{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q9UPY3","secondaryAccessions":["A7E2D3","B3KRG4","E0AD28","O95943","Q9UQ02"],"uniProtkbId":"DICER_HUMAN","entryAudit":{"firstPublicDate":"2002-10-25","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2009-09-01","entryVersion":221,"sequenceVersion":3},"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":"Endoribonuclease Dicer"},"ecNumbers":[{"value":"3.1.26.3"}]},"alternativeNames":[{"fullName":{"value":"Helicase with RNase motif"},"shortNames":[{"value":"Helicase MOI"}]}]},"genes":[{"geneName":{"value":"DICER1"},"synonyms":[{"value":"DICER"},{"value":"HERNA"},{"value":"KIAA0928"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15242644"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15973356"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16142218"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16271387"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16289642"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16357216"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16424907"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17452327"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18178619"}],"value":"Double-stranded RNA (dsRNA) endoribonuclease playing a central role in short dsRNA-mediated post-transcriptional gene silencing. Cleaves naturally occurring long dsRNAs and short hairpin pre-microRNAs (miRNA) into fragments of twenty-one to twenty-three nucleotides with 3' overhang of two nucleotides, producing respectively short interfering RNAs (siRNA) and mature microRNAs. SiRNAs and miRNAs serve as guide to direct the RNA-induced silencing complex (RISC) to complementary RNAs to degrade them or prevent their translation. Gene silencing mediated by siRNAs, also called RNA interference, controls the elimination of transcripts from mobile and repetitive DNA elements of the genome but also the degradation of exogenous RNA of viral origin for instance. The miRNA pathway on the other side is a mean to specifically regulate the expression of target genes"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"Endonucleolytic cleavage to 5'-phosphomonoester.","ecNumber":"3.1.26.3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15242644"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17920623"}]}},{"commentType":"COFACTOR","cofactors":[{"name":"Mg(2+)","evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"17920623"}],"cofactorCrossReference":{"database":"ChEBI","id":"CHEBI:18420"}},{"name":"Mn(2+)","evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"17920623"}],"cofactorCrossReference":{"database":"ChEBI","id":"CHEBI:29035"}}],"note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"17920623"}],"value":"Binds 2 magnesium or manganese ions per subunit."}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14749716"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15973356"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16142218"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16271387"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16289642"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16357216"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16424907"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17452327"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17507929"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17531811"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17920623"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18178619"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18690212"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19022417"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23063121"}],"value":"Component of the RISC loading complex (RLC), or micro-RNA (miRNA) loading complex (miRLC), which is composed of DICER1, AGO2 and TARBP2; DICER1 and TARBP2 are required to process precursor miRNAs (pre-miRNAs) to mature miRNAs and then load them onto AGO2. Note that the trimeric RLC/miRLC is also referred to as RISC. Interacts with DHX9, AGO1, PIWIL1 and PRKRA. Associates with the 60S ribosome. Interacts with BCDIN3D. Interacts with AGO2, TARBP2, EIF6, MOV10 and RPL7A (60S ribosome subunit); they form a large RNA-induced silencing complex (RISC) (PubMed:17507929). Interacts (via Dicer dsRNA-binding fold domain) with ALOX5 (via PLAT domain); this interaction enhances arachidonate 5-lipoxygenase activity and modifies the miRNA precursor processing activity of DICER1 (PubMed:19022417)"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21228243"}],"value":"(Microbial infection) Interacts with ebolavirus transcriptional activator VP30; this interaction prevents TARBP2/TRBP binding to DICER1 and thus allows the virus to counteract host RNA silencing"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21228243"}],"value":"(Microbial infection) Interacts with ebolavirus transcriptional activator VP35; this interaction prevents TARBP2/TRBP binding to DICER1 and thus allows the virus to counteract host RNA silencing"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q9UPY3","intActId":"EBI-395506"},"interactantTwo":{"uniProtKBAccession":"P55265-1","geneName":"ADAR","intActId":"EBI-6913056"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9UPY3","intActId":"EBI-395506"},"interactantTwo":{"uniProtKBAccession":"P55265-5","geneName":"ADAR","intActId":"EBI-6913210"},"numberOfExperiments":8,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9UPY3","intActId":"EBI-395506"},"interactantTwo":{"uniProtKBAccession":"Q9UL18","geneName":"AGO1","intActId":"EBI-527363"},"numberOfExperiments":9,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9UPY3","intActId":"EBI-395506"},"interactantTwo":{"uniProtKBAccession":"Q9UKV8","geneName":"AGO2","intActId":"EBI-528269"},"numberOfExperiments":21,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9UPY3","intActId":"EBI-395506"},"interactantTwo":{"uniProtKBAccession":"Q96C10","geneName":"DHX58","intActId":"EBI-744193"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9UPY3","intActId":"EBI-395506"},"interactantTwo":{"uniProtKBAccession":"P19525","geneName":"EIF2AK2","intActId":"EBI-640775"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9UPY3","intActId":"EBI-395506"},"interactantTwo":{"uniProtKBAccession":"Q96J94","geneName":"PIWIL1","intActId":"EBI-527417"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9UPY3","intActId":"EBI-395506"},"interactantTwo":{"uniProtKBAccession":"O75569","geneName":"PRKRA","intActId":"EBI-713955"},"numberOfExperiments":9,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9UPY3","intActId":"EBI-395506"},"interactantTwo":{"uniProtKBAccession":"Q15633","geneName":"TARBP2","intActId":"EBI-978581"},"numberOfExperiments":25,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9UPY3","intActId":"EBI-395506"},"interactantTwo":{"uniProtKBAccession":"O43508","geneName":"TNFSF12","intActId":"EBI-6932080"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9UPY3","intActId":"EBI-395506"},"interactantTwo":{"uniProtKBAccession":"Q8CJG0","geneName":"Ago2","intActId":"EBI-528299"},"numberOfExperiments":2,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"Q9UPY3","intActId":"EBI-395506"},"interactantTwo":{"uniProtKBAccession":"Q9IK90","geneName":"M","intActId":"EBI-25747115"},"numberOfExperiments":3,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"Q9UPY3","intActId":"EBI-395506"},"interactantTwo":{"uniProtKBAccession":"P0C205","intActId":"EBI-8332963"},"numberOfExperiments":7,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"Q9UPY3-1","intActId":"EBI-15569571"},"interactantTwo":{"uniProtKBAccession":"Q9UKV8","geneName":"AGO2","intActId":"EBI-528269"},"numberOfExperiments":14,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9UPY3-1","intActId":"EBI-15569571"},"interactantTwo":{"uniProtKBAccession":"Q92945","geneName":"KHSRP","intActId":"EBI-1049099"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9UPY3-1","intActId":"EBI-15569571"},"interactantTwo":{"uniProtKBAccession":"P24928","geneName":"POLR2A","intActId":"EBI-295301"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9UPY3-1","intActId":"EBI-15569571"},"interactantTwo":{"uniProtKBAccession":"Q15633","geneName":"TARBP2","intActId":"EBI-978581"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9UPY3-1","intActId":"EBI-15569571"},"interactantTwo":{"uniProtKBAccession":"Q61496","geneName":"Ddx4","intActId":"EBI-15569589"},"numberOfExperiments":3,"organismDiffer":true}]},{"commentType":"SUBCELLULAR 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The tumor arises from the lung, pleura, or both, and appears to be purely mesenchymal in phenotype. It lacks malignant epithelial elements, a feature that distinguishes it from the classic adult-type pulmonary blastoma. It arises during fetal lung development and is often part of an inherited cancer syndrome. The tumor contain both epithelial and mesenchymal cells. Early in tumorigenesis, cysts form in lung airspaces, and these cysts are lined with benign-appearing epithelium. Mesenchymal cells susceptible to malignant transformation reside within the cyst walls and form a dense layer beneath the epithelial lining. In a subset of patients, overgrowth of the mesenchymal cells produces a sarcoma, a transition that is associated with a poorer prognosis. Some patients have multilocular cystic nephroma, a benign kidney tumor.","diseaseCrossReference":{"database":"MIM","id":"601200"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19556464"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26925222"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"commentType":"DISEASE","disease":{"diseaseId":"Goiter multinodular 1, with or without Sertoli-Leydig cell tumors","diseaseAccession":"DI-03075","acronym":"MNG1","description":"A common disorder characterized by nodular overgrowth of the thyroid gland. 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It occurs in four forms: alveolar, pleomorphic, embryonal and botryoidal rhabdomyosarcomas.","diseaseCrossReference":{"database":"MIM","id":"180295"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21882293"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"commentType":"DISEASE","disease":{"diseaseId":"Global developmental delay, lung cysts, overgrowth, and Wilms tumor","diseaseAccession":"DI-05455","acronym":"GLOW","description":"A disease characterized by the association of congenital nephromegaly, bilateral Wilms tumor, somatic overgrowth, developmental delay, macrocephaly, and bilateral lung cysts.","diseaseCrossReference":{"database":"MIM","id":"618272"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24676357"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"commentType":"DISEASE","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21882293"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22187960"}],"value":"DICER1 mutations have been found in uterine cervix embryonal rhabdomyosarcoma, primitive neuroectodermal tumor, Wilms tumor, pulmonary sequestration and juvenile intestinal polyp (PubMed:21882293). Somatic missense mutations affecting the RNase IIIb domain of DICER1 are common in non-epithelial ovarian tumors. These mutations do not abolish DICER1 function but alter it in specific cell types, a novel mechanism through which perturbation of microRNA processing may be oncogenic (PubMed:22187960)"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00657"}],"value":"Belongs to the helicase family. Dicer subfamily"}],"commentType":"SIMILARITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"It is uncertain whether Met-1 or Met-11 is the initiator"}],"commentType":"CAUTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"19219043"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"26813765"}],"value":"A paper describing truncating mutations of TARBP2 in tumor cells and resultant effects on DICER1 stability and miRNA processing has been retracted, due to concerns of image duplication in some of the figures"}],"commentType":"CAUTION"},{"commentType":"SEQUENCE CAUTION","sequenceCautionType":"Erroneous initiation","sequence":"CAB38857.2","note":"Truncated N-terminus.","evidences":[{"evidenceCode":"ECO:0000305"}]},{"commentType":"WEB RESOURCE","resourceName":"Protein Spotlight","resourceUrl":"https://www.proteinspotlight.org/back_issues/087","ftp":false,"note":"The dark side of RNA - Issue 87 of October 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