Q8R418 (DICER_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Endoribonuclease Dicer
EC=3.1.26.-

Alternative name(s):
Double-strand-specific ribonuclease mDCR-1

Gene names

Name:	Dicer1
Synonyms:	Dicer, Mdcr

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1916 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Required for formation of the RNA induced silencing complex (RISC). Component of the RISC loading complex (RLC), also known as the micro-RNA (miRNA) loading complex (miRLC), which is composed of DICER1, EIF2C2/AGO2 and TARBP2. Within the RLC/miRLC, DICER1 and TARBP2 are required to process precursor miRNAs (pre-miRNAs) to mature miRNAs and then load them onto EIF2C2/AGO2. EIF2C2/AGO2 bound to the mature miRNA constitutes the minimal RISC and may subsequently dissociate from DICER1 and TARBP2. Also cleaves double-stranded RNA to produce short interfering RNAs (siRNAs) which target the selective destruction of complementary RNAs By similarity. Involved in cleaving double-stranded RNA in the RNA interference (RNAi) pathway. It produces 21 to 23 bp dsRNAs (siRNAs) which target the selective destruction of homologous RNAs.
Cofactor	Binds 2 magnesium or manganese ions per subunit Probable.
Subunit structure	Component of the RISC loading complex (RLC), or micro-RNA (miRNA) loading complex (miRLC), which is composed of DICER1, EIF2C2/AGO2 and TARBP2. Note that the trimeric RLC/miRLC is also referred to as RISC. Interacts with DHX9, EIF2C1, PIWIL1 and PRKRA. Associates with the 60S ribosome. Interacts with BCDIN3D By similarity.
Subcellular location	Cytoplasm By similarity.
Tissue specificity	Expressed in a wide variety of tissues.
Sequence similarities	Belongs to the helicase family. Dicer subfamily. Contains 1 Dicer dsRNA-binding fold domain. Contains 1 DRBM (double-stranded RNA-binding) domain. Contains 1 helicase ATP-binding domain. Contains 1 helicase C-terminal domain. Contains 1 PAZ domain. Contains 2 RNase III domains.
Caution	It is uncertain whether Met-1 or Met-11 is the initiator.
Sequence caution	The sequence AAM21495.1 differs from that shown. Reason: Frameshift at position 8. The sequence BAC15765.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	RNA-mediated gene silencing
Cellular component	Cytoplasm
Domain	Repeat
Ligand	ATP-binding Magnesium Manganese Metal-binding Nucleotide-binding RNA-binding
Molecular function	Endonuclease Helicase Hydrolase Nuclease
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	angiogenesis Inferred from mutant phenotype PubMed 15613470PubMed 17613256. Source: MGI apoptotic process Inferred from mutant phenotype PubMed 18184563. Source: MGI branching morphogenesis of an epithelial tube Inferred from mutant phenotype PubMed 16452165. Source: MGI cardiac muscle cell development Inferred from mutant phenotype PubMed 18256189. Source: MGI cerebral cortex development Inferred from mutant phenotype PubMed 18997113. Source: MGI defense response to virus Inferred from mutant phenotype PubMed 17613256. Source: MGI embryonic hindlimb morphogenesis Inferred from mutant phenotype PubMed 16319892. Source: MGI hair follicle cell proliferation Inferred from mutant phenotype PubMed 16682203. Source: MGI hair follicle morphogenesis Inferred from mutant phenotype PubMed 16682203. Source: MGI inner ear receptor cell development Inferred from mutant phenotype PubMed 19416898. Source: MGI intestinal epithelial cell development Inferred from genetic interaction PubMed 21307095. Source: MGI lung development Inferred from mutant phenotype PubMed 16452165. Source: MGI multicellular organism growth Inferred from mutant phenotype PubMed 16682203. Source: MGI negative regulation of Schwann cell proliferation Inferred from mutant phenotype PubMed 20805985. Source: BHF-UCL negative regulation of apoptotic process Inferred from mutant phenotype PubMed 16682203. Source: MGI negative regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype PubMed 20463238PubMed 20805985. Source: BHF-UCL nerve development Inferred from mutant phenotype PubMed 20463238. Source: BHF-UCL neuron projection morphogenesis Inferred from mutant phenotype PubMed 20463238. Source: BHF-UCL olfactory bulb interneuron differentiation Inferred from mutant phenotype PubMed 18184563. Source: MGI peripheral nervous system myelin formation Inferred from mutant phenotype PubMed 20463238PubMed 20805985. Source: BHF-UCL positive regulation of Schwann cell differentiation Inferred from mutant phenotype PubMed 20463238PubMed 20805985. Source: BHF-UCL positive regulation of miRNA metabolic process Inferred from mutant phenotype PubMed 20975942. Source: MGI positive regulation of myelination Inferred from mutant phenotype PubMed 20463238PubMed 20805985. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype PubMed 20805985. Source: BHF-UCL post-embryonic development Inferred from mutant phenotype PubMed 16682203PubMed 18997113. Source: MGI pre-miRNA processing Inferred from sequence or structural similarity. Source: UniProtKB production of siRNA involved in RNA interference Inferred from sequence or structural similarity. Source: UniProtKB rRNA catabolic process Inferred from electronic annotation. Source: InterPro regulation of Notch signaling pathway Inferred by curator PubMed 20805985. Source: BHF-UCL regulation of cell cycle Inferred from mutant phenotype PubMed 20708584. Source: MGI regulation of enamel mineralization Inferred from mutant phenotype PubMed 20102707. Source: MGI regulation of neuron differentiation Inferred from mutant phenotype PubMed 17761882PubMed 18997113. Source: MGI regulation of oligodendrocyte differentiation Inferred from mutant phenotype PubMed 20223197. Source: MGI regulation of protein phosphorylation Inferred from mutant phenotype PubMed 20805985. Source: BHF-UCL regulation of viral genome replication Inferred from mutant phenotype PubMed 17613256. Source: MGI spinal cord motor neuron differentiation Inferred from mutant phenotype PubMed 21338882. Source: MGI spindle assembly Inferred from mutant phenotype PubMed 17369397. Source: MGI spleen development Inferred from mutant phenotype PubMed 21307095. Source: MGI stem cell maintenance Inferred from mutant phenotype PubMed 14528307. Source: MGI targeting of mRNA for destruction involved in RNA interference Inferred from sequence or structural similarity. Source: UniProtKB zygote asymmetric cell division Inferred from mutant phenotype PubMed 17369397. Source: MGI
Cellular_component	RNA-induced silencing complex Inferred from sequence or structural similarity. Source: UniProtKB cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ATP-dependent helicase activity Inferred from electronic annotation. Source: InterPro double-stranded RNA binding Inferred from electronic annotation. Source: InterPro metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW miRNA binding Inferred from direct assay PubMed 18604195. Source: MGI ribonuclease III activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1916

1916

Endoribonuclease Dicer

PRO_0000180471

Regions

Domain

51 – 227

177

Helicase ATP-binding

Domain

433 – 602

170

Helicase C-terminal

Domain

630 – 722

93

Dicer dsRNA-binding fold

Domain

891 – 1042

152

PAZ

Domain

1276 – 1403

128

RNase III 1

Domain

1660 – 1818

159

RNase III 2

Domain

1843 – 1908

66

DRBM

Nucleotide binding

64 – 71

8

ATP By similarity

Region

256 – 595

340

Required for interaction with PRKRA and TARBP2 By similarity

Motif

175 – 178

4

DECH box

Sites

Metal binding

1316

1

Magnesium or manganese 1 By similarity

Metal binding

1395

1

Magnesium or manganese 1 By similarity

Metal binding

1398

1

Magnesium or manganese 1 By similarity

Metal binding

1699

1

Magnesium or manganese 2

Metal binding

1804

1

Magnesium or manganese 2

Metal binding

1807

1

Magnesium or manganese 2

Site

1800

1

Important for activity

Amino acid modifications

Modified residue

413

1

Phosphoserine By similarity

Modified residue

415

1

Phosphoserine By similarity

Modified residue

1016

1

Phosphoserine By similarity

Experimental info

Mutagenesis

1800

1

K → A, R, S or T: Loss of activity. Ref.4

Sequence conflict

1

1

M → L in BAC15765. Ref.2

Sequence conflict

107

1

A → C in AAM21495. Ref.3

Sequence conflict

167

1

S → P in BAC15765. Ref.2

Sequence conflict

289

1

H → Y in AAM21495. Ref.3

Sequence conflict

610

1

A → T in BAC15765. Ref.2

Sequence conflict

759

1

E → D in AAM21495. Ref.3

Sequence conflict

837

1

T → I in AAM21495. Ref.3

Sequence conflict

888

1

G → S in AAL84638. Ref.1

Sequence conflict

965

1

Y → C in BAC15765. Ref.2

Sequence conflict

993

1

T → A in BAC15765. Ref.2

Sequence conflict

1090

1

R → G in BAC15765. Ref.2

Sequence conflict

1110

1

T → S in BAC15765. Ref.2

Sequence conflict

1336

1

P → H in AAL84638. Ref.1

Sequence conflict

1619

1

A → S in AAL84637. Ref.1

Sequence conflict

1619

1

A → S in BAC15765. Ref.2

Sequence conflict

1860

1

K → E in BAC15765. Ref.2

Secondary structure

1

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1916

Helix Strand Turn

Details...

Helix

1649 – 1656

8

Turn

1657 – 1659

3

Helix

1660 – 1667

8

Helix

1674 – 1681

8

Helix

1696 – 1716

21

Helix

1723 – 1733

11

Helix

1736 – 1745

10

Helix

1748 – 1750

3

Helix

1757 – 1774

18

Helix

1800 – 1816

17

Helix

1821 – 1842

22

Helix

1847 – 1854

8

Turn

1856 – 1858

3

Beta strand

1859 – 1861

3

Beta strand

1872 – 1878

7

Turn

1879 – 1881

3

Beta strand

1882 – 1890

9

Helix

1891 – 1908

18

Sequences

	Sequence		Length	Mass (Da)
	Q8R418 [UniParc]. Last modified September 1, 2009. Version 3. Checksum: D97EA17922D7E79C	FASTA	1,916	216,821
	10 20 30 40 50 60 MKSPALQPLS MAGLQLMTPA SSPMGPFFGL PWQQEAIHDN IYTPRKYQVE LLEAALDHNT 70 80 90 100 110 120 IVCLNTGSGK TFIAVLLTKE LAHQIRGDLN PHAKRTVFLV NSANQVAQQV SAVRTHSDLK 130 140 150 160 170 180 VGEYSDLEVN ASWTKERWSQ EFTKHQVLIM TCYVALTVLK NGYLSLSDIN LLVFDECHLA 190 200 210 220 230 240 ILDHPYREIM KLCESCPSCP RILGLTASIL NGKCDPEELE EKIQKLERIL RSDAETATDL 250 260 270 280 290 300 VVLDRYTSQP CEIVVDCGPF TDRSGLYERL LMELEAALDF INDCNVAVHS KERDSTLISK 310 320 330 340 350 360 QILSDCRAVL VVLGPWCADK VAGMMVRELQ KYIKHEQEEL HRKFLLFTDT LLRKIHALCE 370 380 390 400 410 420 EYFSPASLDL KYVTPKVMKL LEILRKYKPY ERQQFESVEW YNNRNQDNYV SWSDSEDDDD 430 440 450 460 470 480 DEEIEEKEKP ETNFPSPFTN ILCGIIFVER RYTAVVLNRL IKEAGKQDPE LAYISSNFIT 490 500 510 520 530 540 GHGIGKNQPR SKQMEAEFRK QEEVLRKFRA HETNLLIATS VVEEGVDIPK CNLVVRFDLP 550 560 570 580 590 600 TEYRSYVQSK GRARAPISNY VMLADTDKIK SFEEDLKTYK AIEKILRNKC SKSADGAEAD 610 620 630 640 650 660 VHAGVDDEDA FPPYVLRPDD GGPRVTINTA IGHINRYCAR LPSDPFTHLA PKCRTRELPD 670 680 690 700 710 720 GTFYSTLYLP INSPLRASIV GPPMDSVRLA ERVVALICCE KLHKIGELDE HLMPVGKETV 730 740 750 760 770 780 KYEEELDLHD EEETSVPGRP GSTKRRQCYP KAIPECLRES YPKPDQPCYL YVIGMVLTTP 790 800 810 820 830 840 LPDELNFRRR KLYPPEDTTR CFGILTAKPI PQIPHFPVYT RSGEVTISIE LKKSGFTLSQ 850 860 870 880 890 900 QMLELITRLH QYIFSHILRL EKPALEFKPT GAESAYCVLP LNVVNDSGTL DIDFKFMEDI 910 920 930 940 950 960 EKSEARIGIP STKYSKETPF VFKLEDYQDA VIIPRYRNFD QPHRFYVADV YTDLTPLSKF 970 980 990 1000 1010 1020 PSPEYETFAE YYKTKYNLDL TNLNQPLLDV DHTSSRLNLL TPRHLNQKGK ALPLSSAEKR 1030 1040 1050 1060 1070 1080 KAKWESLQNK QILVPELCAI HPIPASLWRK AVCLPSILYR LHCLLTAEEL RAQTASDAGV 1090 1100 1110 1120 1130 1140 GVRSLPVDFR YPNLDFGWKK SIDSKSFIST CNSSLAESDN YCKHSTTVVP EHAAHQGATR 1150 1160 1170 1180 1190 1200 PSLENHDQMS VNCKRLPAES PAKLQSEVST DLTAINGLSY NKNLANGSYD LVNRDFCQGN 1210 1220 1230 1240 1250 1260 QLNYFKQEIP VQPTTSYPIQ NLYNYENQPK PSNECPLLSN TYLDGNANTS TSDGSPAVST 1270 1280 1290 1300 1310 1320 MPAMMNAVKA LKDRMDSEQS PSVGYSSRTL GPNPGLILQA LTLSNASDGF NLERLEMLGD 1330 1340 1350 1360 1370 1380 SFLKHAITTY LFCTYPDAHE GRLSYMRSKK VSNCNLYRLG KKKGLPSRMV VSIFDPPVNW 1390 1400 1410 1420 1430 1440 LPPGYVVNQD KSNSEKWEKD EMTKDCLLAN GKLGEACEEE EDLTWRAPKE EAEDEDDFLE 1450 1460 1470 1480 1490 1500 YDQEHIQFID SMLMGSGAFV RKISLSPFSA SDSAYEWKMP KKASLGSMPF ASGLEDFDYS 1510 1520 1530 1540 1550 1560 SWDAMCYLDP SKAVEEDDFV VGFWNPSEEN CGVDTGKQSI SYDLHTEQCI ADKSIADCVE 1570 1580 1590 1600 1610 1620 ALLGCYLTSC GERAAQLFLC SLGLKVLPVI KRTSREKALD PAQENGSSQQ KSLSGSCAAP 1630 1640 1650 1660 1670 1680 VGPRSSAGKD LEYGCLKIPP RCMFDHPDAE KTLNHLISGF ETFEKKINYR FKNKAYLLQA 1690 1700 1710 1720 1730 1740 FTHASYHYNT ITDCYQRLEF LGDAILDYLI TKHLYEDPRQ HSPGVLTDLR SALVNNTIFA 1750 1760 1770 1780 1790 1800 SLAVKYDYHK YFKAVSPELF HVIDDFVKFQ LEKNEMQGMD SELRRSEEDE EKEEDIEVPK 1810 1820 1830 1840 1850 1860 AMGDIFESLA GAIYMDSGMS LEVVWQVYYP MMQPLIEKFS ANVPRSPVRE LLEMEPETAK 1870 1880 1890 1900 1910 FSPAERTYDG KVRVTVEVVG KGKFKGVGRS YRIAKSAAAR RALRSLKANQ PQVPNS

References

[1]	"Molecular characterization of a mouse cDNA encoding Dicer, a ribonuclease III ortholog involved in RNA interference." Nicholson R.H., Nicholson A.W. Mamm. Genome 13:67-73(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 17-1916. Strain: C57BL/6J.
[2]	"Short-interfering-RNA-mediated gene silencing in mammalian cells requires Dicer and eIF2C translation initiation factors." Doi N., Zenno S., Ueda R., Ohki-Hamazaki H., Ui-Tei K., Saigo K. Curr. Biol. 13:41-46(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"RNAi and expression of retrotransposons MuERV-L and IAP in preimplantation mouse embryos." Svoboda P., Stein P., Anger M., Bernstein E., Hannon G.J., Schultz R.M. Dev. Biol. 269:276-285(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Czech II.
[4]	"Structural and biochemical insights into the dicing mechanism of mouse Dicer: a conserved lysine is critical for dsRNA cleavage." Du Z., Lee J.K., Tjhen R., Stroud R.M., James T.L. Proc. Natl. Acad. Sci. U.S.A. 105:2391-2396(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.68 ANGSTROMS) OF 1647-1910, MUTAGENESIS OF LYS-1800.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00227881.

UniGene

Mm.21135.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3C4B	X-ray	1.68	A	1647-1910	[»]
3C4T	X-ray	2.80	A	1647-1910	[»]

ProteinModelPortal

Q8R418.

SMR

Q8R418. Positions 1648-1910.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29721N.

IntAct

Q8R418. 1 interaction.

PTM databases

PhosphoSite

Q8R418.

Proteomic databases

PaxDb

Q8R418.

PRIDE

Q8R418.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

UCSC

uc007oxi.1. mouse.

Organism-specific databases

MGI

MGI:2177178. Dicer1.

Phylogenomic databases

eggNOG

COG1111.

HOGENOM

HOG000001567.

HOVERGEN

HBG107811.

InParanoid

Q8R419.

OrthoDB

EOG4JDH5W.

Gene expression databases

CleanEx

MM_DICER1.

Genevestigator

Q8R418.

GermOnline

ENSMUSG00000041415. Mus musculus.

Family and domain databases

Gene3D

1.10.1520.10. 4 hits.
3.30.160.20. 1 hit.

InterPro

IPR005034. Dicer_dsRNA_binding_fold.
IPR011545. DNA/RNA_helicase_DEAD/DEAH_N.
IPR001159. Ds-RNA-bd.
IPR014720. dsRNA-bd-like_dom.
IPR014001. Helicase_ATP-bd.
IPR001650. Helicase_C.
IPR003100. PAZ.
IPR011907. RNase_III.
IPR000999. RNase_III_dom.
[Graphical view]

Pfam

PF00270. DEAD. 1 hit.
PF03368. dsRNA_bind. 1 hit.
PF00271. Helicase_C. 1 hit.
PF02170. PAZ. 1 hit.
PF00636. Ribonuclease_3. 2 hits.
[Graphical view]

SMART

SM00487. DEXDc. 1 hit.
SM00358. DSRM. 1 hit.
SM00490. HELICc. 1 hit.
SM00949. PAZ. 1 hit.
SM00535. RIBOc. 2 hits.
[Graphical view]

SUPFAM

SSF101690. PAZ. 1 hit.
SSF69065. RNase_III. 2 hits.

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.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q8R418.

SOURCE

Search...

Entry information

Entry name

DICER_MOUSE

Accession

Primary (citable) accession number: Q8R418
Secondary accession number(s): Q8R419

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 25, 2002
Last sequence update:	September 1, 2009
Last modified:	May 1, 2013
This is version 107 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program