ID FGF4_HUMAN Reviewed; 206 AA. AC P08620; B7U994; DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1988, sequence version 1. DT 01-OCT-2014, entry version 143. DE RecName: Full=Fibroblast growth factor 4; DE Short=FGF-4; DE AltName: Full=Heparin secretory-transforming protein 1; DE Short=HST; DE Short=HST-1; DE Short=HSTF-1; DE AltName: Full=Heparin-binding growth factor 4; DE Short=HBGF-4; DE AltName: Full=Transforming protein KS3; DE Flags: Precursor; GN Name=FGF4; Synonyms=HST, HSTF1, KS3; 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] (ISOFORM 2), AND ALTERNATIVE SPLICING. RX PubMed=18192227; DOI=10.1634/stemcells.2007-1037; RA Mayshar Y., Rom E., Chumakov I., Kronman A., Yayon A., Benvenisty N.; RT "Fibroblast growth factor 4 and its novel splice isoform have opposing RT effects on the maintenance of human embryonic stem cell self- RT renewal."; RL Stem Cells 26:767-774(2008). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=2959959; DOI=10.1073/pnas.84.20.7305; RA Yoshida T., Miyagawa K., Odagiri H., Sakamoto H., Little P.F.R., RA Terada M., Sugimura T.; RT "Genomic sequence of hst, a transforming gene encoding a protein RT homologous to fibroblast growth factors and the int-2-encoded RT protein."; RL Proc. Natl. Acad. Sci. U.S.A. 84:7305-7309(1987). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=2953031; DOI=10.1073/pnas.84.9.2980; RA Taira M., Yoshida T., Miyagawa K., Sakamoto H., Terada M., RA Sugimura T.; RT "cDNA sequence of human transforming gene hst and identification of RT the coding sequence required for transforming activity."; RL Proc. Natl. Acad. Sci. U.S.A. 84:2980-2984(1987). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=2957062; DOI=10.1016/0092-8674(87)90331-X; RA Delli-Bovi P., Curatola A.M., Kern F.G., Greco A., Ittmann M., RA Basilico C.; RT "An oncogene isolated by transfection of Kaposi's sarcoma DNA encodes RT a growth factor that is a member of the FGF family."; RL Cell 50:729-737(1987). RN [5] RP INTERACTION WITH FGFR1; FGFR2; FGFR3 AND FGFR4, AND FUNCTION IN CELL RP 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., RA Coulier F., Gao G., Goldfarb M.; RT "Receptor specificity of the fibroblast growth factor family."; RL J. Biol. Chem. 271:15292-15297(1996). RN [6] 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 [7] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 79-206. RX PubMed=11486033; DOI=10.1128/MCB.21.17.5946-5957.2001; RA Bellosta P., Iwahori A., Plotnikov A.N., Eliseenkova A.V., RA Basilico C., Mohammadi M.; RT "Identification of receptor and heparin binding sites in fibroblast RT growth factor 4 by structure-based mutagenesis."; RL Mol. Cell. Biol. 21:5946-5957(2001). CC -!- FUNCTION: Plays an important role in the regulation of embryonic CC development, cell proliferation, and cell differentiation. CC Required for normal limb and cardiac valve development during CC embryogenesis. {ECO:0000269|PubMed:8663044}. CC -!- SUBUNIT: Interacts with FGFR1, FGFR2, FGFR3 and FGFR4. Affinity CC between fibroblast growth factors (FGFs) and their receptors is CC increased by heparan sulfate glycosaminoglycans that function as CC coreceptors. {ECO:0000269|PubMed:8663044}. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P08620-1; Sequence=Displayed; CC Name=2; Synonyms=FGF4si; CC IsoId=P08620-2; Sequence=VSP_053541; CC Note=Antagonist of isoform 1, shutting down FGF4-induced Erk1/2 CC phosphorylation.; 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; FJ456981; ACJ68447.1; -; mRNA. DR EMBL; J02986; AAB59555.1; -; Genomic_DNA. DR EMBL; M17446; AAA59473.1; -; mRNA. DR CCDS; CCDS8194.1; -. [P08620-1] DR PIR; A28417; TVHUHS. DR RefSeq; NP_001998.1; NM_002007.2. [P08620-1] DR RefSeq; XP_005273904.1; XM_005273847.1. [P08620-2] DR RefSeq; XP_006718538.1; XM_006718475.1. [P08620-1] DR UniGene; Hs.1755; -. DR PDB; 1IJT; X-ray; 1.80 A; A=79-206. DR PDBsum; 1IJT; -. DR ProteinModelPortal; P08620; -. DR SMR; P08620; 79-206. DR DIP; DIP-4017N; -. DR STRING; 9606.ENSP00000168712; -. DR DrugBank; DB00686; Pentosan Polysulfate. DR PhosphoSite; P08620; -. DR DMDM; 122750; -. DR PaxDb; P08620; -. DR PRIDE; P08620; -. DR DNASU; 2249; -. DR Ensembl; ENST00000168712; ENSP00000168712; ENSG00000075388. [P08620-1] DR GeneID; 2249; -. DR KEGG; hsa:2249; -. DR UCSC; uc001opg.1; human. [P08620-1] DR CTD; 2249; -. DR GeneCards; GC11M069588; -. DR HGNC; HGNC:3682; FGF4. DR HPA; HPA011209; -. DR MIM; 164980; gene. DR neXtProt; NX_P08620; -. DR PharmGKB; PA28121; -. DR eggNOG; NOG290420; -. DR HOGENOM; HOG000236341; -. DR HOVERGEN; HBG007580; -. DR InParanoid; P08620; -. DR KO; K04358; -. DR OMA; YNAYESH; -. DR OrthoDB; EOG7992S1; -. DR PhylomeDB; P08620; -. DR TreeFam; TF317805; -. DR Reactome; REACT_111184; Negative regulation of FGFR signaling. DR Reactome; REACT_120863; Activated point mutants of FGFR2. DR Reactome; REACT_121153; Signaling by activated point mutants of FGFR1. DR Reactome; REACT_121249; Signaling by FGFR3 mutants. DR Reactome; REACT_121337; Signaling by activated point mutants of FGFR3. DR Reactome; REACT_121398; Signaling by FGFR mutants. DR Reactome; REACT_147727; Constitutive PI3K/AKT Signaling in Cancer. DR Reactome; REACT_21247; FRS2-mediated cascade. DR Reactome; REACT_21270; PI-3K cascade. DR Reactome; REACT_21310; Phospholipase C-mediated cascade. DR Reactome; REACT_21374; SHC-mediated cascade. DR Reactome; REACT_75829; PIP3 activates AKT signaling. DR Reactome; REACT_9413; FGFR2c ligand binding and activation. DR Reactome; REACT_9452; FGFR4 ligand binding and activation. DR Reactome; REACT_9510; FGFR3c ligand binding and activation. DR Reactome; REACT_9515; FGFR1c ligand binding and activation. DR Reactome; REACT_976; PI3K Cascade. DR SignaLink; P08620; -. DR EvolutionaryTrace; P08620; -. DR GeneWiki; FGF4; -. DR GenomeRNAi; 2249; -. DR NextBio; 35478625; -. DR PRO; PR:P08620; -. DR Bgee; P08620; -. DR CleanEx; HS_FGF4; -. DR Genevestigator; P08620; -. DR GO; GO:0005829; C:cytosol; IEA:Ensembl. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IEA:Ensembl. DR GO; GO:0008083; F:growth factor activity; TAS:ProtInc. DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW. DR GO; GO:0060561; P:apoptotic process involved in morphogenesis; IEA:Ensembl. DR GO; GO:0001502; P:cartilage condensation; IEA:Ensembl. DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc. DR GO; GO:0060591; P:chondroblast differentiation; IDA:UniProtKB. DR GO; GO:0060363; P:cranial suture morphogenesis; IEA:Ensembl. DR GO; GO:0035116; P:embryonic hindlimb morphogenesis; IEA:Ensembl. DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome. DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome. DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; IGI:MGI. DR GO; GO:0045087; P:innate immune response; TAS:Reactome. DR GO; GO:0008286; P:insulin receptor signaling pathway; TAS:Reactome. DR GO; GO:0010463; P:mesenchymal cell proliferation; IDA:UniProtKB. DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl. DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome. DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IEA:Ensembl. DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; TAS:Reactome. DR GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW. DR GO; GO:0008284; P:positive regulation of cell proliferation; IGI:MGI. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:UniProtKB. DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IEA:Ensembl. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0019827; P:stem cell maintenance; IEA:Ensembl. DR InterPro; IPR008996; Cytokine_IL1-like. DR InterPro; IPR028239; FGF4. DR InterPro; IPR002209; Fibroblast_GF_fam. DR InterPro; IPR028142; IL-1_fam/FGF_fam. DR PANTHER; PTHR11486; PTHR11486; 1. DR PANTHER; PTHR11486:SF31; PTHR11486:SF31; 1. DR Pfam; PF00167; FGF; 1. DR PRINTS; PR00263; HBGFFGF. DR PRINTS; PR00262; IL1HBGF. 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; Alternative splicing; Complete proteome; KW Developmental protein; Differentiation; Growth factor; KW Heparin-binding; Mitogen; Proto-oncogene; Reference proteome; KW Secreted; Signal. FT SIGNAL 1 30 {ECO:0000255}. FT CHAIN 31 206 Fibroblast growth factor 4. FT /FTId=PRO_0000008953. FT VAR_SEQ 114 206 SLLELSPVERGVVSIFGVASRFFVAMSSKGKLYGSPFFTDE FT CTFKEILLPNNYNAYESYKYPGMFIALSKNGKTKKGNRVSP FT TMKVTHFLPRL -> TLLHR (in isoform 2). FT {ECO:0000303|PubMed:18192227}. FT /FTId=VSP_053541. FT STRAND 82 88 FT STRAND 94 98 FT STRAND 104 109 FT HELIX 112 114 FT STRAND 116 122 FT STRAND 125 130 FT TURN 131 134 FT STRAND 135 139 FT STRAND 145 150 FT STRAND 155 161 FT HELIX 163 165 FT STRAND 167 174 FT STRAND 185 187 FT HELIX 190 192 FT HELIX 198 200 FT STRAND 202 205 SQ SEQUENCE 206 AA; 22048 MW; C7FD54A0272A1569 CRC64; MSGPGTAAVA LLPAVLLALL APWAGRGGAA APTAPNGTLE AELERRWESL VALSLARLPV AAQPKEAAVQ SGAGDYLLGI KRLRRLYCNV GIGFHLQALP DGRIGGAHAD TRDSLLELSP VERGVVSIFG VASRFFVAMS SKGKLYGSPF FTDECTFKEI LLPNNYNAYE SYKYPGMFIA LSKNGKTKKG NRVSPTMKVT HFLPRL //