O95750 (FGF19_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Fibroblast growth factor 19
Short name=FGF-19

Gene names

Name:	FGF19
ORF Names:	UNQ334/PRO533

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	216 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 component	Secreted
Domain	Signal
Molecular function	Growth factor
PTM	Disulfide bond
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	fibroblast growth factor receptor signaling pathway Inferred from genetic interaction PubMed 18187602. Source: MGI heart development Inferred from electronic annotation. Source: Compara 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: Compara 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_component	extracellular region Traceable author statement. Source: Reactome
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 24

24

Ref.6

Chain

25 – 216

192

Fibroblast growth factor 19

PRO_0000008993

Amino acid modifications

Disulfide bond

58 ↔ 70

Ref.13

Disulfide bond

102 ↔ 120

Ref.13

Secondary structure

1

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216

Helix Strand Turn

Details...

Beta strand

42 – 49

8

Beta strand

58 – 62

5

Beta strand

66 – 73

8

Helix

76 – 78

3

Beta strand

80 – 86

7

Beta strand

89 – 94

6

Turn

95 – 97

3

Beta strand

100 – 103

4

Helix

105 – 107

3

Beta strand

109 – 114

6

Helix

117 – 120

4

Beta strand

121 – 126

6

Beta strand

132 – 136

5

Turn

137 – 140

4

Helix

150 – 152

3

Helix

153 – 156

4

Beta strand

165 – 168

4

Sequences

	Sequence		Length	Mass (Da)
	O95750 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: E0BCBC9C220F9832	FASTA	216	24,003
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.

IPI

IPI00032908.

RefSeq

NP_005108.1. NM_005117.2.

UniGene

Hs.249200.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1PWA	X-ray	1.30	A	39-196	[»]
2P23	X-ray	1.80	A/B	23-216	[»]

ProteinModelPortal

O95750.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-6039N.

STRING

9606.ENSP00000294312.

PTM databases

PhosphoSite

O95750.

Proteomic databases

PaxDb

O95750.

PRIDE

O95750.

Protocols and materials databases

DNASU

9965.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000294312; ENSP00000294312; ENSG00000162344.

GeneID

9965.

KEGG

hsa:9965.

UCSC

uc001opf.3. human.

Organism-specific databases

CTD

9965.

GeneCards

GC11M069513.

HGNC

HGNC:3675. FGF19.

HPA

HPA036082.

MIM

603891. gene.

neXtProt

NX_O95750.

PharmGKB

PA28114.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG294039.

HOGENOM

HOG000112572.

HOVERGEN

HBG051611.

InParanoid

O95750.

KO

K04358.

OMA

DGYNVYR.

OrthoDB

EOG45X7X5.

PhylomeDB

O95750.

Enzyme and pathway databases

Pathway_Interaction_DB

fgf_pathway. FGF signaling pathway.

Reactome

REACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_6900. Immune System.

Gene expression databases

Bgee

O95750.

CleanEx

HS_FGF19.

Genevestigator

O95750.

GermOnline

ENSG00000162344. Homo sapiens.

Family and domain databases

InterPro

IPR008996. Cytokine_IL1-like.
IPR017338. Fibroblast_GF_15/19/21.
IPR002209. GF_heparin-bd.
IPR002348. IL1_HBGF.
[Graphical view]

PANTHER

PTHR11486. PTHR11486. 1 hit.

Pfam

PF00167. FGF. 1 hit.
[Graphical view]

PIRSF

PIRSF037961. FGF-19_FGF-21. 1 hit.

PRINTS

PR00263. HBGFFGF.
PR00262. IL1HBGF.

SMART

SM00442. FGF. 1 hit.
[Graphical view]

SUPFAM

SSF50353. Cytok_IL1_like. 1 hit.

PROSITE

PS00247. HBGF_FGF. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

O95750.

GenomeRNAi

9965.

NextBio

37606.

SOURCE

Search...

Entry information

Entry name

FGF19_HUMAN

Accession

Primary (citable) accession number: O95750

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	May 1, 1999
Last modified:	May 1, 2013
This is version 123 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.