METRL_MOUSE
ID METRL_MOUSE Reviewed; 311 AA.
AC Q8VE43; Q8R1J2;
DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=Meteorin-like protein;
DE AltName: Full=Subfatin;
DE Flags: Precursor;
GN Name=Metrnl;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Embryo;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=FVB/N; TISSUE=Colon, Kidney, and Mammary tumor;
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, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=24906147; DOI=10.1016/j.cell.2014.03.065;
RA Rao R.R., Long J.Z., White J.P., Svensson K.J., Lou J., Lokurkar I.,
RA Jedrychowski M.P., Ruas J.L., Wrann C.D., Lo J.C., Camera D.M., Lachey J.,
RA Gygi S., Seehra J., Hawley J.A., Spiegelman B.M.;
RT "Meteorin-like is a hormone that regulates immune-adipose interactions to
RT increase beige fat thermogenesis.";
RL Cell 157:1279-1291(2014).
RN [5]
RP SUBCELLULAR LOCATION, GLYCOSYLATION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=24393292; DOI=10.1111/cns.12219;
RA Li Z.Y., Zheng S.L., Wang P., Xu T.Y., Guan Y.F., Zhang Y.J., Miao C.Y.;
RT "Subfatin is a novel adipokine and unlike Meteorin in adipose and brain
RT expression.";
RL CNS Neurosci. Ther. 20:344-354(2014).
CC -!- FUNCTION: Hormone induced following exercise or cold exposure that
CC promotes energy expenditure. Induced either in the skeletal muscle
CC after exercise or in adipose tissue following cold exposure and is
CC present in the circulation. Able to stimulate energy expenditure
CC associated with the browning of the white fat depots and improves
CC glucose tolerance. Does not promote an increase in a thermogenic gene
CC program via direct action on adipocytes, but acts by stimulating
CC several immune cell subtypes to enter the adipose tissue and activate
CC their prothermogenic actions. Stimulates an eosinophil-dependent
CC increase in IL4 expression and promotes alternative activation of
CC adipose tissue macrophages, which are required for the increased
CC expression of the thermogenic and anti-inflammatory gene programs in
CC fat. Required for some cold-induced thermogenic responses, suggesting a
CC role in metabolic adaptations to cold temperatures.
CC {ECO:0000269|PubMed:24906147}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:24393292,
CC ECO:0000269|PubMed:24906147}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8VE43-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8VE43-2; Sequence=VSP_025897;
CC -!- TISSUE SPECIFICITY: Highly expressed in subcutaneous adipose tissue.
CC {ECO:0000269|PubMed:24393292, ECO:0000269|PubMed:24906147}.
CC -!- INDUCTION: Up-regulated during adipogenesis and obesity. Induced either
CC in muscle after exercise or in adipose tissue upon cold exposure (at
CC protein level). Expression is induced by Ppargc1a isoform 4
CC (PubMed:24906147). {ECO:0000269|PubMed:24393292,
CC ECO:0000269|PubMed:24906147}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:24393292}.
CC -!- SIMILARITY: Belongs to the meteorin family. {ECO:0000305}.
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DR EMBL; AK034855; BAC28856.1; -; mRNA.
DR EMBL; AL645972; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC019776; AAH19776.1; -; mRNA.
DR EMBL; BC024445; AAH24445.1; -; mRNA.
DR EMBL; BC024497; AAH24497.1; -; mRNA.
DR EMBL; BC026646; AAH26646.1; -; mRNA.
DR CCDS; CCDS25781.1; -. [Q8VE43-1]
DR RefSeq; NP_659046.1; NM_144797.3. [Q8VE43-1]
DR AlphaFoldDB; Q8VE43; -.
DR STRING; 10090.ENSMUSP00000038126; -.
DR GlyGen; Q8VE43; 1 site.
DR PhosphoSitePlus; Q8VE43; -.
DR MaxQB; Q8VE43; -.
DR PaxDb; Q8VE43; -.
DR PeptideAtlas; Q8VE43; -.
DR PRIDE; Q8VE43; -.
DR ProteomicsDB; 295552; -. [Q8VE43-1]
DR ProteomicsDB; 295553; -. [Q8VE43-2]
DR Antibodypedia; 19928; 106 antibodies from 17 providers.
DR DNASU; 210029; -.
DR Ensembl; ENSMUST00000036742; ENSMUSP00000038126; ENSMUSG00000039208. [Q8VE43-1]
DR Ensembl; ENSMUST00000106089; ENSMUSP00000101695; ENSMUSG00000039208. [Q8VE43-2]
DR GeneID; 210029; -.
DR KEGG; mmu:210029; -.
DR UCSC; uc007mwd.1; mouse. [Q8VE43-1]
DR CTD; 284207; -.
DR MGI; MGI:2384806; Metrnl.
DR VEuPathDB; HostDB:ENSMUSG00000039208; -.
DR eggNOG; ENOG502QUQB; Eukaryota.
DR GeneTree; ENSGT00390000001390; -.
DR HOGENOM; CLU_069970_0_0_1; -.
DR InParanoid; Q8VE43; -.
DR OMA; GAVEWMY; -.
DR OrthoDB; 1364884at2759; -.
DR PhylomeDB; Q8VE43; -.
DR TreeFam; TF330918; -.
DR BioGRID-ORCS; 210029; 2 hits in 71 CRISPR screens.
DR ChiTaRS; Metrnl; mouse.
DR PRO; PR:Q8VE43; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q8VE43; protein.
DR Bgee; ENSMUSG00000039208; Expressed in lip and 206 other tissues.
DR ExpressionAtlas; Q8VE43; baseline and differential.
DR Genevisible; Q8VE43; MM.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005179; F:hormone activity; IDA:UniProtKB.
DR GO; GO:0050873; P:brown fat cell differentiation; IDA:UniProtKB.
DR GO; GO:0097009; P:energy homeostasis; IDA:UniProtKB.
DR GO; GO:0045444; P:fat cell differentiation; IDA:UniProtKB.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IDA:UniProtKB.
DR GO; GO:0090336; P:positive regulation of brown fat cell differentiation; IDA:UniProtKB.
DR GO; GO:0009409; P:response to cold; IDA:UniProtKB.
DR GO; GO:0014850; P:response to muscle activity; IDA:UniProtKB.
DR InterPro; IPR039224; Meteorin-like.
DR PANTHER; PTHR28593:SF1; PTHR28593:SF1; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disulfide bond; Glycoprotein; Hormone;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..45
FT /evidence="ECO:0000255"
FT CHAIN 46..311
FT /note="Meteorin-like protein"
FT /id="PRO_0000289105"
FT CARBOHYD 103
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 52..75
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 107..143
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 188..260
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 191..284
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 201..306
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 1..82
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_025897"
SQ SEQUENCE 311 AA; 34530 MW; C8062688E2B6DFA0 CRC64;
MRGAVWAARR RAGQQWPRSP GPGPGPPPPP PLLLLLLLLL GGASAQYSSD LCSWKGSGLT
REARSKEVEQ VYLRCSAGSV EWMYPTGALI VNLRPNTFSP AQNLTVCIKP FRDSSGANIY
LEKTGELRLL VRDIRGEPGQ VQCFSLEQGG LFVEATPQQD ISRRTTGFQY ELMSGQRGLD
LHVLSAPCRP CSDTEVLLAI CTSDFVVRGF IEDVTHVPEQ QVSVIYLRVN RLHRQKSRVF
QPAPEDSGHW LGHVTTLLQC GVRPGHGEFL FTGHVHFGEA QLGCAPRFSD FQRMYRKAEE
MGINPCEINM E
