FGF5_HUMAN
ID FGF5_HUMAN Reviewed; 268 AA.
AC P12034; B2R554; O75846; Q3Y8M3; Q8NF90;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 24-JAN-2006, sequence version 4.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Fibroblast growth factor 5;
DE Short=FGF-5;
DE AltName: Full=Heparin-binding growth factor 5;
DE Short=HBGF-5;
DE AltName: Full=Smag-82;
DE Flags: Precursor;
GN Name=FGF5;
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 LONG).
RC TISSUE=Brain stem;
RX PubMed=1700424; DOI=10.1073/pnas.87.20.8022;
RA Haub O., Drucker B., Goldfarb M.;
RT "Expression of the murine fibroblast growth factor 5 gene in the adult
RT central nervous system.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:8022-8026(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3211147; DOI=10.1128/mcb.8.8.3487-3495.1988;
RA Zhan X., Bates B., Hu X., Goldfarb M.;
RT "The human FGF-5 oncogene encodes a novel protein related to fibroblast
RT growth factors.";
RL Mol. Cell. Biol. 8:3487-3495(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
RA Ozawa K., Suzuki S., Asada M., Tomooka Y., Li A., Yoneda A., Komi A.,
RA Imamura T.;
RT "An alternatively-spliced FGF-5 mRNA is abundant in brain and translates
RT into a partial agonist/antagonist for FGF-5 neurotrophic activity.";
RL Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
RC TISSUE=Umbilical artery;
RX PubMed=10823842; DOI=10.1074/jbc.m910099199;
RA de Vries C.J.M., van Achterberg T.A.E., Horrevoets A.J.G., ten Cate J.W.,
RA Pannekoek H.;
RT "Differential display identification of 40 genes with altered expression in
RT activated human smooth muscle cells. Local expression in atherosclerotic
RT lesions of smags, smooth muscle activation-specific genes.";
RL J. Biol. Chem. 275:23939-23947(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
RX PubMed=11454700;
RA Hanada K.-I., Perry-Lalley D.M., Ohnmacht G.A., Bettinotti M.P., Yang J.C.;
RT "Identification of fibroblast growth factor-5 as an overexpressed antigen
RT in multiple human adenocarcinomas.";
RL Cancer Res. 61:5511-5516(2001).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT VAL-54.
RG NIEHS SNPs program;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS SHORT AND LONG).
RC TISSUE=Cerebellum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [8]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
RC TISSUE=Lung;
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 [10]
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 [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 INVOLVEMENT IN TCMGLY, AND VARIANT TCMGLY HIS-174.
RX PubMed=24989505; DOI=10.1073/pnas.1402862111;
RA Higgins C.A., Petukhova L., Harel S., Ho Y.Y., Drill E., Shapiro L.,
RA Wajid M., Christiano A.M.;
RT "FGF5 is a crucial regulator of hair length in humans.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:10648-10653(2014).
CC -!- FUNCTION: Plays an important role in the regulation of cell
CC proliferation and cell differentiation. Required for normal regulation
CC of the hair growth cycle. Functions as an inhibitor of hair elongation
CC by promoting progression from anagen, the growth phase of the hair
CC follicle, into catagen the apoptosis-induced regression phase (By
CC similarity). {ECO:0000250|UniProtKB:Q20FD0,
CC 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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=P12034-1; Sequence=Displayed;
CC Name=Short; Synonyms=FGF-5S;
CC IsoId=P12034-2; Sequence=VSP_001518, VSP_001519;
CC -!- TISSUE SPECIFICITY: Expressed in neonatal brain.
CC -!- DEVELOPMENTAL STAGE: Can transform NIH 3T3 cells.
CC -!- DISEASE: Trichomegaly (TCMGLY) [MIM:190330]: A morphologic trait
CC characterized by unusually long eyelashes and mild hypertrichosis of
CC eyebrows. It can be observed in association with corneal irritation,
CC cataracts, and hereditary spherocytosis. {ECO:0000269|PubMed:24989505}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- MISCELLANEOUS: [Isoform Short]: Seems to have an antagonistic effect
CC compared to that of the isoform Long. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the heparin-binding growth factors family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB60698.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/fgf5/";
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DR EMBL; M37825; AAB06463.1; -; mRNA.
DR EMBL; M23536; AAB60699.1; -; Genomic_DNA.
DR EMBL; M23534; AAB60699.1; JOINED; Genomic_DNA.
DR EMBL; M23535; AAB60699.1; JOINED; Genomic_DNA.
DR EMBL; M23534; AAB60698.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AB016517; BAA33738.1; -; mRNA.
DR EMBL; AF171928; AAF89742.1; -; mRNA.
DR EMBL; AF535149; AAN04097.1; -; mRNA.
DR EMBL; DQ151636; AAZ67914.1; -; Genomic_DNA.
DR EMBL; AK291962; BAF84651.1; -; mRNA.
DR EMBL; AK312065; BAG35001.1; -; mRNA.
DR EMBL; CH471057; EAX05859.1; -; Genomic_DNA.
DR EMBL; CH471057; EAX05860.1; -; Genomic_DNA.
DR EMBL; BC074858; AAH74858.1; -; mRNA.
DR EMBL; BC074859; AAH74859.1; -; mRNA.
DR EMBL; BC131502; AAI31503.1; -; mRNA.
DR CCDS; CCDS34021.1; -. [P12034-1]
DR CCDS; CCDS3586.1; -. [P12034-2]
DR PIR; A31194; TVHUF5.
DR PIR; B31194; B31194.
DR RefSeq; NP_004455.2; NM_004464.3. [P12034-1]
DR RefSeq; NP_149134.1; NM_033143.2. [P12034-2]
DR AlphaFoldDB; P12034; -.
DR SMR; P12034; -.
DR BioGRID; 108541; 6.
DR DIP; DIP-4018N; -.
DR IntAct; P12034; 4.
DR STRING; 9606.ENSP00000311697; -.
DR GlyGen; P12034; 1 site.
DR iPTMnet; P12034; -.
DR PhosphoSitePlus; P12034; -.
DR BioMuta; FGF5; -.
DR DMDM; 85700417; -.
DR MassIVE; P12034; -.
DR PaxDb; P12034; -.
DR PeptideAtlas; P12034; -.
DR PRIDE; P12034; -.
DR ProteomicsDB; 52818; -. [P12034-1]
DR Antibodypedia; 4148; 296 antibodies from 37 providers.
DR DNASU; 2250; -.
DR Ensembl; ENST00000312465.12; ENSP00000311697.7; ENSG00000138675.17. [P12034-1]
DR Ensembl; ENST00000456523.3; ENSP00000398353.3; ENSG00000138675.17. [P12034-2]
DR GeneID; 2250; -.
DR KEGG; hsa:2250; -.
DR MANE-Select; ENST00000312465.12; ENSP00000311697.7; NM_004464.4; NP_004455.2.
DR UCSC; uc003hmd.4; human. [P12034-1]
DR CTD; 2250; -.
DR DisGeNET; 2250; -.
DR GeneCards; FGF5; -.
DR HGNC; HGNC:3683; FGF5.
DR HPA; ENSG00000138675; Group enriched (brain, gallbladder).
DR MalaCards; FGF5; -.
DR MIM; 165190; gene.
DR MIM; 190330; phenotype.
DR neXtProt; NX_P12034; -.
DR OpenTargets; ENSG00000138675; -.
DR Orphanet; 411788; Familial isolated trichomegaly.
DR PharmGKB; PA28122; -.
DR VEuPathDB; HostDB:ENSG00000138675; -.
DR eggNOG; KOG3885; Eukaryota.
DR GeneTree; ENSGT00940000158449; -.
DR HOGENOM; CLU_081609_7_0_1; -.
DR InParanoid; P12034; -.
DR OMA; TQVKYWP; -.
DR PhylomeDB; P12034; -.
DR TreeFam; TF317805; -.
DR PathwayCommons; P12034; -.
DR Reactome; R-HSA-109704; PI3K Cascade. [P12034-1]
DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling. [P12034-1]
DR Reactome; R-HSA-1839122; Signaling by activated point mutants of FGFR1. [P12034-1]
DR Reactome; R-HSA-1839130; Signaling by activated point mutants of FGFR3. [P12034-1]
DR Reactome; R-HSA-190372; FGFR3c ligand binding and activation. [P12034-1]
DR Reactome; R-HSA-190373; FGFR1c ligand binding and activation. [P12034-1]
DR Reactome; R-HSA-190375; FGFR2c ligand binding and activation. [P12034-1]
DR Reactome; R-HSA-2033519; Activated point mutants of FGFR2. [P12034-1]
DR Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer. [P12034-1]
DR Reactome; R-HSA-5654219; Phospholipase C-mediated cascade: FGFR1. [P12034-1]
DR Reactome; R-HSA-5654221; Phospholipase C-mediated cascade, FGFR2. [P12034-1]
DR Reactome; R-HSA-5654227; Phospholipase C-mediated cascade, FGFR3. [P12034-1]
DR Reactome; R-HSA-5654687; Downstream signaling of activated FGFR1. [P12034-1]
DR Reactome; R-HSA-5654688; SHC-mediated cascade:FGFR1. [P12034-1]
DR Reactome; R-HSA-5654689; PI-3K cascade:FGFR1. [P12034-1]
DR Reactome; R-HSA-5654693; FRS-mediated FGFR1 signaling. [P12034-1]
DR Reactome; R-HSA-5654695; PI-3K cascade:FGFR2. [P12034-1]
DR Reactome; R-HSA-5654699; SHC-mediated cascade:FGFR2. [P12034-1]
DR Reactome; R-HSA-5654700; FRS-mediated FGFR2 signaling. [P12034-1]
DR Reactome; R-HSA-5654704; SHC-mediated cascade:FGFR3. [P12034-1]
DR Reactome; R-HSA-5654706; FRS-mediated FGFR3 signaling. [P12034-1]
DR Reactome; R-HSA-5654710; PI-3K cascade:FGFR3. [P12034-1]
DR Reactome; R-HSA-5654726; Negative regulation of FGFR1 signaling. [P12034-1]
DR Reactome; R-HSA-5654727; Negative regulation of FGFR2 signaling. [P12034-1]
DR Reactome; R-HSA-5654732; Negative regulation of FGFR3 signaling. [P12034-1]
DR Reactome; R-HSA-5655253; Signaling by FGFR2 in disease. [P12034-1]
DR Reactome; R-HSA-5655302; Signaling by FGFR1 in disease. [P12034-1]
DR Reactome; R-HSA-5655332; Signaling by FGFR3 in disease. [P12034-1]
DR Reactome; R-HSA-5658623; FGFRL1 modulation of FGFR1 signaling. [P12034-1]
DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade. [P12034-1]
DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling. [P12034-1]
DR SignaLink; P12034; -.
DR SIGNOR; P12034; -.
DR BioGRID-ORCS; 2250; 8 hits in 1071 CRISPR screens.
DR ChiTaRS; FGF5; human.
DR GeneWiki; FGF5; -.
DR GenomeRNAi; 2250; -.
DR Pharos; P12034; Tbio.
DR PRO; PR:P12034; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; P12034; protein.
DR Bgee; ENSG00000138675; Expressed in buccal mucosa cell and 78 other tissues.
DR ExpressionAtlas; P12034; baseline and differential.
DR Genevisible; P12034; 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; IDA:MGI.
DR GO; GO:0008083; F:growth factor activity; IBA:GO_Central.
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; IDA:MGI.
DR GO; GO:0010001; P:glial cell differentiation; IEA:Ensembl.
DR GO; GO:0007399; P:nervous system development; TAS:ProtInc.
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: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:0023019; P:signal transduction involved in regulation of gene expression; IEA:Ensembl.
DR CDD; cd00058; FGF; 1.
DR InterPro; IPR028240; FGF5.
DR InterPro; IPR002209; Fibroblast_GF_fam.
DR InterPro; IPR008996; IL1/FGF.
DR PANTHER; PTHR11486; PTHR11486; 1.
DR PANTHER; PTHR11486:SF23; PTHR11486:SF23; 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 Alternative splicing; Disease variant; Glycoprotein; Growth factor;
KW Mitogen; Proto-oncogene; Reference proteome; Secreted; Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..268
FT /note="Fibroblast growth factor 5"
FT /id="PRO_0000008958"
FT REGION 26..81
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 233..255
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 38..81
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 110
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 120..123
FT /note="VLEI -> QVHR (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:10823842,
FT ECO:0000303|PubMed:14702039, ECO:0000303|Ref.3"
FT /id="VSP_001518"
FT VAR_SEQ 124..268
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:10823842,
FT ECO:0000303|PubMed:14702039, ECO:0000303|Ref.3"
FT /id="VSP_001519"
FT VARIANT 54
FT /note="M -> V (in dbSNP:rs33950145)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_025174"
FT VARIANT 174
FT /note="Y -> H (in TCMGLY; dbSNP:rs587777581)"
FT /evidence="ECO:0000269|PubMed:24989505"
FT /id="VAR_072566"
FT CONFLICT 42
FT /note="R -> I (in Ref. 1; AAB06463)"
FT /evidence="ECO:0000305"
FT CONFLICT 83..86
FT /note="PSGR -> LGA (in Ref. 2; AAB60699)"
FT /evidence="ECO:0000305"
FT CONFLICT 224
FT /note="Q -> QQ (in Ref. 6; AAZ67914)"
FT /evidence="ECO:0000305"
FT CONFLICT 238
FT /note="K -> N (in Ref. 1; AAB06463 and 2; AAB60699)"
FT /evidence="ECO:0000305"
FT CONFLICT 245
FT /note="P -> S (in Ref. 1; AAB06463 and 2; AAB60699)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 268 AA; 29551 MW; 28B7268B26781BCF CRC64;
MSLSFLLLLF FSHLILSAWA HGEKRLAPKG QPGPAATDRN PRGSSSRQSS SSAMSSSSAS
SSPAASLGSQ GSGLEQSSFQ WSPSGRRTGS LYCRVGIGFH LQIYPDGKVN GSHEANMLSV
LEIFAVSQGI VGIRGVFSNK FLAMSKKGKL HASAKFTDDC KFRERFQENS YNTYASAIHR
TEKTGREWYV ALNKRGKAKR GCSPRVKPQH ISTHFLPRFK QSEQPELSFT VTVPEKKKPP
SPIKPKIPLS APRKNTNSVK YRLKFRFG
