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 24-JAN-2024, entry version 198. 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/"; 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; 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 GlyCosmos; P12034; 1 site, No reported glycans. DR GlyGen; P12034; 1 site. DR iPTMnet; P12034; -. DR PhosphoSitePlus; P12034; -. DR BioMuta; FGF5; -. DR DMDM; 85700417; -. DR MassIVE; P12034; -. DR PaxDb; 9606-ENSP00000311697; -. DR PeptideAtlas; P12034; -. DR ProteomicsDB; 52818; -. [P12034-1] DR Antibodypedia; 4148; 328 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 AGR; HGNC:3683; -. DR CTD; 2250; -. DR DisGeNET; 2250; -. DR GeneCards; FGF5; -. DR HGNC; HGNC:3683; FGF5. DR HPA; ENSG00000138675; Tissue enhanced (brain, gallbladder, intestine). 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; AKFTEDC; -. DR OrthoDB; 2883843at2759; -. 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; 9 hits in 1149 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 cell types or tissues. DR ExpressionAtlas; P12034; baseline and differential. 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 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:SF23; FIBROBLAST GROWTH FACTOR 5; 1. DR Pfam; PF00167; FGF; 1. DR PRINTS; PR00263; HBGFFGF. DR PRINTS; PR00262; IL1HBGF. DR SMART; SM00442; FGF; 1. DR SUPFAM; SSF50353; Cytokine; 1. DR PROSITE; PS00247; HBGF_FGF; 1. DR Genevisible; P12034; HS. 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 //