METRL_HUMAN
ID METRL_HUMAN Reviewed; 311 AA.
AC Q641Q3; B3KSJ5; Q86VM0;
DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 25-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 116.
DE RecName: Full=Meteorin-like protein;
DE AltName: Full=Subfatin;
DE Flags: Precursor;
GN Name=METRNL;
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 [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Thymus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Blood, and Spleen;
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 TISSUE SPECIFICITY.
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 TISSUE SPECIFICITY.
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 (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q641Q3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q641Q3-2; Sequence=VSP_056101;
CC -!- TISSUE SPECIFICITY: Highly expressed in the skeletal muscle, in
CC subcutaneous adipose tissue, epididymal white adipose tissue depots and
CC heart. Also expressed in brown adipose tissues and kidney.
CC {ECO:0000269|PubMed:24393292, ECO:0000269|PubMed:24906147}.
CC -!- SIMILARITY: Belongs to the meteorin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH50568.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK093748; BAG52757.1; -; mRNA.
DR EMBL; AC130371; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC144831; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC050568; AAH50568.1; ALT_INIT; mRNA.
DR EMBL; BC082252; AAH82252.1; -; mRNA.
DR CCDS; CCDS32779.1; -. [Q641Q3-1]
DR CCDS; CCDS86656.1; -. [Q641Q3-2]
DR RefSeq; NP_001004431.1; NM_001004431.2. [Q641Q3-1]
DR RefSeq; XP_016880012.1; XM_017024523.1. [Q641Q3-2]
DR AlphaFoldDB; Q641Q3; -.
DR BioGRID; 129788; 112.
DR IntAct; Q641Q3; 3.
DR STRING; 9606.ENSP00000315731; -.
DR iPTMnet; Q641Q3; -.
DR PhosphoSitePlus; Q641Q3; -.
DR BioMuta; METRNL; -.
DR DMDM; 74736273; -.
DR EPD; Q641Q3; -.
DR jPOST; Q641Q3; -.
DR MassIVE; Q641Q3; -.
DR PaxDb; Q641Q3; -.
DR PeptideAtlas; Q641Q3; -.
DR PRIDE; Q641Q3; -.
DR ProteomicsDB; 3644; -.
DR ProteomicsDB; 65912; -. [Q641Q3-1]
DR Antibodypedia; 19928; 106 antibodies from 17 providers.
DR DNASU; 284207; -.
DR Ensembl; ENST00000320095.12; ENSP00000315731.6; ENSG00000176845.13. [Q641Q3-1]
DR Ensembl; ENST00000570778.5; ENSP00000458566.1; ENSG00000176845.13. [Q641Q3-2]
DR Ensembl; ENST00000571814.1; ENSP00000460798.1; ENSG00000176845.13. [Q641Q3-2]
DR Ensembl; ENST00000616599.2; ENSP00000481759.2; ENSG00000275031.2. [Q641Q3-2]
DR Ensembl; ENST00000633913.1; ENSP00000488860.1; ENSG00000275031.2. [Q641Q3-1]
DR Ensembl; ENST00000634158.1; ENSP00000488881.1; ENSG00000275031.2. [Q641Q3-2]
DR GeneID; 284207; -.
DR KEGG; hsa:284207; -.
DR MANE-Select; ENST00000320095.12; ENSP00000315731.6; NM_001004431.3; NP_001004431.1.
DR UCSC; uc002kgh.4; human. [Q641Q3-1]
DR CTD; 284207; -.
DR DisGeNET; 284207; -.
DR GeneCards; METRNL; -.
DR HGNC; HGNC:27584; METRNL.
DR HPA; ENSG00000176845; Tissue enhanced (skin).
DR MIM; 616241; gene.
DR neXtProt; NX_Q641Q3; -.
DR OpenTargets; ENSG00000176845; -.
DR PharmGKB; PA134970048; -.
DR VEuPathDB; HostDB:ENSG00000176845; -.
DR eggNOG; ENOG502QUQB; Eukaryota.
DR GeneTree; ENSGT00390000001390; -.
DR HOGENOM; CLU_069970_0_0_1; -.
DR InParanoid; Q641Q3; -.
DR OMA; GAVEWMY; -.
DR OrthoDB; 1364884at2759; -.
DR PhylomeDB; Q641Q3; -.
DR TreeFam; TF330918; -.
DR PathwayCommons; Q641Q3; -.
DR SignaLink; Q641Q3; -.
DR BioGRID-ORCS; 284207; 20 hits in 1068 CRISPR screens.
DR ChiTaRS; METRNL; human.
DR GenomeRNAi; 284207; -.
DR Pharos; Q641Q3; Tbio.
DR PRO; PR:Q641Q3; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q641Q3; protein.
DR Bgee; ENSG00000176845; Expressed in lower esophagus mucosa and 96 other tissues.
DR ExpressionAtlas; Q641Q3; baseline and differential.
DR Genevisible; Q641Q3; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0005179; F:hormone activity; ISS:UniProtKB.
DR GO; GO:0050873; P:brown fat cell differentiation; ISS:UniProtKB.
DR GO; GO:0097009; P:energy homeostasis; ISS:UniProtKB.
DR GO; GO:0045444; P:fat cell differentiation; ISS:CAFA.
DR GO; GO:0050728; P:negative regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0090336; P:positive regulation of brown fat cell differentiation; ISS:UniProtKB.
DR GO; GO:0009409; P:response to cold; ISS:UniProtKB.
DR GO; GO:0014850; P:response to muscle activity; ISS:UniProtKB.
DR InterPro; IPR039224; Meteorin-like.
DR PANTHER; PTHR28593:SF1; PTHR28593:SF1; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Disulfide bond; Hormone; Reference proteome;
KW Secreted; Signal.
FT SIGNAL 1..45
FT /evidence="ECO:0000255"
FT CHAIN 46..311
FT /note="Meteorin-like protein"
FT /id="PRO_0000289104"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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:14702039"
FT /id="VSP_056101"
SQ SEQUENCE 311 AA; 34398 MW; 0E3CA8262E23B97D CRC64;
MRGAARAAWG RAGQPWPRPP APGPPPPPLP LLLLLLAGLL GGAGAQYSSD RCSWKGSGLT
HEAHRKEVEQ VYLRCAAGAV EWMYPTGALI VNLRPNTFSP ARHLTVCIRS FTDSSGANIY
LEKTGELRLL VPDGDGRPGR VQCFGLEQGG LFVEATPQQD IGRRTTGFQY ELVRRHRASD
LHELSAPCRP CSDTEVLLAV CTSDFAVRGS IQQVTHEPER QDSAIHLRVS RLYRQKSRVF
EPVPEGDGHW QGRVRTLLEC GVRPGHGDFL FTGHMHFGEA RLGCAPRFKD FQRMYRDAQE
RGLNPCEVGT D
