DICER1

Protein identityUniProt · HPA

UniProt accession

Q9UPY3

Gene

DICER1

Ensembl

ENSG00000100697

Chromosome

14

Canonical length

1922 aa

Protein class

Cancer-related genes, Disease related genes, Enzymes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Cytosol

OverviewNCBI Gene

This gene encodes a protein possessing an RNA helicase motif containing a DEXH box in its amino terminus and an RNA motif in the carboxy terminus. The encoded protein functions as a ribonuclease and is required by the RNA interference and small temporal RNA (stRNA) pathways to produce the active small RNA component that represses gene expression. This protein also acts as a strong antiviral agent with activity against RNA viruses, including the Zika and SARS-CoV-2 viruses. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2021]

Canonical amino-acid sequenceUniProt

1922 residues, UniProt reviewed canonical sequence.

>Q9UPY3|DICER1
     1  MKSPALQPLS MAGLQLMTPA SSPMGPFFGL PWQQEAIHDN IYTPRKYQVE LLEAALDHNT
    61  IVCLNTGSGK TFIAVLLTKE LSYQIRGDFS RNGKRTVFLV NSANQVAQQV SAVRTHSDLK
   121  VGEYSNLEVN ASWTKERWNQ EFTKHQVLIM TCYVALNVLK NGYLSLSDIN LLVFDECHLA
   181  ILDHPYREIM KLCENCPSCP RILGLTASIL NGKCDPEELE EKIQKLEKIL KSNAETATDL
   241  VVLDRYTSQP CEIVVDCGPF TDRSGLYERL LMELEEALNF INDCNISVHS KERDSTLISK
   301  QILSDCRAVL VVLGPWCADK VAGMMVRELQ KYIKHEQEEL HRKFLLFTDT FLRKIHALCE
   361  EHFSPASLDL KFVTPKVIKL LEILRKYKPY ERQQFESVEW YNNRNQDNYV SWSDSEDDDE
   421  DEEIEEKEKP ETNFPSPFTN ILCGIIFVER RYTAVVLNRL IKEAGKQDPE LAYISSNFIT
   481  GHGIGKNQPR NKQMEAEFRK QEEVLRKFRA HETNLLIATS IVEEGVDIPK CNLVVRFDLP
   541  TEYRSYVQSK GRARAPISNY IMLADTDKIK SFEEDLKTYK AIEKILRNKC SKSVDTGETD
   601  IDPVMDDDDV FPPYVLRPDD GGPRVTINTA IGHINRYCAR LPSDPFTHLA PKCRTRELPD
   661  GTFYSTLYLP INSPLRASIV GPPMSCVRLA ERVVALICCE KLHKIGELDD HLMPVGKETV
   721  KYEEELDLHD EEETSVPGRP GSTKRRQCYP KAIPECLRDS YPRPDQPCYL YVIGMVLTTP
   781  LPDELNFRRR KLYPPEDTTR CFGILTAKPI PQIPHFPVYT RSGEVTISIE LKKSGFMLSL
   841  QMLELITRLH QYIFSHILRL EKPALEFKPT DADSAYCVLP LNVVNDSSTL DIDFKFMEDI
   901  EKSEARIGIP STKYTKETPF VFKLEDYQDA VIIPRYRNFD QPHRFYVADV YTDLTPLSKF
   961  PSPEYETFAE YYKTKYNLDL TNLNQPLLDV DHTSSRLNLL TPRHLNQKGK ALPLSSAEKR
  1021  KAKWESLQNK QILVPELCAI HPIPASLWRK AVCLPSILYR LHCLLTAEEL RAQTASDAGV
  1081  GVRSLPADFR YPNLDFGWKK SIDSKSFISI SNSSSAENDN YCKHSTIVPE NAAHQGANRT
  1141  SSLENHDQMS VNCRTLLSES PGKLHVEVSA DLTAINGLSY NQNLANGSYD LANRDFCQGN
  1201  QLNYYKQEIP VQPTTSYSIQ NLYSYENQPQ PSDECTLLSN KYLDGNANKS TSDGSPVMAV
  1261  MPGTTDTIQV LKGRMDSEQS PSIGYSSRTL GPNPGLILQA LTLSNASDGF NLERLEMLGD
  1321  SFLKHAITTY LFCTYPDAHE GRLSYMRSKK VSNCNLYRLG KKKGLPSRMV VSIFDPPVNW
  1381  LPPGYVVNQD KSNTDKWEKD EMTKDCMLAN GKLDEDYEEE DEEEESLMWR APKEEADYED
  1441  DFLEYDQEHI RFIDNMLMGS GAFVKKISLS PFSTTDSAYE WKMPKKSSLG SMPFSSDFED
  1501  FDYSSWDAMC YLDPSKAVEE DDFVVGFWNP SEENCGVDTG KQSISYDLHT EQCIADKSIA
  1561  DCVEALLGCY LTSCGERAAQ LFLCSLGLKV LPVIKRTDRE KALCPTRENF NSQQKNLSVS
  1621  CAAASVASSR SSVLKDSEYG CLKIPPRCMF DHPDADKTLN HLISGFENFE KKINYRFKNK
  1681  AYLLQAFTHA SYHYNTITDC YQRLEFLGDA ILDYLITKHL YEDPRQHSPG VLTDLRSALV
  1741  NNTIFASLAV KYDYHKYFKA VSPELFHVID DFVQFQLEKN EMQGMDSELR RSEEDEEKEE
  1801  DIEVPKAMGD IFESLAGAIY MDSGMSLETV WQVYYPMMRP LIEKFSANVP RSPVRELLEM
  1861  EPETAKFSPA ERTYDGKVRV TVEVVGKGKF KGVGRSYRIA KSAAARRALR SLKANQPQVP
  1921  NS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against DICER1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.36

Highest tissue expression

17 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about DICER1.

Disease | AllUniProt

Conditions DICER1 is implicated in, by any mechanism.

• Pleuropulmonary blastoma (PPB) MIM:601200
• Goiter multinodular 1, with or without Sertoli-Leydig cell tumors (MNG1) MIM:138800
• Rhabdomyosarcoma, embryonal, 2 (RMSE2) MIM:180295
• Global developmental delay, lung cysts, overgrowth, and Wilms tumor (GLOW) MIM:618272

Disease | GeneticClinVar

845 pathogenic / likely-pathogenic of 7,679 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• DICER1-related tumor predisposition
• Hereditary cancer-predisposing syndrome
• Pleuropulmonary blastoma
• Global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome
• Euthyroid goiter

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.17

gnomAD pLI

1

gnomAD missense Z

4.23

DepMap mean gene effect

-0.44

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• apoptotic DNA fragmentation
• global gene silencing by mRNA cleavage
• miRNA metabolic process
• miRNA processing
• negative regulation of gene expression
• negative regulation of Schwann cell proliferation
• negative regulation of transcription by RNA polymerase II
• negative regulation of tumor necrosis factor production
• negative regulation of tumor necrosis factor-mediated signaling pathway
• nerve development
• neuron projection morphogenesis
• peripheral nervous system myelin formation
• positive regulation of myelination
• positive regulation of Schwann cell differentiation
• pre-miRNA processing
• RISC complex assembly
• siRNA processing
• tRNA decay

Molecular functions

• ATP binding
• deoxyribonuclease I activity
• double-stranded RNA binding
• helicase activity
• metal ion binding
• pre-miRNA binding
• protein domain specific binding
• ribonuclease III activity
• RNA binding
• RNA endonuclease activity
• siRNA binding

Cellular components

• cytoplasm
• cytosol
• extracellular exosome
• nucleus
• perinuclear region of cytoplasm
• RISC complex
• RISC-loading complex

Protein domainsUniProt · Pfam · InterPro

• Ribonuclease III domain
• Helicase, C-terminal domain-like
• PAZ domain
• DEAD/DEAH-box helicase domain
• Helicase superfamily 1/2, ATP-binding domain
• Double-stranded RNA-binding domain
• P-loop containing nucleoside triphosphate hydrolase
• PAZ domain superfamily
• Ribonuclease III, endonuclease domain superfamily
• DEAD/DEAH box helicase
• Helicase conserved C-terminal domain
• Ribonuclease III domain
• PAZ domain
• Dicer, dimerisation domain
• Dicer dimerisation domain superfamily
• Dicer, double-stranded RNA-binding domain
• Dicer, platform domain
• Dicer, partner-binding domain
• Dicer dimerisation domain
• Dicer, partner-binding domain
• Dicer, platform domain
• Dicer, dsRNA-binding domain

KeywordsUniProt

• ATP-binding
• Cytoplasm
• Endonuclease
• Helicase
• Host-virus interaction
• Hydrolase
• Magnesium
• Manganese
• Metal-binding
• Nuclease
• Nucleotide-binding
• Phosphoprotein
• Repeat
• RNA-binding
• RNA-mediated gene silencing

InteractionsUniProt · HPA

Protein binding partners of DICER1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• AGO1
• AGO2
• BCDIN3D
• DHX9
• EIF6
• MOV10
• PIWIL1
• PRKRA
• RPL7A
• TARBP2
• DHX58
• EIF2AK2
• RPL13