade.

Miscellaneous databases

EvolutionaryTraceiO95750.
GeneWikiiFGF19.
GenomeRNAii9965.
NextBioi37606.
PROiO95750.
SOURCEiSearch...

Gene expression databases

BgeeiO95750.
CleanExiHS_FGF19.
GenevisibleiO95750. HS.

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.
PRINTSiPR00263. HBGFFGF.
PR00262. IL1HBGF.
SMARTiSM00442. FGF. 1 hit.
[Graphical view]
SUPFAMiSSF50353. SSF50353. 1 hit.
PROSITEiPS00247. HBGF_FGF. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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: June 24, 2015
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

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.