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O95750 (FGF19_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 131. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Fibroblast growth factor 19

Short name=FGF-19
Gene names
Name:FGF19
ORF Names:UNQ334/PRO533
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length216 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.7 Ref.8 Ref.9 Ref.11

Subunit structure

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. Ref.2 Ref.8 Ref.9 Ref.10 Ref.14

Subcellular location

Secreted.

Tissue specificity

Expressed in fetal brain, cartilage, retina, and adult gall bladder. Ref.2

Induction

Induced by the bile acids receptor NR1H4 that binds and activates a NR1H4-responsive element within intron 2. Ref.7

Miscellaneous

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

Sequence similarities

Belongs to the heparin-binding growth factors family.

Ontologies

Keywords
   Cellular componentSecreted
   DomainSignal
   Molecular functionGrowth factor
   PTMDisulfide bond
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processFc-epsilon receptor signaling pathway

Traceable author statement. Source: Reactome

epidermal growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

fibroblast growth factor receptor signaling pathway

Inferred from genetic interaction PubMed 18187602. Source: MGI

heart development

Inferred from electronic annotation. Source: Ensembl

innate immune response

Traceable author statement. Source: Reactome

insulin receptor signaling pathway

Traceable author statement. Source: Reactome

negative regulation of bile acid biosynthetic process

Inferred from direct assay Ref.7. Source: UniProtKB

nervous system development

Traceable author statement Ref.1. Source: ProtInc

neural crest cell migration

Inferred from electronic annotation. Source: Ensembl

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

phosphatidylinositol-mediated signaling

Traceable author statement. Source: Reactome

positive regulation of ERK1 and ERK2 cascade

Inferred from direct assay Ref.9. Source: UniProtKB

positive regulation of JNK cascade

Inferred from direct assay Ref.7. Source: UniProtKB

positive regulation of cell proliferation

Inferred from genetic interaction PubMed 18187602. Source: MGI

positive regulation of glucose import

Inferred from direct assay Ref.9. Source: UniProtKB

   Cellular_componentextracellular region

Traceable author statement. Source: Reactome

   Molecular_functionfibroblast growth factor receptor binding

Inferred from physical interaction Ref.2. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424 Ref.6
Chain25 – 216192Fibroblast growth factor 19
PRO_0000008993

Amino acid modifications

Disulfide bond58 ↔ 70 Ref.13
Disulfide bond102 ↔ 120 Ref.13

Secondary structure

............................... 216
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O95750 [UniParc].

Last modified May 1, 1999. Version 1.
Checksum: E0BCBC9C220F9832

FASTA21624,003
        10         20         30         40         50         60 
MRSGCVVVHV WILAGLWLAV AGRPLAFSDA GPHVHYGWGD PIRLRHLYTS GPHGLSSCFL 

        70         80         90        100        110        120 
RIRADGVVDC ARGQSAHSLL EIKAVALRTV AIKGVHSVRY LCMGADGKMQ GLLQYSEEDC 

       130        140        150        160        170        180 
AFEEEIRPDG YNVYRSEKHR LPVSLSSAKQ RQLYKNRGFL PLSHFLPMLP MVPEEPEDLR 

       190        200        210 
GHLESDMFSS PLETDSMDPF GLVTGLEAVR SPSFEK 

« Hide

References

« Hide 'large scale' references
[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]"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. expand/collapse author list , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.
Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract]
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]"Molecular insights into the klotho-dependent, endocrine mode of action of fibroblast growth factor 19 subfamily members."
Goetz R., Beenken A., Ibrahimi O.A., Kalinina J., Olsen S.K., Eliseenkova A.V., Xu C., Neubert T.A., Zhang F., Linhardt R.J., Yu X., White K.E., Inagaki T., Kliewer S.A., Yamamoto M., Kurosu H., Ogawa Y., Kuro-o M. expand/collapse author list , Lanske B., Razzaque M.S., Mohammadi M.
Mol. Cell. Biol. 27:3417-3428(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 23-216, INTERACTION WITH KLB.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_005108.1. NM_005117.2.
UniGeneHs.249200.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1PWAX-ray1.30A39-196[»]
2P23X-ray1.80A/B23-216[»]
ProteinModelPortalO95750.
SMRO95750. Positions 40-175.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115290. 1 interaction.
DIPDIP-6039N.
STRING9606.ENSP00000294312.

PTM databases

PhosphoSiteO95750.

Proteomic databases

PaxDbO95750.
PRIDEO95750.

Protocols and materials databases

DNASU9965.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000294312; ENSP00000294312; ENSG00000162344.
GeneID9965.
KEGGhsa:9965.
UCSCuc001opf.3. human.

Organism-specific databases

CTD9965.
GeneCardsGC11M069513.
HGNCHGNC:3675. FGF19.
HPAHPA036082.
MIM603891. gene.
neXtProtNX_O95750.
PharmGKBPA28114.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG294039.
HOGENOMHOG000112572.
HOVERGENHBG051611.
InParanoidO95750.
KOK04358.
OMASEEDCAF.
OrthoDBEOG7BS4C1.
PhylomeDBO95750.
TreeFamTF335872.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_6900. Immune System.

Gene expression databases

BgeeO95750.
CleanExHS_FGF19.
GenevestigatorO95750.

Family and domain databases

InterProIPR008996. Cytokine_IL1-like.
IPR028302. FGF19.
IPR002209. Fibroblast_GF_fam.
IPR028142. IL-1_fam/FGF_fam.
[Graphical view]
PANTHERPTHR11486. PTHR11486. 1 hit.
PTHR11486:SF7. PTHR11486:SF7. 1 hit.
PfamPF00167. FGF. 1 hit.
[Graphical view]
PRINTSPR00263. HBGFFGF.
PR00262. IL1HBGF.
SMARTSM00442. FGF. 1 hit.
[Graphical view]
SUPFAMSSF50353. SSF50353. 1 hit.
PROSITEPS00247. HBGF_FGF. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO95750.
GeneWikiFGF19.
GenomeRNAi9965.
NextBio37606.
PROO95750.
SOURCESearch...

Entry information

Entry nameFGF19_HUMAN
AccessionPrimary (citable) accession number: O95750
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: May 1, 1999
Last modified: April 16, 2014
This is version 131 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM