FGF18_HUMAN
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 03-AUG-2022, entry version 175.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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., Bolon B.,
RA Derose M., Luethy R., Simonet W.S., Arakawa T., Danilenko D.M.;
RT "FGF-18, a novel member of the fibroblast growth factor family, stimulates
RT 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 growth
RT 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., Hansen B.,
RA 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 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., 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 [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 project:
RT 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., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT 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., 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 [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 for
CC normal ossification and bone development. Stimulates hepatic and
CC intestinal proliferation. {ECO:0000269|PubMed:16597617}.
CC -!- SUBUNIT: Interacts with FGFR3 and FGFR4. {ECO:0000269|PubMed:16597617}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the heparin-binding growth factors family.
CC {ECO:0000305}.
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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 PDB; 4CJM; X-ray; 2.70 A; A/B/C/D=50-190.
DR PDBsum; 4CJM; -.
DR AlphaFoldDB; O76093; -.
DR SMR; O76093; -.
DR BioGRID; 114344; 2.
DR IntAct; O76093; 1.
DR STRING; 9606.ENSP00000274625; -.
DR GlyGen; O76093; 2 sites.
DR iPTMnet; O76093; -.
DR PhosphoSitePlus; O76093; -.
DR BioMuta; FGF18; -.
DR EPD; O76093; -.
DR MassIVE; O76093; -.
DR PaxDb; O76093; -.
DR PeptideAtlas; O76093; -.
DR PRIDE; O76093; -.
DR ProteomicsDB; 50411; -.
DR Antibodypedia; 16955; 235 antibodies from 30 providers.
DR DNASU; 8817; -.
DR Ensembl; ENST00000274625.6; ENSP00000274625.5; ENSG00000156427.8.
DR GeneID; 8817; -.
DR KEGG; hsa:8817; -.
DR MANE-Select; ENST00000274625.6; ENSP00000274625.5; NM_003862.3; NP_003853.1.
DR UCSC; uc003mbk.4; human.
DR CTD; 8817; -.
DR DisGeNET; 8817; -.
DR GeneCards; FGF18; -.
DR HGNC; HGNC:3674; FGF18.
DR HPA; ENSG00000156427; Tissue enhanced (heart).
DR MIM; 603726; gene.
DR neXtProt; NX_O76093; -.
DR OpenTargets; ENSG00000156427; -.
DR PharmGKB; PA28113; -.
DR VEuPathDB; HostDB:ENSG00000156427; -.
DR eggNOG; KOG3885; Eukaryota.
DR GeneTree; ENSGT00940000159553; -.
DR HOGENOM; CLU_090682_1_0_1; -.
DR InParanoid; O76093; -.
DR OMA; FRCIQML; -.
DR OrthoDB; 1190450at2759; -.
DR PhylomeDB; O76093; -.
DR TreeFam; TF331233; -.
DR PathwayCommons; O76093; -.
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-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-5655332; Signaling by FGFR3 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; O76093; -.
DR SIGNOR; O76093; -.
DR BioGRID-ORCS; 8817; 7 hits in 1070 CRISPR screens.
DR ChiTaRS; FGF18; human.
DR GeneWiki; FGF18; -.
DR GenomeRNAi; 8817; -.
DR Pharos; O76093; Tbio.
DR PRO; PR:O76093; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; O76093; protein.
DR Bgee; ENSG00000156427; Expressed in tendon of biceps brachii and 115 other tissues.
DR Genevisible; O76093; 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:0005730; C:nucleolus; IDA:LIFEdb.
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: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:0009887; P:animal organ morphogenesis; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0008283; P:cell population proliferation; 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:0070371; P:ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0001957; P:intramembranous ossification; IEA:Ensembl.
DR GO; GO:0030324; P:lung development; IEA:Ensembl.
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; IBA:GO_Central.
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:0010628; P:positive regulation of gene expression; IBA:GO_Central.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IDA:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IBA:GO_Central.
DR GO; GO:0030949; P:positive regulation of vascular endothelial growth factor receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0030334; P:regulation of cell migration; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; IEA:Ensembl.
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:SF4; PTHR11486:SF4; 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; Disulfide bond; Glycoprotein; Growth factor;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..207
FT /note="Fibroblast growth factor 18"
FT /id="PRO_0000008990"
FT REGION 157..186
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 163..180
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 39
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 137
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 109..127
FT /evidence="ECO:0000269|Ref.9"
FT STRAND 52..59
FT /evidence="ECO:0007829|PDB:4CJM"
FT TURN 60..62
FT /evidence="ECO:0007829|PDB:4CJM"
FT STRAND 63..68
FT /evidence="ECO:0007829|PDB:4CJM"
FT STRAND 73..77
FT /evidence="ECO:0007829|PDB:4CJM"
FT HELIX 82..84
FT /evidence="ECO:0007829|PDB:4CJM"
FT STRAND 86..90
FT /evidence="ECO:0007829|PDB:4CJM"
FT STRAND 94..101
FT /evidence="ECO:0007829|PDB:4CJM"
FT TURN 102..104
FT /evidence="ECO:0007829|PDB:4CJM"
FT STRAND 107..110
FT /evidence="ECO:0007829|PDB:4CJM"
FT STRAND 116..120
FT /evidence="ECO:0007829|PDB:4CJM"
FT HELIX 125..127
FT /evidence="ECO:0007829|PDB:4CJM"
FT STRAND 129..133
FT /evidence="ECO:0007829|PDB:4CJM"
FT STRAND 139..146
FT /evidence="ECO:0007829|PDB:4CJM"
FT HELIX 162..164
FT /evidence="ECO:0007829|PDB:4CJM"
FT HELIX 170..172
FT /evidence="ECO:0007829|PDB:4CJM"
FT STRAND 174..177
FT /evidence="ECO:0007829|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
