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Q9UPY3 (DICER_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 134. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Endoribonuclease Dicer

EC=3.1.26.3
Alternative name(s):
Helicase with RNase motif
Short name=Helicase MOI
Gene names
Name:DICER1
Synonyms:DICER, HERNA, KIAA0928
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1922 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.10 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.23 Ref.25

Catalytic activity

Endonucleolytic cleavage to 5'-phosphomonoester. Ref.10 Ref.31

Cofactor

Binds 2 magnesium or manganese ions per subunit Probable. Ref.31

Subunit structure

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. Associates with the 60S ribosome. Interacts with BCDIN3D. Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.23 Ref.29 Ref.31

Subcellular location

Cytoplasm Ref.17.

Involvement in disease

Pleuropulmonary blastoma (PPB) [MIM:601200]: A rare pediatric intrathoracic neoplasm. The tumor arises from the lung, pleura, or both, and appears to be purely mesenchymal in phenotype. It lacks malignant epithelial elements, a feature that distinguishes it from the classic adult-type pulmonary blastoma. It arises during fetal lung development and is often part of an inherited cancer syndrome. The tumor contain both epithelial and mesenchymal cells. Early in tumorigenesis, cysts form in lung airspaces, and these cysts are lined with benign-appearing epithelium. Mesenchymal cells susceptible to malignant transformation reside within the cyst walls and form a dense layer beneath the epithelial lining. In a subset of patients, overgrowth of the mesenchymal cells produces a sarcoma, a transition that is associated with a poorer prognosis. Some patients have multilocular cystic nephroma, a benign kidney tumor.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.32

Goiter multinodular 1, with or without Sertoli-Leydig cell tumors (MNG1) [MIM:138800]: A common disorder characterized by nodular overgrowth of the thyroid gland. Some individuals may also develop Sertoli-Leydig cell tumors, usually of the ovary.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.33

Rhabdomyosarcoma, embryonal, 2 (RMSE2) [MIM:180295]: A form of rhabdomyosarcoma, a highly malignant tumor of striated muscle derived from primitive mesenchymal cells and exhibiting differentiation along rhabdomyoblastic lines. Rhabdomyosarcoma is one of the most frequently occurring soft tissue sarcomas and the most common in children. It occurs in four forms: alveolar, pleomorphic, embryonal and botryoidal rhabdomyosarcomas.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.27

DICER1 mutations have been found in uterine cervix embryonal rhabdomyosarcoma, primitive neuroectodermal tumor, Wilms tumor, pulmonary sequestration and juvenile intestinal polyp (Ref.27). Somatic missense mutations affecting the RNase IIIb domain of DICER1 are common in non-epithelial ovarian tumors. These mutations do not abolish DICER1 function but alter it in specific cell types, a novel mechanism through which perturbation of microRNA processing may be oncogenic (Ref.30).

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 CAB38857.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Biological processRNA-mediated gene silencing
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
   DomainRepeat
   LigandATP-binding
Magnesium
Manganese
Metal-binding
Nucleotide-binding
RNA-binding
   Molecular functionEndonuclease
Helicase
Hydrolase
Nuclease
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processRNA phosphodiester bond hydrolysis

Inferred from direct assay PubMed 12560494. Source: GOC

RNA phosphodiester bond hydrolysis, endonucleolytic

Inferred from direct assay PubMed 12560494. Source: GOC

angiogenesis

Inferred from electronic annotation. Source: Ensembl

branching morphogenesis of an epithelial tube

Inferred from electronic annotation. Source: Ensembl

cardiac muscle cell development

Inferred from electronic annotation. Source: Ensembl

cerebral cortex development

Inferred from electronic annotation. Source: Ensembl

defense response to virus

Inferred from electronic annotation. Source: Ensembl

embryonic hindlimb morphogenesis

Inferred from electronic annotation. Source: Ensembl

gene expression

Traceable author statement. Source: Reactome

hair follicle cell proliferation

Inferred from electronic annotation. Source: Ensembl

hair follicle morphogenesis

Inferred from electronic annotation. Source: Ensembl

inner ear receptor cell development

Inferred from electronic annotation. Source: Ensembl

intestinal epithelial cell development

Inferred from electronic annotation. Source: Ensembl

lung development

Inferred from electronic annotation. Source: Ensembl

multicellular organism growth

Inferred from electronic annotation. Source: Ensembl

negative regulation of Schwann cell proliferation

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: BHF-UCL

nerve development

Inferred from sequence or structural similarity. Source: BHF-UCL

neuron projection morphogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

olfactory bulb interneuron differentiation

Inferred from electronic annotation. Source: Ensembl

peripheral nervous system myelin formation

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of Schwann cell differentiation

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of miRNA metabolic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of myelination

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

post-embryonic development

Inferred from electronic annotation. Source: Ensembl

pre-miRNA processing

Inferred from direct assay Ref.16. Source: UniProtKB

production of miRNAs involved in gene silencing by miRNA

Inferred from sequence or structural similarity. Source: BHF-UCL

production of siRNA involved in RNA interference

Inferred from direct assay Ref.16Ref.18. Source: UniProtKB

regulation of cell cycle

Inferred from electronic annotation. Source: Ensembl

regulation of enamel mineralization

Inferred from electronic annotation. Source: Ensembl

regulation of neuron differentiation

Inferred from electronic annotation. Source: Ensembl

regulation of oligodendrocyte differentiation

Inferred from electronic annotation. Source: Ensembl

regulation of viral genome replication

Inferred from electronic annotation. Source: Ensembl

spinal cord motor neuron differentiation

Inferred from electronic annotation. Source: Ensembl

spindle assembly

Inferred from electronic annotation. Source: Ensembl

spleen development

Inferred from electronic annotation. Source: Ensembl

stem cell maintenance

Inferred from electronic annotation. Source: Ensembl

targeting of mRNA for destruction involved in RNA interference

Inferred from mutant phenotype Ref.16Ref.18. Source: UniProtKB

zygote asymmetric cell division

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentRISC complex

Inferred from direct assay Ref.16. Source: UniProtKB

axon

Inferred from electronic annotation. Source: Ensembl

cytosol

Traceable author statement. Source: Reactome

dendrite

Inferred from electronic annotation. Source: Ensembl

endoplasmic reticulum-Golgi intermediate compartment

Inferred from electronic annotation. Source: Ensembl

growth cone

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

ATP-dependent helicase activity

Inferred from electronic annotation. Source: InterPro

double-stranded RNA binding

Inferred from direct assay PubMed 12411504. Source: UniProtKB

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

miRNA binding

Inferred from electronic annotation. Source: Ensembl

ribonuclease III activity

Inferred from direct assay PubMed 12560494. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9UPY3-1)

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.
Isoform 2 (identifier: Q9UPY3-2)

Also known as: t-Dicer;

The sequence of this isoform differs from the canonical sequence as follows:
     1789-1922: LRRSEEDEEK...KANQPQVPNS → KSFLQMYPVP...TTGRSESLWK

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 19221922Endoribonuclease Dicer
PRO_0000180470

Regions

Domain51 – 227177Helicase ATP-binding
Domain433 – 602170Helicase C-terminal
Domain630 – 72293Dicer dsRNA-binding fold
Domain891 – 1042152PAZ
Domain1276 – 1403128RNase III 1
Domain1666 – 1824159RNase III 2
Domain1849 – 191466DRBM
Nucleotide binding64 – 718ATP By similarity
Region256 – 595340Required for interaction with PRKRA and TARBP2
Motif175 – 1784DECH box

Sites

Metal binding13161Magnesium or manganese 1 By similarity
Metal binding13951Magnesium or manganese 1 By similarity
Metal binding13981Magnesium or manganese 1 By similarity
Metal binding17051Magnesium or manganese 2
Metal binding18101Magnesium or manganese 2
Metal binding18131Magnesium or manganese 2
Site18061Important for activity By similarity

Amino acid modifications

Modified residue4131Phosphoserine Ref.28
Modified residue4151Phosphoserine Ref.28
Modified residue10161Phosphoserine Ref.22

Natural variations

Alternative sequence1789 – 1922134LRRSE…QVPNS → KSFLQMYPVPLCENCLKWNQ KLPNLARLRELTTGRSESLW K in isoform 2.
VSP_042832
Natural variant8391S → F in MNG1. Ref.33
VAR_065301
Natural variant15831L → R in PPB. Ref.32
VAR_063150
Natural variant17051E → K in non-epithelial ovarian tumor; somatic mutation; results in reduced RNase IIIb activity but retention of RNase IIIa activity. Ref.30
VAR_067091
Natural variant17091D → E in non-epithelial ovarian tumor; somatic mutation; results in reduced RNase IIIb activity but retention of RNase IIIa activity. Ref.30
VAR_067092
Natural variant17091D → G in non-epithelial ovarian tumor; somatic mutation. Ref.30
VAR_067093
Natural variant17091D → N in non-epithelial ovarian tumor; somatic mutation; results in reduced RNase IIIb activity but retention of RNase IIIa activity. Ref.30
VAR_067094
Natural variant18101D → H in non-epithelial ovarian tumor; somatic mutation. Ref.30
VAR_067095
Natural variant18101D → N in non-epithelial ovarian tumor; somatic mutation. Ref.30
VAR_067096
Natural variant18101D → Y in non-epithelial ovarian tumor; somatic mutation. Ref.30
VAR_067097
Natural variant18131E → G in non-epithelial ovarian tumor; somatic mutation. Ref.30
VAR_067098
Natural variant18131E → K in non-epithelial ovarian tumor; somatic mutation. Ref.30
VAR_067099
Natural variant18131E → Q in non-epithelial ovarian tumor; somatic mutation. Ref.30
VAR_067100

Experimental info

Mutagenesis9601F → A: 2-fold decrease in activity.
Mutagenesis9711Y → A: 10-fold decrease in activity; when associated with Y-972.
Mutagenesis9721Y → A: 10-fold decrease in activity; when associated with Y-971.
Mutagenesis10361E → A: 5-fold decrease in activity.
Mutagenesis13131E → A: No effect on activity. Ref.10
Mutagenesis13201D → A: Decreased activity. Loss of activity; when associated with D-1709. Ref.10
Mutagenesis13401E → A: No effect on activity. Ref.10
Mutagenesis14441E → A: Decreased activity. Loss of activity; when associated with E-1813. Ref.10
Mutagenesis17021Q → A: No effect on activity. Ref.10
Mutagenesis17091D → A: Decreased activity. Loss of activity; when associated with D-1320. Ref.10
Mutagenesis17291P → E: No effect on activity. Ref.10
Mutagenesis18131E → A: Decreased activity. Loss of activity; when associated with E-1444. Ref.10
Sequence conflict75 – 9016VLLTK…RGDFS → STTLLKSCLYLDLGETSA in BAA78691. Ref.1
Sequence conflict1891I → F in BAA78691. Ref.1
Sequence conflict1951N → I in BAA78691. Ref.1
Sequence conflict2141C → W in BAA78691. Ref.1
Sequence conflict2181E → D in BAA78691. Ref.1
Sequence conflict2231I → F in BAA78691. Ref.1
Sequence conflict393 – 3942QQ → HS in BAA78691. Ref.1
Sequence conflict492 – 4932KQ → NT in BAA78691. Ref.1
Sequence conflict6091D → H in BAA78691. Ref.1

Secondary structure

.................... 1922
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified September 1, 2009. Version 3.
Checksum: 9452B96A601D4551

FASTA1,922218,682
        10         20         30         40         50         60 
MKSPALQPLS MAGLQLMTPA SSPMGPFFGL PWQQEAIHDN IYTPRKYQVE LLEAALDHNT 

        70         80         90        100        110        120 
IVCLNTGSGK TFIAVLLTKE LSYQIRGDFS RNGKRTVFLV NSANQVAQQV SAVRTHSDLK 

       130        140        150        160        170        180 
VGEYSNLEVN ASWTKERWNQ EFTKHQVLIM TCYVALNVLK NGYLSLSDIN LLVFDECHLA 

       190        200        210        220        230        240 
ILDHPYREIM KLCENCPSCP RILGLTASIL NGKCDPEELE EKIQKLEKIL KSNAETATDL 

       250        260        270        280        290        300 
VVLDRYTSQP CEIVVDCGPF TDRSGLYERL LMELEEALNF INDCNISVHS KERDSTLISK 

       310        320        330        340        350        360 
QILSDCRAVL VVLGPWCADK VAGMMVRELQ KYIKHEQEEL HRKFLLFTDT FLRKIHALCE 

       370        380        390        400        410        420 
EHFSPASLDL KFVTPKVIKL LEILRKYKPY ERQQFESVEW YNNRNQDNYV SWSDSEDDDE 

       430        440        450        460        470        480 
DEEIEEKEKP ETNFPSPFTN ILCGIIFVER RYTAVVLNRL IKEAGKQDPE LAYISSNFIT 

       490        500        510        520        530        540 
GHGIGKNQPR NKQMEAEFRK QEEVLRKFRA HETNLLIATS IVEEGVDIPK CNLVVRFDLP 

       550        560        570        580        590        600 
TEYRSYVQSK GRARAPISNY IMLADTDKIK SFEEDLKTYK AIEKILRNKC SKSVDTGETD 

       610        620        630        640        650        660 
IDPVMDDDDV FPPYVLRPDD GGPRVTINTA IGHINRYCAR LPSDPFTHLA PKCRTRELPD 

       670        680        690        700        710        720 
GTFYSTLYLP INSPLRASIV GPPMSCVRLA ERVVALICCE KLHKIGELDD HLMPVGKETV 

       730        740        750        760        770        780 
KYEEELDLHD EEETSVPGRP GSTKRRQCYP KAIPECLRDS YPRPDQPCYL YVIGMVLTTP 

       790        800        810        820        830        840 
LPDELNFRRR KLYPPEDTTR CFGILTAKPI PQIPHFPVYT RSGEVTISIE LKKSGFMLSL 

       850        860        870        880        890        900 
QMLELITRLH QYIFSHILRL EKPALEFKPT DADSAYCVLP LNVVNDSSTL DIDFKFMEDI 

       910        920        930        940        950        960 
EKSEARIGIP STKYTKETPF 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 
GVRSLPADFR YPNLDFGWKK SIDSKSFISI SNSSSAENDN YCKHSTIVPE NAAHQGANRT 

      1150       1160       1170       1180       1190       1200 
SSLENHDQMS VNCRTLLSES PGKLHVEVSA DLTAINGLSY NQNLANGSYD LANRDFCQGN 

      1210       1220       1230       1240       1250       1260 
QLNYYKQEIP VQPTTSYSIQ NLYSYENQPQ PSDECTLLSN KYLDGNANKS TSDGSPVMAV 

      1270       1280       1290       1300       1310       1320 
MPGTTDTIQV LKGRMDSEQS PSIGYSSRTL GPNPGLILQA LTLSNASDGF NLERLEMLGD 

      1330       1340       1350       1360       1370       1380 
SFLKHAITTY LFCTYPDAHE GRLSYMRSKK VSNCNLYRLG KKKGLPSRMV VSIFDPPVNW 

      1390       1400       1410       1420       1430       1440 
LPPGYVVNQD KSNTDKWEKD EMTKDCMLAN GKLDEDYEEE DEEEESLMWR APKEEADYED 

      1450       1460       1470       1480       1490       1500 
DFLEYDQEHI RFIDNMLMGS GAFVKKISLS PFSTTDSAYE WKMPKKSSLG SMPFSSDFED 

      1510       1520       1530       1540       1550       1560 
FDYSSWDAMC YLDPSKAVEE DDFVVGFWNP SEENCGVDTG KQSISYDLHT EQCIADKSIA 

      1570       1580       1590       1600       1610       1620 
DCVEALLGCY LTSCGERAAQ LFLCSLGLKV LPVIKRTDRE KALCPTRENF NSQQKNLSVS 

      1630       1640       1650       1660       1670       1680 
CAAASVASSR SSVLKDSEYG CLKIPPRCMF DHPDADKTLN HLISGFENFE KKINYRFKNK 

      1690       1700       1710       1720       1730       1740 
AYLLQAFTHA SYHYNTITDC YQRLEFLGDA ILDYLITKHL YEDPRQHSPG VLTDLRSALV 

      1750       1760       1770       1780       1790       1800 
NNTIFASLAV KYDYHKYFKA VSPELFHVID DFVQFQLEKN EMQGMDSELR RSEEDEEKEE 

      1810       1820       1830       1840       1850       1860 
DIEVPKAMGD IFESLAGAIY MDSGMSLETV WQVYYPMMRP LIEKFSANVP RSPVRELLEM 

      1870       1880       1890       1900       1910       1920 
EPETAKFSPA ERTYDGKVRV TVEVVGKGKF KGVGRSYRIA KSAAARRALR SLKANQPQVP 


NS 

« Hide

Isoform 2 (t-Dicer) [UniParc].

Checksum: 8F52FAB99C876358
Show »

FASTA1,829208,448

References

« Hide 'large scale' references
[1]"Molecular cloning and characterization of a novel human gene (HERNA) which encodes a putative RNA-helicase."
Matsuda S., Ichigotani Y., Okuda T., Irimura T., Nakatsugawa S., Hamaguchi M.
Biochim. Biophys. Acta 1490:163-169(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"A novel splice variant of the human dicer gene is expressed in neuroblastoma cells."
Potenza N., Papa U., Scaruffi P., Mosca N., Tonini G.P., Russo A.
FEBS Lett. 584:3452-3457(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING.
Tissue: Neuroblastoma.
[3]"RNA binding and processing by recombinant human Dicer."
Provost P., Dishart D., Doucet D., Hermansson A., Frendewey D., Samuelsson B., Radmark O.
Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Lung.
[4]"Prediction of the coding sequences of unidentified human genes. XIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
DNA Res. 6:63-70(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[5]"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones."
Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.
DNA Res. 9:99-106(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SEQUENCE REVISION.
[6]"The DNA sequence and analysis of human chromosome 14."
Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. expand/collapse author list , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[9]"Interaction of 5-lipoxygenase with cellular proteins."
Provost P., Samuelsson B., Radmark O.
Proc. Natl. Acad. Sci. U.S.A. 96:1881-1885(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1248-1922 (ISOFORM 1).
Tissue: Lung.
[10]"Single processing center models for human Dicer and bacterial RNase III."
Zhang H., Kolb F.A., Jaskiewicz L., Westhof E., Filipowicz W.
Cell 118:57-68(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF GLU-1313; ASP-1320; GLU-1340; GLU-1444; GLN-1702; ASP-1709; PRO-1729 AND GLU-1813.
[11]"Characterization of the interactions between mammalian PAZ PIWI domain proteins and Dicer."
Tahbaz N., Kolb F.A., Zhang H., Jaronczyk K., Filipowicz W., Hobman T.C.
EMBO Rep. 5:189-194(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PIWIL1.
[12]"Human RISC couples microRNA biogenesis and posttranscriptional gene silencing."
Gregory R.I., Chendrimada T.P., Cooch N., Shiekhattar R.
Cell 123:631-640(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH AGO2 AND TARBP2.
[13]"Identification of novel argonaute-associated proteins."
Meister G., Landthaler M., Peters L., Chen P.Y., Urlaub H., Luehrmann R., Tuschl T.
Curr. Biol. 15:2149-2155(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, INTERACTION WITH AGO1 AND AGO2.
[14]"TRBP, a regulator of cellular PKR and HIV-1 virus expression, interacts with Dicer and functions in RNA silencing."
Haase A.D., Jaskiewicz L., Zhang H., Laine S., Sack R., Gatignol A., Filipowicz W.
EMBO Rep. 6:961-967(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH TARBP2.
[15]"A human, ATP-independent, RISC assembly machine fueled by pre-miRNA."
Maniataki E., Mourelatos Z.
Genes Dev. 19:2979-2990(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH AGO2.
[16]"TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing."
Chendrimada T.P., Gregory R.I., Kumaraswamy E., Norman J., Cooch N., Nishikura K., Shiekhattar R.
Nature 436:740-744(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, INTERACTION WITH AGO2 AND TARBP2.
[17]"The role of PACT in the RNA silencing pathway."
Lee Y., Hur I., Park S.-Y., Kim Y.-K., Suh M.R., Kim V.N.
EMBO J. 25:522-532(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH PRKRA AND TARBP2, SUBCELLULAR LOCATION.
[18]"Human TRBP and PACT directly interact with each other and associate with dicer to facilitate the production of small interfering RNA."
Kok K.H., Ng M.-H., Ching Y.-P., Jin D.-Y.
J. Biol. Chem. 282:17649-17657(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH PRKRA AND TARBP2.
[19]"RNA helicase A interacts with RISC in human cells and functions in RISC loading."
Robb G.B., Rana T.M.
Mol. Cell 26:523-537(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DHX9.
[20]"MicroRNA silencing through RISC recruitment of eIF6."
Chendrimada T.P., Finn K.J., Ji X., Baillat D., Gregory R.I., Liebhaber S.A., Pasquinelli A.E., Shiekhattar R.
Nature 447:823-828(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH AGO2; EIF6; MOV10 AND TARBP2, ASSOCIATION WITH THE 60S RIBOSOME.
[21]"Prolyl 4-hydroxylation regulates Argonaute 2 stability."
Qi H.H., Ongusaha P.P., Myllyharju J., Cheng D., Pakkanen O., Shi Y., Lee S.W., Peng J., Shi Y.
Nature 455:421-424(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH AGO2.
[22]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1016, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[23]"In vitro reconstitution of the human RISC-loading complex."
MacRae I.J., Ma E., Zhou M., Robinson C.V., Doudna J.A.
Proc. Natl. Acad. Sci. U.S.A. 105:512-517(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, INTERACTION WITH AGO2 AND TARBP2.
[24]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[25]"A TARBP2 mutation in human cancer impairs microRNA processing and DICER1 function."
Melo S.A., Ropero S., Moutinho C., Aaltonen L.A., Yamamoto H., Calin G.A., Rossi S., Fernandez A.F., Carneiro F., Oliveira C., Ferreira B., Liu C.-G., Villanueva A., Capella G., Schwartz S. Jr., Shiekhattar R., Esteller M.
Nat. Genet. 41:365-370(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[26]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[27]"Extending the phenotypes associated with DICER1 mutations."
Foulkes W.D., Bahubeshi A., Hamel N., Pasini B., Asioli S., Baynam G., Choong C.S., Charles A., Frieder R.P., Dishop M.K., Graf N., Ekim M., Bouron-Dal Soglio D., Arseneau J., Young R.H., Sabbaghian N., Srivastava A., Tischkowitz M.D., Priest J.R.
Hum. Mutat. 32:1381-1384(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMET IN RMSE2.
[28]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-413 AND SER-415, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[29]"Human RNA methyltransferase BCDIN3D regulates microRNA processing."
Xhemalce B., Robson S.C., Kouzarides T.
Cell 151:278-288(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH BCDIN3D.
[30]"Recurrent somatic DICER1 mutations in nonepithelial ovarian cancers."
Heravi-Moussavi A., Anglesio M.S., Cheng S.W., Senz J., Yang W., Prentice L., Fejes A.P., Chow C., Tone A., Kalloger S.E., Hamel N., Roth A., Ha G., Wan A.N., Maines-Bandiera S., Salamanca C., Pasini B., Clarke B.A. expand/collapse author list , Lee A.F., Lee C.H., Zhao C., Young R.H., Aparicio S.A., Sorensen P.H., Woo M.M., Boyd N., Jones S.J., Hirst M., Marra M.A., Gilks B., Shah S.P., Foulkes W.D., Morin G.B., Huntsman D.G.
N. Engl. J. Med. 366:234-242(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN NON-EPITHELIAL OVARIAN TUMORS, VARIANTS LYS-1705; ASN-1709; GLU-1709; GLY-1709; HIS-1810; TYR-1810; ASN-1810; GLN-1813; GLY-1813 AND LYS-1813, CHARACTERIZATION OF VARIANTS LYS-1705; ASN-1709 AND GLU-1709.
[31]"Homodimeric structure and double-stranded RNA cleavage activity of the C-terminal RNase III domain of human dicer."
Takeshita D., Zenno S., Lee W.C., Nagata K., Saigo K., Tanokura M.
J. Mol. Biol. 374:106-120(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1660-1852, CATALYTIC ACTIVITY, COFACTOR, SUBUNIT.
[32]"DICER1 mutations in familial pleuropulmonary blastoma."
Hill D.A., Ivanovich J., Priest J.R., Gurnett C.A., Dehner L.P., Desruisseau D., Jarzembowski J.A., Wikenheiser-Brokamp K.A., Suarez B.K., Whelan A.J., Williams G., Bracamontes D., Messinger Y., Goodfellow P.J.
Science 325:965-965(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PPB ARG-1583.
[33]"DICER1 mutations in familial multinodular goiter with and without ovarian Sertoli-Leydig cell tumors."
Rio Frio T., Bahubeshi A., Kanellopoulou C., Hamel N., Niedziela M., Sabbaghian N., Pouchet C., Gilbert L., O'Brien P.K., Serfas K., Broderick P., Houlston R.S., Lesueur F., Bonora E., Muljo S., Schimke R.N., Bouron-Dal Soglio D., Arseneau J. expand/collapse author list , Schultz K.A., Priest J.R., Nguyen V.H., Harach H.R., Livingston D.M., Foulkes W.D., Tischkowitz M.
JAMA 305:68-77(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MNG1 PHE-839.
+Additional computationally mapped references.

Web resources

Protein Spotlight

The dark side of RNA - Issue 87 of October 2007

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB028449 mRNA. Translation: BAA78691.1.
HM595745 mRNA. Translation: ADK25182.1.
AJ132261 mRNA. Translation: CAB38857.2. Different initiation.
AB023145 mRNA. Translation: BAA76772.2.
AL356017 Genomic DNA. No translation available.
AL390254 Genomic DNA. No translation available.
CH471061 Genomic DNA. Translation: EAW81596.1.
BC150287 mRNA. Translation: AAI50288.1.
RefSeqNP_001182502.1. NM_001195573.1.
NP_001258211.1. NM_001271282.1.
NP_085124.2. NM_030621.3.
NP_803187.1. NM_177438.2.
UniGeneHs.87889.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2EB1X-ray2.00A/B/C1660-1842[»]
4NGBX-ray2.25A765-1065[»]
4NGCX-ray2.10A765-1065[»]
4NGDX-ray1.96A765-1065[»]
4NGFX-ray3.10A/B/C/D765-1065[»]
4NGGX-ray2.60A765-1065[»]
4NH3X-ray2.62A765-1065[»]
4NH5X-ray2.55A765-1065[»]
4NH6X-ray2.55A765-1065[»]
4NHAX-ray3.40A765-1065[»]
ProteinModelPortalQ9UPY3.
SMRQ9UPY3. Positions 42-722, 925-1042, 1293-1370, 1654-1916.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116978. 32 interactions.
DIPDIP-29664N.
IntActQ9UPY3. 20 interactions.
MINTMINT-1957525.
STRING9606.ENSP00000343745.

Chemistry

ChEMBLCHEMBL2311232.

PTM databases

PhosphoSiteQ9UPY3.

Polymorphism databases

DMDM257051056.

Proteomic databases

PaxDbQ9UPY3.
PRIDEQ9UPY3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000343455; ENSP00000343745; ENSG00000100697. [Q9UPY3-1]
ENST00000393063; ENSP00000376783; ENSG00000100697. [Q9UPY3-1]
ENST00000526495; ENSP00000437256; ENSG00000100697. [Q9UPY3-1]
ENST00000527414; ENSP00000435681; ENSG00000100697. [Q9UPY3-1]
ENST00000541352; ENSP00000444719; ENSG00000100697. [Q9UPY3-2]
GeneID23405.
KEGGhsa:23405.
UCSCuc001ydv.3. human. [Q9UPY3-1]
uc021sbc.1. human. [Q9UPY3-2]

Organism-specific databases

CTD23405.
GeneCardsGC14M095552.
HGNCHGNC:17098. DICER1.
HPAHPA000694.
MIM138800. phenotype.
180295. phenotype.
601200. phenotype.
606241. gene.
neXtProtNX_Q9UPY3.
Orphanet276399. Familial multinodular goiter.
99916. Ovarian malignant Sertoli-Leydig cell tumor.
284343. Pleuropulmonary blastoma family tumor susceptibility syndrome.
PharmGKBPA38437.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1111.
HOGENOMHOG000001567.
HOVERGENHBG107811.
InParanoidQ9UPY3.
KOK11592.
OMAKSNTDKW.
OrthoDBEOG78PV82.
PhylomeDBQ9UPY3.
TreeFamTF330258.

Enzyme and pathway databases

BRENDA3.1.26.3. 2681.
ReactomeREACT_71. Gene Expression.

Gene expression databases

ArrayExpressQ9UPY3.
BgeeQ9UPY3.
CleanExHS_DICER1.
GenevestigatorQ9UPY3.

Family and domain databases

Gene3D1.10.1520.10. 4 hits.
3.30.160.20. 1 hit.
3.40.50.300. 2 hits.
InterProIPR005034. Dicer_dimerisation_dom.
IPR011545. DNA/RNA_helicase_DEAD/DEAH_N.
IPR014720. dsRNA-bd_dom.
IPR014001. Helicase_ATP-bd.
IPR001650. Helicase_C.
IPR027417. P-loop_NTPase.
IPR003100. PAZ_dom.
IPR000999. RNase_III_dom.
[Graphical view]
PfamPF00270. DEAD. 1 hit.
PF03368. Dicer_dimer. 1 hit.
PF00271. Helicase_C. 1 hit.
PF02170. PAZ. 1 hit.
PF00636. Ribonuclease_3. 2 hits.
[Graphical view]
SMARTSM00487. DEXDc. 1 hit.
SM00358. DSRM. 1 hit.
SM00490. HELICc. 1 hit.
SM00949. PAZ. 1 hit.
SM00535. RIBOc. 2 hits.
[Graphical view]
SUPFAMSSF101690. SSF101690. 1 hit.
SSF52540. SSF52540. 2 hits.
SSF69065. SSF69065. 4 hits.
PROSITEPS51327. 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]
ProtoNetSearch...

Other

ChiTaRSDICER1. human.
EvolutionaryTraceQ9UPY3.
GeneWikiDICER1.
GenomeRNAi23405.
NextBio45577.
PROQ9UPY3.
SOURCESearch...

Entry information

Entry nameDICER_HUMAN
AccessionPrimary (citable) accession number: Q9UPY3
Secondary accession number(s): A7E2D3 expand/collapse secondary AC list , E0AD28, O95943, Q9UQ02
Entry history
Integrated into UniProtKB/Swiss-Prot: October 25, 2002
Last sequence update: September 1, 2009
Last modified: April 16, 2014
This is version 134 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Protein Spotlight

Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM