DICER_HUMAN
ID DICER_HUMAN Reviewed; 1922 AA.
AC Q9UPY3; A7E2D3; B3KRG4; E0AD28; O95943; Q9UQ02;
DT 25-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-SEP-2009, sequence version 3.
DT 03-AUG-2022, entry version 202.
DE RecName: Full=Endoribonuclease Dicer;
DE EC=3.1.26.3;
DE AltName: Full=Helicase with RNase motif;
DE Short=Helicase MOI;
GN Name=DICER1; Synonyms=DICER, HERNA, KIAA0928;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=10786632; DOI=10.1016/s0167-4781(99)00221-3;
RA Matsuda S., Ichigotani Y., Okuda T., Irimura T., Nakatsugawa S.,
RA Hamaguchi M.;
RT "Molecular cloning and characterization of a novel human gene (HERNA) which
RT encodes a putative RNA-helicase.";
RL Biochim. Biophys. Acta 1490:163-169(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND ALTERNATIVE SPLICING.
RC TISSUE=Neuroblastoma;
RX PubMed=20615407; DOI=10.1016/j.febslet.2010.06.045;
RA Potenza N., Papa U., Scaruffi P., Mosca N., Tonini G.P., Russo A.;
RT "A novel splice variant of the human dicer gene is expressed in
RT neuroblastoma cells.";
RL FEBS Lett. 584:3452-3457(2010).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Lung;
RA Provost P., Dishart D., Doucet D., Hermansson A., Frendewey D.,
RA Samuelsson B., Radmark O.;
RT "RNA binding and processing by recombinant human Dicer.";
RL Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10231032; DOI=10.1093/dnares/6.1.63;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:63-70(1999).
RN [5]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1248-1922 (ISOFORM 1).
RC TISSUE=Lung;
RX PubMed=10051563; DOI=10.1073/pnas.96.5.1881;
RA Provost P., Samuelsson B., Radmark O.;
RT "Interaction of 5-lipoxygenase with cellular proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:1881-1885(1999).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF GLU-1313; ASP-1320;
RP GLU-1340; GLU-1444; GLN-1702; ASP-1709; PRO-1729 AND GLU-1813.
RX PubMed=15242644; DOI=10.1016/j.cell.2004.06.017;
RA Zhang H., Kolb F.A., Jaskiewicz L., Westhof E., Filipowicz W.;
RT "Single processing center models for human Dicer and bacterial RNase III.";
RL Cell 118:57-68(2004).
RN [12]
RP INTERACTION WITH PIWIL1.
RX PubMed=14749716; DOI=10.1038/sj.embor.7400070;
RA Tahbaz N., Kolb F.A., Zhang H., Jaronczyk K., Filipowicz W., Hobman T.C.;
RT "Characterization of the interactions between mammalian PAZ PIWI domain
RT proteins and Dicer.";
RL EMBO Rep. 5:189-194(2004).
RN [13]
RP FUNCTION, AND INTERACTION WITH AGO2 AND TARBP2.
RX PubMed=16271387; DOI=10.1016/j.cell.2005.10.022;
RA Gregory R.I., Chendrimada T.P., Cooch N., Shiekhattar R.;
RT "Human RISC couples microRNA biogenesis and posttranscriptional gene
RT silencing.";
RL Cell 123:631-640(2005).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, AND INTERACTION WITH AGO1
RP AND AGO2.
RX PubMed=16289642; DOI=10.1016/j.cub.2005.10.048;
RA Meister G., Landthaler M., Peters L., Chen P.Y., Urlaub H., Luehrmann R.,
RA Tuschl T.;
RT "Identification of novel argonaute-associated proteins.";
RL Curr. Biol. 15:2149-2155(2005).
RN [15]
RP FUNCTION, AND INTERACTION WITH TARBP2.
RX PubMed=16142218; DOI=10.1038/sj.embor.7400509;
RA Haase A.D., Jaskiewicz L., Zhang H., Laine S., Sack R., Gatignol A.,
RA Filipowicz W.;
RT "TRBP, a regulator of cellular PKR and HIV-1 virus expression, interacts
RT with Dicer and functions in RNA silencing.";
RL EMBO Rep. 6:961-967(2005).
RN [16]
RP FUNCTION, AND INTERACTION WITH AGO2.
RX PubMed=16357216; DOI=10.1101/gad.1384005;
RA Maniataki E., Mourelatos Z.;
RT "A human, ATP-independent, RISC assembly machine fueled by pre-miRNA.";
RL Genes Dev. 19:2979-2990(2005).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, AND INTERACTION WITH AGO2
RP AND TARBP2.
RX PubMed=15973356; DOI=10.1038/nature03868;
RA Chendrimada T.P., Gregory R.I., Kumaraswamy E., Norman J., Cooch N.,
RA Nishikura K., Shiekhattar R.;
RT "TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene
RT silencing.";
RL Nature 436:740-744(2005).
RN [18]
RP FUNCTION, INTERACTION WITH PRKRA AND TARBP2, AND SUBCELLULAR LOCATION.
RX PubMed=16424907; DOI=10.1038/sj.emboj.7600942;
RA Lee Y., Hur I., Park S.-Y., Kim Y.-K., Suh M.R., Kim V.N.;
RT "The role of PACT in the RNA silencing pathway.";
RL EMBO J. 25:522-532(2006).
RN [19]
RP FUNCTION, AND INTERACTION WITH PRKRA AND TARBP2.
RX PubMed=17452327; DOI=10.1074/jbc.m611768200;
RA Kok K.H., Ng M.-H., Ching Y.-P., Jin D.-Y.;
RT "Human TRBP and PACT directly interact with each other and associate with
RT dicer to facilitate the production of small interfering RNA.";
RL J. Biol. Chem. 282:17649-17657(2007).
RN [20]
RP INTERACTION WITH DHX9.
RX PubMed=17531811; DOI=10.1016/j.molcel.2007.04.016;
RA Robb G.B., Rana T.M.;
RT "RNA helicase A interacts with RISC in human cells and functions in RISC
RT loading.";
RL Mol. Cell 26:523-537(2007).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH AGO2; EIF6; MOV10;
RP RPL7A AND TARBP2, AND ASSOCIATION WITH THE 60S RIBOSOME.
RX PubMed=17507929; DOI=10.1038/nature05841;
RA Chendrimada T.P., Finn K.J., Ji X., Baillat D., Gregory R.I.,
RA Liebhaber S.A., Pasquinelli A.E., Shiekhattar R.;
RT "MicroRNA silencing through RISC recruitment of eIF6.";
RL Nature 447:823-828(2007).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND INTERACTION WITH AGO2.
RX PubMed=18690212; DOI=10.1038/nature07186;
RA Qi H.H., Ongusaha P.P., Myllyharju J., Cheng D., Pakkanen O., Shi Y.,
RA Lee S.W., Peng J., Shi Y.;
RT "Prolyl 4-hydroxylation regulates Argonaute 2 stability.";
RL Nature 455:421-424(2008).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1016, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [24]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, AND INTERACTION WITH AGO2
RP AND TARBP2.
RX PubMed=18178619; DOI=10.1073/pnas.0710869105;
RA MacRae I.J., Ma E., Zhou M., Robinson C.V., Doudna J.A.;
RT "In vitro reconstitution of the human RISC-loading complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:512-517(2008).
RN [25]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [26]
RP INTERACTION WITH ALOX5, AND SUBCELLULAR LOCATION.
RX PubMed=19022417; DOI=10.1016/j.bbagrm.2008.10.002;
RA Dincbas-Renqvist V., Pepin G., Rakonjac M., Plante I., Ouellet D.L.,
RA Hermansson A., Goulet I., Doucet J., Samuelsson B., Raadmark O.,
RA Provost P.;
RT "Human Dicer C-terminus functions as a 5-lipoxygenase binding domain.";
RL Biochim. Biophys. Acta 1789:99-108(2009).
RN [27]
RP RETRACTED PAPER.
RX PubMed=19219043; DOI=10.1038/ng.317;
RA Melo S.A., Ropero S., Moutinho C., Aaltonen L.A., Yamamoto H., Calin G.A.,
RA Rossi S., Fernandez A.F., Carneiro F., Oliveira C., Ferreira B., Liu C.-G.,
RA Villanueva A., Capella G., Schwartz S. Jr., Shiekhattar R., Esteller M.;
RT "A TARBP2 mutation in human cancer impairs microRNA processing and DICER1
RT function.";
RL Nat. Genet. 41:365-370(2009).
RN [28]
RP RETRACTION NOTICE OF PUBMED:19219043 NOTICE FOR PUBMED:19219043.
RX PubMed=26813765; DOI=10.1038/ng0216-221;
RA Melo S.A., Ropero S., Moutinho C., Aaltonen L.A., Yamamoto H., Calin G.A.,
RA Rossi S., Fernandez A.F., Carneiro F., Oliveira C., Ferreira B., Liu C.-G.,
RA Villanueva A., Capella G., Schwartz S. Jr., Shiekhattar R., Esteller M.;
RT "Retraction: A TARBP2 mutation in human cancer impairs microRNA processing
RT and DICER1 function.";
RL Nat. Genet. 48:221-221(2016).
RN [29]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [30]
RP INVOLVEMENT IN RMSE2.
RX PubMed=21882293; DOI=10.1002/humu.21600;
RA Foulkes W.D., Bahubeshi A., Hamel N., Pasini B., Asioli S., Baynam G.,
RA Choong C.S., Charles A., Frieder R.P., Dishop M.K., Graf N., Ekim M.,
RA Bouron-Dal Soglio D., Arseneau J., Young R.H., Sabbaghian N.,
RA Srivastava A., Tischkowitz M.D., Priest J.R.;
RT "Extending the phenotypes associated with DICER1 mutations.";
RL Hum. Mutat. 32:1381-1384(2011).
RN [31]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-413 AND SER-415, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [32]
RP INTERACTION WITH EBOLAVIRUS VP30 (MICROBIAL INFECTION), AND INTERACTION
RP WITH EBOLAVIRUS VP35 (MICROBIAL INFECTION).
RX PubMed=21228243; DOI=10.1128/jvi.01160-10;
RA Fabozzi G., Nabel C.S., Dolan M.A., Sullivan N.J.;
RT "Ebolavirus proteins suppress the effects of small interfering RNA by
RT direct interaction with the mammalian RNA interference pathway.";
RL J. Virol. 85:2512-2523(2011).
RN [33]
RP INTERACTION WITH BCDIN3D.
RX PubMed=23063121; DOI=10.1016/j.cell.2012.08.041;
RA Xhemalce B., Robson S.C., Kouzarides T.;
RT "Human RNA methyltransferase BCDIN3D regulates microRNA processing.";
RL Cell 151:278-288(2012).
RN [34]
RP INVOLVEMENT IN NON-EPITHELIAL OVARIAN TUMORS, VARIANTS LYS-1705; ASN-1709;
RP GLU-1709; GLY-1709; HIS-1810; TYR-1810; ASN-1810; GLN-1813; GLY-1813 AND
RP LYS-1813, AND CHARACTERIZATION OF VARIANTS LYS-1705; ASN-1709 AND GLU-1709.
RX PubMed=22187960; DOI=10.1056/nejmoa1102903;
RA Heravi-Moussavi A., Anglesio M.S., Cheng S.W., Senz J., Yang W.,
RA Prentice L., Fejes A.P., Chow C., Tone A., Kalloger S.E., Hamel N.,
RA Roth A., Ha G., Wan A.N., Maines-Bandiera S., Salamanca C., Pasini B.,
RA Clarke B.A., Lee A.F., Lee C.H., Zhao C., Young R.H., Aparicio S.A.,
RA Sorensen P.H., Woo M.M., Boyd N., Jones S.J., Hirst M., Marra M.A.,
RA Gilks B., Shah S.P., Foulkes W.D., Morin G.B., Huntsman D.G.;
RT "Recurrent somatic DICER1 mutations in nonepithelial ovarian cancers.";
RL N. Engl. J. Med. 366:234-242(2012).
RN [35]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1160; SER-1460; SER-1470 AND
RP SER-1868, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [36]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [37] {ECO:0007744|PDB:2EB1}
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1660-1852 IN COMPLEX WITH
RP MAGNESIUM, CATALYTIC ACTIVITY, COFACTOR, AND SUBUNIT.
RX PubMed=17920623; DOI=10.1016/j.jmb.2007.08.069;
RA Takeshita D., Zenno S., Lee W.C., Nagata K., Saigo K., Tanokura M.;
RT "Homodimeric structure and double-stranded RNA cleavage activity of the C-
RT terminal RNase III domain of human dicer.";
RL J. Mol. Biol. 374:106-120(2007).
RN [38]
RP VARIANT PPB ARG-1583.
RX PubMed=19556464; DOI=10.1126/science.1174334;
RA Hill D.A., Ivanovich J., Priest J.R., Gurnett C.A., Dehner L.P.,
RA Desruisseau D., Jarzembowski J.A., Wikenheiser-Brokamp K.A., Suarez B.K.,
RA Whelan A.J., Williams G., Bracamontes D., Messinger Y., Goodfellow P.J.;
RT "DICER1 mutations in familial pleuropulmonary blastoma.";
RL Science 325:965-965(2009).
RN [39]
RP VARIANT MNG1 PHE-839.
RX PubMed=21205968; DOI=10.1001/jama.2010.1910;
RA Rio Frio T., Bahubeshi A., Kanellopoulou C., Hamel N., Niedziela M.,
RA Sabbaghian N., Pouchet C., Gilbert L., O'Brien P.K., Serfas K.,
RA Broderick P., Houlston R.S., Lesueur F., Bonora E., Muljo S., Schimke R.N.,
RA Bouron-Dal Soglio D., Arseneau J., Schultz K.A., Priest J.R., Nguyen V.H.,
RA Harach H.R., Livingston D.M., Foulkes W.D., Tischkowitz M.;
RT "DICER1 mutations in familial multinodular goiter with and without ovarian
RT Sertoli-Leydig cell tumors.";
RL JAMA 305:68-77(2011).
RN [40]
RP VARIANTS LEU-435 AND GLY-1898, VARIANTS GLOW TYR-1709 AND VAL-1713, AND
RP INVOLVEMENT IN GLOW.
RX PubMed=24676357; DOI=10.1136/jmedgenet-2013-101943;
RA Klein S., Lee H., Ghahremani S., Kempert P., Ischander M., Teitell M.A.,
RA Nelson S.F., Martinez-Agosto J.A.;
RT "Expanding the phenotype of mutations in DICER1: mosaic missense mutations
RT in the RNase IIIb domain of DICER1 cause GLOW syndrome.";
RL J. Med. Genet. 51:294-302(2014).
CC -!- FUNCTION: Double-stranded RNA (dsRNA) endoribonuclease playing a
CC central role in short dsRNA-mediated post-transcriptional gene
CC silencing. Cleaves naturally occurring long dsRNAs and short hairpin
CC pre-microRNAs (miRNA) into fragments of twenty-one to twenty-three
CC nucleotides with 3' overhang of two nucleotides, producing respectively
CC short interfering RNAs (siRNA) and mature microRNAs. SiRNAs and miRNAs
CC serve as guide to direct the RNA-induced silencing complex (RISC) to
CC complementary RNAs to degrade them or prevent their translation. Gene
CC silencing mediated by siRNAs, also called RNA interference, controls
CC the elimination of transcripts from mobile and repetitive DNA elements
CC of the genome but also the degradation of exogenous RNA of viral origin
CC for instance. The miRNA pathway on the other side is a mean to
CC specifically regulate the expression of target genes.
CC {ECO:0000269|PubMed:15242644, ECO:0000269|PubMed:15973356,
CC ECO:0000269|PubMed:16142218, ECO:0000269|PubMed:16271387,
CC ECO:0000269|PubMed:16289642, ECO:0000269|PubMed:16357216,
CC ECO:0000269|PubMed:16424907, ECO:0000269|PubMed:17452327,
CC ECO:0000269|PubMed:18178619}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Endonucleolytic cleavage to 5'-phosphomonoester.; EC=3.1.26.3;
CC Evidence={ECO:0000269|PubMed:15242644, ECO:0000269|PubMed:17920623};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000305|PubMed:17920623};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000305|PubMed:17920623};
CC Note=Binds 2 magnesium or manganese ions per subunit.
CC {ECO:0000305|PubMed:17920623};
CC -!- SUBUNIT: Component of the RISC loading complex (RLC), or micro-RNA
CC (miRNA) loading complex (miRLC), which is composed of DICER1, AGO2 and
CC TARBP2; DICER1 and TARBP2 are required to process precursor miRNAs
CC (pre-miRNAs) to mature miRNAs and then load them onto AGO2. Note that
CC the trimeric RLC/miRLC is also referred to as RISC. Interacts with
CC DHX9, AGO1, PIWIL1 and PRKRA. Associates with the 60S ribosome.
CC Interacts with BCDIN3D. Interacts with AGO2, TARBP2, EIF6, MOV10 and
CC RPL7A (60S ribosome subunit); they form a large RNA-induced silencing
CC complex (RISC) (PubMed:17507929). Interacts (via Dicer dsRNA-binding
CC fold domain) with ALOX5 (via PLAT domain); this interaction enhances
CC arachidonate 5-lipoxygenase activity and modifies the miRNA precursor
CC processing activity of DICER1 (PubMed:19022417).
CC {ECO:0000269|PubMed:14749716, ECO:0000269|PubMed:15973356,
CC ECO:0000269|PubMed:16142218, ECO:0000269|PubMed:16271387,
CC ECO:0000269|PubMed:16289642, ECO:0000269|PubMed:16357216,
CC ECO:0000269|PubMed:16424907, ECO:0000269|PubMed:17452327,
CC ECO:0000269|PubMed:17507929, ECO:0000269|PubMed:17531811,
CC ECO:0000269|PubMed:17920623, ECO:0000269|PubMed:18178619,
CC ECO:0000269|PubMed:18690212, ECO:0000269|PubMed:19022417,
CC ECO:0000269|PubMed:23063121}.
CC -!- SUBUNIT: (Microbial infection) Interacts with ebolavirus
CC transcriptional activator VP30; this interaction prevents TARBP2/TRBP
CC binding to DICER1 and thus allows the virus to counteract host RNA
CC silencing. {ECO:0000269|PubMed:21228243}.
CC -!- SUBUNIT: (Microbial infection) Interacts with ebolavirus
CC transcriptional activator VP35; this interaction prevents TARBP2/TRBP
CC binding to DICER1 and thus allows the virus to counteract host RNA
CC silencing. {ECO:0000269|PubMed:21228243}.
CC -!- INTERACTION:
CC Q9UPY3; P55265-1: ADAR; NbExp=4; IntAct=EBI-395506, EBI-6913056;
CC Q9UPY3; P55265-5: ADAR; NbExp=8; IntAct=EBI-395506, EBI-6913210;
CC Q9UPY3; Q9UL18: AGO1; NbExp=5; IntAct=EBI-395506, EBI-527363;
CC Q9UPY3; Q9UKV8: AGO2; NbExp=20; IntAct=EBI-395506, EBI-528269;
CC Q9UPY3; Q96C10: DHX58; NbExp=2; IntAct=EBI-395506, EBI-744193;
CC Q9UPY3; P19525: EIF2AK2; NbExp=2; IntAct=EBI-395506, EBI-640775;
CC Q9UPY3; Q96J94: PIWIL1; NbExp=2; IntAct=EBI-395506, EBI-527417;
CC Q9UPY3; O75569: PRKRA; NbExp=8; IntAct=EBI-395506, EBI-713955;
CC Q9UPY3; Q15633: TARBP2; NbExp=25; IntAct=EBI-395506, EBI-978581;
CC Q9UPY3; O43508: TNFSF12; NbExp=3; IntAct=EBI-395506, EBI-6932080;
CC Q9UPY3; Q8CJG0: Ago2; Xeno; NbExp=2; IntAct=EBI-395506, EBI-528299;
CC Q9UPY3; Q9IK90: M; Xeno; NbExp=3; IntAct=EBI-395506, EBI-25747115;
CC Q9UPY3; P0C205; Xeno; NbExp=7; IntAct=EBI-395506, EBI-8332963;
CC Q9UPY3-1; Q9UKV8: AGO2; NbExp=14; IntAct=EBI-15569571, EBI-528269;
CC Q9UPY3-1; Q92945: KHSRP; NbExp=3; IntAct=EBI-15569571, EBI-1049099;
CC Q9UPY3-1; P24928: POLR2A; NbExp=3; IntAct=EBI-15569571, EBI-295301;
CC Q9UPY3-1; Q15633: TARBP2; NbExp=5; IntAct=EBI-15569571, EBI-978581;
CC Q9UPY3-1; Q61496: Ddx4; Xeno; NbExp=3; IntAct=EBI-15569571, EBI-15569589;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16424907}.
CC Cytoplasm, perinuclear region {ECO:0000269|PubMed:19022417}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9UPY3-1; Sequence=Displayed;
CC Name=2; Synonyms=t-Dicer;
CC IsoId=Q9UPY3-2; Sequence=VSP_042832;
CC Name=3;
CC IsoId=Q9UPY3-3; Sequence=VSP_055341, VSP_055342;
CC -!- DISEASE: Pleuropulmonary blastoma (PPB) [MIM:601200]: A rare pediatric
CC intrathoracic neoplasm. The tumor arises from the lung, pleura, or
CC both, and appears to be purely mesenchymal in phenotype. It lacks
CC malignant epithelial elements, a feature that distinguishes it from the
CC classic adult-type pulmonary blastoma. It arises during fetal lung
CC development and is often part of an inherited cancer syndrome. The
CC tumor contain both epithelial and mesenchymal cells. Early in
CC tumorigenesis, cysts form in lung airspaces, and these cysts are lined
CC with benign-appearing epithelium. Mesenchymal cells susceptible to
CC malignant transformation reside within the cyst walls and form a dense
CC layer beneath the epithelial lining. In a subset of patients,
CC overgrowth of the mesenchymal cells produces a sarcoma, a transition
CC that is associated with a poorer prognosis. Some patients have
CC multilocular cystic nephroma, a benign kidney tumor.
CC {ECO:0000269|PubMed:19556464}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Goiter multinodular 1, with or without Sertoli-Leydig cell
CC tumors (MNG1) [MIM:138800]: A common disorder characterized by nodular
CC overgrowth of the thyroid gland. Some individuals may also develop
CC Sertoli-Leydig cell tumors, usually of the ovary.
CC {ECO:0000269|PubMed:21205968}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Rhabdomyosarcoma, embryonal, 2 (RMSE2) [MIM:180295]: A form of
CC rhabdomyosarcoma, a highly malignant tumor of striated muscle derived
CC from primitive mesenchymal cells and exhibiting differentiation along
CC rhabdomyoblastic lines. Rhabdomyosarcoma is one of the most frequently
CC occurring soft tissue sarcomas and the most common in children. It
CC occurs in four forms: alveolar, pleomorphic, embryonal and botryoidal
CC rhabdomyosarcomas. {ECO:0000269|PubMed:21882293}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Global developmental delay, lung cysts, overgrowth, and Wilms
CC tumor (GLOW) [MIM:618272]: A disease characterized by the association
CC of congenital nephromegaly, bilateral Wilms tumor, somatic overgrowth,
CC developmental delay, macrocephaly, and bilateral lung cysts.
CC {ECO:0000269|PubMed:24676357}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Note=DICER1 mutations have been found in uterine cervix
CC embryonal rhabdomyosarcoma, primitive neuroectodermal tumor, Wilms
CC tumor, pulmonary sequestration and juvenile intestinal polyp
CC (PubMed:21882293). Somatic missense mutations affecting the RNase IIIb
CC domain of DICER1 are common in non-epithelial ovarian tumors. These
CC mutations do not abolish DICER1 function but alter it in specific cell
CC types, a novel mechanism through which perturbation of microRNA
CC processing may be oncogenic (PubMed:22187960).
CC {ECO:0000269|PubMed:21882293, ECO:0000269|PubMed:22187960}.
CC -!- SIMILARITY: Belongs to the helicase family. Dicer subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00657}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-11 is the initiator.
CC {ECO:0000305}.
CC -!- CAUTION: A paper describing truncating mutations of TARBP2 in tumor
CC cells and resultant effects on DICER1 stability and miRNA processing
CC has been retracted, due to concerns of image duplication in some of the
CC figures. {ECO:0000305|PubMed:19219043, ECO:0000305|PubMed:26813765}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAB38857.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=The dark side of RNA - Issue
CC 87 of October 2007;
CC URL="https://web.expasy.org/spotlight/back_issues/087";
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DR EMBL; AB028449; BAA78691.1; -; mRNA.
DR EMBL; HM595745; ADK25182.1; -; mRNA.
DR EMBL; AJ132261; CAB38857.2; ALT_INIT; mRNA.
DR EMBL; AB023145; BAA76772.2; -; mRNA.
DR EMBL; AK091513; BAG52376.1; -; mRNA.
DR EMBL; AL356017; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL390254; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471061; EAW81596.1; -; Genomic_DNA.
DR EMBL; BC150287; AAI50288.1; -; mRNA.
DR CCDS; CCDS55941.1; -. [Q9UPY3-2]
DR CCDS; CCDS9931.1; -. [Q9UPY3-1]
DR RefSeq; NP_001182502.1; NM_001195573.1. [Q9UPY3-2]
DR RefSeq; NP_001258211.1; NM_001271282.2. [Q9UPY3-1]
DR RefSeq; NP_001278557.1; NM_001291628.1. [Q9UPY3-1]
DR RefSeq; NP_085124.2; NM_030621.4. [Q9UPY3-1]
DR RefSeq; NP_803187.1; NM_177438.2. [Q9UPY3-1]
DR RefSeq; XP_011534901.1; XM_011536599.1. [Q9UPY3-1]
DR RefSeq; XP_011534902.1; XM_011536600.2. [Q9UPY3-1]
DR RefSeq; XP_011534903.1; XM_011536601.2. [Q9UPY3-1]
DR RefSeq; XP_011534904.1; XM_011536602.2. [Q9UPY3-1]
DR RefSeq; XP_016876609.1; XM_017021120.1. [Q9UPY3-1]
DR RefSeq; XP_016876610.1; XM_017021121.1. [Q9UPY3-1]
DR PDB; 2EB1; X-ray; 2.00 A; A/B/C=1660-1852.
DR PDB; 4NGB; X-ray; 2.25 A; A=765-1065.
DR PDB; 4NGC; X-ray; 2.10 A; A=765-1065.
DR PDB; 4NGD; X-ray; 1.96 A; A=765-1065.
DR PDB; 4NGF; X-ray; 3.10 A; A/B/C/D=765-1065.
DR PDB; 4NGG; X-ray; 2.60 A; A=765-1065.
DR PDB; 4NH3; X-ray; 2.62 A; A=765-1065.
DR PDB; 4NH5; X-ray; 2.55 A; A=765-1065.
DR PDB; 4NH6; X-ray; 2.55 A; A=765-1065.
DR PDB; 4NHA; X-ray; 3.40 A; A=765-1065.
DR PDB; 4WYQ; X-ray; 3.20 A; A/D=267-389.
DR PDB; 5ZAK; EM; 4.40 A; A=1-1922.
DR PDB; 5ZAL; EM; 4.70 A; A=1-1922.
DR PDB; 5ZAM; EM; 5.70 A; A=1-1922.
DR PDBsum; 2EB1; -.
DR PDBsum; 4NGB; -.
DR PDBsum; 4NGC; -.
DR PDBsum; 4NGD; -.
DR PDBsum; 4NGF; -.
DR PDBsum; 4NGG; -.
DR PDBsum; 4NH3; -.
DR PDBsum; 4NH5; -.
DR PDBsum; 4NH6; -.
DR PDBsum; 4NHA; -.
DR PDBsum; 4WYQ; -.
DR PDBsum; 5ZAK; -.
DR PDBsum; 5ZAL; -.
DR PDBsum; 5ZAM; -.
DR AlphaFoldDB; Q9UPY3; -.
DR SMR; Q9UPY3; -.
DR BioGRID; 116978; 162.
DR ComplexPortal; CPX-1072; RISC-loading complex, PRKRA variant.
DR ComplexPortal; CPX-134; RISC-loading complex, TARBP2 variant.
DR CORUM; Q9UPY3; -.
DR DIP; DIP-29664N; -.
DR IntAct; Q9UPY3; 144.
DR MINT; Q9UPY3; -.
DR STRING; 9606.ENSP00000437256; -.
DR ChEMBL; CHEMBL2311232; -.
DR GlyGen; Q9UPY3; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9UPY3; -.
DR MetOSite; Q9UPY3; -.
DR PhosphoSitePlus; Q9UPY3; -.
DR BioMuta; DICER1; -.
DR DMDM; 257051056; -.
DR EPD; Q9UPY3; -.
DR jPOST; Q9UPY3; -.
DR MassIVE; Q9UPY3; -.
DR MaxQB; Q9UPY3; -.
DR PaxDb; Q9UPY3; -.
DR PeptideAtlas; Q9UPY3; -.
DR PRIDE; Q9UPY3; -.
DR ProteomicsDB; 3598; -.
DR ProteomicsDB; 85471; -. [Q9UPY3-1]
DR ProteomicsDB; 85472; -. [Q9UPY3-2]
DR Antibodypedia; 19; 540 antibodies from 39 providers.
DR DNASU; 23405; -.
DR Ensembl; ENST00000343455.8; ENSP00000343745.3; ENSG00000100697.15. [Q9UPY3-1]
DR Ensembl; ENST00000393063.6; ENSP00000376783.1; ENSG00000100697.15. [Q9UPY3-1]
DR Ensembl; ENST00000526495.6; ENSP00000437256.1; ENSG00000100697.15. [Q9UPY3-1]
DR Ensembl; ENST00000527414.5; ENSP00000435681.1; ENSG00000100697.15. [Q9UPY3-1]
DR Ensembl; ENST00000541352.5; ENSP00000444719.1; ENSG00000100697.15. [Q9UPY3-2]
DR GeneID; 23405; -.
DR KEGG; hsa:23405; -.
DR MANE-Select; ENST00000343455.8; ENSP00000343745.3; NM_177438.3; NP_803187.1.
DR UCSC; uc001ydv.4; human. [Q9UPY3-1]
DR CTD; 23405; -.
DR DisGeNET; 23405; -.
DR GeneCards; DICER1; -.
DR GeneReviews; DICER1; -.
DR HGNC; HGNC:17098; DICER1.
DR HPA; ENSG00000100697; Low tissue specificity.
DR MalaCards; DICER1; -.
DR MIM; 138800; phenotype.
DR MIM; 180295; phenotype.
DR MIM; 601200; phenotype.
DR MIM; 606241; gene.
DR MIM; 618272; phenotype.
DR neXtProt; NX_Q9UPY3; -.
DR OpenTargets; ENSG00000100697; -.
DR Orphanet; 276399; Familial multinodular goiter.
DR Orphanet; 404476; Global developmental delay-lung cysts-overgrowth-Wilms tumor syndrome.
DR Orphanet; 99914; Gynandroblastoma.
DR Orphanet; 99915; Maligant granulosa cell tumor of the ovary.
DR Orphanet; 99916; Malignant Sertoli-Leydig cell tumor of the ovary.
DR Orphanet; 284343; Pleuropulmonary blastoma familial tumor susceptibility syndrome.
DR PharmGKB; PA38437; -.
DR VEuPathDB; HostDB:ENSG00000100697; -.
DR eggNOG; KOG0701; Eukaryota.
DR GeneTree; ENSGT00940000156287; -.
DR HOGENOM; CLU_000907_4_4_1; -.
DR InParanoid; Q9UPY3; -.
DR OMA; TTYLYCT; -.
DR OrthoDB; 1337630at2759; -.
DR PhylomeDB; Q9UPY3; -.
DR TreeFam; TF330258; -.
DR BRENDA; 3.1.26.3; 2681.
DR PathwayCommons; Q9UPY3; -.
DR Reactome; R-HSA-203927; MicroRNA (miRNA) biogenesis.
DR Reactome; R-HSA-426486; Small interfering RNA (siRNA) biogenesis.
DR Reactome; R-HSA-9708296; tRNA-derived small RNA (tsRNA or tRNA-related fragment, tRF) biogenesis.
DR SignaLink; Q9UPY3; -.
DR SIGNOR; Q9UPY3; -.
DR BioGRID-ORCS; 23405; 362 hits in 1094 CRISPR screens.
DR ChiTaRS; DICER1; human.
DR EvolutionaryTrace; Q9UPY3; -.
DR GeneWiki; DICER1; -.
DR GenomeRNAi; 23405; -.
DR Pharos; Q9UPY3; Tbio.
DR PRO; PR:Q9UPY3; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q9UPY3; protein.
DR Bgee; ENSG00000100697; Expressed in cauda epididymis and 209 other tissues.
DR ExpressionAtlas; Q9UPY3; baseline and differential.
DR Genevisible; Q9UPY3; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; IDA:BHF-UCL.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0016442; C:RISC complex; IDA:UniProtKB.
DR GO; GO:0070578; C:RISC-loading complex; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004530; F:deoxyribonuclease I activity; IBA:GO_Central.
DR GO; GO:0003677; F:DNA binding; IEA:InterPro.
DR GO; GO:0003725; F:double-stranded RNA binding; IDA:UniProtKB.
DR GO; GO:0004521; F:endoribonuclease activity; IDA:BHF-UCL.
DR GO; GO:0004386; F:helicase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0070883; F:pre-miRNA binding; IDA:BHF-UCL.
DR GO; GO:0019904; F:protein domain specific binding; IPI:BHF-UCL.
DR GO; GO:0004525; F:ribonuclease III activity; IDA:BHF-UCL.
DR GO; GO:0003723; F:RNA binding; IBA:GO_Central.
DR GO; GO:0035197; F:siRNA binding; IDA:BHF-UCL.
DR GO; GO:0006309; P:apoptotic DNA fragmentation; IBA:GO_Central.
DR GO; GO:0098795; P:global gene silencing by mRNA cleavage; IMP:UniProtKB.
DR GO; GO:0010586; P:miRNA metabolic process; TAS:Reactome.
DR GO; GO:0035196; P:miRNA processing; IDA:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:ARUK-UCL.
DR GO; GO:0010626; P:negative regulation of Schwann cell proliferation; ISS:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:BHF-UCL.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IMP:ARUK-UCL.
DR GO; GO:0021675; P:nerve development; ISS:BHF-UCL.
DR GO; GO:0048812; P:neuron projection morphogenesis; ISS:BHF-UCL.
DR GO; GO:0038061; P:NIK/NF-kappaB signaling; IDA:ARUK-UCL.
DR GO; GO:0032290; P:peripheral nervous system myelin formation; ISS:BHF-UCL.
DR GO; GO:0031643; P:positive regulation of myelination; ISS:BHF-UCL.
DR GO; GO:0014040; P:positive regulation of Schwann cell differentiation; ISS:BHF-UCL.
DR GO; GO:0031054; P:pre-miRNA processing; IDA:UniProtKB.
DR GO; GO:0070922; P:RISC complex assembly; IDA:BHF-UCL.
DR GO; GO:0090501; P:RNA phosphodiester bond hydrolysis; IBA:GO_Central.
DR GO; GO:0090502; P:RNA phosphodiester bond hydrolysis, endonucleolytic; IDA:BHF-UCL.
DR GO; GO:0030422; P:siRNA processing; IDA:UniProtKB.
DR GO; GO:0016078; P:tRNA catabolic process; TAS:Reactome.
DR CDD; cd10843; DSRM_DICER; 1.
DR CDD; cd00593; RIBOc; 2.
DR Gene3D; 1.10.1520.10; -; 2.
DR Gene3D; 3.30.160.380; -; 1.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR038248; Dicer_dimer_sf.
DR InterPro; IPR005034; Dicer_dimerisation_dom.
DR InterPro; IPR044441; DICER_DSRM.
DR InterPro; IPR014720; dsRBD_dom.
DR InterPro; IPR006935; Helicase/UvrB_N.
DR InterPro; IPR014001; Helicase_ATP-bd.
DR InterPro; IPR001650; Helicase_C.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR003100; PAZ_dom.
DR InterPro; IPR036085; PAZ_dom_sf.
DR InterPro; IPR000999; RNase_III_dom.
DR InterPro; IPR036389; RNase_III_sf.
DR Pfam; PF00271; Helicase_C; 1.
DR Pfam; PF02170; PAZ; 1.
DR Pfam; PF04851; ResIII; 1.
DR Pfam; PF00636; Ribonuclease_3; 2.
DR SMART; SM00487; DEXDc; 1.
DR SMART; SM00358; DSRM; 1.
DR SMART; SM00490; HELICc; 1.
DR SMART; SM00949; PAZ; 1.
DR SMART; SM00535; RIBOc; 2.
DR SUPFAM; SSF101690; SSF101690; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF69065; SSF69065; 2.
DR PROSITE; PS51327; DICER_DSRBF; 1.
DR PROSITE; PS50137; DS_RBD; 1.
DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1.
DR PROSITE; PS51194; HELICASE_CTER; 1.
DR PROSITE; PS50821; PAZ; 1.
DR PROSITE; PS00517; RNASE_3_1; 1.
DR PROSITE; PS50142; RNASE_3_2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cytoplasm;
KW Disease variant; Endonuclease; Helicase; Host-virus interaction; Hydrolase;
KW Magnesium; Manganese; Metal-binding; Nuclease; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Repeat; RNA-binding;
KW RNA-mediated gene silencing.
FT CHAIN 1..1922
FT /note="Endoribonuclease Dicer"
FT /id="PRO_0000180470"
FT DOMAIN 51..227
FT /note="Helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT DOMAIN 433..602
FT /note="Helicase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542"
FT DOMAIN 630..722
FT /note="Dicer dsRNA-binding fold"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00657"
FT DOMAIN 891..1042
FT /note="PAZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00142"
FT DOMAIN 1276..1403
FT /note="RNase III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00177"
FT DOMAIN 1666..1824
FT /note="RNase III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00177"
FT DOMAIN 1849..1914
FT /note="DRBM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00266"
FT REGION 256..595
FT /note="Required for interaction with PRKRA and TARBP2"
FT REGION 409..433
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 175..178
FT /note="DECH box"
FT COMPBIAS 412..427
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 64..71
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT BINDING 1316
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 1395
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 1398
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 1705
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:17920623,
FT ECO:0007744|PDB:2EB1"
FT BINDING 1810
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:17920623,
FT ECO:0007744|PDB:2EB1"
FT BINDING 1813
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:17920623,
FT ECO:0007744|PDB:2EB1"
FT SITE 1806
FT /note="Important for activity"
FT /evidence="ECO:0000250|UniProtKB:Q8R418"
FT MOD_RES 413
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 415
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 1016
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1160
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1460
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1468
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8R418"
FT MOD_RES 1470
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1868
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..13
FT /note="MKSPALQPLSMAG -> MLAWESDHFLRIL (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055341"
FT VAR_SEQ 14..1115
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055342"
FT VAR_SEQ 1789..1922
FT /note="LRRSEEDEEKEEDIEVPKAMGDIFESLAGAIYMDSGMSLETVWQVYYPMMRP
FT LIEKFSANVPRSPVRELLEMEPETAKFSPAERTYDGKVRVTVEVVGKGKFKGVGRSYRI
FT AKSAAARRALRSLKANQPQVPNS -> KSFLQMYPVPLCENCLKWNQKLPNLARLRELT
FT TGRSESLWK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:20615407"
FT /id="VSP_042832"
FT VARIANT 435
FT /note="P -> L (found in Wilms tumor from a patient with
FT GLOW syndrome; somatic mutation; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:24676357"
FT /id="VAR_081917"
FT VARIANT 839
FT /note="S -> F (in MNG1; dbSNP:rs387906934)"
FT /evidence="ECO:0000269|PubMed:21205968"
FT /id="VAR_065301"
FT VARIANT 1583
FT /note="L -> R (in PPB; dbSNP:rs137852976)"
FT /evidence="ECO:0000269|PubMed:19556464"
FT /id="VAR_063150"
FT VARIANT 1705
FT /note="E -> K (in non-epithelial ovarian tumor; somatic
FT mutation; results in reduced RNase IIIb activity but
FT retention of RNase IIIa activity)"
FT /evidence="ECO:0000269|PubMed:22187960"
FT /id="VAR_067091"
FT VARIANT 1709
FT /note="D -> E (in non-epithelial ovarian tumor; somatic
FT mutation; results in reduced RNase IIIb activity but
FT retention of RNase IIIa activity)"
FT /evidence="ECO:0000269|PubMed:22187960"
FT /id="VAR_067092"
FT VARIANT 1709
FT /note="D -> G (in non-epithelial ovarian tumor; somatic
FT mutation; dbSNP:rs1555366979)"
FT /evidence="ECO:0000269|PubMed:22187960"
FT /id="VAR_067093"
FT VARIANT 1709
FT /note="D -> N (in non-epithelial ovarian tumor; somatic
FT mutation; results in reduced RNase IIIb activity but
FT retention of RNase IIIa activity)"
FT /evidence="ECO:0000269|PubMed:22187960"
FT /id="VAR_067094"
FT VARIANT 1709
FT /note="D -> Y (in GLOW; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:24676357"
FT /id="VAR_081918"
FT VARIANT 1713
FT /note="D -> V (in GLOW; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:24676357"
FT /id="VAR_081919"
FT VARIANT 1810
FT /note="D -> H (in non-epithelial ovarian tumor; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:22187960"
FT /id="VAR_067095"
FT VARIANT 1810
FT /note="D -> N (in non-epithelial ovarian tumor; somatic
FT mutation; dbSNP:rs775912475)"
FT /evidence="ECO:0000269|PubMed:22187960"
FT /id="VAR_067096"
FT VARIANT 1810
FT /note="D -> Y (in non-epithelial ovarian tumor; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:22187960"
FT /id="VAR_067097"
FT VARIANT 1813
FT /note="E -> G (in non-epithelial ovarian tumor; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:22187960"
FT /id="VAR_067098"
FT VARIANT 1813
FT /note="E -> K (in non-epithelial ovarian tumor; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:22187960"
FT /id="VAR_067099"
FT VARIANT 1813
FT /note="E -> Q (in non-epithelial ovarian tumor; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:22187960"
FT /id="VAR_067100"
FT VARIANT 1898
FT /note="R -> G (found in Wilms tumor from a patient with
FT GLOW syndrome; somatic mutation; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:24676357"
FT /id="VAR_081920"
FT MUTAGEN 960
FT /note="F->A: 2-fold decrease in activity."
FT MUTAGEN 971
FT /note="Y->A: 10-fold decrease in activity; when associated
FT with Y-972."
FT MUTAGEN 972
FT /note="Y->A: 10-fold decrease in activity; when associated
FT with Y-971."
FT MUTAGEN 1036
FT /note="E->A: 5-fold decrease in activity."
FT MUTAGEN 1313
FT /note="E->A: No effect on activity."
FT /evidence="ECO:0000269|PubMed:15242644"
FT MUTAGEN 1320
FT /note="D->A: Decreased activity. Loss of activity; when
FT associated with D-1709."
FT /evidence="ECO:0000269|PubMed:15242644"
FT MUTAGEN 1340
FT /note="E->A: No effect on activity."
FT /evidence="ECO:0000269|PubMed:15242644"
FT MUTAGEN 1444
FT /note="E->A: Decreased activity. Loss of activity; when
FT associated with E-1813."
FT /evidence="ECO:0000269|PubMed:15242644"
FT MUTAGEN 1702
FT /note="Q->A: No effect on activity."
FT /evidence="ECO:0000269|PubMed:15242644"
FT MUTAGEN 1709
FT /note="D->A: Decreased activity. Loss of activity; when
FT associated with D-1320."
FT /evidence="ECO:0000269|PubMed:15242644"
FT MUTAGEN 1729
FT /note="P->E: No effect on activity."
FT /evidence="ECO:0000269|PubMed:15242644"
FT MUTAGEN 1813
FT /note="E->A: Decreased activity. Loss of activity; when
FT associated with E-1444."
FT /evidence="ECO:0000269|PubMed:15242644"
FT CONFLICT 75..90
FT /note="VLLTKELSYQIRGDFS -> STTLLKSCLYLDLGETSA (in Ref. 1;
FT BAA78691)"
FT /evidence="ECO:0000305"
FT CONFLICT 189
FT /note="I -> F (in Ref. 1; BAA78691)"
FT /evidence="ECO:0000305"
FT CONFLICT 195
FT /note="N -> I (in Ref. 1; BAA78691)"
FT /evidence="ECO:0000305"
FT CONFLICT 214
FT /note="C -> W (in Ref. 1; BAA78691)"
FT /evidence="ECO:0000305"
FT CONFLICT 218
FT /note="E -> D (in Ref. 1; BAA78691)"
FT /evidence="ECO:0000305"
FT CONFLICT 223
FT /note="I -> F (in Ref. 1; BAA78691)"
FT /evidence="ECO:0000305"
FT CONFLICT 393..394
FT /note="QQ -> HS (in Ref. 1; BAA78691)"
FT /evidence="ECO:0000305"
FT CONFLICT 492..493
FT /note="KQ -> NT (in Ref. 1; BAA78691)"
FT /evidence="ECO:0000305"
FT CONFLICT 609
FT /note="D -> H (in Ref. 1; BAA78691)"
FT /evidence="ECO:0000305"
FT HELIX 268..282
FT /evidence="ECO:0007829|PDB:4WYQ"
FT HELIX 297..313
FT /evidence="ECO:0007829|PDB:4WYQ"
FT HELIX 315..335
FT /evidence="ECO:0007829|PDB:4WYQ"
FT HELIX 339..361
FT /evidence="ECO:0007829|PDB:4WYQ"
FT STRAND 363..367
FT /evidence="ECO:0007829|PDB:4WYQ"
FT HELIX 375..385
FT /evidence="ECO:0007829|PDB:4WYQ"
FT STRAND 768..780
FT /evidence="ECO:0007829|PDB:4NGD"
FT HELIX 783..785
FT /evidence="ECO:0007829|PDB:4NGD"
FT HELIX 795..797
FT /evidence="ECO:0007829|PDB:4NGD"
FT STRAND 801..808
FT /evidence="ECO:0007829|PDB:4NGD"
FT STRAND 816..820
FT /evidence="ECO:0007829|PDB:4NGD"
FT STRAND 823..836
FT /evidence="ECO:0007829|PDB:4NGD"
FT HELIX 840..855
FT /evidence="ECO:0007829|PDB:4NGD"
FT STRAND 877..883
FT /evidence="ECO:0007829|PDB:4NGD"
FT STRAND 890..892
FT /evidence="ECO:0007829|PDB:4NGD"
FT HELIX 894..902
FT /evidence="ECO:0007829|PDB:4NGD"
FT STRAND 906..908
FT /evidence="ECO:0007829|PDB:4NGD"
FT STRAND 916..918
FT /evidence="ECO:0007829|PDB:4NGD"
FT HELIX 924..927
FT /evidence="ECO:0007829|PDB:4NGD"
FT STRAND 931..937
FT /evidence="ECO:0007829|PDB:4NGD"
FT STRAND 939..941
FT /evidence="ECO:0007829|PDB:4NGD"
FT STRAND 945..951
FT /evidence="ECO:0007829|PDB:4NGD"
FT HELIX 968..976
FT /evidence="ECO:0007829|PDB:4NGD"
FT STRAND 987..992
FT /evidence="ECO:0007829|PDB:4NGD"
FT HELIX 1016..1030
FT /evidence="ECO:0007829|PDB:4NGD"
FT HELIX 1035..1037
FT /evidence="ECO:0007829|PDB:4NGD"
FT STRAND 1038..1040
FT /evidence="ECO:0007829|PDB:4NGD"
FT HELIX 1045..1051
FT /evidence="ECO:0007829|PDB:4NGD"
FT HELIX 1054..1061
FT /evidence="ECO:0007829|PDB:4NGD"
FT TURN 1662..1665
FT /evidence="ECO:0007829|PDB:2EB1"
FT HELIX 1666..1673
FT /evidence="ECO:0007829|PDB:2EB1"
FT HELIX 1680..1687
FT /evidence="ECO:0007829|PDB:2EB1"
FT HELIX 1702..1722
FT /evidence="ECO:0007829|PDB:2EB1"
FT HELIX 1729..1739
FT /evidence="ECO:0007829|PDB:2EB1"
FT HELIX 1742..1751
FT /evidence="ECO:0007829|PDB:2EB1"
FT HELIX 1754..1756
FT /evidence="ECO:0007829|PDB:2EB1"
FT HELIX 1763..1778
FT /evidence="ECO:0007829|PDB:2EB1"
FT HELIX 1806..1822
FT /evidence="ECO:0007829|PDB:2EB1"
FT HELIX 1827..1847
FT /evidence="ECO:0007829|PDB:2EB1"
SQ SEQUENCE 1922 AA; 218682 MW; 9452B96A601D4551 CRC64;
MKSPALQPLS MAGLQLMTPA SSPMGPFFGL PWQQEAIHDN IYTPRKYQVE LLEAALDHNT
IVCLNTGSGK TFIAVLLTKE LSYQIRGDFS RNGKRTVFLV NSANQVAQQV SAVRTHSDLK
VGEYSNLEVN ASWTKERWNQ EFTKHQVLIM TCYVALNVLK NGYLSLSDIN LLVFDECHLA
ILDHPYREIM KLCENCPSCP RILGLTASIL NGKCDPEELE EKIQKLEKIL KSNAETATDL
VVLDRYTSQP CEIVVDCGPF TDRSGLYERL LMELEEALNF INDCNISVHS KERDSTLISK
QILSDCRAVL VVLGPWCADK VAGMMVRELQ KYIKHEQEEL HRKFLLFTDT FLRKIHALCE
EHFSPASLDL KFVTPKVIKL LEILRKYKPY ERQQFESVEW YNNRNQDNYV SWSDSEDDDE
DEEIEEKEKP ETNFPSPFTN ILCGIIFVER RYTAVVLNRL IKEAGKQDPE LAYISSNFIT
GHGIGKNQPR NKQMEAEFRK QEEVLRKFRA HETNLLIATS IVEEGVDIPK CNLVVRFDLP
TEYRSYVQSK GRARAPISNY IMLADTDKIK SFEEDLKTYK AIEKILRNKC SKSVDTGETD
IDPVMDDDDV FPPYVLRPDD GGPRVTINTA IGHINRYCAR LPSDPFTHLA PKCRTRELPD
GTFYSTLYLP INSPLRASIV GPPMSCVRLA ERVVALICCE KLHKIGELDD HLMPVGKETV
KYEEELDLHD EEETSVPGRP GSTKRRQCYP KAIPECLRDS YPRPDQPCYL YVIGMVLTTP
LPDELNFRRR KLYPPEDTTR CFGILTAKPI PQIPHFPVYT RSGEVTISIE LKKSGFMLSL
QMLELITRLH QYIFSHILRL EKPALEFKPT DADSAYCVLP LNVVNDSSTL DIDFKFMEDI
EKSEARIGIP STKYTKETPF VFKLEDYQDA VIIPRYRNFD QPHRFYVADV YTDLTPLSKF
PSPEYETFAE YYKTKYNLDL TNLNQPLLDV DHTSSRLNLL TPRHLNQKGK ALPLSSAEKR
KAKWESLQNK QILVPELCAI HPIPASLWRK AVCLPSILYR LHCLLTAEEL RAQTASDAGV
GVRSLPADFR YPNLDFGWKK SIDSKSFISI SNSSSAENDN YCKHSTIVPE NAAHQGANRT
SSLENHDQMS VNCRTLLSES PGKLHVEVSA DLTAINGLSY NQNLANGSYD LANRDFCQGN
QLNYYKQEIP VQPTTSYSIQ NLYSYENQPQ PSDECTLLSN KYLDGNANKS TSDGSPVMAV
MPGTTDTIQV LKGRMDSEQS PSIGYSSRTL GPNPGLILQA LTLSNASDGF NLERLEMLGD
SFLKHAITTY LFCTYPDAHE GRLSYMRSKK VSNCNLYRLG KKKGLPSRMV VSIFDPPVNW
LPPGYVVNQD KSNTDKWEKD EMTKDCMLAN GKLDEDYEEE DEEEESLMWR APKEEADYED
DFLEYDQEHI RFIDNMLMGS GAFVKKISLS PFSTTDSAYE WKMPKKSSLG SMPFSSDFED
FDYSSWDAMC YLDPSKAVEE DDFVVGFWNP SEENCGVDTG KQSISYDLHT EQCIADKSIA
DCVEALLGCY LTSCGERAAQ LFLCSLGLKV LPVIKRTDRE KALCPTRENF NSQQKNLSVS
CAAASVASSR SSVLKDSEYG CLKIPPRCMF DHPDADKTLN HLISGFENFE KKINYRFKNK
AYLLQAFTHA SYHYNTITDC YQRLEFLGDA ILDYLITKHL YEDPRQHSPG VLTDLRSALV
NNTIFASLAV KYDYHKYFKA VSPELFHVID DFVQFQLEKN EMQGMDSELR RSEEDEEKEE
DIEVPKAMGD IFESLAGAIY MDSGMSLETV WQVYYPMMRP LIEKFSANVP RSPVRELLEM
EPETAKFSPA ERTYDGKVRV TVEVVGKGKF KGVGRSYRIA KSAAARRALR SLKANQPQVP
NS
