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 16-OCT-2019, entry version 146. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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., RA Shiokawa K., 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., RA 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 RP 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., RA 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., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA 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 RT project: 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., 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 [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., RA Scott W.K., 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., RA Lynch T., Dickson D.W., Uitti R.J., Wszolek Z.K., Farrer M.J., RA Ross O.A.; RT "FGF20 and Parkinson's disease: no evidence of association or RT pathogenicity 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 RT and 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., RA Eliseenkova A.V., Larochelle W.J., Dhanabal M., Blais S., Ornitz D.M., RA Day L.A., 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 CC between fibroblast growth factors (FGFs) and their receptors is CC increased by heparan sulfate glycosaminoglycans that function as CC coreceptors. {ECO:0000269|PubMed:16597617, CC 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 CC aplasia, hypoplasia, (cystic) dysplasia, and severe obstructive CC uropathy. {ECO:0000269|PubMed:22698282}. Note=The disease is CC caused by mutations 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 CC associated with Parkinson disease. Some authors mention CC association with the disease (PubMed:18252210). In contrast, some CC others do not observe any association (PubMed:19133659). CC {ECO:0000305|PubMed:18252210, 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; HOG000236341; -. 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; -. DR PRO; PR:Q9NP95; -. DR Proteomes; UP000005640; Chromosome 8. DR Bgee; ENSG00000078579; Expressed in 69 organ(s), highest expression level in buccal mucosa cell. 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; Complete proteome; Growth factor; Polymorphism; KW Reference proteome; Secreted. FT CHAIN 1 211 Fibroblast growth factor 20. FT /FTId=PRO_0000147616. FT VARIANT 116 116 G -> R (in dbSNP:rs3793405). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_020946. FT VARIANT 175 175 P -> A (in dbSNP:rs10089600). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_020947. FT VARIANT 206 206 D -> N (in dbSNP:rs17550360). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_020948. FT HELIX 56 64 {ECO:0000244|PDB:3F1R}. FT STRAND 66 71 {ECO:0000244|PDB:3F1R}. FT TURN 72 74 {ECO:0000244|PDB:3F1R}. FT STRAND 75 79 {ECO:0000244|PDB:3F1R}. FT STRAND 85 89 {ECO:0000244|PDB:3F1R}. FT STRAND 94 104 {ECO:0000244|PDB:3F1R}. FT STRAND 107 112 {ECO:0000244|PDB:3F1R}. FT TURN 113 115 {ECO:0000244|PDB:3F1R}. FT STRAND 118 121 {ECO:0000244|PDB:3F1R}. FT STRAND 127 132 {ECO:0000244|PDB:3F1R}. FT HELIX 135 137 {ECO:0000244|PDB:3F1R}. FT STRAND 139 145 {ECO:0000244|PDB:3F1R}. FT STRAND 148 157 {ECO:0000244|PDB:3F1R}. FT TURN 159 161 {ECO:0000244|PDB:3F1R}. FT STRAND 164 166 {ECO:0000244|PDB:3F1R}. FT STRAND 173 175 {ECO:0000244|PDB:3F1R}. FT HELIX 178 180 {ECO:0000244|PDB:3F1R}. FT HELIX 186 188 {ECO:0000244|PDB:3F1R}. FT STRAND 190 193 {ECO:0000244|PDB:3F1R}. FT HELIX 197 199 {ECO:0000244|PDB:3F1R}. FT HELIX 201 203 {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 //