{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q921L3","secondaryAccessions":["Q3TS11"],"uniProtkbId":"TMCO1_MOUSE","entryAudit":{"firstPublicDate":"2006-06-27","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2001-12-01","entryVersion":153,"sequenceVersion":1},"annotationScore":5.0,"organism":{"scientificName":"Mus musculus","commonName":"Mouse","taxonId":10090,"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":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9UM00"}],"value":"Calcium load-activated calcium channel"},"shortNames":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9UM00"}],"value":"CLAC channel"}]},"alternativeNames":[{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"GEL complex subunit TMCO1"}},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Transmembrane and coiled-coil domain-containing protein 1"}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000312","source":"MGI","id":"MGI:1921173"}],"value":"Tmco1"}}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9UM00"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27212239"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29467381"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30962442"}],"value":"Endoplasmic reticulum (ER) calcium-selective channel preventing intracellular Ca2(+) stores from overfilling and maintaining calcium homeostasis in the ER. In response to endoplasmic reticulum (ER) Ca2(+) overloading, assembles into a homotetramer, forming a functional calcium-selective channel facilitating Ca2(+) release (PubMed:27212239, PubMed:29467381, PubMed:30962442). Mediates ER Ca2(+) homeostasis in osteoblasts and plays a key role in bone formation, via the CaMKII-HDAC4-RUNX2 signaling axis (PubMed:30962442). Component of the multi-pass translocon (MPT) complex that mediates insertion of multi-pass membrane proteins into the lipid bilayer of membranes (By similarity). The MPT complex takes over after the SEC61 complex: following membrane insertion of the first few transmembrane segments of proteins by the SEC61 complex, the MPT complex occludes the lateral gate of the SEC61 complex to promote insertion of subsequent transmembrane regions (By similarity). Within the MPT complex, the GEL subcomplex may mediate insertion of transmembrane regions into the membrane (By similarity)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"Ca(2+)(in) = Ca(2+)(out)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:29671"},{"database":"ChEBI","id":"CHEBI:29108"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27212239"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9UM00"}],"value":"Homodimer and homotetramer. Homodimer under resting conditions; forms homotetramers following ER calcium overload. Component of the GET- and EMC-like (GEL) complex, composed of RAB5IF/OPTI and TMCO1. The GEL complex is part of the multi-pass translocon (MPT) complex, composed of three subcomplexes, the GEL complex (composed of RAB5IF/OPTI and TMCO1), the BOS complex (composed of NCLN/Nicalin, NOMO1 and TMEM147) and the PAT complex (composed of WDR83OS/Asterix and CCDC47). The MPT complex associates with the SEC61 complex"}],"commentType":"SUBUNIT"},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9UM00"}],"value":"The first transmembrane region is required for localization to the endoplasmic reticulum"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9UM00"}],"value":"Endoplasmic reticulum membrane","id":"SL-0097"},"topology":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9UM00"}],"value":"Multi-pass membrane protein","id":"SL-9909"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9UM00"}],"value":"Golgi apparatus membrane","id":"SL-0134"},"topology":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9UM00"}],"value":"Multi-pass membrane protein","id":"SL-9909"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"C5HGF3"}],"value":"Mitochondrion membrane","id":"SL-0171"},"topology":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9UM00"}],"value":"Multi-pass membrane protein","id":"SL-9909"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27212239"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29467381"}],"value":"Mice are born at a much lower rate than predicted by the Mendelian ratio. Surviving mice show a reduced body size, low survival rate and delayed osteogenesis. Adult mice display craniofacial dysmorphism such as open cranial sutures, flattened faces with shorten nasal bones and skull anomalies. Moreover, magnetic resonance imaging (MRI) of brain shows significantly enlarged brain ventricles. Adult mice show defects in spatial recognition memory in a Y-maze task assay and a significant deficiency in motor coordination in rotarod assessments. Defects are probably due to calcium overload, calcium imaging results revealing a significant overload of endoplasmic reticulum calcium in osteoblasts (PubMed:27212239, PubMed:29467381). Additionally female Tmco1-/- mice show impaired follicle development, subfertility, and premature ovarian failure (PubMed:29467381)"}],"commentType":"DISRUPTION PHENOTYPE"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the TMCO1 family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":188,"modifier":"EXACT"}},"description":"Calcium load-activated calcium channel","featureId":"PRO_0000244077"},{"type":"Topological domain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":4,"modifier":"EXACT"}},"description":"Lumenal","evidences":[{"evidenceCode":"ECO:0000305"}]},{"type":"Transmembrane","location":{"start":{"value":5,"modifier":"EXACT"},"end":{"value":32,"modifier":"EXACT"}},"description":"Helical","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"A0A8I3PI99"}]},{"type":"Topological 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