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Protein

Endoribonuclease Dicer

Gene

Dicer1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Double-stranded RNA (dsRNA) endoribonuclease playing a central role in short dsRNA-mediated post-transcriptional gene silencing. Cleaves naturally occurring long dsRNAs and short hairpin pre-microRNAs (miRNA) into fragments of twenty-one to twenty-three nucleotides with 3' overhang of two nucleotides, producing respectively short interfering RNAs (siRNA) and mature microRNAs. SiRNAs and miRNAs serve as guide to direct the RNA-induced silencing complex (RISC) to complementary RNAs to degrade them or prevent their translation. Gene silencing mediated by siRNAs, also called RNA interference, controls the elimination of transcripts from mobile and repetitive DNA elements of the genome but also the degradation of exogenous RNA of viral origin for instance. The miRNA pathway on the other side is a mean to specifically regulate the expression of target genes (By similarity).By similarity
Isoform 2: More active than isoform 1 to process long double-stranded RNA into siRNAs. Responsible for the accumulation of endogenous siRNAs observed in mouse oocytes compared to somatic cells and it regulates meiotic spindle organization in female germline.

Caution

It is uncertain whether Met-1 or Met-11 is the initiator.Curated

Catalytic activityi

Endonucleolytic cleavage to 5'-phosphomonoester.

Cofactori

Mg2+Curated, Mn2+CuratedNote: Binds 2 magnesium or manganese ions per subunit.Curated

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi1316Magnesium or manganese 1By similarity1
Metal bindingi1395Magnesium or manganese 1By similarity1
Metal bindingi1398Magnesium or manganese 1By similarity1
Metal bindingi1699Magnesium or manganese 2By similarity1
Sitei1800Important for activity1 Publication1
Metal bindingi1804Magnesium or manganese 2By similarity1
Metal bindingi1807Magnesium or manganese 2By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi64 – 71ATPBy similarity8

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionEndonuclease, Helicase, Hydrolase, Nuclease, RNA-binding
Biological processRNA-mediated gene silencing
LigandATP-binding, Magnesium, Manganese, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi3.1.26.3 3474

Names & Taxonomyi

Protein namesi
Recommended name:
Endoribonuclease Dicer (EC:3.1.26.3)
Alternative name(s):
Double-strand-specific ribonuclease mDCR-1
Gene namesi
Name:Dicer1
Synonyms:Dicer, Mdcr
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:2177178 Dicer1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Disruption phenotypei

Isoform 2: Mice lacking isoform 2 are viable and males are fertile. However, females are sterile, their oocytes displaying meiotic spindle defects.

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1800K → A, R, S or T: Loss of activity. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001804711 – 1916Endoribonuclease DicerAdd BLAST1916

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei413PhosphoserineBy similarity1
Modified residuei415PhosphoserineBy similarity1
Modified residuei1016PhosphoserineBy similarity1
Modified residuei1160PhosphoserineBy similarity1
Modified residuei1456PhosphoserineBy similarity1
Modified residuei1464PhosphoserineCombined sources1
Modified residuei1466PhosphoserineBy similarity1
Modified residuei1862PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ8R418
PaxDbiQ8R418
PeptideAtlasiQ8R418
PRIDEiQ8R418

PTM databases

iPTMnetiQ8R418
PhosphoSitePlusiQ8R418

Expressioni

Tissue specificityi

Isoform 1 is expressed in a wide variety of tissues. Isoform 2 is specifically expressed in oocytes during their growth (at protein level).

Gene expression databases

CleanExiMM_DICER1

Interactioni

Subunit structurei

Component of the RISC loading complex (RLC), or micro-RNA (miRNA) loading complex (miRLC), which is composed of DICER1, AGO2 and TARBP2; DICER1 and TARBP2 are required to process precursor miRNAs (pre-miRNAs) to mature miRNAs and then load them onto AGO2. Note that the trimeric RLC/miRLC is also referred to as RISC. Interacts with DHX9, AGO1, PIWIL1 and PRKRA. Interacts with AGO2, TARBP2, EIF6, MOV10 and RPL7A (60S ribosome subunit); they form a large RNA-induced silencing complex (RISC). Interacts with BCDIN3D (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

ComplexPortaliCPX-1073 RISC-loading complex, PRKRA variant
CPX-135 RISC-loading complex, TARBP2 variant
DIPiDIP-29721N
IntActiQ8R418, 4 interactors
STRINGi10090.ENSMUSP00000043676

Structurei

Secondary structure

11916
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ8R418
SMRiQ8R418
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ8R418

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini51 – 227Helicase ATP-bindingAdd BLAST177
Domaini433 – 602Helicase C-terminalAdd BLAST170
Domaini630 – 722Dicer dsRNA-binding foldAdd BLAST93
Domaini891 – 1042PAZAdd BLAST152
Domaini1276 – 1403RNase III 1Add BLAST128
Domaini1660 – 1818RNase III 2Add BLAST159
Domaini1843 – 1908DRBMAdd BLAST66

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni256 – 595Required for interaction with PRKRA and TARBP2By similarityAdd BLAST340

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi175 – 178DECH box4

Sequence similaritiesi

Belongs to the helicase family. Dicer subfamily.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0701 Eukaryota
COG0571 LUCA
COG1111 LUCA
HOGENOMiHOG000001567
HOVERGENiHBG107811
InParanoidiQ8R418
PhylomeDBiQ8R418

Family and domain databases

CDDicd00048 DSRM, 1 hit
cd00079 HELICc, 1 hit
cd00593 RIBOc, 2 hits
Gene3Di1.10.1520.10, 1 hit
3.30.160.380, 1 hit
HAMAPiMF_00104 RNase_III, 1 hit
InterProiView protein in InterPro
IPR038248 Dicer_dimer_sf
IPR005034 Dicer_dimerisation_dom
IPR014720 dsRBD_dom
IPR006935 Helicase/UvrB_N
IPR014001 Helicase_ATP-bd
IPR001650 Helicase_C
IPR027417 P-loop_NTPase
IPR003100 PAZ_dom
IPR036085 PAZ_dom_sf
IPR011907 RNase_III
IPR000999 RNase_III_dom
IPR036389 RNase_III_sf
PfamiView protein in Pfam
PF03368 Dicer_dimer, 1 hit
PF00271 Helicase_C, 1 hit
PF02170 PAZ, 1 hit
PF04851 ResIII, 1 hit
PF00636 Ribonuclease_3, 2 hits
SMARTiView protein in SMART
SM00487 DEXDc, 1 hit
SM00358 DSRM, 1 hit
SM00490 HELICc, 1 hit
SM00949 PAZ, 1 hit
SM00535 RIBOc, 2 hits
SUPFAMiSSF101690 SSF101690, 1 hit
SSF52540 SSF52540, 1 hit
SSF69065 SSF69065, 2 hits
PROSITEiView protein in PROSITE
PS51327 DICER_DSRBF, 1 hit
PS50137 DS_RBD, 1 hit
PS51192 HELICASE_ATP_BIND_1, 1 hit
PS51194 HELICASE_CTER, 1 hit
PS50821 PAZ, 1 hit
PS00517 RNASE_3_1, 1 hit
PS50142 RNASE_3_2, 2 hits

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative promoter usage. AlignAdd to basket

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q8R418-1) [UniParc]FASTAAdd to basket
Also known as: DicerS

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MKSPALQPLS MAGLQLMTPA SSPMGPFFGL PWQQEAIHDN IYTPRKYQVE
60 70 80 90 100
LLEAALDHNT IVCLNTGSGK TFIAVLLTKE LAHQIRGDLN PHAKRTVFLV
110 120 130 140 150
NSANQVAQQV SAVRTHSDLK VGEYSDLEVN ASWTKERWSQ EFTKHQVLIM
160 170 180 190 200
TCYVALTVLK NGYLSLSDIN LLVFDECHLA ILDHPYREIM KLCESCPSCP
210 220 230 240 250
RILGLTASIL NGKCDPEELE EKIQKLERIL RSDAETATDL VVLDRYTSQP
260 270 280 290 300
CEIVVDCGPF TDRSGLYERL LMELEAALDF INDCNVAVHS KERDSTLISK
310 320 330 340 350
QILSDCRAVL VVLGPWCADK VAGMMVRELQ KYIKHEQEEL HRKFLLFTDT
360 370 380 390 400
LLRKIHALCE EYFSPASLDL KYVTPKVMKL LEILRKYKPY ERQQFESVEW
410 420 430 440 450
YNNRNQDNYV SWSDSEDDDD DEEIEEKEKP ETNFPSPFTN ILCGIIFVER
460 470 480 490 500
RYTAVVLNRL IKEAGKQDPE LAYISSNFIT GHGIGKNQPR SKQMEAEFRK
510 520 530 540 550
QEEVLRKFRA HETNLLIATS VVEEGVDIPK CNLVVRFDLP TEYRSYVQSK
560 570 580 590 600
GRARAPISNY VMLADTDKIK SFEEDLKTYK AIEKILRNKC SKSADGAEAD
610 620 630 640 650
VHAGVDDEDA FPPYVLRPDD GGPRVTINTA IGHINRYCAR LPSDPFTHLA
660 670 680 690 700
PKCRTRELPD GTFYSTLYLP INSPLRASIV GPPMDSVRLA ERVVALICCE
710 720 730 740 750
KLHKIGELDE HLMPVGKETV KYEEELDLHD EEETSVPGRP GSTKRRQCYP
760 770 780 790 800
KAIPECLRES YPKPDQPCYL YVIGMVLTTP LPDELNFRRR KLYPPEDTTR
810 820 830 840 850
CFGILTAKPI PQIPHFPVYT RSGEVTISIE LKKSGFTLSQ QMLELITRLH
860 870 880 890 900
QYIFSHILRL EKPALEFKPT GAESAYCVLP LNVVNDSGTL DIDFKFMEDI
910 920 930 940 950
EKSEARIGIP STKYSKETPF VFKLEDYQDA VIIPRYRNFD QPHRFYVADV
960 970 980 990 1000
YTDLTPLSKF PSPEYETFAE YYKTKYNLDL TNLNQPLLDV DHTSSRLNLL
1010 1020 1030 1040 1050
TPRHLNQKGK ALPLSSAEKR KAKWESLQNK QILVPELCAI HPIPASLWRK
1060 1070 1080 1090 1100
AVCLPSILYR LHCLLTAEEL RAQTASDAGV GVRSLPVDFR YPNLDFGWKK
1110 1120 1130 1140 1150
SIDSKSFIST CNSSLAESDN YCKHSTTVVP EHAAHQGATR PSLENHDQMS
1160 1170 1180 1190 1200
VNCKRLPAES PAKLQSEVST DLTAINGLSY NKNLANGSYD LVNRDFCQGN
1210 1220 1230 1240 1250
QLNYFKQEIP VQPTTSYPIQ NLYNYENQPK PSNECPLLSN TYLDGNANTS
1260 1270 1280 1290 1300
TSDGSPAVST MPAMMNAVKA LKDRMDSEQS PSVGYSSRTL GPNPGLILQA
1310 1320 1330 1340 1350
LTLSNASDGF NLERLEMLGD SFLKHAITTY LFCTYPDAHE GRLSYMRSKK
1360 1370 1380 1390 1400
VSNCNLYRLG KKKGLPSRMV VSIFDPPVNW LPPGYVVNQD KSNSEKWEKD
1410 1420 1430 1440 1450
EMTKDCLLAN GKLGEACEEE EDLTWRAPKE EAEDEDDFLE YDQEHIQFID
1460 1470 1480 1490 1500
SMLMGSGAFV RKISLSPFSA SDSAYEWKMP KKASLGSMPF ASGLEDFDYS
1510 1520 1530 1540 1550
SWDAMCYLDP SKAVEEDDFV VGFWNPSEEN CGVDTGKQSI SYDLHTEQCI
1560 1570 1580 1590 1600
ADKSIADCVE ALLGCYLTSC GERAAQLFLC SLGLKVLPVI KRTSREKALD
1610 1620 1630 1640 1650
PAQENGSSQQ KSLSGSCAAP VGPRSSAGKD LEYGCLKIPP RCMFDHPDAE
1660 1670 1680 1690 1700
KTLNHLISGF ETFEKKINYR FKNKAYLLQA FTHASYHYNT ITDCYQRLEF
1710 1720 1730 1740 1750
LGDAILDYLI TKHLYEDPRQ HSPGVLTDLR SALVNNTIFA SLAVKYDYHK
1760 1770 1780 1790 1800
YFKAVSPELF HVIDDFVKFQ LEKNEMQGMD SELRRSEEDE EKEEDIEVPK
1810 1820 1830 1840 1850
AMGDIFESLA GAIYMDSGMS LEVVWQVYYP MMQPLIEKFS ANVPRSPVRE
1860 1870 1880 1890 1900
LLEMEPETAK FSPAERTYDG KVRVTVEVVG KGKFKGVGRS YRIAKSAAAR
1910
RALRSLKANQ PQVPNS
Length:1,916
Mass (Da):216,821
Last modified:September 1, 2009 - v3
Checksum:iD97EA17922D7E79C
GO
Isoform 2 (identifier: Q8R418-2) [UniParc]FASTAAdd to basket
Also known as: DicerO

The sequence of this isoform differs from the canonical sequence as follows:
     1-245: MKSPALQPLS...TATDLVVLDR → MSRDTEV

Note: An MT-C retrotransposon in intron 6 of the mouse DICER gene functions as a promoter producing a transcript lacking exons 1 to 6. A new alternative first exon is directly derived from the retrotransposon.
Show »
Length:1,678
Mass (Da):190,213
Checksum:i4F445FDFB774C3EB
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F8VQ54F8VQ54_MOUSE
Endoribonuclease Dicer
Dicer1
1,906Annotation score:
A0A1Y7VJD6A0A1Y7VJD6_MOUSE
Endoribonuclease Dicer
Dicer1
411Annotation score:

Sequence cautioni

The sequence AAM21495 differs from that shown. Reason: Frameshift at position 8.Curated
The sequence BAC15765 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAC15765 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1M → L in BAC15765 (PubMed:12526743).Curated1
Sequence conflicti107A → C in AAM21495 (PubMed:15081373).Curated1
Sequence conflicti167S → P in BAC15765 (PubMed:12526743).Curated1
Sequence conflicti289H → Y in AAM21495 (PubMed:15081373).Curated1
Sequence conflicti610A → T in BAC15765 (PubMed:12526743).Curated1
Sequence conflicti759E → D in AAM21495 (PubMed:15081373).Curated1
Sequence conflicti837T → I in AAM21495 (PubMed:15081373).Curated1
Sequence conflicti888G → S in AAL84638 (PubMed:11889553).Curated1
Sequence conflicti965Y → C in BAC15765 (PubMed:12526743).Curated1
Sequence conflicti993T → A in BAC15765 (PubMed:12526743).Curated1
Sequence conflicti1090R → G in BAC15765 (PubMed:12526743).Curated1
Sequence conflicti1110T → S in BAC15765 (PubMed:12526743).Curated1
Sequence conflicti1336P → H in AAL84638 (PubMed:11889553).Curated1
Sequence conflicti1619A → S in AAL84637 (PubMed:11889553).Curated1
Sequence conflicti1619A → S in BAC15765 (PubMed:12526743).Curated1
Sequence conflicti1860K → E in BAC15765 (PubMed:12526743).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0535861 – 245MKSPA…VVLDR → MSRDTEV in isoform 2. CuratedAdd BLAST245

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF484523 Genomic DNA Translation: AAL84637.1
AF484524 Genomic DNA Translation: AAL84638.1
AB081470 mRNA Translation: BAC15765.1 Different initiation.
AF430845 mRNA Translation: AAM21495.1 Frameshift.
UniGeneiMm.21135

Keywords - Coding sequence diversityi

Alternative promoter usage

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF484523 Genomic DNA Translation: AAL84637.1
AF484524 Genomic DNA Translation: AAL84638.1
AB081470 mRNA Translation: BAC15765.1 Different initiation.
AF430845 mRNA Translation: AAM21495.1 Frameshift.
UniGeneiMm.21135

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3C4BX-ray1.68A1648-1910[»]
3C4TX-ray2.80A1648-1910[»]
ProteinModelPortaliQ8R418
SMRiQ8R418
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

ComplexPortaliCPX-1073 RISC-loading complex, PRKRA variant
CPX-135 RISC-loading complex, TARBP2 variant
DIPiDIP-29721N
IntActiQ8R418, 4 interactors
STRINGi10090.ENSMUSP00000043676

PTM databases

iPTMnetiQ8R418
PhosphoSitePlusiQ8R418

Proteomic databases

EPDiQ8R418
PaxDbiQ8R418
PeptideAtlasiQ8R418
PRIDEiQ8R418

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

MGIiMGI:2177178 Dicer1

Phylogenomic databases

eggNOGiKOG0701 Eukaryota
COG0571 LUCA
COG1111 LUCA
HOGENOMiHOG000001567
HOVERGENiHBG107811
InParanoidiQ8R418
PhylomeDBiQ8R418

Enzyme and pathway databases

BRENDAi3.1.26.3 3474

Miscellaneous databases

EvolutionaryTraceiQ8R418
PROiPR:Q8R418
SOURCEiSearch...

Gene expression databases

CleanExiMM_DICER1

Family and domain databases

CDDicd00048 DSRM, 1 hit
cd00079 HELICc, 1 hit
cd00593 RIBOc, 2 hits
Gene3Di1.10.1520.10, 1 hit
3.30.160.380, 1 hit
HAMAPiMF_00104 RNase_III, 1 hit
InterProiView protein in InterPro
IPR038248 Dicer_dimer_sf
IPR005034 Dicer_dimerisation_dom
IPR014720 dsRBD_dom
IPR006935 Helicase/UvrB_N
IPR014001 Helicase_ATP-bd
IPR001650 Helicase_C
IPR027417 P-loop_NTPase
IPR003100 PAZ_dom
IPR036085 PAZ_dom_sf
IPR011907 RNase_III
IPR000999 RNase_III_dom
IPR036389 RNase_III_sf
PfamiView protein in Pfam
PF03368 Dicer_dimer, 1 hit
PF00271 Helicase_C, 1 hit
PF02170 PAZ, 1 hit
PF04851 ResIII, 1 hit
PF00636 Ribonuclease_3, 2 hits
SMARTiView protein in SMART
SM00487 DEXDc, 1 hit
SM00358 DSRM, 1 hit
SM00490 HELICc, 1 hit
SM00949 PAZ, 1 hit
SM00535 RIBOc, 2 hits
SUPFAMiSSF101690 SSF101690, 1 hit
SSF52540 SSF52540, 1 hit
SSF69065 SSF69065, 2 hits
PROSITEiView protein in PROSITE
PS51327 DICER_DSRBF, 1 hit
PS50137 DS_RBD, 1 hit
PS51192 HELICASE_ATP_BIND_1, 1 hit
PS51194 HELICASE_CTER, 1 hit
PS50821 PAZ, 1 hit
PS00517 RNASE_3_1, 1 hit
PS50142 RNASE_3_2, 2 hits
ProtoNetiSearch...

Entry informationi

Entry nameiDICER_MOUSE
AccessioniPrimary (citable) accession number: Q8R418
Secondary accession number(s): Q8R419
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 25, 2002
Last sequence update: September 1, 2009
Last modified: November 7, 2018
This is version 157 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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