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   24-JAN-2024, entry version 123.
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.
DR   AlphaFoldDB; Q641Q3; -.
DR   SMR; Q641Q3; -.
DR   BioGRID; 129788; 112.
DR   IntAct; Q641Q3; 3.
DR   STRING; 9606.ENSP00000315731; -.
DR   GlyGen; Q641Q3; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q641Q3; -.
DR   PhosphoSitePlus; Q641Q3; -.
DR   BioMuta; METRNL; -.
DR   DMDM; 74736273; -.
DR   EPD; Q641Q3; -.
DR   jPOST; Q641Q3; -.
DR   MassIVE; Q641Q3; -.
DR   PaxDb; 9606-ENSP00000315731; -.
DR   PeptideAtlas; Q641Q3; -.
DR   ProteomicsDB; 3644; -.
DR   ProteomicsDB; 65912; -. [Q641Q3-1]
DR   Antibodypedia; 19928; 120 antibodies from 18 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   AGR; HGNC:27584; -.
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; ISFCQYS; -.
DR   OrthoDB; 3030333at2759; -.
DR   PhylomeDB; Q641Q3; -.
DR   TreeFam; TF330918; -.
DR   PathwayCommons; Q641Q3; -.
DR   SignaLink; Q641Q3; -.
DR   BioGRID-ORCS; 284207; 23 hits in 1146 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 98 other cell types or tissues.
DR   ExpressionAtlas; Q641Q3; baseline and differential.
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   PANTHER; PTHR28593; METEORIN-LIKE PROTEIN; 1.
DR   PANTHER; PTHR28593:SF1; METEORIN-LIKE PROTEIN; 1.
DR   Genevisible; Q641Q3; HS.
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
//