ID   FGF21_HUMAN             Reviewed;         209 AA.
AC   Q9NSA1; Q8N683;
DT   27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2000, sequence version 1.
DT   19-JAN-2010, entry version 80.
DE   RecName: Full=Fibroblast growth factor 21;
DE            Short=FGF-21;
DE   Flags: Precursor;
GN   Name=FGF21; ORFNames=UNQ3115/PRO10196;
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   MEDLINE=20461777; PubMed=10858549; DOI=10.1016/S0167-4781(00)00067-1;
RA   Nishimura T., Nakatake Y., Konishi M., Itoh N.;
RT   "Identification of a novel FGF, FGF-21, preferentially expressed in
RT   the liver.";
RL   Biochim. Biophys. Acta 1492:203-206(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   MEDLINE=22887296; 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   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-141 AND PRO-174.
RG   NIEHS SNPs program;
RL   Submitted (JUL-2006) to the EMBL/GenBank/DDBJ databases.
RN   [4]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Lung;
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   [6]
RP   PROTEIN SEQUENCE OF 29-43.
RX   PubMed=15340161; DOI=10.1110/ps.04682504;
RA   Zhang Z., Henzel W.J.;
RT   "Signal peptide prediction based on analysis of experimentally
RT   verified cleavage sites.";
RL   Protein Sci. 13:2819-2824(2004).
RN   [7]
RP   FUNCTION.
RX   PubMed=15902306; DOI=10.1172/JCI23606;
RA   Kharitonenkov A., Shiyanova T.L., Koester A., Ford A.M., Micanovic R.,
RA   Galbreath E.J., Sandusky G.E., Hammond L.J., Moyers J.S., Owens R.A.,
RA   Gromada J., Brozinick J.T., Hawkins E.D., Wroblewski V.J., Li D.-S.,
RA   Mehrbod F., Jaskunas S.R., Shanafelt A.B.;
RT   "FGF-21 as a novel metabolic regulator.";
RL   J. Clin. Invest. 115:1627-1635(2005).
RN   [8]
RP   FUNCTION.
RX   PubMed=17623664; DOI=10.1074/jbc.M704165200;
RA   Kurosu H., Choi M., Ogawa Y., Dickson A.S., Goetz R.,
RA   Eliseenkova A.V., Mohammadi M., Rosenblatt K.P., Kliewer S.A.,
RA   Kuro-o M.;
RT   "Tissue-specific expression of betaKlotho and fibroblast growth factor
RT   (FGF) receptor isoforms determines metabolic activity of FGF19 and
RT   FGF21.";
RL   J. Biol. Chem. 282:26687-26695(2007).
RN   [9]
RP   INTERACTION WITH KLB.
RX   PubMed=18829467; DOI=10.1074/jbc.M803319200;
RA   Wu X., Lemon B., Li X., Gupte J., Weiszmann J., Stevens J.,
RA   Hawkins N., Shen W., Lindberg R., Chen J.-L., Tian H., Li Y.;
RT   "C-terminal tail of FGF19 determines its specificity toward Klotho co-
RT   receptors.";
RL   J. Biol. Chem. 283:33304-33309(2008).
RN   [10]
RP   INTERACTION WITH KLB.
RX   PubMed=19117008; DOI=10.1002/jcp.21675;
RA   Micanovic R., Raches D.W., Dunbar J.D., Driver D.A., Bina H.A.,
RA   Dickinson C.D., Kharitonenkov A.;
RT   "Different roles of N- and C- termini in the functional activity of
RT   FGF21.";
RL   J. Cell. Physiol. 219:227-234(2009).
CC   -!- FUNCTION: Stimulates glucose uptake in differentiated adipocytes
CC       via the induction of glucose transporter SLC2A1/GLUT1 expression
CC       (but not SLC2A4/GLUT4 expression). Activity requires the presence
CC       of KLB.
CC   -!- SUBUNIT: Interacts (via C-terminus) with KLB; this interaction is
CC       direct.
CC   -!- SUBCELLULAR LOCATION: Secreted (Potential).
CC   -!- SIMILARITY: Belongs to the heparin-binding growth factors family.
CC   -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC       URL="http://egp.gs.washington.edu/data/fgf21/";
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DR   EMBL; AB021975; BAA99415.1; -; mRNA.
DR   EMBL; AY359086; AAQ89444.1; -; mRNA.
DR   EMBL; DQ847413; ABI75345.1; -; Genomic_DNA.
DR   EMBL; CH471177; EAW52402.1; -; Genomic_DNA.
DR   EMBL; BC018404; AAH18404.1; -; mRNA.
DR   IPI; IPI00017149; -.
DR   RefSeq; NP_061986.1; -.
DR   UniGene; Hs.283015; -.
DR   SMR; Q9NSA1; 35-172.
DR   STRING; Q9NSA1; -.
DR   PRIDE; Q9NSA1; -.
DR   Ensembl; ENST00000222157; ENSP00000222157; ENSG00000105550; Homo sapiens.
DR   GeneID; 26291; -.
DR   KEGG; hsa:26291; -.
DR   UCSC; uc002pkn.1; human.
DR   CTD; 26291; -.
DR   GeneCards; GC19P053951; -.
DR   H-InvDB; HIX0027440; -.
DR   HGNC; HGNC:3678; FGF21.
DR   MIM; 609436; gene.
DR   PharmGKB; PA28117; -.
DR   eggNOG; prNOG16938; -.
DR   HOGENOM; HBG126920; -.
DR   HOVERGEN; Q9NSA1; -.
DR   InParanoid; Q9NSA1; -.
DR   OMA; HPIPDSS; -.
DR   OrthoDB; EOG9HHRMK; -.
DR   PhylomeDB; Q9NSA1; -.
DR   NextBio; 48635; -.
DR   ArrayExpress; Q9NSA1; -.
DR   Bgee; Q9NSA1; -.
DR   CleanEx; HS_FGF21; -.
DR   Genevestigator; Q9NSA1; -.
DR   GermOnline; ENSG00000105550; Homo sapiens.
DR   GO; GO:0005576; C:extracellular region; TAS:ProtInc.
DR   GO; GO:0005625; C:soluble fraction; TAS:ProtInc.
DR   GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR   GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR   GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:UniProtKB.
DR   GO; GO:0046326; P:positive regulation of glucose import; IDA:UniProtKB.
DR   GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR   InterPro; IPR008996; Cytokine_IL1-like.
DR   InterPro; IPR017338; Fibroblast_GF_15/19/21.
DR   InterPro; IPR002209; GF_heparin_bd.
DR   InterPro; IPR002348; IL1_HBGF.
DR   PANTHER; PTHR11486; IL1_HBGF; 1.
DR   Pfam; PF00167; FGF; 1.
DR   PIRSF; PIRSF037961; FGF-19_FGF-21; 1.
DR   PRINTS; PR00263; HBGFFGF.
DR   PRINTS; PR00262; IL1HBGF.
DR   SMART; SM00442; FGF; 1.
DR   PROSITE; PS00247; HBGF_FGF; 1.
PE   1: Evidence at protein level;
KW   Complete proteome; Direct protein sequencing; Growth factor;
KW   Polymorphism; Secreted; Signal.
FT   SIGNAL        1     28
FT   CHAIN        29    209       Fibroblast growth factor 21.
FT                                /FTId=PRO_0000008994.
FT   VARIANT     141    141       G -> S (in dbSNP:rs41308776).
FT                                /FTId=VAR_055375.
FT   VARIANT     174    174       L -> P (in dbSNP:rs739320).
FT                                /FTId=VAR_049064.
FT   CONFLICT     23     23       Missing (in Ref. 2; AAQ89444).
SQ   SEQUENCE   209 AA;  22300 MW;  27925C52A0023823 CRC64;
     MDSDETGFEH SGLWVSVLAG LLLGACQAHP IPDSSPLLQF GGQVRQRYLY TDDAQQTEAH
     LEIREDGTVG GAADQSPESL LQLKALKPGV IQILGVKTSR FLCQRPDGAL YGSLHFDPEA
     CSFRELLLED GYNVYQSEAH GLPLHLPGNK SPHRDPAPRG PARFLPLPGL PPALPEPPGI
     LAPQPPDVGS SDPLSMVGPS QGRSPSYAS
//