FGF21_MOUSE
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 03-AUG-2022, entry version 150.
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; Q9JJN1; -.
DR PRIDE; Q9JJN1; -.
DR ProteomicsDB; 271694; -.
DR Antibodypedia; 31805; 785 antibodies from 38 providers.
DR DNASU; 56636; -.
DR Ensembl; ENSMUST00000033099; ENSMUSP00000033099; ENSMUSG00000030827.
DR GeneID; 56636; -.
DR KEGG; mmu:56636; -.
DR UCSC; uc009gwe.1; mouse.
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; REVHLYT; -.
DR OrthoDB; 1365711at2759; -.
DR PhylomeDB; Q9JJN1; -.
DR TreeFam; TF335872; -.
DR Reactome; R-MMU-189200; Cellular hexose transport.
DR BioGRID-ORCS; 56636; 3 hits in 72 CRISPR screens.
DR PRO; PR:Q9JJN1; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q9JJN1; protein.
DR Bgee; ENSMUSG00000030827; Expressed in pyloric antrum and 28 other tissues.
DR Genevisible; Q9JJN1; MM.
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:1901215; P:negative regulation of neuron death; 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 CDD; cd00058; FGF; 1.
DR InterPro; IPR035444; FGF15/19/21.
DR InterPro; IPR028292; FGF21.
DR InterPro; IPR002209; Fibroblast_GF_fam.
DR InterPro; IPR008996; IL1/FGF.
DR PANTHER; PTHR11486; PTHR11486; 1.
DR PANTHER; PTHR11486:SF81; PTHR11486:SF81; 1.
DR Pfam; PF00167; FGF; 1.
DR PIRSF; PIRSF037961; FGF-19_FGF-21; 1.
DR PRINTS; PR00263; HBGFFGF.
DR SMART; SM00442; FGF; 1.
DR SUPFAM; SSF50353; SSF50353; 1.
DR PROSITE; PS00247; HBGF_FGF; 1.
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
