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 27-MAR-2024, entry version 168.
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 variants
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/";
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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 AlphaFoldDB; Q9NP95; -.
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; 9606-ENSP00000180166; -.
DR PeptideAtlas; Q9NP95; -.
DR Antibodypedia; 58634; 206 antibodies from 30 providers.
DR DNASU; 26281; -.
DR Ensembl; ENST00000180166.6; ENSP00000180166.5; ENSG00000078579.9.
DR GeneID; 26281; -.
DR KEGG; hsa:26281; -.
DR MANE-Select; ENST00000180166.6; ENSP00000180166.5; NM_019851.3; NP_062825.1.
DR UCSC; uc003wxc.2; human.
DR AGR; HGNC:3677; -.
DR CTD; 26281; -.
DR DisGeNET; 26281; -.
DR GeneCards; FGF20; -.
DR HGNC; HGNC:3677; FGF20.
DR HPA; ENSG00000078579; Tissue enhanced (brain).
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 VEuPathDB; HostDB:ENSG00000078579; -.
DR eggNOG; KOG3885; Eukaryota.
DR GeneTree; ENSGT00940000158380; -.
DR HOGENOM; CLU_081609_0_0_1; -.
DR InParanoid; Q9NP95; -.
DR OMA; NIHKHGD; -.
DR OrthoDB; 2883843at2759; -.
DR PhylomeDB; Q9NP95; -.
DR TreeFam; TF317805; -.
DR PathwayCommons; Q9NP95; -.
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-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-5655332; Signaling by FGFR3 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 SignaLink; Q9NP95; -.
DR BioGRID-ORCS; 26281; 16 hits in 1146 CRISPR screens.
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 94 other cell types or tissues.
DR ExpressionAtlas; Q9NP95; baseline and differential.
DR Genevisible; Q9NP95; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005104; F:fibroblast growth factor receptor binding; IBA:GO_Central.
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:0009887; P:animal organ morphogenesis; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0042491; P:inner ear auditory receptor cell differentiation; IEA:Ensembl.
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; IBA:GO_Central.
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:0010628; P:positive regulation of gene expression; IBA:GO_Central.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IBA:GO_Central.
DR GO; GO:0060043; P:regulation of cardiac muscle cell proliferation; IEA:Ensembl.
DR GO; GO:0030334; P:regulation of cell migration; IBA:GO_Central.
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 Gene3D; 2.80.10.50; -; 1.
DR InterPro; IPR002209; Fibroblast_GF_fam.
DR InterPro; IPR008996; IL1/FGF.
DR PANTHER; PTHR11486; FIBROBLAST GROWTH FACTOR; 1.
DR PANTHER; PTHR11486:SF72; FIBROBLAST GROWTH FACTOR 20; 1.
DR Pfam; PF00167; FGF; 1.
DR PRINTS; PR00263; HBGFFGF.
DR PRINTS; PR00262; IL1HBGF.
DR SMART; SM00442; FGF; 1.
DR SUPFAM; SSF50353; Cytokine; 1.
DR PROSITE; PS00247; HBGF_FGF; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Growth factor; Reference proteome; Secreted.
FT CHAIN 1..211
FT /note="Fibroblast growth factor 20"
FT /id="PRO_0000147616"
FT REGION 31..53
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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:0007829|PDB:3F1R"
FT STRAND 66..71
FT /evidence="ECO:0007829|PDB:3F1R"
FT TURN 72..74
FT /evidence="ECO:0007829|PDB:3F1R"
FT STRAND 75..79
FT /evidence="ECO:0007829|PDB:3F1R"
FT STRAND 85..89
FT /evidence="ECO:0007829|PDB:3F1R"
FT STRAND 94..104
FT /evidence="ECO:0007829|PDB:3F1R"
FT STRAND 107..112
FT /evidence="ECO:0007829|PDB:3F1R"
FT TURN 113..115
FT /evidence="ECO:0007829|PDB:3F1R"
FT STRAND 118..121
FT /evidence="ECO:0007829|PDB:3F1R"
FT STRAND 127..132
FT /evidence="ECO:0007829|PDB:3F1R"
FT HELIX 135..137
FT /evidence="ECO:0007829|PDB:3F1R"
FT STRAND 139..145
FT /evidence="ECO:0007829|PDB:3F1R"
FT STRAND 148..157
FT /evidence="ECO:0007829|PDB:3F1R"
FT TURN 159..161
FT /evidence="ECO:0007829|PDB:3F1R"
FT STRAND 164..166
FT /evidence="ECO:0007829|PDB:3F1R"
FT STRAND 173..175
FT /evidence="ECO:0007829|PDB:3F1R"
FT HELIX 178..180
FT /evidence="ECO:0007829|PDB:3F1R"
FT HELIX 186..188
FT /evidence="ECO:0007829|PDB:3F1R"
FT STRAND 190..193
FT /evidence="ECO:0007829|PDB:3F1R"
FT HELIX 197..199
FT /evidence="ECO:0007829|PDB:3F1R"
FT HELIX 201..203
FT /evidence="ECO:0007829|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
//
