ID   FGF6_HUMAN              Reviewed;         208 AA.
AC   P10767; Q0VAE1;
DT   01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1995, sequence version 4.
DT   24-JAN-2024, entry version 201.
DE   RecName: Full=Fibroblast growth factor 6;
DE            Short=FGF-6;
DE   AltName: Full=Heparin secretory-transforming protein 2;
DE            Short=HST-2;
DE            Short=HSTF-2;
DE   AltName: Full=Heparin-binding growth factor 6;
DE            Short=HBGF-6;
DE   Flags: Precursor;
GN   Name=FGF6; Synonyms=HST2, HSTF2;
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 [GENOMIC DNA].
RX   PubMed=1886714;
RA   Coulier F., Batoz M., Marics I., de Lapeyriere O., Birnbaum D.;
RT   "Putative structure of the FGF6 gene product and role of the signal
RT   peptide.";
RL   Oncogene 6:1437-1444(1991).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ALA-36; VAL-63; VAL-174 AND
RP   TRP-191.
RG   NIEHS SNPs program;
RL   Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 11-208.
RX   PubMed=1549352;
RA   Iida S., Yoshida T., Naito K., Sakamoto H., Katoh O., Hirohashi S.,
RA   Sato T., Onda M., Sugimura T., Terada M.;
RT   "Human hst-2 (FGF-6) oncogene: cDNA cloning and characterization.";
RL   Oncogene 7:303-309(1992).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 81-208.
RX   PubMed=2649847;
RA   Marics I., Adelaide J., Raybaud F., Mattei M.-G., Coulier F., Planche J.,
RA   de Lapeyriere O., Birnbaum D.;
RT   "Characterization of the HST-related FGF.6 gene, a new member of the
RT   fibroblast growth factor gene family.";
RL   Oncogene 4:335-340(1989).
RN   [6]
RP   INTERACTION WITH FGFR1; FGFR2 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., 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   [7]
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, angiogenesis and myogenesis, and
CC       is required for normal muscle regeneration.
CC       {ECO:0000269|PubMed:8663044}.
CC   -!- SUBUNIT: Interacts with FGFR1, FGFR2 and FGFR4. Affinity between
CC       fibroblast growth factors (FGFs) and their receptors is increased by
CC       heparan sulfate glycosaminoglycans that function as coreceptors.
CC       {ECO:0000269|PubMed:8663044}.
CC   -!- INTERACTION:
CC       P10767; P61601: NCALD; NbExp=3; IntAct=EBI-11479013, EBI-749635;
CC   -!- SUBCELLULAR LOCATION: Secreted, extracellular space.
CC   -!- TISSUE SPECIFICITY: Leukemia cell lines with platelet/ megakaryocytic
CC       differentiation potential.
CC   -!- SIMILARITY: Belongs to the heparin-binding growth factors family.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAA40359.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC       Sequence=CAA40360.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC   -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC       URL="http://egp.gs.washington.edu/data/fgf6/";
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DR   EMBL; X57075; CAA40358.1; -; Genomic_DNA.
DR   EMBL; X57075; CAA40359.1; ALT_INIT; Genomic_DNA.
DR   EMBL; X57075; CAA40360.1; ALT_INIT; Genomic_DNA.
DR   EMBL; AY581424; AAS79318.1; -; Genomic_DNA.
DR   EMBL; BC121097; AAI21098.1; -; mRNA.
DR   EMBL; BC121098; AAI21099.1; -; mRNA.
DR   EMBL; X63454; CAA45054.1; -; mRNA.
DR   EMBL; X14071; CAB37648.2; -; Genomic_DNA.
DR   EMBL; X14072; CAB37648.2; JOINED; Genomic_DNA.
DR   EMBL; X14073; CAB37648.2; JOINED; Genomic_DNA.
DR   CCDS; CCDS8527.1; -.
DR   PIR; S20102; S20102.
DR   RefSeq; NP_066276.2; NM_020996.2.
DR   AlphaFoldDB; P10767; -.
DR   SMR; P10767; -.
DR   BioGRID; 108542; 4.
DR   DIP; DIP-6035N; -.
DR   IntAct; P10767; 2.
DR   STRING; 9606.ENSP00000228837; -.
DR   GlyCosmos; P10767; 1 site, No reported glycans.
DR   GlyGen; P10767; 1 site.
DR   PhosphoSitePlus; P10767; -.
DR   BioMuta; FGF6; -.
DR   DMDM; 1169676; -.
DR   MassIVE; P10767; -.
DR   PaxDb; 9606-ENSP00000228837; -.
DR   Antibodypedia; 41814; 212 antibodies from 22 providers.
DR   DNASU; 2251; -.
DR   Ensembl; ENST00000228837.3; ENSP00000228837.2; ENSG00000111241.3.
DR   GeneID; 2251; -.
DR   KEGG; hsa:2251; -.
DR   MANE-Select; ENST00000228837.3; ENSP00000228837.2; NM_020996.3; NP_066276.2.
DR   UCSC; uc001qmr.2; human.
DR   AGR; HGNC:3684; -.
DR   CTD; 2251; -.
DR   DisGeNET; 2251; -.
DR   GeneCards; FGF6; -.
DR   HGNC; HGNC:3684; FGF6.
DR   HPA; ENSG00000111241; Group enriched (skeletal muscle, tongue).
DR   MIM; 134921; gene.
DR   neXtProt; NX_P10767; -.
DR   OpenTargets; ENSG00000111241; -.
DR   PharmGKB; PA28123; -.
DR   VEuPathDB; HostDB:ENSG00000111241; -.
DR   eggNOG; KOG3885; Eukaryota.
DR   GeneTree; ENSGT00940000157821; -.
DR   HOGENOM; CLU_081609_4_1_1; -.
DR   InParanoid; P10767; -.
DR   OMA; RISGAHN; -.
DR   OrthoDB; 2883843at2759; -.
DR   PhylomeDB; P10767; -.
DR   TreeFam; TF317805; -.
DR   PathwayCommons; P10767; -.
DR   Reactome; R-HSA-109704; PI3K Cascade.
DR   Reactome; R-HSA-1257604; PIP3 activates AKT signaling.
DR   Reactome; R-HSA-1839122; Signaling by activated point mutants of FGFR1.
DR   Reactome; R-HSA-190322; FGFR4 ligand binding and activation.
DR   Reactome; R-HSA-190373; FGFR1c 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-5654219; Phospholipase C-mediated cascade: FGFR1.
DR   Reactome; R-HSA-5654221; Phospholipase C-mediated cascade, FGFR2.
DR   Reactome; R-HSA-5654228; Phospholipase C-mediated cascade, FGFR4.
DR   Reactome; R-HSA-5654687; Downstream signaling of activated FGFR1.
DR   Reactome; R-HSA-5654688; SHC-mediated cascade:FGFR1.
DR   Reactome; R-HSA-5654689; PI-3K cascade:FGFR1.
DR   Reactome; R-HSA-5654693; FRS-mediated FGFR1 signaling.
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-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-5654726; Negative regulation of FGFR1 signaling.
DR   Reactome; R-HSA-5654727; Negative regulation of FGFR2 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-5655302; Signaling by FGFR1 in disease.
DR   Reactome; R-HSA-5673001; RAF/MAP kinase cascade.
DR   Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR   SignaLink; P10767; -.
DR   SIGNOR; P10767; -.
DR   BioGRID-ORCS; 2251; 16 hits in 1150 CRISPR screens.
DR   GeneWiki; FGF6; -.
DR   GenomeRNAi; 2251; -.
DR   Pharos; P10767; Tbio.
DR   PRO; PR:P10767; -.
DR   Proteomes; UP000005640; Chromosome 12.
DR   RNAct; P10767; Protein.
DR   Bgee; ENSG00000111241; Expressed in hindlimb stylopod muscle and 54 other cell types or tissues.
DR   ExpressionAtlas; P10767; 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:0042383; C:sarcolemma; IEA:Ensembl.
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:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR   GO; GO:0009887; P:animal organ morphogenesis; IBA:GO_Central.
DR   GO; GO:0001502; P:cartilage condensation; IEA:Ensembl.
DR   GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR   GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; IGI:MGI.
DR   GO; GO:0045445; P:myoblast differentiation; IEA:Ensembl.
DR   GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; IGI: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   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:SF25; FIBROBLAST GROWTH FACTOR 6; 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; P10767; HS.
PE   1: Evidence at protein level;
KW   Angiogenesis; Developmental protein; Differentiation; Disulfide bond;
KW   Glycoprotein; Growth factor; Mitogen; Proto-oncogene; Reference proteome;
KW   Secreted; Signal.
FT   SIGNAL          1..37
FT                   /evidence="ECO:0000255"
FT   CHAIN           38..208
FT                   /note="Fibroblast growth factor 6"
FT                   /id="PRO_0000008961"
FT   CARBOHYD        45
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        90..157
FT                   /evidence="ECO:0000255"
FT   VARIANT         36
FT                   /note="V -> A (in dbSNP:rs11613495)"
FT                   /evidence="ECO:0000269|Ref.2"
FT                   /id="VAR_018882"
FT   VARIANT         63
FT                   /note="A -> V (in dbSNP:rs17183529)"
FT                   /evidence="ECO:0000269|Ref.2"
FT                   /id="VAR_018883"
FT   VARIANT         174
FT                   /note="D -> V (in dbSNP:rs7961645)"
FT                   /evidence="ECO:0000269|Ref.2"
FT                   /id="VAR_018884"
FT   VARIANT         191
FT                   /note="R -> W (in dbSNP:rs17183778)"
FT                   /evidence="ECO:0000269|Ref.2"
FT                   /id="VAR_018885"
FT   CONFLICT        100
FT                   /note="V -> G (in Ref. 5; CAB37648)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   208 AA;  22905 MW;  79EF44685B324322 CRC64;
     MALGQKLFIT MSRGAGRLQG TLWALVFLGI LVGMVVPSPA GTRANNTLLD SRGWGTLLSR
     SRAGLAGEIA GVNWESGYLV GIKRQRRLYC NVGIGFHLQV LPDGRISGTH EENPYSLLEI
     STVERGVVSL FGVRSALFVA MNSKGRLYAT PSFQEECKFR ETLLPNNYNA YESDLYQGTY
     IALSKYGRVK RGSKVSPIMT VTHFLPRI
//