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Fibroblast growth factor 17 (FGF-17)

 FGF17_HUMAN             Reviewed;         216 AA.
O60258; B7ZLG4; Q2M2W1;
15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
01-AUG-1998, sequence version 1.
25-OCT-2017, entry version 156.
RecName: Full=Fibroblast growth factor 17;
Short=FGF-17;
Flags: Precursor;
Name=FGF17; ORFNames=UNQ161/PRO187;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
TISSUE=Fetal brain;
PubMed=9514906; DOI=10.1006/bbrc.1998.8239;
Hoshikawa M., Ohbayashi N., Yonamine A., Konishi M., Ozaki K.,
Fukui S., Itoh N.;
"Structure and expression of a novel fibroblast growth factor, FGF-17,
preferentially expressed in the embryonic brain.";
Biochem. Biophys. Res. Commun. 244:187-191(1998).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
PubMed=12975309; DOI=10.1101/gr.1293003;
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S.,
Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J.,
Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J.,
Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A.,
Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H.,
Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D.,
Wood W.I., Godowski P.J., Gray A.M.;
"The secreted protein discovery initiative (SPDI), a large-scale
effort to identify novel human secreted and transmembrane proteins: a
bioinformatics assessment.";
Genome Res. 13:2265-2270(2003).
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
NIEHS SNPs program;
Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
Venter J.C.;
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[6]
INTERACTION WITH FGFR3 AND FGFR4, AND FUNCTION IN STIMULATION OF CELL
PROLIFERATION.
PubMed=16597617; DOI=10.1074/jbc.M601252200;
Zhang X., Ibrahimi O.A., Olsen S.K., Umemori H., Mohammadi M.,
Ornitz D.M.;
"Receptor specificity of the fibroblast growth factor family. The
complete mammalian FGF family.";
J. Biol. Chem. 281:15694-15700(2006).
[7]
REVIEW.
PubMed=20094046; DOI=10.1038/nrc2780;
Turner N., Grose R.;
"Fibroblast growth factor signalling: from development to cancer.";
Nat. Rev. Cancer 10:116-129(2010).
[8]
VARIANTS HH20 THR-108; HIS-177 AND SER-187, AND CHARACTERIZATION OF
VARIANTS HH20 THR-108 AND HIS-177.
PubMed=23643382; DOI=10.1016/j.ajhg.2013.04.008;
Miraoui H., Dwyer A.A., Sykiotis G.P., Plummer L., Chung W., Feng B.,
Beenken A., Clarke J., Pers T.H., Dworzynski P., Keefe K.,
Niedziela M., Raivio T., Crowley W.F. Jr., Seminara S.B., Quinton R.,
Hughes V.A., Kumanov P., Young J., Yialamas M.A., Hall J.E.,
Van Vliet G., Chanoine J.P., Rubenstein J., Mohammadi M., Tsai P.S.,
Sidis Y., Lage K., Pitteloud N.;
"Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in
individuals with congenital hypogonadotropic hypogonadism.";
Am. J. Hum. Genet. 92:725-743(2013).
-!- FUNCTION: Plays an important role in the regulation of embryonic
development and as signaling molecule in the induction and
patterning of the embryonic brain. Required for normal brain
development. {ECO:0000269|PubMed:16597617}.
-!- SUBUNIT: Interacts with FGFR3 and FGFR4.
{ECO:0000269|PubMed:16597617}.
-!- SUBCELLULAR LOCATION: Secreted.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1;
IsoId=O60258-1; Sequence=Displayed;
Name=2;
IsoId=O60258-2; Sequence=VSP_008715;
Note=No experimental confirmation available.;
-!- TISSUE SPECIFICITY: Preferentially expressed in the embryonic
brain.
-!- DEVELOPMENTAL STAGE: Detected in embryos at E14.5, but not at
E10.5 and E19.5. Preferentially expressed in the neuroepithelia of
the isthmus and septum of the embryonic brain at E14.5.
-!- DISEASE: Hypogonadotropic hypogonadism 20 with or without anosmia
(HH20) [MIM:615270]: A disorder characterized by absent or
incomplete sexual maturation by the age of 18 years, in
conjunction with low levels of circulating gonadotropins and
testosterone and no other abnormalities of the hypothalamic-
pituitary axis. In some cases, it is associated with non-
reproductive phenotypes, such as anosmia, cleft palate, and
sensorineural hearing loss. Anosmia or hyposmia is related to the
absence or hypoplasia of the olfactory bulbs and tracts.
Hypogonadism is due to deficiency in gonadotropin-releasing
hormone and probably results from a failure of embryonic migration
of gonadotropin-releasing hormone-synthesizing neurons. In the
presence of anosmia, idiopathic hypogonadotropic hypogonadism is
referred to as Kallmann syndrome, whereas in the presence of a
normal sense of smell, it has been termed normosmic idiopathic
hypogonadotropic hypogonadism (nIHH).
{ECO:0000269|PubMed:23643382}. Note=The disease is caused by
mutations affecting distinct genetic loci, including the gene
represented in this entry. Some patients carrying mutations in
FGF17 also have a mutation in another HH-associated gene including
FGFR1, HS6ST1 and FLRT3 (PubMed:23643382).
{ECO:0000269|PubMed:23643382}.
-!- SIMILARITY: Belongs to the heparin-binding growth factors family.
{ECO:0000305}.
-!- WEB RESOURCE: Name=NIEHS-SNPs;
URL="http://egp.gs.washington.edu/data/fgf17/";
-----------------------------------------------------------------------
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Distributed under the Creative Commons Attribution-NoDerivs License
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EMBL; AB009249; BAA25429.1; -; mRNA.
EMBL; AY358869; AAQ89228.1; -; mRNA.
EMBL; AF497475; AAM09570.1; -; Genomic_DNA.
EMBL; CH471080; EAW63729.1; -; Genomic_DNA.
EMBL; BC069475; AAH69475.1; -; mRNA.
EMBL; BC105131; AAI05132.1; -; mRNA.
EMBL; BC113489; AAI13490.1; -; mRNA.
EMBL; BC143789; AAI43790.1; -; mRNA.
CCDS; CCDS6019.1; -. [O60258-1]
CCDS; CCDS78310.1; -. [O60258-2]
RefSeq; NP_001291407.1; NM_001304478.1. [O60258-2]
RefSeq; NP_003858.1; NM_003867.3. [O60258-1]
UniGene; Hs.248192; -.
ProteinModelPortal; O60258; -.
SMR; O60258; -.
BioGrid; 114349; 43.
IntAct; O60258; 1.
STRING; 9606.ENSP00000352414; -.
iPTMnet; O60258; -.
PhosphoSitePlus; O60258; -.
BioMuta; FGF17; -.
PaxDb; O60258; -.
PeptideAtlas; O60258; -.
PRIDE; O60258; -.
Ensembl; ENST00000359441; ENSP00000352414; ENSG00000158815. [O60258-1]
Ensembl; ENST00000518533; ENSP00000431041; ENSG00000158815. [O60258-2]
GeneID; 8822; -.
KEGG; hsa:8822; -.
UCSC; uc003xag.4; human. [O60258-1]
CTD; 8822; -.
DisGeNET; 8822; -.
EuPathDB; HostDB:ENSG00000158815.10; -.
GeneCards; FGF17; -.
HGNC; HGNC:3673; FGF17.
HPA; HPA052600; -.
MalaCards; FGF17; -.
MIM; 603725; gene.
MIM; 615270; phenotype.
neXtProt; NX_O60258; -.
OpenTargets; ENSG00000158815; -.
Orphanet; 478; Kallmann syndrome.
Orphanet; 432; Normosmic congenital hypogonadotropic hypogonadism.
PharmGKB; PA28112; -.
eggNOG; KOG3885; Eukaryota.
eggNOG; ENOG4111IPH; LUCA.
GeneTree; ENSGT00730000110785; -.
HOGENOM; HOG000115986; -.
HOVERGEN; HBG005659; -.
InParanoid; O60258; -.
KO; K04358; -.
OMA; REVHFIK; -.
OrthoDB; EOG091G0NQH; -.
PhylomeDB; O60258; -.
TreeFam; TF331233; -.
Reactome; R-HSA-109704; PI3K Cascade.
Reactome; R-HSA-1257604; PIP3 activates AKT signaling.
Reactome; R-HSA-1839122; Signaling by activated point mutants of FGFR1.
Reactome; R-HSA-1839130; Signaling by activated point mutants of FGFR3.
Reactome; R-HSA-190322; FGFR4 ligand binding and activation.
Reactome; R-HSA-190371; FGFR3b ligand binding and activation.
Reactome; R-HSA-190372; FGFR3c ligand binding and activation.
Reactome; R-HSA-190373; FGFR1c ligand binding and activation.
Reactome; R-HSA-190375; FGFR2c ligand binding and activation.
Reactome; R-HSA-2033514; FGFR3 mutant receptor activation.
Reactome; R-HSA-2033519; Activated point mutants of FGFR2.
Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer.
Reactome; R-HSA-5654219; Phospholipase C-mediated cascade: FGFR1.
Reactome; R-HSA-5654221; Phospholipase C-mediated cascade, FGFR2.
Reactome; R-HSA-5654227; Phospholipase C-mediated cascade, FGFR3.
Reactome; R-HSA-5654228; Phospholipase C-mediated cascade, FGFR4.
Reactome; R-HSA-5654687; Downstream signaling of activated FGFR1.
Reactome; R-HSA-5654688; SHC-mediated cascade:FGFR1.
Reactome; R-HSA-5654689; PI-3K cascade:FGFR1.
Reactome; R-HSA-5654693; FRS-mediated FGFR1 signaling.
Reactome; R-HSA-5654695; PI-3K cascade:FGFR2.
Reactome; R-HSA-5654699; SHC-mediated cascade:FGFR2.
Reactome; R-HSA-5654700; FRS-mediated FGFR2 signaling.
Reactome; R-HSA-5654704; SHC-mediated cascade:FGFR3.
Reactome; R-HSA-5654706; FRS-mediated FGFR3 signaling.
Reactome; R-HSA-5654710; PI-3K cascade:FGFR3.
Reactome; R-HSA-5654712; FRS-mediated FGFR4 signaling.
Reactome; R-HSA-5654719; SHC-mediated cascade:FGFR4.
Reactome; R-HSA-5654720; PI-3K cascade:FGFR4.
Reactome; R-HSA-5654726; Negative regulation of FGFR1 signaling.
Reactome; R-HSA-5654727; Negative regulation of FGFR2 signaling.
Reactome; R-HSA-5654732; Negative regulation of FGFR3 signaling.
Reactome; R-HSA-5654733; Negative regulation of FGFR4 signaling.
Reactome; R-HSA-5655253; Signaling by FGFR2 in disease.
Reactome; R-HSA-5655302; Signaling by FGFR1 in disease.
Reactome; R-HSA-5658623; FGFRL1 modulation of FGFR1 signaling.
Reactome; R-HSA-5673001; RAF/MAP kinase cascade.
Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
Reactome; R-HSA-8853338; Signaling by FGFR3 point mutants in cancer.
SignaLink; O60258; -.
SIGNOR; O60258; -.
GeneWiki; FGF17; -.
GenomeRNAi; 8822; -.
PRO; PR:O60258; -.
Proteomes; UP000005640; Chromosome 8.
Bgee; ENSG00000158815; -.
CleanEx; HS_FGF17; -.
Genevisible; O60258; HS.
GO; GO:0005576; C:extracellular region; TAS:Reactome.
GO; GO:0005615; C:extracellular space; TAS:ProtInc.
GO; GO:0005622; C:intracellular; IEA:GOC.
GO; GO:0016303; F:1-phosphatidylinositol-3-kinase activity; TAS:Reactome.
GO; GO:0008083; F:growth factor activity; TAS:ProtInc.
GO; GO:0046934; F:phosphatidylinositol-4,5-bisphosphate 3-kinase activity; TAS:Reactome.
GO; GO:0004713; F:protein tyrosine kinase activity; TAS:Reactome.
GO; GO:0005088; F:Ras guanyl-nucleotide exchange factor activity; TAS:Reactome.
GO; GO:0005105; F:type 1 fibroblast growth factor receptor binding; IDA:UniProtKB.
GO; GO:0005111; F:type 2 fibroblast growth factor receptor binding; IDA:UniProtKB.
GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
GO; GO:0038111; P:interleukin-7-mediated signaling pathway; TAS:Reactome.
GO; GO:0000165; P:MAPK cascade; TAS:Reactome.
GO; GO:0007399; P:nervous system development; TAS:ProtInc.
GO; GO:0048015; P:phosphatidylinositol-mediated signaling; TAS:Reactome.
GO; GO:0008284; P:positive regulation of cell proliferation; IEA:Ensembl.
GO; GO:0014066; P:regulation of phosphatidylinositol 3-kinase signaling; TAS:Reactome.
GO; GO:0007165; P:signal transduction; TAS:ProtInc.
CDD; cd00058; FGF; 1.
InterPro; IPR028287; FGF17.
InterPro; IPR002209; Fibroblast_GF_fam.
InterPro; IPR008996; IL1/FGF.
PANTHER; PTHR11486; PTHR11486; 1.
PANTHER; PTHR11486:SF71; PTHR11486:SF71; 1.
Pfam; PF00167; FGF; 1.
SMART; SM00442; FGF; 1.
SUPFAM; SSF50353; SSF50353; 1.
PROSITE; PS00247; HBGF_FGF; 1.
1: Evidence at protein level;
Alternative splicing; Complete proteome; Developmental protein;
Disease mutation; Glycoprotein; Growth factor;
Hypogonadotropic hypogonadism; Kallmann syndrome; Reference proteome;
Secreted; Signal.
SIGNAL 1 22 {ECO:0000255}.
CHAIN 23 216 Fibroblast growth factor 17.
/FTId=PRO_0000008985.
CARBOHYD 137 137 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
VAR_SEQ 25 35 Missing (in isoform 2).
{ECO:0000303|PubMed:12975309,
ECO:0000303|PubMed:15489334}.
/FTId=VSP_008715.
VARIANT 108 108 I -> T (in HH20; rare variant associated
with susceptibility to disease; some
patients have a second mutation in
another HH-associated gene including
FGFR1, HS6ST1 and FLRT3; the mutant has
reduced ability to activate FGFR1;
dbSNP:rs398123024).
{ECO:0000269|PubMed:23643382}.
/FTId=VAR_069947.
VARIANT 177 177 R -> H (in HH20; the mutant has reduced
ability to activate FGFR1;
dbSNP:rs398123025).
{ECO:0000269|PubMed:23643382}.
/FTId=VAR_069948.
VARIANT 187 187 N -> S (in HH20; dbSNP:rs398123026).
{ECO:0000269|PubMed:23643382}.
/FTId=VAR_069949.
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


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