ID   FGF21_MOUSE             Reviewed;         210 AA.
AC   Q9JJN1;
DT   27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2000, sequence version 1.
DT   24-JAN-2024, entry version 158.
DE   RecName: Full=Fibroblast growth factor 21;
DE            Short=FGF-21;
DE   Flags: Precursor;
GN   Name=Fgf21;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX   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 the
RT   liver.";
RL   Biochim. Biophys. Acta 1492:203-206(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Pancreas;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Testis;
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   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   [5]
RP   TISSUE SPECIFICITY, AND INDUCTION.
RX   PubMed=30389664; DOI=10.15252/embj.201898942;
RA   Wei J., Chen L., Li F., Yuan Y., Wang Y., Xia W., Zhang Y., Xu Y., Yang Z.,
RA   Gao B., Jin C., Melo-Cardenas J., Green R.M., Pan H., Wang J., He F.,
RA   Zhang K., Fang D.;
RT   "HRD1-ERAD controls production of the hepatokine FGF21 through CREBH
RT   polyubiquitination.";
RL   EMBO J. 37:0-0(2018).
RN   [6]
RP   FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=30605666; DOI=10.1016/j.celrep.2018.12.031;
RA   Turpin-Nolan S.M., Hammerschmidt P., Chen W., Jais A., Timper K.,
RA   Awazawa M., Brodesser S., Bruening J.C.;
RT   "CerS1-Derived C18:0 Ceramide in Skeletal Muscle Promotes Obesity-Induced
RT   Insulin Resistance.";
RL   Cell Rep. 26:1-10(2019).
CC   -!- FUNCTION: Stimulates glucose uptake in differentiated adipocytes via
CC       the induction of glucose transporter SLC2A1/GLUT1 expression (but not
CC       SLC2A4/GLUT4 expression). Activity probably requires the presence of
CC       KLB. Regulates systemic glucose homeostasis and insulin sensitivity.
CC       {ECO:0000269|PubMed:15902306, ECO:0000269|PubMed:30605666}.
CC   -!- SUBUNIT: Interacts (via C-terminus) with KLB; this interaction is
CC       direct. Interacts with FGFR4 (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:30605666}.
CC   -!- TISSUE SPECIFICITY: Most abundantly expressed in the liver, also
CC       expressed in the thymus at lower levels (PubMed:10858549,
CC       PubMed:30389664). Expressed in skeletal muscle (at protein level).
CC       Secreted in plasma (at protein level) (PubMed:30605666).
CC       {ECO:0000269|PubMed:10858549, ECO:0000269|PubMed:30389664,
CC       ECO:0000269|PubMed:30605666}.
CC   -!- INDUCTION: In the liver, down-regulated in postprandial conditions
CC       (PubMed:30389664). Up-regulated at the transcriptional level by CREB3L3
CC       (PubMed:30389664). {ECO:0000269|PubMed:30389664}.
CC   -!- SIMILARITY: Belongs to the heparin-binding growth factors family.
CC       {ECO:0000305}.
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DR   EMBL; AB025718; BAA99416.1; -; mRNA.
DR   EMBL; AK007574; BAB25115.1; -; mRNA.
DR   EMBL; BC049592; AAH49592.1; -; mRNA.
DR   CCDS; CCDS21253.1; -.
DR   RefSeq; NP_064397.1; NM_020013.4.
DR   RefSeq; XP_011249181.1; XM_011250879.1.
DR   RefSeq; XP_011249182.1; XM_011250880.1.
DR   AlphaFoldDB; Q9JJN1; -.
DR   SMR; Q9JJN1; -.
DR   DIP; DIP-60919N; -.
DR   IntAct; Q9JJN1; 2.
DR   STRING; 10090.ENSMUSP00000033099; -.
DR   PaxDb; 10090-ENSMUSP00000033099; -.
DR   ProteomicsDB; 271694; -.
DR   Antibodypedia; 31805; 942 antibodies from 38 providers.
DR   DNASU; 56636; -.
DR   Ensembl; ENSMUST00000033099.6; ENSMUSP00000033099.5; ENSMUSG00000030827.6.
DR   GeneID; 56636; -.
DR   KEGG; mmu:56636; -.
DR   UCSC; uc009gwe.1; mouse.
DR   AGR; MGI:1861377; -.
DR   CTD; 26291; -.
DR   MGI; MGI:1861377; Fgf21.
DR   VEuPathDB; HostDB:ENSMUSG00000030827; -.
DR   eggNOG; KOG3885; Eukaryota.
DR   GeneTree; ENSGT00940000161866; -.
DR   HOGENOM; CLU_094251_2_0_1; -.
DR   InParanoid; Q9JJN1; -.
DR   OMA; CQAYPIP; -.
DR   OrthoDB; 4138817at2759; -.
DR   PhylomeDB; Q9JJN1; -.
DR   TreeFam; TF335872; -.
DR   Reactome; R-MMU-189200; Cellular hexose transport.
DR   BioGRID-ORCS; 56636; 3 hits in 77 CRISPR screens.
DR   PRO; PR:Q9JJN1; -.
DR   Proteomes; UP000000589; Chromosome 7.
DR   RNAct; Q9JJN1; Protein.
DR   Bgee; ENSMUSG00000030827; Expressed in pyloric antrum and 29 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
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:0009887; P:animal organ morphogenesis; IBA:GO_Central.
DR   GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR   GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; IBA:GO_Central.
DR   GO; GO:2000352; P:negative regulation of endothelial cell apoptotic process; ISO:MGI.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; IGI:MGI.
DR   GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; IMP:YuBioLab.
DR   GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:MGI.
DR   GO; GO:0010628; P:positive regulation of gene expression; IBA:GO_Central.
DR   GO; GO:0046326; P:positive regulation of glucose import; ISO:MGI.
DR   GO; GO:0090080; P:positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway; IGI:MGI.
DR   GO; GO:0001934; P:positive regulation of protein phosphorylation; IBA:GO_Central.
DR   GO; GO:0010898; P:positive regulation of triglyceride catabolic process; ISO:MGI.
DR   GO; GO:0030334; P:regulation of cell migration; IBA:GO_Central.
DR   Gene3D; 2.80.10.50; -; 1.
DR   InterPro; IPR035444; FGF15/19/21.
DR   InterPro; IPR002209; Fibroblast_GF_fam.
DR   InterPro; IPR008996; IL1/FGF.
DR   PANTHER; PTHR11486; FIBROBLAST GROWTH FACTOR; 1.
DR   PANTHER; PTHR11486:SF81; FIBROBLAST GROWTH FACTOR 21; 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   SUPFAM; SSF50353; Cytokine; 1.
DR   PROSITE; PS00247; HBGF_FGF; 1.
DR   Genevisible; Q9JJN1; MM.
PE   1: Evidence at protein level;
KW   Growth factor; Reference proteome; Secreted; Signal.
FT   SIGNAL          1..28
FT                   /evidence="ECO:0000255"
FT   CHAIN           29..210
FT                   /note="Fibroblast growth factor 21"
FT                   /id="PRO_0000008995"
FT   REGION          144..210
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   210 AA;  23237 MW;  AE02AABA6477E6F0 CRC64;
     MEWMRSRVGT LGLWVRLLLA VFLLGVYQAY PIPDSSPLLQ FGGQVRQRYL YTDDDQDTEA
     HLEIREDGTV VGAAHRSPES LLELKALKPG VIQILGVKAS RFLCQQPDGA LYGSPHFDPE
     ACSFRELLLE DGYNVYQSEA HGLPLRLPQK DSPNQDATSW GPVRFLPMPG LLHEPQDQAG
     FLPPEPPDVG SSDPLSMVEP LQGRSPSYAS
//