FGF8_HUMAN
ID FGF8_HUMAN Reviewed; 233 AA.
AC P55075; A1A514; Q14915; Q15766;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Fibroblast growth factor 8;
DE Short=FGF-8;
DE AltName: Full=Androgen-induced growth factor;
DE Short=AIGF;
DE AltName: Full=Heparin-binding growth factor 8;
DE Short=HBGF-8;
DE Flags: Precursor;
GN Name=FGF8; Synonyms=AIGF;
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 [GENOMIC DNA] (ISOFORM FGF-8A).
RX PubMed=7737407; DOI=10.1016/0014-5793(95)00324-3;
RA Tanaka A., Miyamoto K., Matsuo H., Matsumoto K., Yoshida H.;
RT "Human androgen-induced growth factor in prostate and breast cancer cells:
RT its molecular cloning and growth properties.";
RL FEBS Lett. 363:226-230(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS FGF-8A; FGF-8B AND FGF-8E).
RC TISSUE=Prostate;
RX PubMed=8891346;
RA Ghosh A.K., Shankar D.B., Shackleford G.M., Wu K., T'Ang A., Miller G.J.,
RA Zheng J., Roy-Burman P.;
RT "Molecular cloning and characterization of human FGF8 alternative messenger
RT RNA forms.";
RL Cell Growth Differ. 7:1425-1434(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING (ISOFORMS
RP FGF-8B; FGF-8E AND FGF-8F).
RC TISSUE=Placenta;
RX PubMed=8661131; DOI=10.1006/geno.1996.0349;
RA Gemel J., Gorry M., Ehrlich G.D., Macarthur C.A.;
RT "Structure and sequence of human FGF8.";
RL Genomics 35:253-257(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS FGF-8A AND FGF-8F).
RX PubMed=8700553;
RA Payson R.A., Wu J., Liu Y., Chiu I.-M.;
RT "The human FGF-8 gene localizes on chromosome 10q24 and is subjected to
RT induction by androgen in breast cancer cells.";
RL Oncogene 13:47-53(1996).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM FGF-8F).
RC TISSUE=Esophageal carcinoma;
RX PubMed=11341643; DOI=10.1023/a:1010753826788;
RA Tanaka S., Ueo H., Mafune K., Mori M., Wands J.R., Sugimachi K.;
RT "A novel isoform of human fibroblast growth factor 8 is induced by
RT androgens and associated with progression of esophageal carcinoma.";
RL Dig. Dis. Sci. 46:1016-1021(2001).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING (ISOFORM
RP FGF-8F).
RG NIEHS SNPs program;
RL Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases.
RN [7]
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM FGF-8A).
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 [9]
RP INTERACTION WITH FGFR3 AND FGFR4, AND FUNCTION IN CELL PROLIFERATION.
RX PubMed=8663044; DOI=10.1074/jbc.271.25.15292;
RA Ornitz D.M., Xu J., Colvin J.S., McEwen D.G., MacArthur C.A., Coulier F.,
RA Gao G., Goldfarb M.;
RT "Receptor specificity of the fibroblast growth factor family.";
RL J. Biol. Chem. 271:15292-15297(1996).
RN [10]
RP INTERACTION WITH FGFR1; FGFR2; FGFR3 AND FGFR4, AND FUNCTION IN STIMULATION
RP OF CELL 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 [11]
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 [12]
RP FUNCTION.
RX PubMed=21576111; DOI=10.1093/brain/awr084;
RA Vantaggiato C., Bondioni S., Airoldi G., Bozzato A., Borsani G.,
RA Rugarli E.I., Bresolin N., Clementi E., Bassi M.T.;
RT "Senataxin modulates neurite growth through fibroblast growth factor 8
RT signalling.";
RL Brain 134:1808-1828(2011).
RN [13]
RP INVOLVEMENT IN HYPOFP.
RX PubMed=34433009; DOI=10.1016/j.ajhg.2021.08.001;
RA Socha M., Sowinska-Seidler A., Melo U.S., Kragesteen B.K., Franke M.,
RA Heinrich V., Schoepflin R., Nagel I., Gruchy N., Mundlos S.,
RA Sreenivasan V.K.A., Lopez C., Vingron M., Bukowska-Olech E., Spielmann M.,
RA Jamsheer A.;
RT "Position effects at the FGF8 locus are associated with femoral
RT hypoplasia.";
RL Am. J. Hum. Genet. 108:1725-1734(2021).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.28 ANGSTROMS) OF 52-204 IN COMPLEX WITH FGFR2, AND
RP FUNCTION.
RX PubMed=16384934; DOI=10.1101/gad.1365406;
RA Olsen S.K., Li J.Y.H., Bromleigh C., Eliseenkova A.V., Ibrahimi O.A.,
RA Lao Z., Zhang F., Linhardt R.J., Joyner A.L., Mohammadi M.;
RT "Structural basis by which alternative splicing modulates the organizer
RT activity of FGF8 in the brain.";
RL Genes Dev. 20:185-198(2006).
RN [15]
RP VARIANTS HH6 ASN-14; LEU-26; LEU-40; GLU-89; GLY-116 AND MET-218.
RX PubMed=18596921; DOI=10.1172/jci34538;
RA Falardeau J., Chung W.C.J., Beenken A., Raivio T., Plummer L., Sidis Y.,
RA Jacobson-Dickman E.E., Eliseenkova A.V., Ma J., Dwyer A., Quinton R.,
RA Na S., Hall J.E., Huot C., Alois N., Pearce S.H., Cole L.W., Hughes V.,
RA Mohammadi M., Tsai P., Pitteloud N.;
RT "Decreased FGF8 signaling causes deficiency of gonadotropin-releasing
RT hormone in humans and mice.";
RL J. Clin. Invest. 118:2822-2831(2008).
RN [16]
RP VARIANTS HH6 LEU-40 AND GLU-89.
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, cell proliferation, cell differentiation and cell
CC migration. Required for normal brain, eye, ear and limb development
CC during embryogenesis. Required for normal development of the
CC gonadotropin-releasing hormone (GnRH) neuronal system (PubMed:16384934,
CC PubMed:16597617, PubMed:8663044). Plays a role in neurite outgrowth in
CC hippocampal cells (PubMed:21576111). {ECO:0000269|PubMed:16384934,
CC ECO:0000269|PubMed:16597617, ECO:0000269|PubMed:21576111,
CC ECO:0000269|PubMed:8663044}.
CC -!- SUBUNIT: Monomer. Homodimer. Interacts with FGFR1, FGFR2, FGFR3 and
CC FGFR4. Affinity between fibroblast growth factors (FGFs) and their
CC receptors is increased by heparan sulfate glycosaminoglycans that
CC function as coreceptors. {ECO:0000269|PubMed:16384934,
CC ECO:0000269|PubMed:16597617, ECO:0000269|PubMed:8663044}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Comment=Additional isoforms seem to exist.;
CC Name=FGF-8E;
CC IsoId=P55075-1; Sequence=Displayed;
CC Name=FGF-8A;
CC IsoId=P55075-2; Sequence=VSP_001525;
CC Name=FGF-8B;
CC IsoId=P55075-3; Sequence=VSP_001524;
CC Name=FGF-8F;
CC IsoId=P55075-4; Sequence=VSP_001526;
CC -!- DEVELOPMENTAL STAGE: In adults expression is restricted to the gonads.
CC -!- DISEASE: Hypogonadotropic hypogonadism 6 with or without anosmia (HH6)
CC [MIM:612702]: A disorder characterized by absent or incomplete sexual
CC maturation by the age of 18 years, in conjunction with low levels of
CC circulating gonadotropins and testosterone and no other abnormalities
CC of the hypothalamic-pituitary axis. In some cases, it is associated
CC with non-reproductive phenotypes, such as anosmia, cleft palate, and
CC sensorineural hearing loss. Anosmia or hyposmia is related to the
CC absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism
CC is due to deficiency in gonadotropin-releasing hormone and probably
CC results from a failure of embryonic migration of gonadotropin-releasing
CC hormone-synthesizing neurons. In the presence of anosmia, idiopathic
CC hypogonadotropic hypogonadism is referred to as Kallmann syndrome,
CC whereas in the presence of a normal sense of smell, it has been termed
CC normosmic idiopathic hypogonadotropic hypogonadism (nIHH).
CC {ECO:0000269|PubMed:18596921, ECO:0000269|PubMed:23643382}. Note=The
CC disease is caused by variants affecting distinct genetic loci,
CC including the gene represented in this entry. The genetics of
CC hypogonadotropic hypogonadism involves various modes of transmission.
CC Oligogenic inheritance has been reported in some patients carrying
CC mutations in FGF8 as well as in other HH-associated genes including
CC FGFR1 (PubMed:23643382). {ECO:0000269|PubMed:23643382}.
CC -!- DISEASE: Hypoplastic femurs and pelvis (HYPOFP) [MIM:619545]: An
CC autosomal dominant disorder characterized by isolated bilateral
CC hypoplasia of the femoral and pelvic bones.
CC {ECO:0000269|PubMed:34433009}. Note=The gene represented in this entry
CC is involved in disease pathogenesis. Duplications encompassing the FGF8
CC locus have been found in unrelated families with isolated bilateral
CC hypoplasia of the femoral and pelvic bone. The phenotype is most likely
CC the result of position effects causing altered FGF8 expression rather
CC than gene dosage. {ECO:0000269|PubMed:34433009}.
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/fgf8/";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/FGF8ID40566ch10q24.html";
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DR EMBL; S78466; AAB34255.1; -; Genomic_DNA.
DR EMBL; S78462; AAB34255.1; JOINED; Genomic_DNA.
DR EMBL; S78463; AAB34255.1; JOINED; Genomic_DNA.
DR EMBL; S78464; AAB34255.1; JOINED; Genomic_DNA.
DR EMBL; S78465; AAB34255.1; JOINED; Genomic_DNA.
DR EMBL; D38752; BAA22527.1; -; Genomic_DNA.
DR EMBL; U46213; AAB40955.1; -; mRNA.
DR EMBL; U46212; AAB40954.1; -; mRNA.
DR EMBL; U46211; AAB40953.1; -; mRNA.
DR EMBL; U47011; AAC50784.1; -; Genomic_DNA.
DR EMBL; U47009; AAC50784.1; JOINED; Genomic_DNA.
DR EMBL; U47010; AAC50784.1; JOINED; Genomic_DNA.
DR EMBL; U47011; AAC50785.1; -; Genomic_DNA.
DR EMBL; U47009; AAC50785.1; JOINED; Genomic_DNA.
DR EMBL; U47010; AAC50785.1; JOINED; Genomic_DNA.
DR EMBL; U47011; AAC50782.1; -; Genomic_DNA.
DR EMBL; U47009; AAC50782.1; JOINED; Genomic_DNA.
DR EMBL; U47010; AAC50782.1; JOINED; Genomic_DNA.
DR EMBL; U36223; AAB17893.1; -; mRNA.
DR EMBL; U36228; AAB17894.1; -; Genomic_DNA.
DR EMBL; U36225; AAB17894.1; JOINED; Genomic_DNA.
DR EMBL; U36226; AAB17894.1; JOINED; Genomic_DNA.
DR EMBL; U36227; AAB17894.1; JOINED; Genomic_DNA.
DR EMBL; U47011; AAC50783.1; -; Genomic_DNA.
DR EMBL; U47009; AAC50783.1; JOINED; Genomic_DNA.
DR EMBL; U47010; AAC50783.1; JOINED; Genomic_DNA.
DR EMBL; U56978; AAB03787.1; -; mRNA.
DR EMBL; AB014615; BAA28605.1; -; mRNA.
DR EMBL; AF520763; AAM55238.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49746.1; -; Genomic_DNA.
DR EMBL; BC128235; AAI28236.1; -; mRNA.
DR CCDS; CCDS7515.1; -. [P55075-3]
DR CCDS; CCDS7516.1; -. [P55075-4]
DR CCDS; CCDS7517.1; -. [P55075-1]
DR CCDS; CCDS7518.1; -. [P55075-2]
DR RefSeq; NP_006110.1; NM_006119.4. [P55075-3]
DR RefSeq; NP_149353.1; NM_033163.3. [P55075-4]
DR RefSeq; NP_149354.1; NM_033164.3. [P55075-1]
DR RefSeq; NP_149355.1; NM_033165.3. [P55075-2]
DR PDB; 2FDB; X-ray; 2.28 A; M/N=52-204.
DR PDBsum; 2FDB; -.
DR AlphaFoldDB; P55075; -.
DR SMR; P55075; -.
DR BioGRID; 108544; 115.
DR DIP; DIP-59630N; -.
DR IntAct; P55075; 99.
DR STRING; 9606.ENSP00000321797; -.
DR GlyGen; P55075; 1 site.
DR iPTMnet; P55075; -.
DR PhosphoSitePlus; P55075; -.
DR BioMuta; FGF8; -.
DR DMDM; 1706791; -.
DR MassIVE; P55075; -.
DR PaxDb; P55075; -.
DR PeptideAtlas; P55075; -.
DR PRIDE; P55075; -.
DR ABCD; P55075; 5 sequenced antibodies.
DR Antibodypedia; 31323; 413 antibodies from 36 providers.
DR DNASU; 2253; -.
DR Ensembl; ENST00000320185.7; ENSP00000321797.2; ENSG00000107831.14. [P55075-4]
DR Ensembl; ENST00000344255.8; ENSP00000340039.3; ENSG00000107831.14. [P55075-1]
DR Ensembl; ENST00000346714.7; ENSP00000344306.3; ENSG00000107831.14. [P55075-2]
DR Ensembl; ENST00000347978.2; ENSP00000321945.2; ENSG00000107831.14. [P55075-3]
DR GeneID; 2253; -.
DR KEGG; hsa:2253; -.
DR MANE-Select; ENST00000320185.7; ENSP00000321797.2; NM_033163.5; NP_149353.1. [P55075-4]
DR UCSC; uc001ktp.3; human. [P55075-1]
DR CTD; 2253; -.
DR DisGeNET; 2253; -.
DR GeneCards; FGF8; -.
DR GeneReviews; FGF8; -.
DR HGNC; HGNC:3686; FGF8.
DR HPA; ENSG00000107831; Tissue enriched (skeletal).
DR MalaCards; FGF8; -.
DR MIM; 600483; gene.
DR MIM; 612702; phenotype.
DR MIM; 619545; phenotype.
DR neXtProt; NX_P55075; -.
DR OpenTargets; ENSG00000107831; -.
DR Orphanet; 93925; Alobar holoprosencephaly.
DR Orphanet; 478; Kallmann syndrome.
DR Orphanet; 93924; Lobar holoprosencephaly.
DR Orphanet; 280200; Microform holoprosencephaly.
DR Orphanet; 93926; Midline interhemispheric variant of holoprosencephaly.
DR Orphanet; 432; Normosmic congenital hypogonadotropic hypogonadism.
DR Orphanet; 220386; Semilobar holoprosencephaly.
DR Orphanet; 280195; Septopreoptic holoprosencephaly.
DR PharmGKB; PA28125; -.
DR VEuPathDB; HostDB:ENSG00000107831; -.
DR eggNOG; KOG3885; Eukaryota.
DR GeneTree; ENSGT00940000159518; -.
DR HOGENOM; CLU_090682_0_1_1; -.
DR InParanoid; P55075; -.
DR OMA; NAKYEAW; -.
DR PhylomeDB; P55075; -.
DR TreeFam; TF331233; -.
DR PathwayCommons; P55075; -.
DR Reactome; R-HSA-109704; PI3K Cascade. [P55075-1]
DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling. [P55075-1]
DR Reactome; R-HSA-1839122; Signaling by activated point mutants of FGFR1. [P55075-1]
DR Reactome; R-HSA-1839130; Signaling by activated point mutants of FGFR3. [P55075-1]
DR Reactome; R-HSA-190322; FGFR4 ligand binding and activation. [P55075-1]
DR Reactome; R-HSA-190371; FGFR3b ligand binding and activation. [P55075-1]
DR Reactome; R-HSA-190372; FGFR3c ligand binding and activation. [P55075-1]
DR Reactome; R-HSA-190373; FGFR1c ligand binding and activation. [P55075-1]
DR Reactome; R-HSA-190375; FGFR2c ligand binding and activation. [P55075-1]
DR Reactome; R-HSA-2033519; Activated point mutants of FGFR2. [P55075-1]
DR Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer. [P55075-1]
DR Reactome; R-HSA-5654219; Phospholipase C-mediated cascade: FGFR1. [P55075-1]
DR Reactome; R-HSA-5654221; Phospholipase C-mediated cascade, FGFR2. [P55075-1]
DR Reactome; R-HSA-5654227; Phospholipase C-mediated cascade, FGFR3. [P55075-1]
DR Reactome; R-HSA-5654228; Phospholipase C-mediated cascade, FGFR4. [P55075-1]
DR Reactome; R-HSA-5654687; Downstream signaling of activated FGFR1. [P55075-1]
DR Reactome; R-HSA-5654688; SHC-mediated cascade:FGFR1. [P55075-1]
DR Reactome; R-HSA-5654689; PI-3K cascade:FGFR1. [P55075-1]
DR Reactome; R-HSA-5654693; FRS-mediated FGFR1 signaling. [P55075-1]
DR Reactome; R-HSA-5654695; PI-3K cascade:FGFR2. [P55075-1]
DR Reactome; R-HSA-5654699; SHC-mediated cascade:FGFR2. [P55075-1]
DR Reactome; R-HSA-5654700; FRS-mediated FGFR2 signaling. [P55075-1]
DR Reactome; R-HSA-5654704; SHC-mediated cascade:FGFR3. [P55075-1]
DR Reactome; R-HSA-5654706; FRS-mediated FGFR3 signaling. [P55075-1]
DR Reactome; R-HSA-5654710; PI-3K cascade:FGFR3. [P55075-1]
DR Reactome; R-HSA-5654712; FRS-mediated FGFR4 signaling. [P55075-1]
DR Reactome; R-HSA-5654719; SHC-mediated cascade:FGFR4. [P55075-1]
DR Reactome; R-HSA-5654720; PI-3K cascade:FGFR4. [P55075-1]
DR Reactome; R-HSA-5654726; Negative regulation of FGFR1 signaling. [P55075-1]
DR Reactome; R-HSA-5654727; Negative regulation of FGFR2 signaling. [P55075-1]
DR Reactome; R-HSA-5654732; Negative regulation of FGFR3 signaling. [P55075-1]
DR Reactome; R-HSA-5654733; Negative regulation of FGFR4 signaling. [P55075-1]
DR Reactome; R-HSA-5655253; Signaling by FGFR2 in disease. [P55075-1]
DR Reactome; R-HSA-5655302; Signaling by FGFR1 in disease. [P55075-1]
DR Reactome; R-HSA-5655332; Signaling by FGFR3 in disease. [P55075-1]
DR Reactome; R-HSA-5658623; FGFRL1 modulation of FGFR1 signaling. [P55075-1]
DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade. [P55075-1]
DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling. [P55075-1]
DR SignaLink; P55075; -.
DR SIGNOR; P55075; -.
DR BioGRID-ORCS; 2253; 12 hits in 1072 CRISPR screens.
DR EvolutionaryTrace; P55075; -.
DR GeneWiki; FGF8; -.
DR GenomeRNAi; 2253; -.
DR Pharos; P55075; Tbio.
DR PRO; PR:P55075; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; P55075; protein.
DR Bgee; ENSG00000107831; Expressed in sural nerve and 80 other tissues.
DR ExpressionAtlas; P55075; baseline and differential.
DR Genevisible; P55075; 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; IDA:UniProtKB.
DR GO; GO:0005104; F:fibroblast growth factor receptor binding; IBA:GO_Central.
DR GO; GO:0008083; F:growth factor activity; IDA:UniProtKB.
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:0009653; P:anatomical structure morphogenesis; NAS:UniProtKB.
DR GO; GO:0009887; P:animal organ morphogenesis; IBA:GO_Central.
DR GO; GO:0035909; P:aorta morphogenesis; IEA:Ensembl.
DR GO; GO:0001974; P:blood vessel remodeling; IEA:Ensembl.
DR GO; GO:0060348; P:bone development; IMP:UniProtKB.
DR GO; GO:0001569; P:branching involved in blood vessel morphogenesis; IEA:Ensembl.
DR GO; GO:0060445; P:branching involved in salivary gland morphogenesis; IEA:Ensembl.
DR GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; IEA:Ensembl.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0045165; P:cell fate commitment; IEA:Ensembl.
DR GO; GO:0090134; P:cell migration involved in mesendoderm migration; IEA:Ensembl.
DR GO; GO:0021846; P:cell proliferation in forebrain; IEA:Ensembl.
DR GO; GO:0060128; P:corticotropin hormone secreting cell differentiation; IEA:Ensembl.
DR GO; GO:0071542; P:dopaminergic neuron differentiation; IDA:UniProtKB.
DR GO; GO:0009953; P:dorsal/ventral pattern formation; IBA:GO_Central.
DR GO; GO:0035050; P:embryonic heart tube development; IBA:GO_Central.
DR GO; GO:0035116; P:embryonic hindlimb morphogenesis; IEA:Ensembl.
DR GO; GO:0048702; P:embryonic neurocranium morphogenesis; IEA:Ensembl.
DR GO; GO:0003198; P:epithelial to mesenchymal transition involved in endocardial cushion formation; ISS:BHF-UCL.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; IGI:MGI.
DR GO; GO:0021798; P:forebrain dorsal/ventral pattern formation; IEA:Ensembl.
DR GO; GO:0048853; P:forebrain morphogenesis; IEA:Ensembl.
DR GO; GO:0007369; P:gastrulation; NAS:UniProtKB.
DR GO; GO:0008406; P:gonad development; IMP:UniProtKB.
DR GO; GO:0001947; P:heart looping; IEA:Ensembl.
DR GO; GO:0003007; P:heart morphogenesis; IBA:GO_Central.
DR GO; GO:0120223; P:larynx morphogenesis; IEA:Ensembl.
DR GO; GO:0035108; P:limb morphogenesis; IBA:GO_Central.
DR GO; GO:0060425; P:lung morphogenesis; IEA:Ensembl.
DR GO; GO:0030539; P:male genitalia development; IEA:Ensembl.
DR GO; GO:0000165; P:MAPK cascade; IEA:Ensembl.
DR GO; GO:0008078; P:mesodermal cell migration; IEA:Ensembl.
DR GO; GO:0001823; P:mesonephros development; IEP:UniProtKB.
DR GO; GO:0001656; P:metanephros development; IEP:UniProtKB.
DR GO; GO:0030917; P:midbrain-hindbrain boundary development; IEA:Ensembl.
DR GO; GO:0140014; P:mitotic nuclear division; IEA:Ensembl.
DR GO; GO:0055026; P:negative regulation of cardiac muscle tissue development; IMP:BHF-UCL.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0001839; P:neural plate morphogenesis; IEA:Ensembl.
DR GO; GO:0060563; P:neuroepithelial cell differentiation; IDA:UniProtKB.
DR GO; GO:0051402; P:neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
DR GO; GO:0042476; P:odontogenesis; IEP:UniProtKB.
DR GO; GO:0035265; P:organ growth; IEA:Ensembl.
DR GO; GO:0001759; P:organ induction; IEA:Ensembl.
DR GO; GO:0030916; P:otic vesicle formation; IEA:Ensembl.
DR GO; GO:0003148; P:outflow tract septum morphogenesis; ISS:UniProtKB.
DR GO; GO:0021543; P:pallium development; IEA:Ensembl.
DR GO; GO:0060037; P:pharyngeal system development; IEA:Ensembl.
DR GO; GO:0045597; P:positive regulation of cell differentiation; TAS:ParkinsonsUK-UCL.
DR GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:0045745; P:positive regulation of G protein-coupled receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0010628; P:positive regulation of gene expression; IBA:GO_Central.
DR GO; GO:0045840; P:positive regulation of mitotic nuclear division; IEA:Ensembl.
DR GO; GO:0046622; P:positive regulation of organ growth; IEA:Ensembl.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IEA:Ensembl.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IBA:GO_Central.
DR GO; GO:2000648; P:positive regulation of stem cell proliferation; IEA:Ensembl.
DR GO; GO:0030334; P:regulation of cell migration; IBA:GO_Central.
DR GO; GO:0042487; P:regulation of odontogenesis of dentin-containing tooth; IEA:Ensembl.
DR GO; GO:0023019; P:signal transduction involved in regulation of gene expression; IEA:Ensembl.
DR GO; GO:0072089; P:stem cell proliferation; IEA:Ensembl.
DR GO; GO:0021544; P:subpallium development; IEA:Ensembl.
DR GO; GO:0030878; P:thyroid gland development; IEA:Ensembl.
DR GO; GO:0060129; P:thyroid-stimulating hormone-secreting cell differentiation; IEA:Ensembl.
DR CDD; cd00058; FGF; 1.
DR IDEAL; IID00557; -.
DR InterPro; IPR028249; FGF8.
DR InterPro; IPR002209; Fibroblast_GF_fam.
DR InterPro; IPR008996; IL1/FGF.
DR PANTHER; PTHR11486; PTHR11486; 1.
DR PANTHER; PTHR11486:SF3; PTHR11486:SF3; 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 3D-structure; Alternative splicing; Developmental protein; Differentiation;
KW Disease variant; Glycoprotein; Growth factor;
KW Hypogonadotropic hypogonadism; Kallmann syndrome; Mitogen;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..233
FT /note="Fibroblast growth factor 8"
FT /id="PRO_0000008970"
FT CARBOHYD 155
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 24..52
FT /note="Missing (in isoform FGF-8A)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:8700553, ECO:0000303|PubMed:8891346"
FT /id="VSP_001525"
FT VAR_SEQ 24..51
FT /note="EGPGRGPALGRELASLFRAGREPQGVSQ -> VTVQSSPNFT (in
FT isoform FGF-8B)"
FT /evidence="ECO:0000303|PubMed:8891346"
FT /id="VSP_001524"
FT VAR_SEQ 52
FT /note="Q -> QVTVQSSPNFTQ (in isoform FGF-8F)"
FT /evidence="ECO:0000303|PubMed:11341643,
FT ECO:0000303|PubMed:8700553"
FT /id="VSP_001526"
FT VARIANT 14
FT /note="H -> N (in HH6; phenotype consistent with normosmic
FT idiopathic hypogonadotropic hypogonadism;
FT dbSNP:rs137852659)"
FT /evidence="ECO:0000269|PubMed:18596921"
FT /id="VAR_057962"
FT VARIANT 26
FT /note="P -> L (in HH6; phenotype consistent with Kallmann
FT syndrome; dbSNP:rs137852660)"
FT /evidence="ECO:0000269|PubMed:18596921"
FT /id="VAR_057963"
FT VARIANT 40
FT /note="F -> L (in HH6; phenotype consistent with normosmic
FT idiopathic hypogonadotropic hypogonadism; some patients
FT also carry mutations in FGFR1; dbSNP:rs137852661)"
FT /evidence="ECO:0000269|PubMed:18596921,
FT ECO:0000269|PubMed:23643382"
FT /id="VAR_057964"
FT VARIANT 89
FT /note="K -> E (in HH6; phenotype consistent with normosmic
FT idiopathic hypogonadotropic hypogonadism; some patients
FT also carry mutations in FGFR1; dbSNP:rs137852662)"
FT /evidence="ECO:0000269|PubMed:18596921,
FT ECO:0000269|PubMed:23643382"
FT /id="VAR_057965"
FT VARIANT 116
FT /note="R -> G (in HH6; phenotype consistent with Kallmann
FT syndrome; dbSNP:rs137852663)"
FT /evidence="ECO:0000269|PubMed:18596921"
FT /id="VAR_057966"
FT VARIANT 218
FT /note="T -> M (in HH6; phenotype consistent with normosmic
FT idiopathic hypogonadotropic hypogonadism;
FT dbSNP:rs137852664)"
FT /evidence="ECO:0000269|PubMed:18596921"
FT /id="VAR_057967"
FT HELIX 52..57
FT /evidence="ECO:0007829|PDB:2FDB"
FT STRAND 63..65
FT /evidence="ECO:0007829|PDB:2FDB"
FT STRAND 69..76
FT /evidence="ECO:0007829|PDB:2FDB"
FT TURN 77..79
FT /evidence="ECO:0007829|PDB:2FDB"
FT STRAND 80..85
FT /evidence="ECO:0007829|PDB:2FDB"
FT STRAND 91..95
FT /evidence="ECO:0007829|PDB:2FDB"
FT HELIX 100..102
FT /evidence="ECO:0007829|PDB:2FDB"
FT STRAND 104..110
FT /evidence="ECO:0007829|PDB:2FDB"
FT TURN 111..113
FT /evidence="ECO:0007829|PDB:2FDB"
FT STRAND 114..119
FT /evidence="ECO:0007829|PDB:2FDB"
FT TURN 120..122
FT /evidence="ECO:0007829|PDB:2FDB"
FT STRAND 125..128
FT /evidence="ECO:0007829|PDB:2FDB"
FT STRAND 134..138
FT /evidence="ECO:0007829|PDB:2FDB"
FT HELIX 143..145
FT /evidence="ECO:0007829|PDB:2FDB"
FT STRAND 146..151
FT /evidence="ECO:0007829|PDB:2FDB"
FT STRAND 157..164
FT /evidence="ECO:0007829|PDB:2FDB"
FT HELIX 180..182
FT /evidence="ECO:0007829|PDB:2FDB"
FT HELIX 188..190
FT /evidence="ECO:0007829|PDB:2FDB"
FT STRAND 192..195
FT /evidence="ECO:0007829|PDB:2FDB"
SQ SEQUENCE 233 AA; 26525 MW; 4C1EAF932A3A211D CRC64;
MGSPRSALSC LLLHLLVLCL QAQEGPGRGP ALGRELASLF RAGREPQGVS QQHVREQSLV
TDQLSRRLIR TYQLYSRTSG KHVQVLANKR INAMAEDGDP FAKLIVETDT FGSRVRVRGA
ETGLYICMNK KGKLIAKSNG KGKDCVFTEI VLENNYTALQ NAKYEGWYMA FTRKGRPRKG
SKTRQHQREV HFMKRLPRGH HTTEQSLRFE FLNYPPFTRS LRGSQRTWAP EPR
