ID:DICER_HUMAN DESCRIPTION: RecName: Full=Endoribonuclease Dicer; EC=3.1.26.-; AltName: Full=Helicase with RNase motif; Short=Helicase MOI; FUNCTION: Required for formation of the RNA induced silencing complex (RISC). Component of the RISC loading complex (RLC), also known as the micro-RNA (miRNA) loading complex (miRLC), which is composed of DICER1, EIF2C2/AGO2 and TARBP2. Within the RLC/miRLC, DICER1 and TARBP2 are required to process precursor miRNAs (pre- miRNAs) to mature miRNAs and then load them onto EIF2C2/AGO2. EIF2C2/AGO2 bound to the mature miRNA constitutes the minimal RISC and may subsequently dissociate from DICER1 and TARBP2. Also cleaves double-stranded RNA to produce short interfering RNAs (siRNAs) which target the selective destruction of complementary RNAs. COFACTOR: Binds 2 magnesium or manganese ions per subunit (Probable). SUBUNIT: Component of the RISC loading complex (RLC), or micro-RNA (miRNA) loading complex (miRLC), which is composed of DICER1, EIF2C2/AGO2 and TARBP2. Note that the trimeric RLC/miRLC is also referred to as RISC. Interacts with DHX9, EIF2C1, PIWIL1 and PRKRA. Associates with the 60S ribosome. Interacts with BCDIN3D. INTERACTION: Q96C10:DHX58; NbExp=2; IntAct=EBI-395506, EBI-744193; P19525:EIF2AK2; NbExp=2; IntAct=EBI-395506, EBI-640775; Q9UL18:EIF2C1; NbExp=2; IntAct=EBI-395506, EBI-527363; Q9UKV8:EIF2C2; NbExp=6; IntAct=EBI-395506, EBI-528269; Q8CJG0:Eif2c2 (xeno); NbExp=2; IntAct=EBI-395506, EBI-528299; Q96J94:PIWIL1; NbExp=2; IntAct=EBI-395506, EBI-527417; Q15633:TARBP2; NbExp=8; IntAct=EBI-395506, EBI-978581; SUBCELLULAR LOCATION: Cytoplasm. DISEASE: Defects in DICER1 are a cause of pleuropulmonary blastoma (PPB) [MIM:601200]. PPB is a rare pediatric tumor of the lung that arises during fetal lung development and is often part of an inherited cancer syndrome. PPBs 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 'cambium' 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. DISEASE: Defects in DICER1 are the cause of goiter multinodular type 1 with or without Sertoli-Leydig cell tumors (MNG1) [MIM:138800]. A common disorder characterized by nodular overgrowth of the thyroid gland. Some individuals may also develop Sertoli-Leydig cell tumors, usually of the ovary. DISEASE: Note=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). SIMILARITY: Belongs to the helicase family. Dicer subfamily. SIMILARITY: Contains 1 Dicer dsRNA-binding fold domain. SIMILARITY: Contains 1 DRBM (double-stranded RNA-binding) domain. SIMILARITY: Contains 1 helicase ATP-binding domain. SIMILARITY: Contains 1 helicase C-terminal domain. SIMILARITY: Contains 1 PAZ domain. SIMILARITY: Contains 2 RNase III domains. CAUTION: It is uncertain whether Met-1 or Met-11 is the initiator. SEQUENCE CAUTION: Sequence=CAB38857.2; Type=Erroneous initiation; Note=Translation N-terminally extended; WEB RESOURCE: Name=Protein Spotlight; Note=The dark side of RNA - Issue 87 of October 2007; URL="http://web.expasy.org/spotlight/back_issues/sptlt087.shtml";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9UPY3
Front
Top
Side
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000122 negative regulation of transcription from RNA polymerase II promoter GO:0006309 apoptotic DNA fragmentation GO:0006396 RNA processing GO:0010586 miRNA metabolic process GO:0010626 negative regulation of Schwann cell proliferation GO:0014040 positive regulation of Schwann cell differentiation GO:0021675 nerve development GO:0030422 production of siRNA involved in RNA interference GO:0030423 targeting of mRNA for destruction involved in RNA interference GO:0031047 gene silencing by RNA GO:0031054 pre-miRNA processing GO:0031643 positive regulation of myelination GO:0032290 peripheral nervous system myelin formation GO:0033168 conversion of ds siRNA to ss siRNA involved in RNA interference GO:0035087 siRNA loading onto RISC involved in RNA interference GO:0035196 production of miRNAs involved in gene silencing by miRNA GO:0035280 miRNA loading onto RISC involved in gene silencing by miRNA GO:0036404 conversion of ds siRNA to ss siRNA GO:0048812 neuron projection morphogenesis GO:0090502 RNA phosphodiester bond hydrolysis, endonucleolytic
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
