DICER_CRIGR
ID DICER_CRIGR Reviewed; 1917 AA.
AC A0MQH0;
DT 05-MAY-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-SEP-2009, sequence version 3.
DT 03-AUG-2022, entry version 91.
DE RecName: Full=Endoribonuclease Dicer;
DE EC=3.1.26.3;
GN Name=DICER1; Synonyms=DICER;
OS Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Cricetulus.
OX NCBI_TaxID=10029;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Wallerstorfer D.;
RL Submitted (SEP-2006) to the EMBL/GenBank/DDBJ databases.
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 (By similarity).
CC {ECO:0000250|UniProtKB:Q9UPY3}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Endonucleolytic cleavage to 5'-phosphomonoester.; EC=3.1.26.3;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC Note=Binds 2 magnesium or manganese ions per subunit. {ECO:0000250};
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. Interacts with AGO2, TARBP2, EIF6, MOV10
CC and RPL7A (60S ribosome subunit); they form a large RNA-induced
CC silencing complex (RISC). Interacts with BCDIN3D (By similarity).
CC Interacts (via Dicer dsRNA-binding fold domain) with ALOX5 (via PLAT
CC domain); this interaction enhances arachidonate 5-lipoxygenase activity
CC and modifies the miRNA precursor processing activity of DICER1 (By
CC similarity). {ECO:0000250|UniProtKB:Q9UPY3}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9UPY3}.
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 ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; EF031271; ABK28790.1; -; mRNA.
DR RefSeq; NP_001231198.1; NM_001244269.1.
DR RefSeq; XP_007647243.1; XM_007649053.1.
DR AlphaFoldDB; A0MQH0; -.
DR SMR; A0MQH0; -.
DR STRING; 10029.NP_001231198.1; -.
DR Ensembl; ENSCGRT00001009453; ENSCGRP00001006065; ENSCGRG00001008088.
DR GeneID; 100689239; -.
DR KEGG; cge:100689239; -.
DR CTD; 23405; -.
DR eggNOG; KOG0701; Eukaryota.
DR GeneTree; ENSGT00940000156287; -.
DR OMA; TTYLYCT; -.
DR OrthoDB; 1337630at2759; -.
DR GO; GO:0070062; C:extracellular exosome; IEA:Ensembl.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0016442; C:RISC complex; ISS:UniProtKB.
DR GO; GO:0070578; C:RISC-loading complex; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003677; F:DNA binding; IEA:InterPro.
DR GO; GO:0003725; F:double-stranded RNA binding; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0019904; F:protein domain specific binding; IEA:Ensembl.
DR GO; GO:0004525; F:ribonuclease III activity; IEA:UniProtKB-EC.
DR GO; GO:0035197; F:siRNA binding; IEA:Ensembl.
DR GO; GO:0098795; P:global gene silencing by mRNA cleavage; ISS:UniProtKB.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IEA:Ensembl.
DR GO; GO:0038061; P:NIK/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:0031054; P:pre-miRNA processing; ISS:UniProtKB.
DR GO; GO:0070922; P:RISC complex assembly; IEA:Ensembl.
DR GO; GO:0030422; P:siRNA processing; ISS:UniProtKB.
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 2: Evidence at transcript level;
KW ATP-binding; Cytoplasm; Endonuclease; Helicase; Hydrolase; Magnesium;
KW Manganese; Metal-binding; Nuclease; Nucleotide-binding; Phosphoprotein;
KW Repeat; RNA-binding; RNA-mediated gene silencing.
FT CHAIN 1..1917
FT /note="Endoribonuclease Dicer"
FT /id="PRO_0000373983"
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 898..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 1661..1819
FT /note="RNase III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00177"
FT DOMAIN 1844..1909
FT /note="DRBM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00266"
FT REGION 256..595
FT /note="Required for interaction with PRKRA and TARBP2"
FT /evidence="ECO:0000250"
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 1700
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 1805
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 1808
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT SITE 1801
FT /note="Important for activity"
FT /evidence="ECO:0000250"
FT MOD_RES 413
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UPY3"
FT MOD_RES 415
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UPY3"
FT MOD_RES 1016
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UPY3"
FT MOD_RES 1160
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UPY3"
FT MOD_RES 1456
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UPY3"
FT MOD_RES 1464
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8R418"
FT MOD_RES 1466
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UPY3"
FT MOD_RES 1863
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UPY3"
SQ SEQUENCE 1917 AA; 217171 MW; E42D6F5412E65A0F CRC64;
MKSPALQPLS MAGLQLMTPA SSPMGPFFGL PWQQEAIHDN IYTPRKYQVE LLEAALDHNT
IVCLNTGSGK TFIAVLLTKE LAHQIRGDLN PRAKRTVFLV NSANQVAQQV SAVRTHSDLK
VGEYSNLEVN ASWTKERWSQ EFTKHQVLIM TCYVALNVLK NGYLSLSDIN LLVFDECHLA
ILDHPYREIM KLCESCPSCP RILGLTASIL NGKCDPEELE EKIQKLEKIL KSNAETATDL
VVLDRYASQP CEIVVDCGPF TDRSGLYERL LMELEEAINF INDCNVSVHS KERDSTLISK
QILSDCRAVL VVLGPWCADK VAGMMVRELQ KYIKHEQEEL HRKFLLFTDT LLRKIHALCE
EHFSPASLDL KYVTPKVMKL LEILRKYKPY ERQQFESVEW YNNRNQDNYV SWSDSEDDDD
DEEIEEKEKP ETNFPSPFTN ILCGIIFVER RYTAVVLNRL IKEAGKQDPE LAYISSNFIT
GHGIGKNQPR SKQMEAEFRK QEEVLRKFRA HETNLLIATS VVEEGVDIPK CNLVVRFDLP
TEYRSYVQSK GRARAPISNY VMLADTDKIQ SFEEDLKTYK AIEKILRNKC SKSVDGAEAD
VDAVVDDDDV FPPYVLRPDD GGPRVTINTA IGHVNRYCAR LPSDPFTHLA PKCRTQELPD
GTFYSTLYLP INSPLRASIV GPPMGCVRLA ERVVALICCE KLHKIGELDE HLMPVGKETV
KYEEELDLHD EEETSVPGRP GSTKRRQCYP KAIPECLRES YPKPDQPCYL YVIGMVLTTP
LPDELNFRRR KLYPPEDTTR CFGILTAKPI PQIPHFPVYT RSGEVTISIE LKKSGFTLSQ
QMLELITRLH QYIFSHILRL EKPALEFKPT GAESAYCVLP LNVVNDSSTL DIDFTFMEDI
EKSEARIGIP STKYSKETPF VFKLEDYQDA VIIPRYRNFD QPHRFYVADV YTDLTPLSKF
PSPEYETFAE YYKTKYNLDL TNLNQPLLDV DHTSSRLNLL TPRHLNQKGK ALPLSSAEKR
KAKWESLQNK QILVPELCAI HPIPASLWRK AVCLPSILYR LHCLLTAEEL RAQTASDAGV
GVRSLPADFR YPNLDFGWKK SIDSKSFIST CNSSLAENDN YCKHSTIIVP ENAAHQGATR
TPLENHDQMS VNCRRLPAES SGKLQIEVST DLTAINGLSY NKNLANGSYD LVNRDFCQGN
QLNYFKQEIP VQPTTSYPIQ NLYHYENQPK PSNECTLLSN KYLDGNANTS TSDGSPAVST
MPAVMSAGRA LKDRMDSEQS PSAGYSSRTL GPNPGLILQA LTLSNASDGF NLERLEMLGD
SFLKHAITTY LFCTYPDAHE GRLSYMRSKK VSNCNLYRLG KKKGLPSRMV VSIFDPPVNW
LPPGYVVNQD KSNAEKWEKD EMTKDCLLAN GKLGKDCEEE EALTWRAPKE EAEYEDDFLE
YDQEHIQFID SMLMGSGAFV KKISLSPFST SDSAYEWKMP KKSSLGSMPF SSDLEDFDYS
SWDAMCYLDP SKAVEEDDFV VGFWNPSEEN CGVDTGKQSI SYDLHTEQCI ADKSIADCVE
ALLGCYLTSC GERAAQLFLC SLGLKVLPVI KRTSREKALY PAQENFSSQQ KSLSGSCAAT
AASPRSSAGK DLEYGCLKIP PRCMFDHPDA EKTLNHLISG FENFEKKINY RFKNKAYLLQ
AFTHASYHYN TITDCYQRLE FLGDAILDYL ITKHLYEDPR QHSPGVLTDL RSALVNNTIF
ASLAVKYDYH KYFKAVSPEL FHVIDDFVQF QLEKNEMQGM DSELRRSEED EEKEEDIEVP
KAMGDIFESL AGAIYMDSGM SLEVVWQVYY PMMRPLIEKF SANVPRSPVR ELLEMEPETA
KFSPAERTYD GKVRVTVEVV GKGKFKGVGR SYRIAKSAAA RRALRSLKAN QPQVPNS
