FGF17_HUMAN
ID FGF17_HUMAN Reviewed; 216 AA.
AC O60258; B7ZLG4; Q2M2W1;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Fibroblast growth factor 17;
DE Short=FGF-17;
DE Flags: Precursor;
GN Name=FGF17; ORFNames=UNQ161/PRO187;
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] (ISOFORM 1).
RC TISSUE=Fetal brain;
RX PubMed=9514906; DOI=10.1006/bbrc.1998.8239;
RA Hoshikawa M., Ohbayashi N., Yonamine A., Konishi M., Ozaki K., Fukui S.,
RA Itoh N.;
RT "Structure and expression of a novel fibroblast growth factor, FGF-17,
RT preferentially expressed in the embryonic brain.";
RL Biochem. Biophys. Res. Commun. 244:187-191(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NIEHS SNPs program;
RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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 [6]
RP INTERACTION WITH FGFR3 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 [7]
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 [8]
RP VARIANTS HH20 THR-108; HIS-177 AND SER-187, AND CHARACTERIZATION OF
RP VARIANTS HH20 THR-108 AND HIS-177.
RX PubMed=23643382; DOI=10.1016/j.ajhg.2013.04.008;
RA Miraoui H., Dwyer A.A., Sykiotis G.P., Plummer L., Chung W., Feng B.,
RA Beenken A., Clarke J., Pers T.H., Dworzynski P., Keefe K., Niedziela M.,
RA Raivio T., Crowley W.F. Jr., Seminara S.B., Quinton R., Hughes V.A.,
RA Kumanov P., Young J., Yialamas M.A., Hall J.E., Van Vliet G.,
RA Chanoine J.P., Rubenstein J., Mohammadi M., Tsai P.S., Sidis Y., Lage K.,
RA Pitteloud N.;
RT "Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in
RT individuals with congenital hypogonadotropic hypogonadism.";
RL Am. J. Hum. Genet. 92:725-743(2013).
CC -!- FUNCTION: Plays an important role in the regulation of embryonic
CC development and as signaling molecule in the induction and patterning
CC of the embryonic brain. Required for normal brain development.
CC {ECO:0000269|PubMed:16597617}.
CC -!- SUBUNIT: Interacts with FGFR3 and FGFR4. {ECO:0000269|PubMed:16597617}.
CC -!- INTERACTION:
CC O60258; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-12184083, EBI-947187;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O60258-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O60258-2; Sequence=VSP_008715;
CC -!- TISSUE SPECIFICITY: Preferentially expressed in the embryonic brain.
CC -!- DEVELOPMENTAL STAGE: Detected in embryos at E14.5, but not at E10.5 and
CC E19.5. Preferentially expressed in the neuroepithelia of the isthmus
CC and septum of the embryonic brain at E14.5.
CC -!- DISEASE: Hypogonadotropic hypogonadism 20 with or without anosmia
CC (HH20) [MIM:615270]: A disorder characterized by absent or incomplete
CC sexual maturation by the age of 18 years, in conjunction with low
CC levels of circulating gonadotropins and testosterone and no other
CC abnormalities of the hypothalamic-pituitary axis. In some cases, it is
CC associated with non-reproductive phenotypes, such as anosmia, cleft
CC palate, and sensorineural hearing loss. Anosmia or hyposmia is related
CC to the absence or hypoplasia of the olfactory bulbs and tracts.
CC Hypogonadism is due to deficiency in gonadotropin-releasing hormone and
CC probably results from a failure of embryonic migration of gonadotropin-
CC releasing hormone-synthesizing neurons. In the presence of anosmia,
CC idiopathic hypogonadotropic hypogonadism is referred to as Kallmann
CC syndrome, whereas in the presence of a normal sense of smell, it has
CC been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH).
CC {ECO:0000269|PubMed:23643382}. Note=The disease is caused by variants
CC affecting distinct genetic loci, including the gene represented in this
CC entry. Some patients carrying mutations in FGF17 also have a mutation
CC in another HH-associated gene including FGFR1, HS6ST1 and FLRT3
CC (PubMed:23643382). {ECO:0000269|PubMed:23643382}.
CC -!- SIMILARITY: Belongs to the heparin-binding growth factors family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/fgf17/";
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DR EMBL; AB009249; BAA25429.1; -; mRNA.
DR EMBL; AY358869; AAQ89228.1; -; mRNA.
DR EMBL; AF497475; AAM09570.1; -; Genomic_DNA.
DR EMBL; CH471080; EAW63729.1; -; Genomic_DNA.
DR EMBL; BC069475; AAH69475.1; -; mRNA.
DR EMBL; BC105131; AAI05132.1; -; mRNA.
DR EMBL; BC113489; AAI13490.1; -; mRNA.
DR EMBL; BC143789; AAI43790.1; -; mRNA.
DR CCDS; CCDS6019.1; -. [O60258-1]
DR CCDS; CCDS78310.1; -. [O60258-2]
DR RefSeq; NP_001291407.1; NM_001304478.1. [O60258-2]
DR RefSeq; NP_003858.1; NM_003867.3. [O60258-1]
DR AlphaFoldDB; O60258; -.
DR SMR; O60258; -.
DR BioGRID; 114349; 42.
DR IntAct; O60258; 2.
DR STRING; 9606.ENSP00000352414; -.
DR GlyGen; O60258; 1 site.
DR iPTMnet; O60258; -.
DR PhosphoSitePlus; O60258; -.
DR BioMuta; FGF17; -.
DR MassIVE; O60258; -.
DR PaxDb; O60258; -.
DR PeptideAtlas; O60258; -.
DR PRIDE; O60258; -.
DR ProteomicsDB; 49284; -. [O60258-1]
DR ProteomicsDB; 49285; -. [O60258-2]
DR Antibodypedia; 22456; 321 antibodies from 29 providers.
DR DNASU; 8822; -.
DR Ensembl; ENST00000359441.4; ENSP00000352414.3; ENSG00000158815.11. [O60258-1]
DR Ensembl; ENST00000518533.5; ENSP00000431041.1; ENSG00000158815.11. [O60258-2]
DR GeneID; 8822; -.
DR KEGG; hsa:8822; -.
DR MANE-Select; ENST00000359441.4; ENSP00000352414.3; NM_003867.4; NP_003858.1.
DR UCSC; uc003xag.4; human. [O60258-1]
DR CTD; 8822; -.
DR DisGeNET; 8822; -.
DR GeneCards; FGF17; -.
DR GeneReviews; FGF17; -.
DR HGNC; HGNC:3673; FGF17.
DR HPA; ENSG00000158815; Tissue enhanced (brain, choroid plexus).
DR MalaCards; FGF17; -.
DR MIM; 603725; gene.
DR MIM; 615270; phenotype.
DR neXtProt; NX_O60258; -.
DR OpenTargets; ENSG00000158815; -.
DR Orphanet; 478; Kallmann syndrome.
DR Orphanet; 432; Normosmic congenital hypogonadotropic hypogonadism.
DR PharmGKB; PA28112; -.
DR VEuPathDB; HostDB:ENSG00000158815; -.
DR eggNOG; KOG3885; Eukaryota.
DR GeneTree; ENSGT00940000161965; -.
DR HOGENOM; CLU_090682_0_0_1; -.
DR InParanoid; O60258; -.
DR OMA; LCCQTQV; -.
DR OrthoDB; 1190450at2759; -.
DR PhylomeDB; O60258; -.
DR TreeFam; TF331233; -.
DR PathwayCommons; O60258; -.
DR Reactome; R-HSA-109704; PI3K Cascade. [O60258-1]
DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling. [O60258-1]
DR Reactome; R-HSA-1839122; Signaling by activated point mutants of FGFR1. [O60258-1]
DR Reactome; R-HSA-1839130; Signaling by activated point mutants of FGFR3. [O60258-1]
DR Reactome; R-HSA-190322; FGFR4 ligand binding and activation. [O60258-1]
DR Reactome; R-HSA-190371; FGFR3b ligand binding and activation. [O60258-1]
DR Reactome; R-HSA-190372; FGFR3c ligand binding and activation. [O60258-1]
DR Reactome; R-HSA-190373; FGFR1c ligand binding and activation. [O60258-1]
DR Reactome; R-HSA-190375; FGFR2c ligand binding and activation. [O60258-1]
DR Reactome; R-HSA-2033519; Activated point mutants of FGFR2. [O60258-1]
DR Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer. [O60258-1]
DR Reactome; R-HSA-5654219; Phospholipase C-mediated cascade: FGFR1. [O60258-1]
DR Reactome; R-HSA-5654221; Phospholipase C-mediated cascade, FGFR2. [O60258-1]
DR Reactome; R-HSA-5654227; Phospholipase C-mediated cascade, FGFR3. [O60258-1]
DR Reactome; R-HSA-5654228; Phospholipase C-mediated cascade, FGFR4. [O60258-1]
DR Reactome; R-HSA-5654687; Downstream signaling of activated FGFR1. [O60258-1]
DR Reactome; R-HSA-5654688; SHC-mediated cascade:FGFR1. [O60258-1]
DR Reactome; R-HSA-5654689; PI-3K cascade:FGFR1. [O60258-1]
DR Reactome; R-HSA-5654693; FRS-mediated FGFR1 signaling. [O60258-1]
DR Reactome; R-HSA-5654695; PI-3K cascade:FGFR2. [O60258-1]
DR Reactome; R-HSA-5654699; SHC-mediated cascade:FGFR2. [O60258-1]
DR Reactome; R-HSA-5654700; FRS-mediated FGFR2 signaling. [O60258-1]
DR Reactome; R-HSA-5654704; SHC-mediated cascade:FGFR3. [O60258-1]
DR Reactome; R-HSA-5654706; FRS-mediated FGFR3 signaling. [O60258-1]
DR Reactome; R-HSA-5654710; PI-3K cascade:FGFR3. [O60258-1]
DR Reactome; R-HSA-5654712; FRS-mediated FGFR4 signaling. [O60258-1]
DR Reactome; R-HSA-5654719; SHC-mediated cascade:FGFR4. [O60258-1]
DR Reactome; R-HSA-5654720; PI-3K cascade:FGFR4. [O60258-1]
DR Reactome; R-HSA-5654726; Negative regulation of FGFR1 signaling. [O60258-1]
DR Reactome; R-HSA-5654727; Negative regulation of FGFR2 signaling. [O60258-1]
DR Reactome; R-HSA-5654732; Negative regulation of FGFR3 signaling. [O60258-1]
DR Reactome; R-HSA-5654733; Negative regulation of FGFR4 signaling. [O60258-1]
DR Reactome; R-HSA-5655253; Signaling by FGFR2 in disease. [O60258-1]
DR Reactome; R-HSA-5655302; Signaling by FGFR1 in disease. [O60258-1]
DR Reactome; R-HSA-5655332; Signaling by FGFR3 in disease. [O60258-1]
DR Reactome; R-HSA-5658623; FGFRL1 modulation of FGFR1 signaling. [O60258-1]
DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade. [O60258-1]
DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling. [O60258-1]
DR SignaLink; O60258; -.
DR SIGNOR; O60258; -.
DR BioGRID-ORCS; 8822; 12 hits in 1071 CRISPR screens.
DR GeneWiki; FGF17; -.
DR GenomeRNAi; 8822; -.
DR Pharos; O60258; Tbio.
DR PRO; PR:O60258; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; O60258; protein.
DR Bgee; ENSG00000158815; Expressed in right hemisphere of cerebellum and 92 other tissues.
DR Genevisible; O60258; 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; IBA:GO_Central.
DR GO; GO:0005105; F:type 1 fibroblast growth factor receptor binding; IDA:UniProtKB.
DR GO; GO:0005111; F:type 2 fibroblast growth factor receptor binding; IDA:UniProtKB.
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:0007399; P:nervous system development; TAS:ProtInc.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IBA:GO_Central.
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:0030334; P:regulation of cell migration; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR CDD; cd00058; FGF; 1.
DR InterPro; IPR028287; FGF17.
DR InterPro; IPR002209; Fibroblast_GF_fam.
DR InterPro; IPR008996; IL1/FGF.
DR PANTHER; PTHR11486; PTHR11486; 1.
DR PANTHER; PTHR11486:SF71; PTHR11486:SF71; 1.
DR Pfam; PF00167; FGF; 1.
DR SMART; SM00442; FGF; 1.
DR SUPFAM; SSF50353; SSF50353; 1.
DR PROSITE; PS00247; HBGF_FGF; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Developmental protein; Disease variant; Glycoprotein;
KW Growth factor; Hypogonadotropic hypogonadism; Kallmann syndrome;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..216
FT /note="Fibroblast growth factor 17"
FT /id="PRO_0000008985"
FT REGION 190..216
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 137
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 25..35
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12975309,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_008715"
FT VARIANT 108
FT /note="I -> T (in HH20; rare variant associated with
FT susceptibility to disease; some patients have a second
FT mutation in another HH-associated gene including FGFR1,
FT HS6ST1 and FLRT3; the mutant has reduced ability to
FT activate FGFR1; dbSNP:rs398123024)"
FT /evidence="ECO:0000269|PubMed:23643382"
FT /id="VAR_069947"
FT VARIANT 177
FT /note="R -> H (in HH20; the mutant has reduced ability to
FT activate FGFR1; dbSNP:rs398123025)"
FT /evidence="ECO:0000269|PubMed:23643382"
FT /id="VAR_069948"
FT VARIANT 187
FT /note="N -> S (in HH20; dbSNP:rs398123026)"
FT /evidence="ECO:0000269|PubMed:23643382"
FT /id="VAR_069949"
SQ SEQUENCE 216 AA; 24891 MW; 2EE0288675220F4C CRC64;
MGAARLLPNL TLCLQLLILC CQTQGENHPS PNFNQYVRDQ GAMTDQLSRR QIREYQLYSR
TSGKHVQVTG RRISATAEDG NKFAKLIVET DTFGSRVRIK GAESEKYICM NKRGKLIGKP
SGKSKDCVFT EIVLENNYTA FQNARHEGWF MAFTRQGRPR QASRSRQNQR EAHFIKRLYQ
GQLPFPNHAE KQKQFEFVGS APTRRTKRTR RPQPLT
