{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"A0A0C5B5G6","uniProtkbId":"MOTSC_HUMAN","entryAudit":{"firstPublicDate":"2016-04-13","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2015-04-29","entryVersion":32,"sequenceVersion":1},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"evidences":[{"evidenceCode":"ECO:0000312","source":"EMBL","id":"AJM13597.1"}],"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"25738459"}],"value":"Mitochondrial-derived peptide MOTS-c"}},"alternativeNames":[{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"25738459"}],"value":"Mitochondrial open reading frame of the 12S rRNA-c"}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:7470"}],"value":"MT-RNR1"}}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25738459"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29886458"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29983246"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30468456"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31081069"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33468709"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33554779"}],"value":"Regulates insulin sensitivity and metabolic homeostasis (PubMed:25738459, PubMed:33468709). Inhibits the folate cycle, thereby reducing de novo purine biosynthesis which leads to the accumulation of the de novo purine synthesis intermediate 5-aminoimidazole-4-carboxamide (AICAR) and the activation of the metabolic regulator 5'-AMP-activated protein kinase (AMPK) (PubMed:25738459). Protects against age-dependent and diet-induced insulin resistance as well as diet-induced obesity (PubMed:25738459). In response to metabolic stress, translocates to the nucleus where it binds to antioxidant response elements (ARE) present in the promoter regions of a number of genes and plays a role in regulating nuclear gene expression in an NFE2L2-dependent manner and increasing cellular resistance to metabolic stress (PubMed:29983246). Increases mitochondrial respiration and levels of CPT1A and cytokines IL1B, IL6, IL8, IL10 and TNF in senescent cells (PubMed:29886458). Increases activity of the serine/threonine protein kinase complex mTORC2 and reduces activity of the PTEN phosphatase, thus promoting phosphorylation of AKT (PubMed:33554779). This promotes AKT-mediated phosphorylation of transcription factor FOXO1 which reduces FOXO1 activity, leading to reduced levels of MSTN and promotion of skeletal muscle growth (PubMed:33554779). Promotes osteogenic differentiation of bone marrow mesenchymal stem cells via the TGFB/SMAD pathway (PubMed:30468456). Promotes osteoblast proliferation and osteoblast synthesis of type I collagens COL1A1 and COL1A2 via the TGFB/SMAD pathway (PubMed:31081069)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29983246"}],"value":"Interacts with transcription factors ATF1 and NFE2L2/NRF2; the interactions occur in the nucleus following metabolic stress (PubMed:29983246). Also interacts with transcription factor NFE2L1/NRF1 (PubMed:29983246)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"A0A0C5B5G6","intActId":"EBI-64093251"},"interactantTwo":{"uniProtKBAccession":"Q16236","geneName":"NFE2L2","intActId":"EBI-2007911"},"numberOfExperiments":2,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29983246"}],"value":"Translocates to the nucleus in response to metabolic stress in an AMPK-dependent manner"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25738459"}],"value":"Secreted","id":"SL-0243"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29983246"}],"value":"Mitochondrion","id":"SL-0173"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29983246"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33473109"}],"value":"Nucleus","id":"SL-0191"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25738459"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32182209"}],"value":"Detected in plasma (at protein level) (PubMed:25738459, PubMed:32182209). 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