ID FGF20_HUMAN Reviewed; 211 AA. AC Q9NP95; B2RPH5; DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2000, sequence version 1. DT 26-FEB-2020, entry version 148. DE RecName: Full=Fibroblast growth factor 20; DE Short=FGF-20; GN Name=FGF20; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=10913340; DOI=10.1006/bbrc.2000.3142; RA Kirikoshi H., Sagara N., Saitoh T., Tanaka K., Sekihara H., Shiokawa K., RA Katoh M.; RT "Molecular cloning and characterization of human FGF-20 on chromosome RT 8p21.3-p22."; RL Biochem. Biophys. Res. Commun. 274:337-343(2000). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Brain; RX PubMed=11032730; DOI=10.1006/bbrc.2000.3675; RA Ohmachi S., Watanabe Y., Mikami T., Kusu N., Ibi T., Akaike A., Itoh N.; RT "FGF-20, a novel neurotrophic factor, preferentially expressed in the RT substantia nigra pars compacta of rat brain."; RL Biochem. Biophys. Res. Commun. 277:355-360(2000). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=11306498; RA Jeffers M., Shimkets R., Prayaga S., Boldog F., Yang M., Burgess C., RA Fernandes E., Rittman B., Shimkets J., LaRochelle W.J., Lichenstein H.S.; RT "Identification of a novel human fibroblast growth factor and RT characterization of its role in oncogenesis."; RL Cancer Res. 61:3131-3138(2001). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ARG-116; ALA-175 AND RP ASN-206. RG NIEHS SNPs program; RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; 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 project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP INTERACTION WITH FGFR2 AND FGFR4, AND FUNCTION IN STIMULATION OF CELL RP PROLIFERATION. RX PubMed=16597617; DOI=10.1074/jbc.m601252200; RA Zhang X., Ibrahimi O.A., Olsen S.K., Umemori H., Mohammadi M., Ornitz D.M.; RT "Receptor specificity of the fibroblast growth factor family. The complete RT mammalian FGF family."; RL J. Biol. Chem. 281:15694-15700(2006). RN [8] RP POSSIBLE ASSOCIATION WITH PARKINSON DISEASE. RX PubMed=18252210; DOI=10.1016/j.ajhg.2007.09.021; RA Wang G., van der Walt J.M., Mayhew G., Li Y.J., Zuchner S., Scott W.K., RA Martin E.R., Vance J.M.; RT "Variation in the miRNA-433 binding site of FGF20 confers risk for RT Parkinson disease by overexpression of alpha-synuclein."; RL Am. J. Hum. Genet. 82:283-289(2008). RN [9] RP NO EVIDENCE OF ASSOCIATION WITH PARKINSON DISEASE. RX PubMed=19133659; DOI=10.1002/mds.22442; RA Wider C., Dachsel J.C., Soto A.I., Heckman M.G., Diehl N.N., Yue M., RA Lincoln S., Aasly J.O., Haugarvoll K., Trojanowski J.Q., RA Papapetropoulos S., Mash D., Rajput A., Rajput A.H., Gibson J.M., Lynch T., RA Dickson D.W., Uitti R.J., Wszolek Z.K., Farrer M.J., Ross O.A.; RT "FGF20 and Parkinson's disease: no evidence of association or pathogenicity RT via alpha-synuclein expression."; RL Mov. Disord. 24:455-459(2009). RN [10] 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 [11] RP INVOLVEMENT IN RHDA2. RX PubMed=22698282; DOI=10.1016/j.devcel.2012.04.018; RA Barak H., Huh S.H., Chen S., Jeanpierre C., Martinovic J., Parisot M., RA Bole-Feysot C., Nitschke P., Salomon R., Antignac C., Ornitz D.M., RA Kopan R.; RT "FGF9 and FGF20 maintain the stemness of nephron progenitors in mice and RT man."; RL Dev. Cell 22:1191-1207(2012). RN [12] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS), SUBUNIT, AND HEPARIN-BINDING. RX PubMed=19564416; DOI=10.1128/mcb.01780-08; RA Kalinina J., Byron S.A., Makarenkova H.P., Olsen S.K., Eliseenkova A.V., RA Larochelle W.J., Dhanabal M., Blais S., Ornitz D.M., Day L.A., RA Neubert T.A., Pollock P.M., Mohammadi M.; RT "Homodimerization controls the fibroblast growth factor 9 subfamily's RT receptor binding and heparan sulfate-dependent diffusion in the RT extracellular matrix."; RL Mol. Cell. Biol. 29:4663-4678(2009). CC -!- FUNCTION: Neurotrophic factor that regulates central nervous CC development and function. {ECO:0000269|PubMed:16597617}. CC -!- SUBUNIT: Homodimer. Interacts with FGFR2 and FGFR4. Affinity between CC fibroblast growth factors (FGFs) and their receptors is increased by CC heparan sulfate glycosaminoglycans that function as coreceptors. CC {ECO:0000269|PubMed:16597617, ECO:0000269|PubMed:19564416}. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:11306498}. CC -!- TISSUE SPECIFICITY: Predominantly expressed in the cerebellum. CC {ECO:0000269|PubMed:11306498}. CC -!- DISEASE: Renal hypodysplasia/aplasia 2 (RHDA2) [MIM:615721]: A CC perinatally lethal renal disease encompassing a spectrum of kidney CC development defects, including renal agenesis, bilateral renal aplasia, CC hypoplasia, (cystic) dysplasia, and severe obstructive uropathy. CC {ECO:0000269|PubMed:22698282}. Note=The disease is caused by mutations CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the heparin-binding growth factors family. CC {ECO:0000305}. CC -!- CAUTION: It is uncertain whether variants in this gene are associated CC with Parkinson disease. Some authors mention association with the CC disease (PubMed:18252210). In contrast, some others do not observe any CC association (PubMed:19133659). {ECO:0000305|PubMed:18252210, CC ECO:0000305|PubMed:19133659}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/fgf20/"; 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; AB044277; BAB03633.1; -; mRNA. DR EMBL; AB030648; BAB03530.1; -; mRNA. DR EMBL; AY696296; AAT85804.1; -; Genomic_DNA. DR EMBL; CH471080; EAW63828.1; -; Genomic_DNA. DR EMBL; BC137446; AAI37447.1; -; mRNA. DR EMBL; BC137447; AAI37448.1; -; mRNA. DR CCDS; CCDS5998.1; -. DR PIR; JC7353; JC7353. DR RefSeq; NP_062825.1; NM_019851.2. DR PDB; 3F1R; X-ray; 2.50 A; A/B=1-211. DR PDBsum; 3F1R; -. DR SMR; Q9NP95; -. DR BioGrid; 117664; 2. DR IntAct; Q9NP95; 1. DR STRING; 9606.ENSP00000180166; -. DR iPTMnet; Q9NP95; -. DR PhosphoSitePlus; Q9NP95; -. DR BioMuta; FGF20; -. DR DMDM; 13626702; -. DR MassIVE; Q9NP95; -. DR PaxDb; Q9NP95; -. DR PRIDE; Q9NP95; -. DR ProteomicsDB; 81938; -. DR Ensembl; ENST00000180166; ENSP00000180166; ENSG00000078579. DR GeneID; 26281; -. DR KEGG; hsa:26281; -. DR UCSC; uc003wxc.2; human. DR CTD; 26281; -. DR DisGeNET; 26281; -. DR GeneCards; FGF20; -. DR HGNC; HGNC:3677; FGF20. DR MalaCards; FGF20; -. DR MIM; 605558; gene. DR MIM; 615721; phenotype. DR neXtProt; NX_Q9NP95; -. DR OpenTargets; ENSG00000078579; -. DR Orphanet; 1848; Renal agenesis, bilateral. DR PharmGKB; PA28116; -. DR eggNOG; KOG3885; Eukaryota. DR eggNOG; ENOG4111IPH; LUCA. DR GeneTree; ENSGT00940000158380; -. DR HOGENOM; CLU_081609_0_0_1; -. DR InParanoid; Q9NP95; -. DR KO; K04358; -. DR OMA; SECVFRE; -. DR OrthoDB; 1097566at2759; -. DR PhylomeDB; Q9NP95; -. DR TreeFam; TF317805; -. DR Reactome; R-HSA-109704; PI3K Cascade. DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling. DR Reactome; R-HSA-1839122; Signaling by activated point mutants of FGFR1. DR Reactome; R-HSA-1839130; Signaling by activated point mutants of FGFR3. DR Reactome; R-HSA-190322; FGFR4 ligand binding and activation. DR Reactome; R-HSA-190371; FGFR3b ligand binding and activation. DR Reactome; R-HSA-190372; FGFR3c ligand binding and activation. DR Reactome; R-HSA-190373; FGFR1c ligand binding and activation. DR Reactome; R-HSA-190375; FGFR2c ligand binding and activation. DR Reactome; R-HSA-2033514; FGFR3 mutant receptor activation. DR Reactome; R-HSA-2033519; Activated point mutants of FGFR2. DR Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer. DR Reactome; R-HSA-5654219; Phospholipase C-mediated cascade: FGFR1. DR Reactome; R-HSA-5654221; Phospholipase C-mediated cascade, FGFR2. DR Reactome; R-HSA-5654227; Phospholipase C-mediated cascade, FGFR3. DR Reactome; R-HSA-5654228; Phospholipase C-mediated cascade, FGFR4. DR Reactome; R-HSA-5654687; Downstream signaling of activated FGFR1. DR Reactome; R-HSA-5654688; SHC-mediated cascade:FGFR1. DR Reactome; R-HSA-5654689; PI-3K cascade:FGFR1. DR Reactome; R-HSA-5654693; FRS-mediated FGFR1 signaling. DR Reactome; R-HSA-5654695; PI-3K cascade:FGFR2. DR Reactome; R-HSA-5654699; SHC-mediated cascade:FGFR2. DR Reactome; R-HSA-5654700; FRS-mediated FGFR2 signaling. DR Reactome; R-HSA-5654704; SHC-mediated cascade:FGFR3. DR Reactome; R-HSA-5654706; FRS-mediated FGFR3 signaling. DR Reactome; R-HSA-5654710; PI-3K cascade:FGFR3. 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-5654726; Negative regulation of FGFR1 signaling. DR Reactome; R-HSA-5654727; Negative regulation of FGFR2 signaling. DR Reactome; R-HSA-5654732; Negative regulation of FGFR3 signaling. DR Reactome; R-HSA-5654733; Negative regulation of FGFR4 signaling. DR Reactome; R-HSA-5655253; Signaling by FGFR2 in disease. DR Reactome; R-HSA-5655302; Signaling by FGFR1 in disease. DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade. DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling. DR Reactome; R-HSA-8853338; Signaling by FGFR3 point mutants in cancer. DR ChiTaRS; FGF20; human. DR EvolutionaryTrace; Q9NP95; -. DR GenomeRNAi; 26281; -. DR Pharos; Q9NP95; Tbio. DR PRO; PR:Q9NP95; -. DR Proteomes; UP000005640; Chromosome 8. DR RNAct; Q9NP95; protein. DR Bgee; ENSG00000078579; Expressed in buccal mucosa cell and 68 other tissues. DR ExpressionAtlas; Q9NP95; baseline and differential. DR Genevisible; Q9NP95; HS. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005104; F:fibroblast growth factor receptor binding; IEA:Ensembl. DR GO; GO:0008083; F:growth factor activity; ISS:ParkinsonsUK-UCL. DR GO; GO:0043395; F:heparan sulfate proteoglycan binding; TAS:ParkinsonsUK-UCL. DR GO; GO:0090722; F:receptor-receptor interaction; IDA:ParkinsonsUK-UCL. DR GO; GO:0005102; F:signaling receptor binding; TAS:ParkinsonsUK-UCL. DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc. DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:ParkinsonsUK-UCL. DR GO; GO:0060113; P:inner ear receptor cell differentiation; IEA:Ensembl. DR GO; GO:0000165; P:MAPK cascade; TAS:Reactome. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IDA:ParkinsonsUK-UCL. DR GO; GO:0008284; P:positive regulation of cell population proliferation; TAS:ParkinsonsUK-UCL. DR GO; GO:1904340; P:positive regulation of dopaminergic neuron differentiation; TAS:ParkinsonsUK-UCL. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Ensembl. DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; TAS:Reactome. DR GO; GO:0060043; P:regulation of cardiac muscle cell proliferation; IEA:Ensembl. DR GO; GO:0014059; P:regulation of dopamine secretion; TAS:ParkinsonsUK-UCL. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR CDD; cd00058; FGF; 1. DR InterPro; IPR028291; FGF20. DR InterPro; IPR002209; Fibroblast_GF_fam. DR InterPro; IPR008996; IL1/FGF. DR PANTHER; PTHR11486; PTHR11486; 1. DR PANTHER; PTHR11486:SF72; PTHR11486:SF72; 1. DR Pfam; PF00167; FGF; 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; Growth factor; Polymorphism; Reference proteome; Secreted. FT CHAIN 1..211 FT /note="Fibroblast growth factor 20" FT /id="PRO_0000147616" FT VARIANT 116 FT /note="G -> R (in dbSNP:rs3793405)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_020946" FT VARIANT 175 FT /note="P -> A (in dbSNP:rs10089600)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_020947" FT VARIANT 206 FT /note="D -> N (in dbSNP:rs17550360)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_020948" FT HELIX 56..64 FT /evidence="ECO:0000244|PDB:3F1R" FT STRAND 66..71 FT /evidence="ECO:0000244|PDB:3F1R" FT TURN 72..74 FT /evidence="ECO:0000244|PDB:3F1R" FT STRAND 75..79 FT /evidence="ECO:0000244|PDB:3F1R" FT STRAND 85..89 FT /evidence="ECO:0000244|PDB:3F1R" FT STRAND 94..104 FT /evidence="ECO:0000244|PDB:3F1R" FT STRAND 107..112 FT /evidence="ECO:0000244|PDB:3F1R" FT TURN 113..115 FT /evidence="ECO:0000244|PDB:3F1R" FT STRAND 118..121 FT /evidence="ECO:0000244|PDB:3F1R" FT STRAND 127..132 FT /evidence="ECO:0000244|PDB:3F1R" FT HELIX 135..137 FT /evidence="ECO:0000244|PDB:3F1R" FT STRAND 139..145 FT /evidence="ECO:0000244|PDB:3F1R" FT STRAND 148..157 FT /evidence="ECO:0000244|PDB:3F1R" FT TURN 159..161 FT /evidence="ECO:0000244|PDB:3F1R" FT STRAND 164..166 FT /evidence="ECO:0000244|PDB:3F1R" FT STRAND 173..175 FT /evidence="ECO:0000244|PDB:3F1R" FT HELIX 178..180 FT /evidence="ECO:0000244|PDB:3F1R" FT HELIX 186..188 FT /evidence="ECO:0000244|PDB:3F1R" FT STRAND 190..193 FT /evidence="ECO:0000244|PDB:3F1R" FT HELIX 197..199 FT /evidence="ECO:0000244|PDB:3F1R" FT HELIX 201..203 FT /evidence="ECO:0000244|PDB:3F1R" SQ SEQUENCE 211 AA; 23499 MW; AB04608C16060CC1 CRC64; MAPLAEVGGF LGGLEGLGQQ VGSHFLLPPA GERPPLLGER RSAAERSARG GPGAAQLAHL HGILRRRQLY CRTGFHLQIL PDGSVQGTRQ DHSLFGILEF ISVAVGLVSI RGVDSGLYLG MNDKGELYGS EKLTSECIFR EQFEENWYNT YSSNIYKHGD TGRRYFVALN KDGTPRDGAR SKRHQKFTHF LPRPVDPERV PELYKDLLMY T //