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   24-JAN-2024, entry version 189.
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 14.5 dpc, but not at 10.5
CC       dpc and 19.5 dpc. Preferentially expressed in the neuroepithelia of the
CC       isthmus and septum of the embryonic brain at 14.5 dpc.
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   GlyCosmos; O60258; 1 site, No reported glycans.
DR   GlyGen; O60258; 1 site.
DR   iPTMnet; O60258; -.
DR   PhosphoSitePlus; O60258; -.
DR   BioMuta; FGF17; -.
DR   MassIVE; O60258; -.
DR   PaxDb; 9606-ENSP00000352414; -.
DR   PeptideAtlas; O60258; -.
DR   ProteomicsDB; 49284; -. [O60258-1]
DR   ProteomicsDB; 49285; -. [O60258-2]
DR   Antibodypedia; 22456; 371 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   AGR; HGNC:3673; -.
DR   CTD; 8822; -.
DR   DisGeNET; 8822; -.
DR   GeneCards; FGF17; -.
DR   GeneReviews; FGF17; -.
DR   HGNC; HGNC:3673; FGF17.
DR   HPA; ENSG00000158815; Tissue enriched (brain).
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; 4098345at2759; -.
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; 13 hits in 1149 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 94 other cell types or tissues.
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: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   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:SF71; FIBROBLAST GROWTH FACTOR 17; 1.
DR   Pfam; PF00167; FGF; 1.
DR   PRINTS; PR00262; IL1HBGF.
DR   SMART; SM00442; FGF; 1.
DR   SUPFAM; SSF50353; Cytokine; 1.
DR   PROSITE; PS00247; HBGF_FGF; 1.
DR   Genevisible; O60258; HS.
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; 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
//