DROSHA

Protein identityUniProt · HPA

UniProt accession

Q9NRR4

Gene

DROSHA

Ensembl

ENSG00000113360

Chromosome

5

Canonical length

1374 aa

Protein class

Cancer-related genes, Enzymes, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Cytosol

OverviewNCBI Gene

This gene encodes a ribonuclease (RNase) III double-stranded RNA-specific ribonuclease and subunit of the microprocessor protein complex, which catalyzes the initial processing step of microRNA (miRNA) synthesis. The encoded protein cleaves the stem loop structure from the primary microRNA (pri-miRNA) in the nucleus, yielding the precursor miRNA (pre-miRNA), which is then exported to the cytoplasm for further processing. In a human cell line lacking a functional copy of this gene, canonical miRNA synthesis is reduced. Somatic mutations in this gene have been observed in human patients with kidney cancer. [provided by RefSeq, Sep 2016]

Canonical amino-acid sequenceUniProt

1374 residues, UniProt reviewed canonical sequence.

>Q9NRR4|DROSHA
     1  MMQGNTCHRM SFHPGRGCPR GRGGHGARPS APSFRPQNLR LLHPQQPPVQ YQYEPPSAPS
    61  TTFSNSPAPN FLPPRPDFVP FPPPMPPSAQ GPLPPCPIRP PFPNHQMRHP FPVPPCFPPM
   121  PPPMPCPNNP PVPGAPPGQG TFPFMMPPPS MPHPPPPPVM PQQVNYQYPP GYSHHNFPPP
   181  SFNSFQNNPS SFLPSANNSS SPHFRHLPPY PLPKAPSERR SPERLKHYDD HRHRDHSHGR
   241  GERHRSLDRR ERGRSPDRRR QDSRYRSDYD RGRTPSRHRS YERSRERERE RHRHRDNRRS
   301  PSLERSYKKE YKRSGRSYGL SVVPEPAGCT PELPGEIIKN TDSWAPPLEI VNHRSPSREK
   361  KRARWEEEKD RWSDNQSSGK DKNYTSIKEK EPEETMPDKN EEEEEELLKP VWIRCTHSEN
   421  YYSSDPMDQV GDSTVVGTSR LRDLYDKFEE ELGSRQEKAK AARPPWEPPK TKLDEDLESS
   481  SESECESDED STCSSSSDSE VFDVIAEIKR KKAHPDRLHD ELWYNDPGQM NDGPLCKCSA
   541  KARRTGIRHS IYPGEEAIKP CRPMTNNAGR LFHYRITVSP PTNFLTDRPT VIEYDDHEYI
   601  FEGFSMFAHA PLTNIPLCKV IRFNIDYTIH FIEEMMPENF CVKGLELFSL FLFRDILELY
   661  DWNLKGPLFE DSPPCCPRFH FMPRFVRFLP DGGKEVLSMH QILLYLLRCS KALVPEEEIA
   721  NMLQWEELEW QKYAEECKGM IVTNPGTKPS SVRIDQLDRE QFNPDVITFP IIVHFGIRPA
   781  QLSYAGDPQY QKLWKSYVKL RHLLANSPKV KQTDKQKLAQ REEALQKIRQ KNTMRREVTV
   841  ELSSQGFWKT GIRSDVCQHA MMLPVLTHHI RYHQCLMHLD KLIGYTFQDR CLLQLAMTHP
   901  SHHLNFGMNP DHARNSLSNC GIRQPKYGDR KVHHMHMRKK GINTLINIMS RLGQDDPTPS
   961  RINHNERLEF LGDAVVEFLT SVHLYYLFPS LEEGGLATYR TAIVQNQHLA MLAKKLELDR
  1021  FMLYAHGPDL CRESDLRHAM ANCFEALIGA VYLEGSLEEA KQLFGRLLFN DPDLREVWLN
  1081  YPLHPLQLQE PNTDRQLIET SPVLQKLTEF EEAIGVIFTH VRLLARAFTL RTVGFNHLTL
  1141  GHNQRMEFLG DSIMQLVATE YLFIHFPDHH EGHLTLLRSS LVNNRTQAKV AEELGMQEYA
  1201  ITNDKTKRPV ALRTKTLADL LESFIAALYI DKDLEYVHTF MNVCFFPRLK EFILNQDWND
  1261  PKSQLQQCCL TLRTEGKEPD IPLYKTLQTV GPSHARTYTV AVYFKGERIG CGKGPSIQQA
  1321  EMGAAMDALE KYNFPQMAHQ KRFIERKYRQ ELKEMRWERE HQEREPDETE DIKK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against DROSHA 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)

0.4

Highest tissue expression

25 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about DROSHA.

Disease | GeneticClinVar

9 pathogenic / likely-pathogenic of 261 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Pineoblastoma
• Hereditary breast ovarian cancer syndrome
• Thyroid cancer, nonmedullary, 1
• Hepatoblastoma

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)

0.35

gnomAD pLI

0.09

gnomAD missense Z

3.98

DepMap mean gene effect

-0.56

DepMap dependency class

common

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 15% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• defense response to Gram-negative bacterium
• defense response to Gram-positive bacterium
• miRNA metabolic process
• positive regulation of gene expression
• pre-miRNA processing
• primary miRNA processing
• regulation of inflammatory response
• regulation of miRNA metabolic process
• regulation of regulatory T cell differentiation
• rRNA processing

Molecular functions

• DEAD/H-box RNA helicase binding
• lipopolysaccharide binding
• metal ion binding
• primary miRNA binding
• protein homodimerization activity
• R-SMAD binding
• ribonuclease III activity
• RNA binding
• SMAD binding

Cellular components

• cytosol
• glutamatergic synapse
• microprocessor complex
• nucleolus
• nucleoplasm
• nucleus
• postsynaptic density

Protein domainsUniProt · Pfam · InterPro

• Ribonuclease III domain
• Double-stranded RNA-binding domain
• Ribonuclease III, endonuclease domain superfamily
• Double-stranded RNA binding motif
• Ribonuclease III domain
• Ribonuclease III
• RNase III, double-stranded RNA binding domain, animal
• Ribonuclease 3, central domain, two antiparallel helical region
• Ribonuclease-III-like
• Ribonuclease 3, central domain, two antiparallel helical region

KeywordsUniProt

• Cytoplasm
• Endonuclease
• Hydrolase
• Magnesium
• Manganese
• Metal-binding
• Nuclease
• Nucleus
• Phosphoprotein
• Repeat
• Ribosome biogenesis
• RNA-binding
• RNA-mediated gene silencing

InteractionsUniProt · HPA

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

• CPSF3
• ISY1
• PUS10
• SNIP1
• SP1
• DGCR8
• SRRT
• NCBP1
• DDX17
• DDX5
• DYRK1A