ID FGF19_HUMAN Reviewed; 216 AA. AC O95750; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1999, sequence version 1. DT 13-FEB-2019, entry version 173. DE RecName: Full=Fibroblast growth factor 19; DE Short=FGF-19; DE Flags: Precursor; GN Name=FGF19; ORFNames=UNQ334/PRO533; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Brain; RX PubMed=9931477; DOI=10.1016/S0167-4781(98)00255-3; RA Nishimura T., Utsunomiya Y., Hoshikawa M., Ohuchi H., Itoh N.; RT "Structure and expression of a novel human FGF, FGF-19, expressed in RT the fetal brain."; RL Biochim. Biophys. Acta 1444:148-151(1999). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, INTERACTION WITH RP FGFR4, AND RECEPTOR SPECIFICITY. RX PubMed=10525310; DOI=10.1006/cyto.1999.0485; RA Xie M.-H., Holcomb I., Deuel B., Dowd P., Huang A., Vagts A., RA Foster J., Liang J., Brush J., Gu Q., Hillan K., Goddard A., RA Gurney A.L.; RT "FGF-19, a novel fibroblast growth factor with unique specificity for RT FGFR4."; RL Cytokine 11:729-735(1999). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., RA Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., RA Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., RA Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., RA Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., RA Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., RA Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale RT effort to identify novel human secreted and transmembrane proteins: a RT bioinformatics assessment."; RL Genome Res. 13:2265-2270(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor RT vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Colon; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP PROTEIN SEQUENCE OF 25-39. RX PubMed=15340161; DOI=10.1110/ps.04682504; RA Zhang Z., Henzel W.J.; RT "Signal peptide prediction based on analysis of experimentally RT verified cleavage sites."; RL Protein Sci. 13:2819-2824(2004). RN [7] RP INDUCTION BY NR1H4, AND FUNCTION. RX PubMed=12815072; DOI=10.1101/gad.1083503; RA Holt J.A., Luo G., Billin A.N., Bisi J., McNeill Y.Y., Kozarsky K.F., RA Donahee M., Wang D.Y., Mansfield T.A., Kliewer S.A., Goodwin B., RA Jones S.A.; RT "Definition of a novel growth factor-dependent signal cascade for the RT suppression of bile acid biosynthesis."; RL Genes Dev. 17:1581-1591(2003). RN [8] RP INTERACTION WITH FGFR1; FGFR2; FGFR3 AND FGFR4, AND FUNCTION IN RP STIMULATION OF CELL PROLIFERATION. RX PubMed=16597617; DOI=10.1074/jbc.M601252200; RA Zhang X., Ibrahimi O.A., Olsen S.K., Umemori H., Mohammadi M., RA Ornitz D.M.; RT "Receptor specificity of the fibroblast growth factor family. The RT complete mammalian FGF family."; RL J. Biol. Chem. 281:15694-15700(2006). RN [9] RP FUNCTION, AND INTERACTION WITH FGFR4 AND KLB. RX PubMed=17623664; DOI=10.1074/jbc.M704165200; RA Kurosu H., Choi M., Ogawa Y., Dickson A.S., Goetz R., RA Eliseenkova A.V., Mohammadi M., Rosenblatt K.P., Kliewer S.A., RA Kuro-o M.; RT "Tissue-specific expression of betaKlotho and fibroblast growth factor RT (FGF) receptor isoforms determines metabolic activity of FGF19 and RT FGF21."; RL J. Biol. Chem. 282:26687-26695(2007). RN [10] RP INTERACTION WITH FGFR4; KL AND KLB. RX PubMed=18829467; DOI=10.1074/jbc.M803319200; RA Wu X., Lemon B., Li X., Gupte J., Weiszmann J., Stevens J., RA Hawkins N., Shen W., Lindberg R., Chen J.-L., Tian H., Li Y.; RT "C-terminal tail of FGF19 determines its specificity toward Klotho co- RT receptors."; RL J. Biol. Chem. 283:33304-33309(2008). RN [11] RP FUNCTION. RX PubMed=19085950; DOI=10.1002/hep.22627; RA Song K.H., Li T., Owsley E., Strom S., Chiang J.Y.; RT "Bile acids activate fibroblast growth factor 19 signaling in human RT hepatocytes to inhibit cholesterol 7alpha-hydroxylase gene RT expression."; RL Hepatology 49:297-305(2009). RN [12] RP REVIEW. RX PubMed=20094046; DOI=10.1038/nrc2780; RA Turner N., Grose R.; RT "Fibroblast growth factor signalling: from development to cancer."; RL Nat. Rev. Cancer 10:116-129(2010). RN [13] RP INTERACTION WITH MALRD1. RX PubMed=23747249; DOI=10.1016/j.cmet.2013.04.007; RA Vergnes L., Lee J.M., Chin R.G., Auwerx J., Reue K.; RT "Diet1 functions in the FGF15/19 enterohepatic signaling axis to RT modulate bile acid and lipid levels."; RL Cell Metab. 17:916-928(2013). RN [14] RP X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) OF 39-196, AND DISULFIDE BONDS. RX PubMed=14730967; DOI=10.1021/bi035320k; RA Harmer N.J., Pellegrini L., Chirgadze D., Fernandez-Recio J., RA Blundell T.L.; RT "The crystal structure of fibroblast growth factor (FGF) 19 reveals RT novel features of the FGF family and offers a structural basis for its RT unusual receptor affinity."; RL Biochemistry 43:629-640(2004). RN [15] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 23-216, AND INTERACTION WITH RP KLB. RX PubMed=17339340; DOI=10.1128/MCB.02249-06; RA Goetz R., Beenken A., Ibrahimi O.A., Kalinina J., Olsen S.K., RA Eliseenkova A.V., Xu C., Neubert T.A., Zhang F., Linhardt R.J., Yu X., RA White K.E., Inagaki T., Kliewer S.A., Yamamoto M., Kurosu H., RA Ogawa Y., Kuro-o M., Lanske B., Razzaque M.S., Mohammadi M.; RT "Molecular insights into the klotho-dependent, endocrine mode of RT action of fibroblast growth factor 19 subfamily members."; RL Mol. Cell. Biol. 27:3417-3428(2007). CC -!- FUNCTION: Involved in the suppression of bile acid biosynthesis CC through down-regulation of CYP7A1 expression, following positive CC regulation of the JNK and ERK1/2 cascades. Stimulates glucose CC uptake in adipocytes. Activity requires the presence of KLB and CC FGFR4. {ECO:0000269|PubMed:12815072, ECO:0000269|PubMed:16597617, CC ECO:0000269|PubMed:17623664, ECO:0000269|PubMed:19085950}. CC -!- SUBUNIT: Interacts with FGFR1, FGFR2, FGFR3 and FGFR4. Affinity CC between fibroblast growth factors (FGFs) and their receptors is CC increased by KL, KLB and heparan sulfate glycosaminoglycans that CC function as coreceptors. Interacts with KL; this interaction is CC direct. Interacts with KLB; this interaction is direct. Interacts CC with FGFR4 in the presence of heparin, KL or KLB. Interacts with CC MALRD1 (PubMed:23747249). {ECO:0000269|PubMed:10525310, CC ECO:0000269|PubMed:16597617, ECO:0000269|PubMed:17339340, CC ECO:0000269|PubMed:17623664, ECO:0000269|PubMed:18829467, CC ECO:0000269|PubMed:23747249}. CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- TISSUE SPECIFICITY: Expressed in fetal brain, cartilage, retina, CC and adult gall bladder. {ECO:0000269|PubMed:10525310}. CC -!- INDUCTION: Induced by the bile acids receptor NR1H4 that binds and CC activates a NR1H4-responsive element within intron 2. CC {ECO:0000269|PubMed:12815072}. CC -!- MISCELLANEOUS: Contrarily to other members of the family that can CC bind several FGF receptors FGF19 is specific for FGFR4. CC -!- SIMILARITY: Belongs to the heparin-binding growth factors family. CC {ECO:0000305}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; AB018122; BAA75500.1; -; mRNA. DR EMBL; AF110400; AAD45973.1; -; mRNA. DR EMBL; AY358302; AAQ88669.1; -; mRNA. DR EMBL; BT006729; AAP35375.1; -; mRNA. DR EMBL; BC017664; AAH17664.1; -; mRNA. DR CCDS; CCDS8193.1; -. DR RefSeq; NP_005108.1; NM_005117.2. DR UniGene; Hs.249200; -. DR PDB; 1PWA; X-ray; 1.30 A; A=39-196. DR PDB; 2P23; X-ray; 1.80 A; A/B=23-216. DR PDBsum; 1PWA; -. DR PDBsum; 2P23; -. DR ProteinModelPortal; O95750; -. DR SMR; O95750; -. DR BioGrid; 115290; 1. DR CORUM; O95750; -. DR DIP; DIP-6039N; -. DR IntAct; O95750; 2. DR STRING; 9606.ENSP00000294312; -. DR iPTMnet; O95750; -. DR PhosphoSitePlus; O95750; -. DR BioMuta; FGF19; -. DR jPOST; O95750; -. DR PaxDb; O95750; -. DR PeptideAtlas; O95750; -. DR PRIDE; O95750; -. DR ProteomicsDB; 51021; -. DR DNASU; 9965; -. DR Ensembl; ENST00000294312; ENSP00000294312; ENSG00000162344. DR GeneID; 9965; -. DR KEGG; hsa:9965; -. DR UCSC; uc001opf.4; human. DR CTD; 9965; -. DR DisGeNET; 9965; -. DR EuPathDB; HostDB:ENSG00000162344.3; -. DR GeneCards; FGF19; -. DR HGNC; HGNC:3675; FGF19. DR HPA; HPA036082; -. DR MIM; 603891; gene. DR neXtProt; NX_O95750; -. DR OpenTargets; ENSG00000162344; -. DR PharmGKB; PA28114; -. DR eggNOG; KOG3885; Eukaryota. DR eggNOG; ENOG4111IPH; LUCA. DR GeneTree; ENSGT00940000160601; -. DR HOGENOM; HOG000112572; -. DR HOVERGEN; HBG051611; -. DR InParanoid; O95750; -. DR KO; K22603; -. DR OMA; YFLPMLP; -. DR OrthoDB; 1157034at2759; -. DR PhylomeDB; O95750; -. DR TreeFam; TF335872; -. DR Reactome; R-HSA-109704; PI3K Cascade. DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling. DR Reactome; R-HSA-1307965; betaKlotho-mediated ligand binding. DR Reactome; R-HSA-190322; FGFR4 ligand binding and activation. DR Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer. DR Reactome; R-HSA-5654228; Phospholipase C-mediated cascade, FGFR4. DR Reactome; R-HSA-5654712; FRS-mediated FGFR4 signaling. DR Reactome; R-HSA-5654719; SHC-mediated cascade:FGFR4. DR Reactome; R-HSA-5654720; PI-3K cascade:FGFR4. DR Reactome; R-HSA-5654733; Negative regulation of FGFR4 signaling. DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade. DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling. DR SIGNOR; O95750; -. DR EvolutionaryTrace; O95750; -. DR GeneWiki; FGF19; -. DR GenomeRNAi; 9965; -. DR PRO; PR:O95750; -. DR Proteomes; UP000005640; Chromosome 11. DR Bgee; ENSG00000162344; Expressed in 14 organ(s), highest expression level in small intestine Peyer's patch. DR Genevisible; O95750; HS. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0016303; F:1-phosphatidylinositol-3-kinase activity; TAS:Reactome. DR GO; GO:0005104; F:fibroblast growth factor receptor binding; IPI:UniProtKB. DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW. DR GO; GO:0046934; F:phosphatidylinositol-4,5-bisphosphate 3-kinase activity; TAS:Reactome. DR GO; GO:0005088; F:Ras guanyl-nucleotide exchange factor activity; TAS:Reactome. DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; IGI:MGI. DR GO; GO:0007507; P:heart development; IEA:Ensembl. DR GO; GO:0000165; P:MAPK cascade; TAS:Reactome. DR GO; GO:0070858; P:negative regulation of bile acid biosynthetic process; IDA:UniProtKB. DR GO; GO:0010629; P:negative regulation of gene expression; IDA:UniProtKB. DR GO; GO:0007399; P:nervous system development; TAS:ProtInc. DR GO; GO:0001755; P:neural crest cell migration; IEA:Ensembl. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IGI:MGI. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:UniProtKB. DR GO; GO:0046326; P:positive regulation of glucose import; IDA:UniProtKB. DR GO; GO:0046330; P:positive regulation of JNK cascade; IDA:UniProtKB. DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; TAS:Reactome. DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:UniProtKB. DR GO; GO:0009617; P:response to bacterium; IEA:Ensembl. DR CDD; cd00058; FGF; 1. DR InterPro; IPR035444; FGF15/19/21. DR InterPro; IPR028303; FGF15/FGF19. DR InterPro; IPR002209; Fibroblast_GF_fam. DR InterPro; IPR008996; IL1/FGF. DR PANTHER; PTHR11486; PTHR11486; 1. DR PANTHER; PTHR11486:SF74; PTHR11486:SF74; 1. DR Pfam; PF00167; FGF; 1. DR PIRSF; PIRSF037961; FGF-19_FGF-21; 1. DR PRINTS; PR00263; HBGFFGF. DR SMART; SM00442; FGF; 1. DR SUPFAM; SSF50353; SSF50353; 1. DR PROSITE; PS00247; HBGF_FGF; 1. PE 1: Evidence at protein level; KW 3D-structure; Complete proteome; Direct protein sequencing; KW Disulfide bond; Growth factor; Reference proteome; Secreted; Signal. FT SIGNAL 1 24 {ECO:0000269|PubMed:15340161}. FT CHAIN 25 216 Fibroblast growth factor 19. FT /FTId=PRO_0000008993. FT DISULFID 58 70 {ECO:0000269|PubMed:14730967}. FT DISULFID 102 120 {ECO:0000269|PubMed:14730967}. FT STRAND 42 49 {ECO:0000244|PDB:1PWA}. FT STRAND 58 62 {ECO:0000244|PDB:1PWA}. FT STRAND 66 73 {ECO:0000244|PDB:1PWA}. FT HELIX 76 78 {ECO:0000244|PDB:1PWA}. FT STRAND 80 86 {ECO:0000244|PDB:1PWA}. FT STRAND 89 94 {ECO:0000244|PDB:1PWA}. FT TURN 95 97 {ECO:0000244|PDB:1PWA}. FT STRAND 100 103 {ECO:0000244|PDB:1PWA}. FT HELIX 105 107 {ECO:0000244|PDB:1PWA}. FT STRAND 109 114 {ECO:0000244|PDB:1PWA}. FT HELIX 117 120 {ECO:0000244|PDB:1PWA}. FT STRAND 121 126 {ECO:0000244|PDB:1PWA}. FT STRAND 132 136 {ECO:0000244|PDB:1PWA}. FT TURN 137 140 {ECO:0000244|PDB:1PWA}. FT HELIX 150 152 {ECO:0000244|PDB:2P23}. FT HELIX 153 156 {ECO:0000244|PDB:2P23}. FT STRAND 165 168 {ECO:0000244|PDB:1PWA}. SQ SEQUENCE 216 AA; 24003 MW; E0BCBC9C220F9832 CRC64; MRSGCVVVHV WILAGLWLAV AGRPLAFSDA GPHVHYGWGD PIRLRHLYTS GPHGLSSCFL RIRADGVVDC ARGQSAHSLL EIKAVALRTV AIKGVHSVRY LCMGADGKMQ GLLQYSEEDC AFEEEIRPDG YNVYRSEKHR LPVSLSSAKQ RQLYKNRGFL PLSHFLPMLP MVPEEPEDLR GHLESDMFSS PLETDSMDPF GLVTGLEAVR SPSFEK //