ID FGF18_HUMAN Reviewed; 207 AA. AC O76093; D3DQL7; Q6UWF1; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1998, sequence version 1. DT 13-FEB-2019, entry version 160. DE RecName: Full=Fibroblast growth factor 18; DE Short=FGF-18; DE AltName: Full=zFGF5; DE Flags: Precursor; GN Name=FGF18; ORFNames=UNQ420/PRO856; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=9742123; DOI=10.1128/MCB.18.10.6063; RA Hu M.C.-T., Qiu W.R., Wang Y.-P., Hill D., Ring B.D., Scully S., RA Bolon B., Derose M., Luethy R., Simonet W.S., Arakawa T., RA Danilenko D.M.; RT "FGF-18, a novel member of the fibroblast growth factor family, RT stimulates hepatic and intestinal proliferation."; RL Mol. Cell. Biol. 18:6063-6074(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Lung; RX PubMed=9660775; DOI=10.1074/jbc.273.29.18161; RA Ohbayashi N., Hoshikawa M., Kimura S., Yamasaki M., Fukui S., Ito N.; RT "Structure and expression of the mRNA encoding a novel fibroblast RT growth factor, FGF-18."; RL J. Biol. Chem. 273:18161-18164(1998). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Deisher T., Conklin D., Raymond F., Bukowski T., Holderman S., RA Hansen B., Sheppard P., O'Hara P.; RT "Homo sapiens homologue of fibroblast growth factor."; RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor RT vector."; RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Ovary; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-156. RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., RA Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., RA Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., RA Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., RA Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., RA Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., RA Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale RT effort to identify novel human secreted and transmembrane proteins: a RT bioinformatics assessment."; RL Genome Res. 13:2265-2270(2003). RN [8] RP INTERACTION WITH FGFR3 AND FGFR4, AND FUNCTION IN STIMULATION OF CELL RP PROLIFERATION. RX PubMed=16597617; DOI=10.1074/jbc.M601252200; RA Zhang X., Ibrahimi O.A., Olsen S.K., Umemori H., Mohammadi M., RA Ornitz D.M.; RT "Receptor specificity of the fibroblast growth factor family. The RT complete mammalian FGF family."; RL J. Biol. Chem. 281:15694-15700(2006). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY, AND DISULFIDE BOND. RA Vilbois F.; RL Submitted (MAR-2010) to UniProtKB. RN [10] 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). CC -!- FUNCTION: Plays an important role in the regulation of cell CC proliferation, cell differentiation and cell migration. Required CC for normal ossification and bone development. Stimulates hepatic CC and intestinal proliferation. {ECO:0000269|PubMed:16597617}. CC -!- SUBUNIT: Interacts with FGFR3 and FGFR4. CC {ECO:0000269|PubMed:16597617}. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}. 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; AF075292; AAC62240.1; -; mRNA. DR EMBL; AB007422; BAA31986.1; -; mRNA. DR EMBL; AF211188; AAF22977.1; -; mRNA. DR EMBL; BT019570; AAV38377.1; -; mRNA. DR EMBL; BT019571; AAV38378.1; -; mRNA. DR EMBL; CH471062; EAW61441.1; -; Genomic_DNA. DR EMBL; CH471062; EAW61442.1; -; Genomic_DNA. DR EMBL; BC006245; AAH06245.1; -; mRNA. DR EMBL; AY358811; AAQ89954.1; -; mRNA. DR CCDS; CCDS4378.1; -. DR RefSeq; NP_003853.1; NM_003862.2. DR UniGene; Hs.87191; -. DR PDB; 4CJM; X-ray; 2.70 A; A/B/C/D=50-190. DR PDBsum; 4CJM; -. DR ProteinModelPortal; O76093; -. DR SMR; O76093; -. DR BioGrid; 114344; 1. DR IntAct; O76093; 1. DR STRING; 9606.ENSP00000274625; -. DR iPTMnet; O76093; -. DR PhosphoSitePlus; O76093; -. DR BioMuta; FGF18; -. DR EPD; O76093; -. DR PaxDb; O76093; -. DR PeptideAtlas; O76093; -. DR PRIDE; O76093; -. DR ProteomicsDB; 50411; -. DR DNASU; 8817; -. DR Ensembl; ENST00000274625; ENSP00000274625; ENSG00000156427. DR GeneID; 8817; -. DR KEGG; hsa:8817; -. DR UCSC; uc003mbk.4; human. DR CTD; 8817; -. DR DisGeNET; 8817; -. DR EuPathDB; HostDB:ENSG00000156427.7; -. DR GeneCards; FGF18; -. DR HGNC; HGNC:3674; FGF18. DR HPA; HPA018795; -. DR MIM; 603726; gene. DR neXtProt; NX_O76093; -. DR OpenTargets; ENSG00000156427; -. DR PharmGKB; PA28113; -. DR eggNOG; KOG3885; Eukaryota. DR eggNOG; ENOG4111IPH; LUCA. DR GeneTree; ENSGT00940000159553; -. DR HOGENOM; HOG000115986; -. DR HOVERGEN; HBG005659; -. DR InParanoid; O76093; -. DR KO; K04358; -. DR OMA; MFVAEEN; -. DR OrthoDB; 1190450at2759; -. DR PhylomeDB; O76093; -. DR TreeFam; TF331233; -. DR Reactome; R-HSA-109704; PI3K Cascade. DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling. DR Reactome; R-HSA-1839130; Signaling by activated point mutants of FGFR3. DR Reactome; R-HSA-190322; FGFR4 ligand binding and activation. DR Reactome; R-HSA-190371; FGFR3b ligand binding and activation. DR Reactome; R-HSA-190372; FGFR3c ligand binding and activation. DR Reactome; R-HSA-190375; FGFR2c ligand binding and activation. DR Reactome; R-HSA-2033514; FGFR3 mutant receptor 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-5654221; Phospholipase C-mediated cascade, FGFR2. DR Reactome; R-HSA-5654227; Phospholipase C-mediated cascade, FGFR3. DR Reactome; R-HSA-5654228; Phospholipase C-mediated cascade, FGFR4. 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-5654704; SHC-mediated cascade:FGFR3. DR Reactome; R-HSA-5654706; FRS-mediated FGFR3 signaling. DR Reactome; R-HSA-5654710; PI-3K cascade:FGFR3. DR Reactome; R-HSA-5654712; FRS-mediated FGFR4 signaling. DR Reactome; R-HSA-5654719; SHC-mediated cascade:FGFR4. DR Reactome; R-HSA-5654720; PI-3K cascade:FGFR4. DR Reactome; R-HSA-5654727; Negative regulation of FGFR2 signaling. DR Reactome; R-HSA-5654732; Negative regulation of FGFR3 signaling. DR Reactome; R-HSA-5654733; Negative regulation of FGFR4 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 Reactome; R-HSA-8853338; Signaling by FGFR3 point mutants in cancer. DR SignaLink; O76093; -. DR SIGNOR; O76093; -. DR ChiTaRS; FGF18; human. DR GeneWiki; FGF18; -. DR GenomeRNAi; 8817; -. DR PRO; PR:O76093; -. DR Proteomes; UP000005640; Chromosome 5. DR Bgee; ENSG00000156427; Expressed in 114 organ(s), highest expression level in myocardium. DR Genevisible; O76093; HS. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; TAS:ProtInc. DR GO; GO:0005730; C:nucleolus; IDA:LIFEdb. DR GO; GO:0016303; F:1-phosphatidylinositol-3-kinase activity; TAS:Reactome. DR GO; GO:0008083; F:growth factor activity; TAS:ProtInc. DR GO; GO:0046934; F:phosphatidylinositol-4,5-bisphosphate 3-kinase activity; TAS:Reactome. DR GO; GO:0004713; F:protein tyrosine kinase activity; TAS:Reactome. DR GO; GO:0005088; F:Ras guanyl-nucleotide exchange factor activity; TAS:Reactome. 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; TAS:ProtInc. DR GO; GO:0001525; P:angiogenesis; IEA:Ensembl. DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc. DR GO; GO:0002063; P:chondrocyte development; IEA:Ensembl. DR GO; GO:0001958; P:endochondral ossification; IEA:Ensembl. DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome. DR GO; GO:0001957; P:intramembranous ossification; IEA:Ensembl. DR GO; GO:0030324; P:lung development; IEA:Ensembl. DR GO; GO:0000165; P:MAPK cascade; TAS:Reactome. DR GO; GO:0045766; P:positive regulation of angiogenesis; IGI:BHF-UCL. DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; IGI:BHF-UCL. DR GO; GO:0008284; P:positive regulation of cell population proliferation; TAS:ProtInc. DR GO; GO:0032332; P:positive regulation of chondrocyte differentiation; IEA:Ensembl. DR GO; GO:2000546; P:positive regulation of endothelial cell chemotaxis to fibroblast growth factor; IDA:UniProtKB. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Ensembl. DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IDA:UniProtKB. DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; TAS:Reactome. DR GO; GO:0030949; P:positive regulation of vascular endothelial growth factor receptor signaling pathway; IEA:Ensembl. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR CDD; cd00058; FGF; 1. DR InterPro; IPR028289; FGF18. DR InterPro; IPR002209; Fibroblast_GF_fam. DR InterPro; IPR008996; IL1/FGF. DR PANTHER; PTHR11486; PTHR11486; 1. DR PANTHER; PTHR11486:SF124; PTHR11486:SF124; 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; Complete proteome; Disulfide bond; Glycoprotein; KW Growth factor; Reference proteome; Secreted; Signal. FT SIGNAL 1 27 {ECO:0000255}. FT CHAIN 28 207 Fibroblast growth factor 18. FT /FTId=PRO_0000008990. FT CARBOHYD 39 39 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 137 137 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 109 127 {ECO:0000269|Ref.9}. FT STRAND 52 59 {ECO:0000244|PDB:4CJM}. FT TURN 60 62 {ECO:0000244|PDB:4CJM}. FT STRAND 63 68 {ECO:0000244|PDB:4CJM}. FT STRAND 73 77 {ECO:0000244|PDB:4CJM}. FT HELIX 82 84 {ECO:0000244|PDB:4CJM}. FT STRAND 86 90 {ECO:0000244|PDB:4CJM}. FT STRAND 94 101 {ECO:0000244|PDB:4CJM}. FT TURN 102 104 {ECO:0000244|PDB:4CJM}. FT STRAND 107 110 {ECO:0000244|PDB:4CJM}. FT STRAND 116 120 {ECO:0000244|PDB:4CJM}. FT HELIX 125 127 {ECO:0000244|PDB:4CJM}. FT STRAND 129 133 {ECO:0000244|PDB:4CJM}. FT STRAND 139 146 {ECO:0000244|PDB:4CJM}. FT HELIX 162 164 {ECO:0000244|PDB:4CJM}. FT HELIX 170 172 {ECO:0000244|PDB:4CJM}. FT STRAND 174 177 {ECO:0000244|PDB:4CJM}. SQ SEQUENCE 207 AA; 23989 MW; 57F69E7B30181500 CRC64; MYSAPSACTC LCLHFLLLCF QVQVLVAEEN VDFRIHVENQ TRARDDVSRK QLRLYQLYSR TSGKHIQVLG RRISARGEDG DKYAQLLVET DTFGSQVRIK GKETEFYLCM NRKGKLVGKP DGTSKECVFI EKVLENNYTA LMSAKYSGWY VGFTKKGRPR KGPKTRENQQ DVHFMKRYPK GQPELQKPFK YTTVTKRSRR IRPTHPA //