FGF3_HUMAN
ID FGF3_HUMAN Reviewed; 239 AA.
AC P11487; Q0VG69;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1989, sequence version 1.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Fibroblast growth factor 3;
DE Short=FGF-3;
DE AltName: Full=Heparin-binding growth factor 3;
DE Short=HBGF-3;
DE AltName: Full=Proto-oncogene Int-2;
DE Flags: Precursor;
GN Name=FGF3; Synonyms=INT2;
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].
RC TISSUE=Placenta;
RX PubMed=2470007;
RA Brooks S., Smith R., Casey G., Dickson C., Peters G.;
RT "Sequence organization of the human int-2 gene and its expression in
RT teratocarcinoma cells.";
RL Oncogene 4:429-436(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [3]
RP INTERACTION WITH FGFR1 AND FGFR2, 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 [4]
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 [5]
RP VARIANT LAMM PRO-156.
RX PubMed=17236138; DOI=10.1086/510920;
RA Tekin M., Hismi B.O., Fitoz S., Oezdag H., Cengiz F.B., Sirmaci A.,
RA Aslan I., Inceoglu B., Yueksel-Konuk E.B., Yilmaz S.T., Yasun O., Akar N.;
RT "Homozygous mutations in fibroblast growth factor 3 are associated with a
RT new form of syndromic deafness characterized by inner ear agenesis,
RT microtia, and microdontia.";
RL Am. J. Hum. Genet. 80:338-344(2007).
RN [6]
RP VARIANT LAMM PRO-6.
RX PubMed=18435799; DOI=10.1111/j.1399-0004.2008.01004.x;
RA Tekin M., Ozturkmen Akay H., Fitoz S., Birnbaum S., Cengiz F.B.,
RA Sennaroglu L., Incesulu A., Yuksel Konuk E.B., Hasanefendioglu Bayrak A.,
RA Senturk S., Cebeci I., Utine G.E., Tuncbilek E., Nance W.E., Duman D.;
RT "Homozygous FGF3 mutations result in congenital deafness with inner ear
RT agenesis, microtia, and microdontia.";
RL Clin. Genet. 73:554-565(2008).
CC -!- FUNCTION: Plays an important role in the regulation of embryonic
CC development, cell proliferation, and cell differentiation. Required for
CC normal ear development. {ECO:0000269|PubMed:8663044}.
CC -!- SUBUNIT: Interacts with FGFR1 and FGFR2. Affinity between fibroblast
CC growth factors (FGFs) and their receptors is increased by heparan
CC sulfate glycosaminoglycans that function as coreceptors.
CC {ECO:0000269|PubMed:8663044}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC -!- DISEASE: Deafness with labyrinthine aplasia, microtia and microdontia
CC (LAMM) [MIM:610706]: Unique autosomal recessive syndrome characterized
CC by type I microtia, microdontia, and profound congenital deafness
CC associated with a complete absence of inner ear structures (Michel
CC aplasia). {ECO:0000269|PubMed:17236138, ECO:0000269|PubMed:18435799}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the heparin-binding growth factors family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X14445; CAA32615.1; -; Genomic_DNA.
DR EMBL; BC113739; AAI13740.1; -; mRNA.
DR CCDS; CCDS8195.1; -.
DR PIR; S04742; S04742.
DR RefSeq; NP_005238.1; NM_005247.2.
DR AlphaFoldDB; P11487; -.
DR SMR; P11487; -.
DR BioGRID; 108539; 64.
DR DIP; DIP-4014N; -.
DR IntAct; P11487; 52.
DR STRING; 9606.ENSP00000334122; -.
DR GlyGen; P11487; 1 site.
DR iPTMnet; P11487; -.
DR PhosphoSitePlus; P11487; -.
DR BioMuta; FGF3; -.
DR DMDM; 122748; -.
DR MassIVE; P11487; -.
DR PaxDb; P11487; -.
DR PeptideAtlas; P11487; -.
DR PRIDE; P11487; -.
DR ProteomicsDB; 52783; -.
DR Antibodypedia; 2164; 217 antibodies from 27 providers.
DR DNASU; 2248; -.
DR Ensembl; ENST00000334134.4; ENSP00000334122.2; ENSG00000186895.4.
DR GeneID; 2248; -.
DR KEGG; hsa:2248; -.
DR MANE-Select; ENST00000334134.4; ENSP00000334122.2; NM_005247.4; NP_005238.1.
DR UCSC; uc001oph.4; human.
DR CTD; 2248; -.
DR DisGeNET; 2248; -.
DR GeneCards; FGF3; -.
DR GeneReviews; FGF3; -.
DR HGNC; HGNC:3681; FGF3.
DR HPA; ENSG00000186895; Tissue enriched (brain).
DR MalaCards; FGF3; -.
DR MIM; 164950; gene.
DR MIM; 610706; phenotype.
DR neXtProt; NX_P11487; -.
DR OpenTargets; ENSG00000186895; -.
DR Orphanet; 90024; Deafness with labyrinthine aplasia, microtia, and microdontia.
DR Orphanet; 99806; Oculootodental syndrome.
DR Orphanet; 2791; Otodental syndrome.
DR PharmGKB; PA28120; -.
DR VEuPathDB; HostDB:ENSG00000186895; -.
DR eggNOG; KOG3885; Eukaryota.
DR GeneTree; ENSGT00940000161128; -.
DR HOGENOM; CLU_081609_1_0_1; -.
DR InParanoid; P11487; -.
DR OMA; TLLQEPW; -.
DR OrthoDB; 1157770at2759; -.
DR PhylomeDB; P11487; -.
DR TreeFam; TF317805; -.
DR PathwayCommons; P11487; -.
DR Reactome; R-HSA-109704; PI3K Cascade.
DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling.
DR Reactome; R-HSA-190370; FGFR1b ligand binding and activation.
DR Reactome; R-HSA-190377; FGFR2b 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-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-5654726; Negative regulation of FGFR1 signaling.
DR Reactome; R-HSA-5654727; Negative regulation of FGFR2 signaling.
DR Reactome; R-HSA-5655253; Signaling by FGFR2 in disease.
DR Reactome; R-HSA-5658623; FGFRL1 modulation of FGFR1 signaling.
DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade.
DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR SignaLink; P11487; -.
DR SIGNOR; P11487; -.
DR BioGRID-ORCS; 2248; 8 hits in 1062 CRISPR screens.
DR GeneWiki; FGF3; -.
DR GenomeRNAi; 2248; -.
DR Pharos; P11487; Tbio.
DR PRO; PR:P11487; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P11487; protein.
DR Bgee; ENSG00000186895; Expressed in cerebellar hemisphere and 18 other tissues.
DR Genevisible; P11487; 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:0009653; P:anatomical structure morphogenesis; TAS:ProtInc.
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; IGI:MGI.
DR GO; GO:0055026; P:negative regulation of cardiac muscle tissue development; IMP:BHF-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; IGI:MGI.
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; IPR028232; FGF3.
DR InterPro; IPR002209; Fibroblast_GF_fam.
DR InterPro; IPR008996; IL1/FGF.
DR PANTHER; PTHR11486; PTHR11486; 1.
DR PANTHER; PTHR11486:SF26; PTHR11486:SF26; 1.
DR Pfam; PF00167; FGF; 1.
DR PRINTS; PR00263; HBGFFGF.
DR SMART; SM00442; FGF; 1.
DR SUPFAM; SSF50353; SSF50353; 1.
DR PROSITE; PS00247; HBGF_FGF; 1.
PE 1: Evidence at protein level;
KW Developmental protein; Differentiation; Disease variant; Glycoprotein;
KW Growth factor; Mitogen; Proto-oncogene; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..239
FT /note="Fibroblast growth factor 3"
FT /id="PRO_0000008946"
FT REGION 193..239
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 219..239
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 65
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 6
FT /note="L -> P (in LAMM; probably impairs secretion;
FT dbSNP:rs121917706)"
FT /evidence="ECO:0000269|PubMed:18435799"
FT /id="VAR_060492"
FT VARIANT 156
FT /note="S -> P (in LAMM; dbSNP:rs121917703)"
FT /evidence="ECO:0000269|PubMed:17236138"
FT /id="VAR_031848"
SQ SEQUENCE 239 AA; 26887 MW; 8DBEF17D2B2E3C63 CRC64;
MGLIWLLLLS LLEPGWPAAG PGARLRRDAG GRGGVYEHLG GAPRRRKLYC ATKYHLQLHP
SGRVNGSLEN SAYSILEITA VEVGIVAIRG LFSGRYLAMN KRGRLYASEH YSAECEFVER
IHELGYNTYA SRLYRTVSST PGARRQPSAE RLWYVSVNGK GRPRRGFKTR RTQKSSLFLP
RVLDHRDHEM VRQLQSGLPR PPGKGVQPRR RRQKQSPDNL EPSHVQASRL GSQLEASAH
