{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q8NET8","secondaryAccessions":["Q8NDW7","Q8NET9","Q8NFH2"],"uniProtkbId":"TRPV3_HUMAN","entryAudit":{"firstPublicDate":"2005-04-26","lastAnnotationUpdateDate":"2026-06-10","lastSequenceUpdateDate":"2005-04-26","entryVersion":175,"sequenceVersion":2},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"Transient receptor potential cation channel subfamily V member 3"},"shortNames":[{"value":"TrpV3"}]},"alternativeNames":[{"fullName":{"value":"Vanilloid receptor-like 3"},"shortNames":[{"value":"VRL-3"}]}]},"genes":[{"geneName":{"value":"TRPV3"}}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12077604"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12077606"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21593771"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26818531"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37648856"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38691614"}],"value":"Non-selective calcium permeant cation channel (PubMed:12077604, PubMed:12077606, PubMed:26818531, PubMed:37648856, PubMed:38691614). It is activated by innocuous (warm) temperatures and shows an increased response at noxious temperatures greater than 39 degrees Celsius (PubMed:12077604, PubMed:12077606). Activation exhibits an outward rectification (PubMed:12077604). The channel pore can dilate to provide permeability to larger cations (PubMed:37648856). May associate with TRPV1 and may modulate its activity (PubMed:12077606). Is a negative regulator of hair growth and cycling: TRPV3-coupled signaling suppresses keratinocyte proliferation in hair follicles and induces apoptosis and premature hair follicle regression (catagen) (PubMed:21593771)"}],"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":"12077604"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12077606"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26818531"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38691614"}]}},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"Mg(2+)(in) = Mg(2+)(out)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:29827"},{"database":"ChEBI","id":"CHEBI:18420"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8K424"}]}},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"Na(+)(in) = Na(+)(out)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:34963"},{"database":"ChEBI","id":"CHEBI:29101"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12077604"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37648856"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38691614"}]}},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"K(+)(in) = K(+)(out)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:29463"},{"database":"ChEBI","id":"CHEBI:29103"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12077604"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37648856"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38691614"}],"value":"Activated by cannabinoid that binds to the vanilloid binding pocket (PubMed:38691614). Diphenylboronic anhydride induces pore dilation and enhances cation permeability by promoting the conversion to a homopentamer (PubMed:37648856)"}],"commentType":"ACTIVITY REGULATION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12077606"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26818531"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37648856"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38691614"}],"value":"Homotetramer (PubMed:37648856, PubMed:38691614). May convert from a homotetramer to a homopentamer to allow pore dilation (PubMed:37648856). Interacts with TRPV1; may form a heteromeric channel with TRPV1 (PubMed:12077606). Interacts with SNX11; this interaction promotes TRPV3 trafficking from the cell membrane to lysosome for degradation (PubMed:26818531)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q8NET8","intActId":"EBI-26563449"},"interactantTwo":{"uniProtKBAccession":"Q02410","geneName":"APBA1","intActId":"EBI-368690"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q8NET8","intActId":"EBI-26563449"},"interactantTwo":{"uniProtKBAccession":"Q99767","geneName":"APBA2","intActId":"EBI-81711"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q8NET8","intActId":"EBI-26563449"},"interactantTwo":{"uniProtKBAccession":"Q12959","geneName":"DLG1","intActId":"EBI-357481"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q8NET8","intActId":"EBI-26563449"},"interactantTwo":{"uniProtKBAccession":"Q15700","geneName":"DLG2","intActId":"EBI-80426"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q8NET8","intActId":"EBI-26563449"},"interactantTwo":{"uniProtKBAccession":"Q92796","geneName":"DLG3","intActId":"EBI-80440"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q8NET8","intActId":"EBI-26563449"},"interactantTwo":{"uniProtKBAccession":"P78352","geneName":"DLG4","intActId":"EBI-80389"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q8NET8","intActId":"EBI-26563449"},"interactantTwo":{"uniProtKBAccession":"Q68DX3","geneName":"FRMPD2","intActId":"EBI-53993476"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q8NET8","intActId":"EBI-26563449"},"interactantTwo":{"uniProtKBAccession":"Q9C0E4","geneName":"GRIP2","intActId":"EBI-949557"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q8NET8","intActId":"EBI-26563449"},"interactantTwo":{"uniProtKBAccession":"Q14005","geneName":"IL16","intActId":"EBI-2831580"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q8NET8","intActId":"EBI-26563449"},"interactantTwo":{"uniProtKBAccession":"Q8TBB1","geneName":"LNX1","intActId":"EBI-739832"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q8NET8","intActId":"EBI-26563449"},"interactantTwo":{"uniProtKBAccession":"Q86UL8","geneName":"MAGI2","intActId":"EBI-311035"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q8NET8","intActId":"EBI-26563449"},"interactantTwo":{"uniProtKBAccession":"Q86UT5","geneName":"NHERF4","intActId":"EBI-8744528"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q8NET8","intActId":"EBI-26563449"},"interactantTwo":{"uniProtKBAccession":"Q8NI35","geneName":"PATJ","intActId":"EBI-724390"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q8NET8","intActId":"EBI-26563449"},"interactantTwo":{"uniProtKBAccession":"Q5T2W1","geneName":"PDZK1","intActId":"EBI-349819"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q8NET8","intActId":"EBI-26563449"},"interactantTwo":{"uniProtKBAccession":"Q14160","geneName":"SCRIB","intActId":"EBI-357345"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q8NET8","intActId":"EBI-26563449"},"interactantTwo":{"uniProtKBAccession":"Q9P202","geneName":"WHRN","intActId":"EBI-310886"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q8NET8-1","intActId":"EBI-26518537"},"interactantTwo":{"uniProtKBAccession":"Q8NET8-1","geneName":"TRPV3","intActId":"EBI-26518537"},"numberOfExperiments":2,"organismDiffer":false}]},{"commentType":"SUBCELLULAR 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Widely expressed at low levels. Detected in dorsal root ganglion (at protein level). Expressed in the keratinocyte layers of the outer root sheath and, to lesser extent, to the matrix of the hair follicles (at protein level)"}],"commentType":"TISSUE SPECIFICITY"},{"commentType":"DISEASE","disease":{"diseaseId":"Olmsted syndrome 1","diseaseAccession":"DI-03430","acronym":"OLMS1","description":"An autosomal dominant, rare congenital disorder characterized by bilateral mutilating palmoplantar keratoderma and periorificial keratotic plaques with severe itching at all lesions. Diffuse alopecia, constriction of digits, and onychodystrophy have also been reported. Infections and squamous cell carcinomas can arise on the keratotic areas. The digital constriction may progress to autoamputation of fingers and toes.","diseaseCrossReference":{"database":"MIM","id":"614594"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22405088"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22835024"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"commentType":"DISEASE","disease":{"diseaseId":"Palmoplantar keratoderma, non-epidermolytic, focal 2","diseaseAccession":"DI-04445","acronym":"FNEPPK2","description":"A dermatological disorder characterized by non-epidermolytic, abnormal thickening of the skin on the palms and soles. 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