{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"D3Z7Q2","uniProtkbId":"SIM20_MOUSE","entryAudit":{"firstPublicDate":"2020-02-26","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2010-04-20","entryVersion":96,"sequenceVersion":1},"annotationScore":4.0,"organism":{"scientificName":"Mus musculus","commonName":"Mouse","taxonId":10090,"evidences":[{"evidenceCode":"ECO:0000312","source":"Proteomes","id":"UP000000589"}],"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Glires","Rodentia","Myomorpha","Muroidea","Muridae","Murinae","Mus","Mus"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"Small integral membrane protein 20"}},"alternativeNames":[{"fullName":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8N5G0"}],"value":"Mitochondrial translation regulation assembly intermediate of cytochrome c oxidase protein of 7 kDa"},"shortNames":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8N5G0"}],"value":"MITRAC7"}]}],"contains":[{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"C0HLM6"}],"value":"Phoenixin-14"},"shortNames":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"C0HLM6"}],"value":"PNX-14"}]}},{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"C0HLM6"}],"value":"Phoenixin-20"},"shortNames":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"C0HLM6"}],"value":"PNX-20"}]}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000312","source":"MGI","id":"MGI:1913528"}],"value":"Smim20"}}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8N5G0"}],"value":"Component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex, that regulates cytochrome c oxidase assembly (By similarity). Promotes the progression of complex assembly after the association of MT-CO1/COX1 with COX4I1 and COX6C (By similarity). Chaperone-like assembly factor required to stabilize newly synthesized MT-CO1/COX1 and to prevent its premature turnover (By similarity)"}],"commentType":"FUNCTION","molecule":"Small integral membrane protein 20"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"C0HLM6"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25687846"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26415767"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26505917"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27268078"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30251651"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30933929"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31422055"}],"value":"Peptide involved in a broad spectrum of regulatory functions (PubMed:25687846, PubMed:26505917, PubMed:27268078). Is a ligand for GPR173 (By similarity). As part of the reproductive cycle, it regulates gonadotropin-releasing hormone (GnRH) signaling in the hypothalamus and pituitary gland which augments the release of luteinizing hormone (PubMed:27268078). More specifically, it regulates the expression of transcription factors CEBPB and POU2F1/OCT1 through the cAMP-PKA signaling pathway, which subsequently regulate the expression of GNRHR and KISS1 (PubMed:27268078). Plays a protective role in memory retention through activation of GNRHR (PubMed:26505917). Regulates the secretion of AVP by hypothalamic neurons (By similarity). Plays a role in the transduction of the itch sensation (PubMed:26415767). Induces anxiolytic effects, reducing behavior associated with anxiety (PubMed:25687846). Regulates food intake as well as satiation and satiety by increasing Nucb2 expression in neurons (By similarity). In the ovary, it regulates follicular growth by stimulating granulosa cell proliferation by increasing the expression of GPR173, CREB1, CYP19A1, KITLG, FSHR, and LHCGR (PubMed:30933929). It also increases the production of estradiol (E2) (PubMed:30933929). In the heart, it regulates contractility and relaxation by activating the AKT1-NOS3 and MAPK1-MAPK3 signaling pathways (By similarity). It also plays a cardioprotective role during ischemia, where it activates the SAFE and RISK pathways (By similarity). Stimulates the proliferation and differentiation of preadipocytes (PubMed:30251651). In pancreatic islet cells, it induces proliferation of islet cells as well as the production of INS through activation of the MAPK1-MAPK3 signaling pathways (PubMed:31422055)"}],"commentType":"FUNCTION","molecule":"Phoenixin-14"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"C0HLM6"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25687846"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26415767"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26505917"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27268078"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30251651"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30933929"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31422055"}],"value":"Peptide involved in a broad spectrum of regulatory functions (PubMed:25687846, PubMed:26505917, PubMed:27268078). Is a ligand for GPR173 (By similarity). As part of the reproductive cycle, it regulates gonadotropin-releasing hormone (GnRH) signaling in the hypothalamus and pituitary gland which augments the release of luteinizing hormone (PubMed:27268078). More specifically, it regulates the expression of transcription factors CEBPB and POU2F1/OCT1 through the cAMP-PKA signaling pathway, which subsequently regulate the expression of GNRHR and KISS1 (PubMed:27268078). Plays a protective role in memory retention through activation of GNRHR (PubMed:26505917). Regulates the secretion of AVP by hypothalamic neurons (By similarity). Plays a role in the transduction of the itch sensation (PubMed:26415767). Induces anxiolytic effects, reducing behavior associated with anxiety (PubMed:25687846). Regulates food intake as well as satiation and satiety by increasing Nucb2 expression in neurons (By similarity). In the ovary, it regulates follicular growth by stimulating granulosa cell proliferation by increasing the expression of GPR173, CREB1, CYP19A1, KITLG, FSHR, and LHCGR (PubMed:30933929). It also increases the production of estradiol (E2) (PubMed:30933929). In the heart, it regulates contractility and relaxation by activating the AKT1-NOS3 and MAPK1-MAPK3 signaling pathways (By similarity). It also plays a cardioprotective role during ischemia, where it activates the SAFE and RISK pathways (By similarity). Stimulates the proliferation and differentiation of preadipocytes (PubMed:30251651). In pancreatic islet cells, it induces proliferation of islet cells as well as the production of INS through activation of the MAPK1-MAPK3 signaling pathways (PubMed:31422055)"}],"commentType":"FUNCTION","molecule":"Phoenixin-20"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8N5G0"}],"value":"Component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex, the core components of this complex being COA3/MITRAC12 and COX14 (By similarity). Interacts with COA3/MITRAC12 and COX4I1 (By similarity). Directly interacts with newly synthesized MT-CO1/COX1 (By similarity)"}],"commentType":"SUBUNIT"},{"commentType":"SUBCELLULAR LOCATION","molecule":"Small integral membrane protein 20","subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8N5G0"}],"value":"Mitochondrion inner membrane","id":"SL-0168"},"topology":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Single-pass membrane protein","id":"SL-9904"}}]},{"commentType":"SUBCELLULAR LOCATION","molecule":"Phoenixin-14","subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30251651"}],"value":"Secreted","id":"SL-0243"}}]},{"commentType":"SUBCELLULAR LOCATION","molecule":"Phoenixin-20","subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30251651"}],"value":"Secreted","id":"SL-0243"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23912037"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26415767"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30251651"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30933929"}],"value":"Highly expressed in the hypothalamus, the spinal cord, and sensory ganglia (at protein level) (PubMed:23912037, PubMed:26415767). Also expressed on in the epidermis and dermis layers of the skin (at protein level) (PubMed:26415767). Expressed in preadipocytes and adipocytes (at protein level) (PubMed:30251651). Expressed in the ovary, specifically in granulosa cells of follicles that have passed the primary stage and in oocytes (at protein level) (PubMed:30933929)"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30524225"}],"value":"By fatty acids, specifically palmitate, docosahexanoic acid and oleate"}],"commentType":"INDUCTION"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":69,"modifier":"EXACT"}},"description":"Small integral membrane protein 20","featureId":"PRO_0000449030"},{"type":"Peptide","location":{"start":{"value":47,"modifier":"EXACT"},"end":{"value":66,"modifier":"EXACT"}},"description":"Phoenixin-20","featureId":"PRO_0000449031"},{"type":"Peptide","location":{"start":{"value":53,"modifier":"EXACT"},"end":{"value":66,"modifier":"EXACT"}},"description":"Phoenixin-14","featureId":"PRO_0000449032"},{"type":"Topological 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