ID   FGF4_HUMAN              Reviewed;         206 AA.
AC   P08620;
DT   01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1988, sequence version 1.
DT   11-JUL-2012, entry version 122.
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 [GENOMIC DNA].
RX   MEDLINE=88041096; 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   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   MEDLINE=87204251; 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   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   MEDLINE=87301716; 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   [4]
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   [5]
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   [6]
RP   X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 79-206.
RX   MEDLINE=21378624; PubMed=11486033;
RX   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.
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.
CC   -!- SUBCELLULAR LOCATION: Secreted (Potential).
CC   -!- SIMILARITY: Belongs to the heparin-binding growth factors family.
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DR   EMBL; J02986; AAB59555.1; -; Genomic_DNA.
DR   EMBL; M17446; AAA59473.1; -; mRNA.
DR   IPI; IPI00029760; -.
DR   PIR; A28417; TVHUHS.
DR   RefSeq; NP_001998.1; NM_002007.2.
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; P08620; -.
DR   PhosphoSite; P08620; -.
DR   DMDM; 122750; -.
DR   PRIDE; P08620; -.
DR   DNASU; 2249; -.
DR   Ensembl; ENST00000168712; ENSP00000168712; ENSG00000075388.
DR   GeneID; 2249; -.
DR   KEGG; hsa:2249; -.
DR   UCSC; uc001opg.1; human.
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   GeneTree; ENSGT00640000091009; -.
DR   HOGENOM; HOG000236341; -.
DR   HOVERGEN; HBG007580; -.
DR   InParanoid; P08620; -.
DR   KO; K04358; -.
DR   OMA; YNAYESH; -.
DR   OrthoDB; EOG4N8R5V; -.
DR   PhylomeDB; P08620; -.
DR   Pathway_Interaction_DB; fgf_pathway; FGF signaling pathway.
DR   Reactome; REACT_111102; Signal Transduction.
DR   DrugBank; DB00686; Pentosan Polysulfate.
DR   EvolutionaryTrace; P08620; -.
DR   NextBio; 9103; -.
DR   ArrayExpress; P08620; -.
DR   Bgee; P08620; -.
DR   CleanEx; HS_FGF4; -.
DR   Genevestigator; P08620; -.
DR   GermOnline; ENSG00000075388; Homo sapiens.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005625; C:soluble fraction; IEA:Compara.
DR   GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR   GO; GO:0060561; P:apoptotic process involved in morphogenesis; IEA:Compara.
DR   GO; GO:0001502; P:cartilage condensation; IEA:Compara.
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:Compara.
DR   GO; GO:0035116; P:embryonic hindlimb morphogenesis; IEA:Compara.
DR   GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; IGI:MGI.
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:Compara.
DR   GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IEA:Compara.
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:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IEA:Compara.
DR   GO; GO:0019827; P:stem cell maintenance; IEA:Compara.
DR   InterPro; IPR008996; Cytokine_IL1-like.
DR   InterPro; IPR002209; GF_heparin-bd.
DR   InterPro; IPR002348; IL1_HBGF.
DR   PANTHER; PTHR11486; IL1_HBGF; 1.
DR   Pfam; PF00167; FGF; 1.
DR   PRINTS; PR00263; HBGFFGF.
DR   PRINTS; PR00262; IL1HBGF.
DR   SMART; SM00442; FGF; 1.
DR   SUPFAM; SSF50353; Cytok_IL1_like; 1.
DR   PROSITE; PS00247; HBGF_FGF; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Complete proteome; Developmental protein;
KW   Differentiation; Growth factor; Heparin-binding; Mitogen;
KW   Proto-oncogene; Reference proteome; Secreted; Signal.
FT   SIGNAL        1     30       Potential.
FT   CHAIN        31    206       Fibroblast growth factor 4.
FT                                /FTId=PRO_0000008953.
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
//