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Database: UniProt
Entry: Q9UPY3
LinkDB: Q9UPY3
Original site: Q9UPY3 
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   16-OCT-2019, entry version 188.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; 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)
RT   which 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.,
RA   Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. XIII.
RT   The complete sequences of 100 new cDNA clones from brain which code
RT   for large 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.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   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.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA   Sun H., Du H., Pepin K., Artiguenave F., Robert C., Cruaud C.,
RA   Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P.,
RA   Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N.,
RA   Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C.,
RA   Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S.,
RA   Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B.,
RA   Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M.,
RA   Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S.,
RA   Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D.,
RA   Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A.,
RA   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.,
RA   Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J.,
RA   Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W.,
RA   Quetier F., 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.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   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
RT   project: 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
RT   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.,
RA   Hobman T.C.;
RT   "Characterization of the interactions between mammalian PAZ PIWI
RT   domain 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
RP   AGO1 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.,
RA   Luehrmann R., 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,
RT   interacts 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-
RT   miRNA.";
RL   Genes Dev. 19:2979-2990(2005).
RN   [17]
RP   IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, AND INTERACTION WITH
RP   AGO2 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
RT   gene 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
RT   with 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
RT   RISC loading.";
RL   Mol. Cell 26:523-537(2007).
RN   [21]
RP   IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH AGO2; EIF6;
RP   MOV10; 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
RP   BY 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
RP   AGO2 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.,
RA   Mohammed S.;
RT   "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT   a refined SCX-based approach.";
RL   Anal. Chem. 81:4493-4501(2009).
RN   [26]
RP   RETRACTED PAPER.
RX   PubMed=19219043; DOI=10.1038/ng.317;
RA   Melo S.A., Ropero S., Moutinho C., Aaltonen L.A., Yamamoto H.,
RA   Calin G.A., Rossi S., Fernandez A.F., Carneiro F., Oliveira C.,
RA   Ferreira B., Liu C.-G., Villanueva A., Capella G., Schwartz S. Jr.,
RA   Shiekhattar R., Esteller M.;
RT   "A TARBP2 mutation in human cancer impairs microRNA processing and
RT   DICER1 function.";
RL   Nat. Genet. 41:365-370(2009).
RN   [27]
RP   RETRACTION 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.,
RA   Calin G.A., Rossi S., Fernandez A.F., Carneiro F., Oliveira C.,
RA   Ferreira B., Liu C.-G., Villanueva A., Capella G., Schwartz S. Jr.,
RA   Shiekhattar R., Esteller M.;
RT   "Retraction: A TARBP2 mutation in human cancer impairs microRNA
RT   processing and DICER1 function.";
RL   Nat. Genet. 48:221-221(2016).
RN   [28]
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.,
RA   Buerckstuemmer T., 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   [29]
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   [30]
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.,
RA   Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA   Blagoev B.;
RT   "System-wide temporal characterization of the proteome and
RT   phosphoproteome of human embryonic stem cell differentiation.";
RL   Sci. Signal. 4:RS3-RS3(2011).
RN   [31]
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   [32]
RP   INVOLVEMENT IN NON-EPITHELIAL OVARIAN TUMORS, VARIANTS LYS-1705;
RP   ASN-1709; GLU-1709; GLY-1709; HIS-1810; TYR-1810; ASN-1810; GLN-1813;
RP   GLY-1813 AND LYS-1813, AND CHARACTERIZATION OF VARIANTS LYS-1705;
RP   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
RT   cancers.";
RL   N. Engl. J. Med. 366:234-242(2012).
RN   [33]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1160; SER-1460; SER-1470
RP   AND SER-1868, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP   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   [34]
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.,
RA   Wang L., Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human
RT   liver phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [35]
RP   X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1660-1852, CATALYTIC
RP   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
RT   the C-terminal RNase III domain of human dicer.";
RL   J. Mol. Biol. 374:106-120(2007).
RN   [36]
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.,
RA   Suarez B.K., Whelan A.J., Williams G., Bracamontes D., Messinger Y.,
RA   Goodfellow P.J.;
RT   "DICER1 mutations in familial pleuropulmonary blastoma.";
RL   Science 325:965-965(2009).
RN   [37]
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.,
RA   Schimke R.N., Bouron-Dal Soglio D., Arseneau J., Schultz K.A.,
RA   Priest J.R., Nguyen V.H., Harach H.R., Livingston D.M., Foulkes W.D.,
RA   Tischkowitz M.;
RT   "DICER1 mutations in familial multinodular goiter with and without
RT   ovarian Sertoli-Leydig cell tumors.";
RL   JAMA 305:68-77(2011).
RN   [38]
RP   VARIANTS LEU-435 AND GLY-1898, VARIANTS GLOW TYR-1709 AND VAL-1713,
RP   AND INVOLVEMENT IN GLOW.
RX   PubMed=24676357; DOI=10.1136/jmedgenet-2013-101943;
RA   Klein S., Lee H., Ghahremani S., Kempert P., Ischander M.,
RA   Teitell M.A., Nelson S.F., Martinez-Agosto J.A.;
RT   "Expanding the phenotype of mutations in DICER1: mosaic missense
RT   mutations 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
CC       hairpin pre-microRNAs (miRNA) into fragments of twenty-one to
CC       twenty-three nucleotides with 3' overhang of two nucleotides,
CC       producing respectively short interfering RNAs (siRNA) and mature
CC       microRNAs. SiRNAs and miRNAs serve as guide to direct the RNA-
CC       induced silencing complex (RISC) to complementary RNAs to degrade
CC       them or prevent their translation. Gene silencing mediated by
CC       siRNAs, also called RNA interference, controls the elimination of
CC       transcripts from mobile and repetitive DNA elements of the genome
CC       but also the degradation of exogenous RNA of viral origin for
CC       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.;
CC         EC=3.1.26.3; Evidence={ECO:0000269|PubMed:15242644,
CC         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
CC       and TARBP2; DICER1 and TARBP2 are required to process precursor
CC       miRNAs (pre-miRNAs) to mature miRNAs and then load them onto AGO2.
CC       Note that the trimeric RLC/miRLC is also referred to as RISC.
CC       Interacts with DHX9, AGO1, PIWIL1 and PRKRA. Associates with the
CC       60S ribosome. Interacts with BCDIN3D. Interacts with AGO2, TARBP2,
CC       EIF6, MOV10 and RPL7A (60S ribosome subunit); they form a large
CC       RNA-induced silencing complex (RISC) (PubMed:17507929).
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:23063121}.
CC   -!- INTERACTION:
CC       P0C205:- (xeno); NbExp=7; IntAct=EBI-395506, EBI-8332963;
CC       P55265-1:ADAR; NbExp=4; IntAct=EBI-395506, EBI-6913056;
CC       P55265-5:ADAR; NbExp=8; IntAct=EBI-395506, EBI-6913210;
CC       Q9UL18:AGO1; NbExp=5; IntAct=EBI-395506, EBI-527363;
CC       Q9UKV8:AGO2; NbExp=20; IntAct=EBI-395506, EBI-528269;
CC       Q8CJG0:Ago2 (xeno); NbExp=2; IntAct=EBI-395506, EBI-528299;
CC       Q61496:Ddx4 (xeno); NbExp=3; IntAct=EBI-15569571, EBI-15569589;
CC       Q96C10:DHX58; NbExp=2; IntAct=EBI-395506, EBI-744193;
CC       P19525:EIF2AK2; NbExp=2; IntAct=EBI-395506, EBI-640775;
CC       Q92945:KHSRP; NbExp=3; IntAct=EBI-15569571, EBI-1049099;
CC       P49790:NUP153; NbExp=3; IntAct=EBI-395506, EBI-286779;
CC       Q96J94:PIWIL1; NbExp=2; IntAct=EBI-395506, EBI-527417;
CC       P24928:POLR2A; NbExp=3; IntAct=EBI-15569571, EBI-295301;
CC       O75569:PRKRA; NbExp=8; IntAct=EBI-395506, EBI-713955;
CC       Q15633:TARBP2; NbExp=23; IntAct=EBI-395506, EBI-978581;
CC       O43508:TNFSF12; NbExp=3; IntAct=EBI-395506, EBI-6932080;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16424907}.
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         Note=No experimental confirmation available.;
CC   -!- DISEASE: Pleuropulmonary blastoma (PPB) [MIM:601200]: A rare
CC       pediatric intrathoracic neoplasm. The tumor arises from the lung,
CC       pleura, or both, and appears to be purely mesenchymal in
CC       phenotype. It lacks malignant epithelial elements, a feature that
CC       distinguishes it from the classic adult-type pulmonary blastoma.
CC       It arises during fetal lung development and is often part of an
CC       inherited cancer syndrome. The tumor contain both epithelial and
CC       mesenchymal cells. Early in tumorigenesis, cysts form in lung
CC       airspaces, and these cysts are lined with benign-appearing
CC       epithelium. Mesenchymal cells susceptible to malignant
CC       transformation reside within the cyst walls and form a dense layer
CC       beneath the epithelial lining. In a subset of patients, overgrowth
CC       of the mesenchymal cells produces a sarcoma, a transition that is
CC       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
CC       mutations affecting the gene represented in this entry.
CC   -!- DISEASE: Goiter multinodular 1, with or without Sertoli-Leydig
CC       cell tumors (MNG1) [MIM:138800]: A common disorder characterized
CC       by nodular overgrowth of the thyroid gland. Some individuals may
CC       also develop Sertoli-Leydig cell tumors, usually of the ovary.
CC       {ECO:0000269|PubMed:21205968}. Note=The disease is caused by
CC       mutations affecting the gene represented in this entry.
CC   -!- DISEASE: Rhabdomyosarcoma, embryonal, 2 (RMSE2) [MIM:180295]: A
CC       form of rhabdomyosarcoma, a highly malignant tumor of striated
CC       muscle derived from primitive mesenchymal cells and exhibiting
CC       differentiation along rhabdomyoblastic lines. Rhabdomyosarcoma is
CC       one of the most frequently occurring soft tissue sarcomas and the
CC       most common in children. It occurs in four forms: alveolar,
CC       pleomorphic, embryonal and botryoidal rhabdomyosarcomas.
CC       {ECO:0000269|PubMed:21882293}. Note=The disease is caused by
CC       mutations affecting the gene represented in this entry.
CC   -!- DISEASE: Global developmental delay, lung cysts, overgrowth, and
CC       Wilms tumor (GLOW) [MIM:618272]: A disease characterized by the
CC       association of congenital nephromegaly, bilateral Wilms tumor,
CC       somatic overgrowth, developmental delay, macrocephaly, and
CC       bilateral lung cysts. {ECO:0000269|PubMed:24676357}. Note=The
CC       disease is caused by mutations affecting the gene represented in
CC       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
CC       IIIb domain of DICER1 are common in non-epithelial ovarian tumors.
CC       These mutations do not abolish DICER1 function but alter it in
CC       specific cell types, a novel mechanism through which perturbation
CC       of microRNA 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
CC       tumor cells and resultant effects on DICER1 stability and miRNA
CC       processing has been retracted, due to concerns of image
CC       duplication in some of the figures. {ECO:0000305|PubMed:19219043,
CC       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
CC       - Issue 87 of October 2007;
CC       URL="https://web.expasy.org/spotlight/back_issues/087";
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   SMR; Q9UPY3; -.
DR   BioGrid; 116978; 97.
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; 131.
DR   MINT; Q9UPY3; -.
DR   STRING; 9606.ENSP00000437256; -.
DR   ChEMBL; CHEMBL2311232; -.
DR   iPTMnet; Q9UPY3; -.
DR   PhosphoSitePlus; Q9UPY3; -.
DR   BioMuta; DICER1; -.
DR   DMDM; 257051056; -.
DR   EPD; Q9UPY3; -.
DR   jPOST; Q9UPY3; -.
DR   MassIVE; Q9UPY3; -.
DR   PaxDb; Q9UPY3; -.
DR   PeptideAtlas; Q9UPY3; -.
DR   PRIDE; Q9UPY3; -.
DR   ProteomicsDB; 3598; -.
DR   ProteomicsDB; 85471; -. [Q9UPY3-1]
DR   ProteomicsDB; 85472; -. [Q9UPY3-2]
DR   Ensembl; ENST00000343455; ENSP00000343745; ENSG00000100697. [Q9UPY3-1]
DR   Ensembl; ENST00000393063; ENSP00000376783; ENSG00000100697. [Q9UPY3-1]
DR   Ensembl; ENST00000526495; ENSP00000437256; ENSG00000100697. [Q9UPY3-1]
DR   Ensembl; ENST00000527414; ENSP00000435681; ENSG00000100697. [Q9UPY3-1]
DR   Ensembl; ENST00000541352; ENSP00000444719; ENSG00000100697. [Q9UPY3-2]
DR   Ensembl; ENST00000556045; ENSP00000451041; ENSG00000100697. [Q9UPY3-3]
DR   GeneID; 23405; -.
DR   KEGG; hsa:23405; -.
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; CAB068185; -.
DR   HPA; HPA000694; -.
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   eggNOG; KOG0701; Eukaryota.
DR   eggNOG; COG0571; LUCA.
DR   eggNOG; COG1111; LUCA.
DR   GeneTree; ENSGT00940000156287; -.
DR   HOGENOM; HOG000001567; -.
DR   InParanoid; Q9UPY3; -.
DR   KO; K11592; -.
DR   OMA; YLMLFDP; -.
DR   OrthoDB; 1337630at2759; -.
DR   PhylomeDB; Q9UPY3; -.
DR   TreeFam; TF330258; -.
DR   BRENDA; 3.1.26.3; 2681.
DR   Reactome; R-HSA-203927; MicroRNA (miRNA) biogenesis.
DR   Reactome; R-HSA-426486; Small interfering RNA (siRNA) biogenesis.
DR   SIGNOR; Q9UPY3; -.
DR   ChiTaRS; DICER1; human.
DR   EvolutionaryTrace; Q9UPY3; -.
DR   GeneWiki; DICER1; -.
DR   GenomeRNAi; 23405; -.
DR   Pharos; Q9UPY3; -.
DR   PRO; PR:Q9UPY3; -.
DR   Proteomes; UP000005640; Chromosome 14.
DR   Bgee; ENSG00000100697; Expressed in 247 organ(s), highest expression level in blood.
DR   ExpressionAtlas; Q9UPY3; baseline and differential.
DR   Genevisible; Q9UPY3; HS.
DR   GO; GO:0033167; C:ARC complex; IC:BHF-UCL.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR   GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; IEA:Ensembl.
DR   GO; GO:0070062; C:extracellular exosome; IDA:BHF-UCL.
DR   GO; GO:0030426; C:growth cone; IEA:Ensembl.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
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:0035197; F:siRNA binding; IDA:BHF-UCL.
DR   GO; GO:0006309; P:apoptotic DNA fragmentation; IBA:GO_Central.
DR   GO; GO:0036404; P:conversion of ds siRNA to ss siRNA; IMP:AgBase.
DR   GO; GO:0033168; P:conversion of ds siRNA to ss siRNA involved in RNA interference; IMP:BHF-UCL.
DR   GO; GO:0035280; P:miRNA loading onto RISC involved in gene silencing by miRNA; IDA:BHF-UCL.
DR   GO; GO:0010586; P:miRNA metabolic process; TAS:Reactome.
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:0035196; P:production of miRNAs involved in gene silencing by miRNA; IDA:UniProtKB.
DR   GO; GO:0030422; P:production of siRNA involved in RNA interference; IDA:UniProtKB.
DR   GO; GO:0090502; P:RNA phosphodiester bond hydrolysis, endonucleolytic; IDA:BHF-UCL.
DR   GO; GO:0035087; P:siRNA loading onto RISC involved in RNA interference; IDA:BHF-UCL.
DR   GO; GO:0030423; P:targeting of mRNA for destruction involved in RNA interference; IMP:UniProtKB.
DR   GO; GO:0035148; P:tube formation; IMP:ARUK-UCL.
DR   CDD; cd00048; DSRM; 1.
DR   CDD; cd00593; RIBOc; 2.
DR   Gene3D; 1.10.1520.10; -; 1.
DR   Gene3D; 3.30.160.380; -; 1.
DR   InterPro; IPR038248; Dicer_dimer_sf.
DR   InterPro; IPR005034; Dicer_dimerisation_dom.
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; PF03368; Dicer_dimer; 1.
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; Complete proteome;
KW   Cytoplasm; Disease mutation; Endonuclease; Helicase; 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       Endoribonuclease Dicer.
FT                                /FTId=PRO_0000180470.
FT   DOMAIN       51    227       Helicase ATP-binding.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00541}.
FT   DOMAIN      433    602       Helicase C-terminal.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00542}.
FT   DOMAIN      630    722       Dicer dsRNA-binding fold.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00657}.
FT   DOMAIN      891   1042       PAZ. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00142}.
FT   DOMAIN     1276   1403       RNase III 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00177}.
FT   DOMAIN     1666   1824       RNase III 2. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00177}.
FT   DOMAIN     1849   1914       DRBM. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00266}.
FT   NP_BIND      64     71       ATP. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00541}.
FT   REGION      256    595       Required for interaction with PRKRA and
FT                                TARBP2.
FT   MOTIF       175    178       DECH box.
FT   METAL      1316   1316       Magnesium or manganese 1. {ECO:0000250}.
FT   METAL      1395   1395       Magnesium or manganese 1. {ECO:0000250}.
FT   METAL      1398   1398       Magnesium or manganese 1. {ECO:0000250}.
FT   METAL      1705   1705       Magnesium or manganese 2.
FT                                {ECO:0000244|PDB:2EB1,
FT                                ECO:0000269|PubMed:17920623}.
FT   METAL      1810   1810       Magnesium or manganese 2.
FT                                {ECO:0000244|PDB:2EB1,
FT                                ECO:0000269|PubMed:17920623}.
FT   METAL      1813   1813       Magnesium or manganese 2.
FT                                {ECO:0000244|PDB:2EB1,
FT                                ECO:0000269|PubMed:17920623}.
FT   SITE       1806   1806       Important for activity.
FT                                {ECO:0000250|UniProtKB:Q8R418}.
FT   MOD_RES     413    413       Phosphoserine.
FT                                {ECO:0000244|PubMed:21406692}.
FT   MOD_RES     415    415       Phosphoserine.
FT                                {ECO:0000244|PubMed:21406692}.
FT   MOD_RES    1016   1016       Phosphoserine.
FT                                {ECO:0000244|PubMed:18669648}.
FT   MOD_RES    1160   1160       Phosphoserine.
FT                                {ECO:0000244|PubMed:23186163}.
FT   MOD_RES    1460   1460       Phosphoserine.
FT                                {ECO:0000244|PubMed:23186163}.
FT   MOD_RES    1468   1468       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q8R418}.
FT   MOD_RES    1470   1470       Phosphoserine.
FT                                {ECO:0000244|PubMed:23186163}.
FT   MOD_RES    1868   1868       Phosphoserine.
FT                                {ECO:0000244|PubMed:23186163}.
FT   VAR_SEQ       1     13       MKSPALQPLSMAG -> MLAWESDHFLRIL (in
FT                                isoform 3).
FT                                {ECO:0000303|PubMed:14702039}.
FT                                /FTId=VSP_055341.
FT   VAR_SEQ      14   1115       Missing (in isoform 3).
FT                                {ECO:0000303|PubMed:14702039}.
FT                                /FTId=VSP_055342.
FT   VAR_SEQ    1789   1922       LRRSEEDEEKEEDIEVPKAMGDIFESLAGAIYMDSGMSLET
FT                                VWQVYYPMMRPLIEKFSANVPRSPVRELLEMEPETAKFSPA
FT                                ERTYDGKVRVTVEVVGKGKFKGVGRSYRIAKSAAARRALRS
FT                                LKANQPQVPNS -> KSFLQMYPVPLCENCLKWNQKLPNLA
FT                                RLRELTTGRSESLWK (in isoform 2).
FT                                {ECO:0000303|PubMed:20615407}.
FT                                /FTId=VSP_042832.
FT   VARIANT     435    435       P -> L (found in Wilms tumor from a
FT                                patient with GLOW syndrome; somatic
FT                                mutation; unknown pathological
FT                                significance).
FT                                {ECO:0000269|PubMed:24676357}.
FT                                /FTId=VAR_081917.
FT   VARIANT     839    839       S -> F (in MNG1; dbSNP:rs387906934).
FT                                {ECO:0000269|PubMed:21205968}.
FT                                /FTId=VAR_065301.
FT   VARIANT    1583   1583       L -> R (in PPB; dbSNP:rs137852976).
FT                                {ECO:0000269|PubMed:19556464}.
FT                                /FTId=VAR_063150.
FT   VARIANT    1705   1705       E -> K (in non-epithelial ovarian tumor;
FT                                somatic mutation; results in reduced
FT                                RNase IIIb activity but retention of
FT                                RNase IIIa activity).
FT                                {ECO:0000269|PubMed:22187960}.
FT                                /FTId=VAR_067091.
FT   VARIANT    1709   1709       D -> E (in non-epithelial ovarian tumor;
FT                                somatic mutation; results in reduced
FT                                RNase IIIb activity but retention of
FT                                RNase IIIa activity).
FT                                {ECO:0000269|PubMed:22187960}.
FT                                /FTId=VAR_067092.
FT   VARIANT    1709   1709       D -> G (in non-epithelial ovarian tumor;
FT                                somatic mutation; dbSNP:rs1555366979).
FT                                {ECO:0000269|PubMed:22187960}.
FT                                /FTId=VAR_067093.
FT   VARIANT    1709   1709       D -> N (in non-epithelial ovarian tumor;
FT                                somatic mutation; results in reduced
FT                                RNase IIIb activity but retention of
FT                                RNase IIIa activity).
FT                                {ECO:0000269|PubMed:22187960}.
FT                                /FTId=VAR_067094.
FT   VARIANT    1709   1709       D -> Y (in GLOW; somatic mutation).
FT                                {ECO:0000269|PubMed:24676357}.
FT                                /FTId=VAR_081918.
FT   VARIANT    1713   1713       D -> V (in GLOW; somatic mutation).
FT                                {ECO:0000269|PubMed:24676357}.
FT                                /FTId=VAR_081919.
FT   VARIANT    1810   1810       D -> H (in non-epithelial ovarian tumor;
FT                                somatic mutation).
FT                                {ECO:0000269|PubMed:22187960}.
FT                                /FTId=VAR_067095.
FT   VARIANT    1810   1810       D -> N (in non-epithelial ovarian tumor;
FT                                somatic mutation; dbSNP:rs775912475).
FT                                {ECO:0000269|PubMed:22187960}.
FT                                /FTId=VAR_067096.
FT   VARIANT    1810   1810       D -> Y (in non-epithelial ovarian tumor;
FT                                somatic mutation).
FT                                {ECO:0000269|PubMed:22187960}.
FT                                /FTId=VAR_067097.
FT   VARIANT    1813   1813       E -> G (in non-epithelial ovarian tumor;
FT                                somatic mutation).
FT                                {ECO:0000269|PubMed:22187960}.
FT                                /FTId=VAR_067098.
FT   VARIANT    1813   1813       E -> K (in non-epithelial ovarian tumor;
FT                                somatic mutation).
FT                                {ECO:0000269|PubMed:22187960}.
FT                                /FTId=VAR_067099.
FT   VARIANT    1813   1813       E -> Q (in non-epithelial ovarian tumor;
FT                                somatic mutation).
FT                                {ECO:0000269|PubMed:22187960}.
FT                                /FTId=VAR_067100.
FT   VARIANT    1898   1898       R -> G (found in Wilms tumor from a
FT                                patient with GLOW syndrome; somatic
FT                                mutation; unknown pathological
FT                                significance).
FT                                {ECO:0000269|PubMed:24676357}.
FT                                /FTId=VAR_081920.
FT   MUTAGEN     960    960       F->A: 2-fold decrease in activity.
FT   MUTAGEN     971    971       Y->A: 10-fold decrease in activity; when
FT                                associated with Y-972.
FT   MUTAGEN     972    972       Y->A: 10-fold decrease in activity; when
FT                                associated with Y-971.
FT   MUTAGEN    1036   1036       E->A: 5-fold decrease in activity.
FT   MUTAGEN    1313   1313       E->A: No effect on activity.
FT                                {ECO:0000269|PubMed:15242644}.
FT   MUTAGEN    1320   1320       D->A: Decreased activity. Loss of
FT                                activity; when associated with D-1709.
FT                                {ECO:0000269|PubMed:15242644}.
FT   MUTAGEN    1340   1340       E->A: No effect on activity.
FT                                {ECO:0000269|PubMed:15242644}.
FT   MUTAGEN    1444   1444       E->A: Decreased activity. Loss of
FT                                activity; when associated with E-1813.
FT                                {ECO:0000269|PubMed:15242644}.
FT   MUTAGEN    1702   1702       Q->A: No effect on activity.
FT                                {ECO:0000269|PubMed:15242644}.
FT   MUTAGEN    1709   1709       D->A: Decreased activity. Loss of
FT                                activity; when associated with D-1320.
FT                                {ECO:0000269|PubMed:15242644}.
FT   MUTAGEN    1729   1729       P->E: No effect on activity.
FT                                {ECO:0000269|PubMed:15242644}.
FT   MUTAGEN    1813   1813       E->A: Decreased activity. Loss of
FT                                activity; when associated with E-1444.
FT                                {ECO:0000269|PubMed:15242644}.
FT   CONFLICT     75     90       VLLTKELSYQIRGDFS -> STTLLKSCLYLDLGETSA
FT                                (in Ref. 1; BAA78691). {ECO:0000305}.
FT   CONFLICT    189    189       I -> F (in Ref. 1; BAA78691).
FT                                {ECO:0000305}.
FT   CONFLICT    195    195       N -> I (in Ref. 1; BAA78691).
FT                                {ECO:0000305}.
FT   CONFLICT    214    214       C -> W (in Ref. 1; BAA78691).
FT                                {ECO:0000305}.
FT   CONFLICT    218    218       E -> D (in Ref. 1; BAA78691).
FT                                {ECO:0000305}.
FT   CONFLICT    223    223       I -> F (in Ref. 1; BAA78691).
FT                                {ECO:0000305}.
FT   CONFLICT    393    394       QQ -> HS (in Ref. 1; BAA78691).
FT                                {ECO:0000305}.
FT   CONFLICT    492    493       KQ -> NT (in Ref. 1; BAA78691).
FT                                {ECO:0000305}.
FT   CONFLICT    609    609       D -> H (in Ref. 1; BAA78691).
FT                                {ECO:0000305}.
FT   HELIX       268    282       {ECO:0000244|PDB:4WYQ}.
FT   HELIX       297    313       {ECO:0000244|PDB:4WYQ}.
FT   HELIX       315    335       {ECO:0000244|PDB:4WYQ}.
FT   HELIX       339    361       {ECO:0000244|PDB:4WYQ}.
FT   STRAND      363    367       {ECO:0000244|PDB:4WYQ}.
FT   HELIX       375    385       {ECO:0000244|PDB:4WYQ}.
FT   STRAND      768    780       {ECO:0000244|PDB:4NGD}.
FT   HELIX       783    785       {ECO:0000244|PDB:4NGD}.
FT   HELIX       795    797       {ECO:0000244|PDB:4NGD}.
FT   STRAND      801    808       {ECO:0000244|PDB:4NGD}.
FT   STRAND      816    820       {ECO:0000244|PDB:4NGD}.
FT   STRAND      823    836       {ECO:0000244|PDB:4NGD}.
FT   HELIX       840    855       {ECO:0000244|PDB:4NGD}.
FT   STRAND      877    883       {ECO:0000244|PDB:4NGD}.
FT   STRAND      890    892       {ECO:0000244|PDB:4NGD}.
FT   HELIX       894    902       {ECO:0000244|PDB:4NGD}.
FT   STRAND      906    908       {ECO:0000244|PDB:4NGD}.
FT   STRAND      916    918       {ECO:0000244|PDB:4NGD}.
FT   HELIX       924    927       {ECO:0000244|PDB:4NGD}.
FT   STRAND      931    937       {ECO:0000244|PDB:4NGD}.
FT   STRAND      939    941       {ECO:0000244|PDB:4NGD}.
FT   STRAND      945    951       {ECO:0000244|PDB:4NGD}.
FT   HELIX       968    976       {ECO:0000244|PDB:4NGD}.
FT   STRAND      987    992       {ECO:0000244|PDB:4NGD}.
FT   HELIX      1016   1030       {ECO:0000244|PDB:4NGD}.
FT   HELIX      1035   1037       {ECO:0000244|PDB:4NGD}.
FT   STRAND     1038   1040       {ECO:0000244|PDB:4NGD}.
FT   HELIX      1045   1051       {ECO:0000244|PDB:4NGD}.
FT   HELIX      1054   1061       {ECO:0000244|PDB:4NGD}.
FT   TURN       1662   1665       {ECO:0000244|PDB:2EB1}.
FT   HELIX      1666   1673       {ECO:0000244|PDB:2EB1}.
FT   HELIX      1680   1687       {ECO:0000244|PDB:2EB1}.
FT   HELIX      1702   1722       {ECO:0000244|PDB:2EB1}.
FT   HELIX      1729   1739       {ECO:0000244|PDB:2EB1}.
FT   HELIX      1742   1751       {ECO:0000244|PDB:2EB1}.
FT   HELIX      1754   1756       {ECO:0000244|PDB:2EB1}.
FT   HELIX      1763   1778       {ECO:0000244|PDB:2EB1}.
FT   HELIX      1806   1822       {ECO:0000244|PDB:2EB1}.
FT   HELIX      1827   1847       {ECO:0000244|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
//
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