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UniProtKB - Q8WYQ5 (DGCR8_HUMAN)

Protein

Microprocessor complex subunit DGCR8

Gene

DGCR8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Component of the microprocessor complex that acts as a RNA- and heme-binding protein that is involved in the initial step of microRNA (miRNA) biogenesis. Component of the microprocessor complex that is required to process primary miRNA transcripts (pri-miRNAs) to release precursor miRNA (pre-miRNA) in the nucleus. Within the microprocessor complex, DGCR8 function as a molecular anchor necessary for the recognition of pri-miRNA at dsRNA-ssRNA junction and directs DROSHA to cleave 11 bp away form the junction to release hairpin-shaped pre-miRNAs that are subsequently cut by the cytoplasmic DICER to generate mature miRNAs (PubMed:26027739, PubMed:26748718). The heme-bound DGCR8 dimer binds pri-miRNAs as a cooperative trimer (of dimers) and is active in triggering pri-miRNA cleavage, whereas the heme-free DGCR8 monomer binds pri-miRNAs as a dimer and is much less active. Both double-stranded and single-stranded regions of a pri-miRNA are required for its binding (PubMed:15531877, PubMed:15574589, PubMed:15589161, PubMed:16751099, PubMed:16906129, PubMed:16963499, PubMed:17159994). Specifically recognizes and binds N6-methyladenosine (m6A)-containing pri-miRNAs, a modification required for pri-miRNAs processing (PubMed:25799998). Involved in the silencing of embryonic stem cell self-renewal (By similarity).By similarity10 Publications

Cofactori

heme1 PublicationNote: Binds 1 heme group per homodimer.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi352Iron (heme axial ligand)1 Publication1

GO - Molecular functioni

  • double-stranded RNA binding Source: UniProtKB
  • heme binding Source: BHF-UCL
  • identical protein binding Source: IntAct
  • metal ion binding Source: UniProtKB-KW
  • primary miRNA binding Source: BHF-UCL
  • protein homodimerization activity Source: BHF-UCL
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionRNA-binding
LigandHeme, Iron, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-203927 MicroRNA (miRNA) biogenesis

Names & Taxonomyi

Protein namesi
Recommended name:
Microprocessor complex subunit DGCR8
Alternative name(s):
DiGeorge syndrome critical region 8
Gene namesi
Name:DGCR8
Synonyms:C22orf12, DGCRK6
ORF Names:LP4941
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

EuPathDBiHostDB:ENSG00000128191.13
HGNCiHGNC:2847 DGCR8
MIMi609030 gene
neXtProtiNX_Q8WYQ5

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

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi352C → A or H: Inhibits heme-binding and dimerization. 1 Publication1
Mutagenesisi430C → A: Does not inhibit heme-binding and dimerization. 1 Publication1
Mutagenesisi561 – 565KKLAK → AALAA: Strongly reduces pri-miRNA binding affinity. 1 Publication5
Mutagenesisi568 – 569AA → KK: Reduces pri-miRNA binding affinity and pri-miRNA processing activity. Does not inhibit interaction with DROSHA. When associated with A-676 and S-677, strongly reduces binding affinity and pri-miRNA processing activity. 1 Publication2
Mutagenesisi669 – 673KRVGK → AAVGA: Strongly reduces pri-miRNA binding affinity. 1 Publication5
Mutagenesisi676 – 677AS → KK: Reduces pri-miRNA binding affinity and pri-miRNA processing activity. Slightly inhibits interaction with DROSHA. When associated with A-568 and A-568, strongly reduces binding affinity and pri-miRNA processing activity. 1 Publication2

Organism-specific databases

DisGeNETi54487
GeneReviewsiDGCR8
MalaCardsiDGCR8
OpenTargetsiENSG00000128191
PharmGKBiPA27309

Polymorphism and mutation databases

BioMutaiDGCR8
DMDMi23813990

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000798781 – 773Microprocessor complex subunit DGCR8Add BLAST773

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei35PhosphoserineCombined sources1
Modified residuei92PhosphoserineCombined sources1
Modified residuei95PhosphoserineCombined sources1
Modified residuei271PhosphoserineCombined sources1
Modified residuei275PhosphoserineCombined sources1
Modified residuei279PhosphothreonineBy similarity1
Modified residuei371PhosphothreonineCombined sources1
Modified residuei373PhosphoserineCombined sources1
Modified residuei377PhosphoserineCombined sources1
Cross-linki424Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki500Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki707Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ8WYQ5
MaxQBiQ8WYQ5
PaxDbiQ8WYQ5
PeptideAtlasiQ8WYQ5
PRIDEiQ8WYQ5
ProteomicsDBi75188
75189 [Q8WYQ5-2]
75190 [Q8WYQ5-3]

PTM databases

iPTMnetiQ8WYQ5
PhosphoSitePlusiQ8WYQ5

Expressioni

Tissue specificityi

Ubiquitously expressed.1 Publication

Gene expression databases

BgeeiENSG00000128191 Expressed in 210 organ(s), highest expression level in cerebellar hemisphere
ExpressionAtlasiQ8WYQ5 baseline and differential
GenevisibleiQ8WYQ5 HS

Interactioni

Subunit structurei

Monomer; in absence of heme. Homodimer; the association with heme promotes its dimerization (PubMed:17159994). Component of the microprocessor complex, or pri-miRNA processing protein complex, which is composed of DROSHA and DGCR8 (PubMed:15589161, PubMed:15574589, PubMed:15531877, PubMed:16751099, PubMed:19135890, PubMed:26027739, PubMed:26748718). The microprocessor complex is a heterotrimer; each of the two DROSHA RNase III domains binds one DGCR8 (via C-terminal region) (PubMed:26027739, PubMed:26748718). Interacts with ILF3, NCL and DROSHA (PubMed:17765891).9 Publications

Binary interactionsi

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi119986, 157 interactors
ComplexPortaliCPX-3080 Microprocessor complex
CORUMiQ8WYQ5
DIPiDIP-29261N
IntActiQ8WYQ5, 28 interactors
MINTiQ8WYQ5
STRINGi9606.ENSP00000263209

Structurei

Secondary structure

1773
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ8WYQ5
SMRiQ8WYQ5
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ8WYQ5

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini301 – 334WWPROSITE-ProRule annotationAdd BLAST34
Domaini511 – 578DRBM 1PROSITE-ProRule annotationAdd BLAST68
Domaini620 – 685DRBM 2PROSITE-ProRule annotationAdd BLAST66

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 342Necessary for interaction with NCL1 PublicationAdd BLAST342
Regioni1 – 275Necessary for nuclear localization and retentionAdd BLAST275
Regioni276 – 751Necessary for heme-binding and pri-miRNA processingAdd BLAST476
Regioni701 – 773Interaction with DROSHA1 PublicationAdd BLAST73

Domaini

Both DRBM domains are required for efficient binding to pri-miRNA. The region between residues 276 and 498 has an autoinhibitory function on pri-miRNA processing activity.

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG4334 Eukaryota
ENOG410XS9I LUCA
GeneTreeiENSGT00390000015977
HOVERGENiHBG051344
InParanoidiQ8WYQ5
KOiK18419
OMAiMETYESP
OrthoDBiEOG091G09GA
PhylomeDBiQ8WYQ5
TreeFamiTF324256

Family and domain databases

CDDicd00048 DSRM, 1 hit
cd00201 WW, 1 hit
InterProiView protein in InterPro
IPR014720 dsRBD_dom
IPR001202 WW_dom
IPR036020 WW_dom_sf
PfamiView protein in Pfam
PF00035 dsrm, 2 hits
SMARTiView protein in SMART
SM00358 DSRM, 2 hits
SM00456 WW, 1 hit
SUPFAMiSSF51045 SSF51045, 1 hit
PROSITEiView protein in PROSITE
PS50137 DS_RBD, 1 hit
PS50020 WW_DOMAIN_2, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: Q8WYQ5-1) [UniParc]FASTAAdd to basket

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
METDESPSPL PCGPAGEAVM ESRARPFQAL PREQSPPPPL QTSSGAEVMD 
        60         70         80         90        100
VGSGGDGQSE LPAEDPFNFY GASLLSKGSF SKGRLLIDPN CSGHSPRTAR 
       110        120        130        140        150
HAPAVRKFSP DLKLLKDVKI SVSFTESCRS KDRKVLYTGA ERDVRAECGL 
       160        170        180        190        200
LLSPVSGDVH ACPFGGSVGD GVGIGGESAD KKDEENELDQ EKRVEYAVLD 
       210        220        230        240        250
ELEDFTDNLE LDEEGAGGFT AKAIVQRDRV DEEALNFPYE DDFDNDVDAL 
       260        270        280        290        300
LEEGLCAPKK RRTEEKYGGD SDHPSDGETS VQPMMTKIKT VLKSRGRPPT 
       310        320        330        340        350
EPLPDGWIMT FHNSGVPVYL HRESRVVTWS RPYFLGTGSI RKHDPPLSSI 
       360        370        380        390        400
PCLHYKKMKD NEEREQSSDL TPSGDVSPVK PLSRSAELEF PLDEPDSMGA 
       410        420        430        440        450
DPGPPDEKDP LGAEAAPGAL GQVKAKVEVC KDESVDLEEF RSYLEKRFDF 
       460        470        480        490        500
EQVTVKKFRT WAERRQFNRE MKRKQAESER PILPANQKLI TLSVQDAPTK 
       510        520        530        540        550
KEFVINPNGK SEVCILHEYM QRVLKVRPVY NFFECENPSE PFGASVTIDG 
       560        570        580        590        600
VTYGSGTASS KKLAKNKAAR ATLEILIPDF VKQTSEEKPK DSEELEYFNH 
       610        620        630        640        650
ISIEDSRVYE LTSKAGLLSP YQILHECLKR NHGMGDTSIK FEVVPGKNQK 
       660        670        680        690        700
SEYVMACGKH TVRGWCKNKR VGKQLASQKI LQLLHPHVKN WGSLLRMYGR 
       710        720        730        740        750
ESSKMVKQET SDKSVIELQQ YAKKNKPNLH ILSKLQEEMK RLAEEREETR 
       760        770 
KKPKMSIVAS AQPGGEPLCT VDV
Length:773
Mass (Da):86,045
Last modified:March 1, 2002 - v1
Checksum:i72D962BBE32890EC
GO
Isoform 2 (identifier: Q8WYQ5-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     303-304: LP → VL
     305-773: Missing.

Show »
Length:304
Mass (Da):32,831
Checksum:iFA7800BFE8FD462A
GO
Isoform 3 (identifier: Q8WYQ5-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     536-568: Missing.

Note: No experimental confirmation available.
Show »
Length:740
Mass (Da):82,750
Checksum:i5EEDDD1111DE7DC6
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9JSD5C9JSD5_HUMAN
Microprocessor complex subunit DGCR...
DGCR8
125Annotation score:

Sequence cautioni

The sequence AAO86726 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAB15165 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAB15238 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti241 – 247DDFDNDV → VCWQPLL in AAF82263 (Ref. 6) Curated7
Sequence conflicti274P → L in BAB15165 (PubMed:14702039).Curated1
Sequence conflicti343H → Y in BAB15165 (PubMed:14702039).Curated1
Sequence conflicti706V → A in BAB15165 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_050952174I → V. Corresponds to variant dbSNP:rs35987994Ensembl.1
Natural variantiVAR_050953725N → D. Corresponds to variant dbSNP:rs11546015Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_003847303 – 304LP → VL in isoform 2. 2 Publications2
Alternative sequenceiVSP_003848305 – 773Missing in isoform 2. 2 PublicationsAdd BLAST469
Alternative sequenceiVSP_012707536 – 568Missing in isoform 3. 1 PublicationAdd BLAST33

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB050770 Genomic DNA Translation: BAB83032.1
CR456356 mRNA Translation: CAG30242.1
AK025539 mRNA Translation: BAB15165.1 Different initiation.
AK025780 mRNA Translation: BAB15238.1 Different initiation.
AK313357 mRNA Translation: BAG36158.1
AC006547 Genomic DNA No translation available.
BC009323 mRNA Translation: AAH09323.2
BC009984 mRNA Translation: AAH09984.1
BC078147 mRNA Translation: AAH78147.1
AF165527 mRNA Translation: AAF82263.1
BX649187 mRNA Translation: CAE46205.2
AY189282 mRNA Translation: AAO86726.1 Different initiation.
CCDSiCCDS13773.1 [Q8WYQ5-1]
CCDS54501.1 [Q8WYQ5-3]
RefSeqiNP_001177255.1, NM_001190326.1 [Q8WYQ5-3]
NP_073557.3, NM_022720.6 [Q8WYQ5-1]
UniGeneiHs.643452
Hs.713579

Genome annotation databases

EnsembliENST00000351989; ENSP00000263209; ENSG00000128191 [Q8WYQ5-1]
ENST00000383024; ENSP00000372488; ENSG00000128191 [Q8WYQ5-3]
ENST00000407755; ENSP00000384726; ENSG00000128191 [Q8WYQ5-3]
GeneIDi54487
KEGGihsa:54487
UCSCiuc002zri.4 human [Q8WYQ5-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB050770 Genomic DNA Translation: BAB83032.1
CR456356 mRNA Translation: CAG30242.1
AK025539 mRNA Translation: BAB15165.1 Different initiation.
AK025780 mRNA Translation: BAB15238.1 Different initiation.
AK313357 mRNA Translation: BAG36158.1
AC006547 Genomic DNA No translation available.
BC009323 mRNA Translation: AAH09323.2
BC009984 mRNA Translation: AAH09984.1
BC078147 mRNA Translation: AAH78147.1
AF165527 mRNA Translation: AAF82263.1
BX649187 mRNA Translation: CAE46205.2
AY189282 mRNA Translation: AAO86726.1 Different initiation.
CCDSiCCDS13773.1 [Q8WYQ5-1]
CCDS54501.1 [Q8WYQ5-3]
RefSeqiNP_001177255.1, NM_001190326.1 [Q8WYQ5-3]
NP_073557.3, NM_022720.6 [Q8WYQ5-1]
UniGeneiHs.643452
Hs.713579

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1X47NMR-A502-586[»]
2YT4X-ray2.60A493-720[»]
3LE4X-ray1.70A275-353[»]
5B16X-ray3.20B/C728-750[»]
ProteinModelPortaliQ8WYQ5
SMRiQ8WYQ5
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119986, 157 interactors
ComplexPortaliCPX-3080 Microprocessor complex
CORUMiQ8WYQ5
DIPiDIP-29261N
IntActiQ8WYQ5, 28 interactors
MINTiQ8WYQ5
STRINGi9606.ENSP00000263209

PTM databases

iPTMnetiQ8WYQ5
PhosphoSitePlusiQ8WYQ5

Polymorphism and mutation databases

BioMutaiDGCR8
DMDMi23813990

Proteomic databases

EPDiQ8WYQ5
MaxQBiQ8WYQ5
PaxDbiQ8WYQ5
PeptideAtlasiQ8WYQ5
PRIDEiQ8WYQ5
ProteomicsDBi75188
75189 [Q8WYQ5-2]
75190 [Q8WYQ5-3]

Protocols and materials databases

DNASUi54487
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000351989; ENSP00000263209; ENSG00000128191 [Q8WYQ5-1]
ENST00000383024; ENSP00000372488; ENSG00000128191 [Q8WYQ5-3]
ENST00000407755; ENSP00000384726; ENSG00000128191 [Q8WYQ5-3]
GeneIDi54487
KEGGihsa:54487
UCSCiuc002zri.4 human [Q8WYQ5-1]

Organism-specific databases

CTDi54487
DisGeNETi54487
EuPathDBiHostDB:ENSG00000128191.13
GeneCardsiDGCR8
GeneReviewsiDGCR8
HGNCiHGNC:2847 DGCR8
MalaCardsiDGCR8
MIMi609030 gene
neXtProtiNX_Q8WYQ5
OpenTargetsiENSG00000128191
PharmGKBiPA27309
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4334 Eukaryota
ENOG410XS9I LUCA
GeneTreeiENSGT00390000015977
HOVERGENiHBG051344
InParanoidiQ8WYQ5
KOiK18419
OMAiMETYESP
OrthoDBiEOG091G09GA
PhylomeDBiQ8WYQ5
TreeFamiTF324256

Enzyme and pathway databases

ReactomeiR-HSA-203927 MicroRNA (miRNA) biogenesis

Miscellaneous databases

ChiTaRSiDGCR8 human
EvolutionaryTraceiQ8WYQ5
GeneWikiiDGCR8_(gene)
GenomeRNAii54487
PROiPR:Q8WYQ5
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000128191 Expressed in 210 organ(s), highest expression level in cerebellar hemisphere
ExpressionAtlasiQ8WYQ5 baseline and differential
GenevisibleiQ8WYQ5 HS

Family and domain databases

CDDicd00048 DSRM, 1 hit
cd00201 WW, 1 hit
InterProiView protein in InterPro
IPR014720 dsRBD_dom
IPR001202 WW_dom
IPR036020 WW_dom_sf
PfamiView protein in Pfam
PF00035 dsrm, 2 hits
SMARTiView protein in SMART
SM00358 DSRM, 2 hits
SM00456 WW, 1 hit
SUPFAMiSSF51045 SSF51045, 1 hit
PROSITEiView protein in PROSITE
PS50137 DS_RBD, 1 hit
PS50020 WW_DOMAIN_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiDGCR8_HUMAN
AccessioniPrimary (citable) accession number: Q8WYQ5
Secondary accession number(s): B2R8G1
, Q6DCB2, Q6MZE9, Q6Y2L0, Q96G39, Q96GP8, Q9H6L8, Q9H6T7, Q9NRW2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 10, 2002
Last sequence update: March 1, 2002
Last modified: September 12, 2018
This is version 168 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
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