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Protein

Microprocessor complex subunit DGCR8

Gene

Dgcr8

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 (PubMed:17259983). 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. 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. Specifically recognizes and binds N6-methyladenosine (m6A)-containing pri-miRNAs, a modification required for pri-miRNAs processing (By similarity). Involved in the silencing of embryonic stem cell self-renewal (PubMed:17259983).By similarity1 Publication

Cofactori

hemeBy similarityNote: Binds 1 heme group per homodimer.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi352Iron (heme axial ligand)By similarity1

GO - Molecular functioni

GO - Biological processi

  • primary miRNA processing Source: MGI
  • regulation of stem cell proliferation Source: MGI
Complete GO annotation...

Keywords - Ligandi

Heme, Iron, Metal-binding, RNA-binding

Enzyme and pathway databases

ReactomeiR-MMU-203927. MicroRNA (miRNA) biogenesis.

Names & Taxonomyi

Protein namesi
Recommended name:
Microprocessor complex subunit DGCR8
Alternative name(s):
DiGeorge syndrome critical region 8 homolog
Gy1
Gene namesi
Name:Dgcr8
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 16

Organism-specific databases

MGIiMGI:2151114. Dgcr8.

Subcellular locationi

  • Nucleus By similarity
  • Nucleusnucleolus By similarity

  • Note: Colocalizes with nucleolin and DROSHA in the nucleolus. Mostly detected in the nucleolus as electron-dense granular patches around the fibrillar center (FC) and granular component (GC). Also detected in the nucleoplasm as small foci adjacent to splicing speckles near the chromatin structure. Localized with DROSHA in GW bodies (GWBs), also known as P-bodies.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000798791 – 773Microprocessor complex subunit DGCR8Add BLAST773

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei35PhosphoserineBy similarity1
Modified residuei92PhosphoserineBy similarity1
Modified residuei95PhosphoserineCombined sources1
Modified residuei271PhosphoserineCombined sources1
Modified residuei275PhosphoserineCombined sources1
Modified residuei279PhosphothreonineCombined sources1
Modified residuei373PhosphoserineBy similarity1
Modified residuei377PhosphoserineCombined sources1
Cross-linki500Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki707Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9EQM6.
MaxQBiQ9EQM6.
PaxDbiQ9EQM6.
PeptideAtlasiQ9EQM6.
PRIDEiQ9EQM6.

PTM databases

iPTMnetiQ9EQM6.
PhosphoSitePlusiQ9EQM6.

Expressioni

Tissue specificityi

Ubiquitously expressed.1 Publication

Developmental stagei

Expressed in embryonic stem cells. During embryo development it is expressed in neuroepithelium of primary brain, limb bud, vessels, thymus, and around the palate.2 Publications

Gene expression databases

BgeeiENSMUSG00000022718.
GenevisibleiQ9EQM6. MM.

Interactioni

Subunit structurei

Monomer; in absence of heme. Homodimer; the association with heme promotes its dimerization. Component of the microprocessor complex, or pri-miRNA processing protein complex, which is composed of DROSHA and DGCR8. The microprocessor complex is a heterotrimer; each of the two DROSHA RNase III domains binds one DGCR8 (via C-terminal region). Interacts with ILF3, NCL and DROSHA.By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi220480. 1 interactor.
IntActiQ9EQM6. 1 interactor.
STRINGi10090.ENSMUSP00000009321.

Structurei

3D structure databases

ProteinModelPortaliQ9EQM6.
SMRiQ9EQM6.
ModBaseiSearch...
MobiDBiSearch...

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 NCLBy similarityAdd BLAST342
Regioni1 – 275Necessary for nuclear localization and retentionBy similarityAdd BLAST275
Regioni276 – 751Necessary for heme-binding and pri-miRNA processingBy similarityAdd BLAST476
Regioni701 – 773Interaction with DROSHABy similarityAdd BLAST73

Sequence similaritiesi

Contains 2 DRBM (double-stranded RNA-binding) domains.PROSITE-ProRule annotation
Contains 1 WW domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG4334. Eukaryota.
ENOG410XS9I. LUCA.
GeneTreeiENSGT00390000015977.
HOGENOMiHOG000232104.
HOVERGENiHBG051344.
InParanoidiQ9EQM6.
KOiK18419.
OMAiMETYESP.
OrthoDBiEOG091G09GA.
PhylomeDBiQ9EQM6.
TreeFamiTF324256.

Family and domain databases

Gene3Di3.30.160.20. 1 hit.
InterProiIPR014720. dsRBD_dom.
IPR001202. WW_dom.
[Graphical view]
PfamiPF00035. dsrm. 2 hits.
[Graphical view]
SMARTiSM00358. DSRM. 2 hits.
SM00456. WW. 1 hit.
[Graphical view]
SUPFAMiSSF51045. SSF51045. 1 hit.
PROSITEiPS50137. DS_RBD. 1 hit.
PS50020. WW_DOMAIN_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9EQM6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
METYESPSPL PREPAGEAMM ENRACPFQVL PHEQSPPPPL QTSSDAEVMD
60 70 80 90 100
VGSGGDGQSE PPADDPFNFY GASLLSKGSF SKGRLLIDPN CSGHSPRTAR
110 120 130 140 150
HAPAVRKFSP DLKLLKDVKI SVSFTESCRS KDRKVLYTGV ERSTRPECGQ
160 170 180 190 200
LLSPVSGDVH ACPFGGSVGN GVGLGGESAD KKDEENELDQ EKRVEYAVLD
210 220 230 240 250
ELEDFTDNLE LDEEGTGGFT AKAIVQRDRV DEEALNFSYE DDFDNDVDAL
260 270 280 290 300
LEEGLCAPKK RRMEEKYGGD SDHPSDGETS VQPMMTKIKT VLKSRGRPPT
310 320 330 340 350
EPLPDGWIMT FHNSGVPVYL HRESRVVTWS RPYFLGTGSI RKHDPPLSSI
360 370 380 390 400
PCLHYKKMKD NEEREQNCDL APSGEVSPVK PLGRSAELDF PLEEPDSMGG
410 420 430 440 450
DSGSMDEKDP LGAEAAAGAL GQVKAKVEVC KDESVDLEEF RNYLEKRFDF
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 YAKKNRPNLH ILSKLQEEMK RLAAEREETR
760 770
KKPKMSIVAS AQPGGEPLCT VDV
Length:773
Mass (Da):86,321
Last modified:July 19, 2004 - v2
Checksum:iDA837BD6017B0446
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti241 – 243DDF → VCW in AAG35599 (Ref. 3) Curated3

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB086857 mRNA. Translation: BAD06468.1.
BC062919 mRNA. Translation: AAH62919.1.
BC066118 mRNA. Translation: AAH66118.1.
AF201683 mRNA. Translation: AAG35599.1.
CCDSiCCDS28018.1.
RefSeqiNP_201581.2. NM_033324.2.
UniGeneiMm.447352.
Mm.482156.

Genome annotation databases

EnsembliENSMUST00000009321; ENSMUSP00000009321; ENSMUSG00000022718.
ENSMUST00000115633; ENSMUSP00000111296; ENSMUSG00000022718.
ENSMUST00000201668; ENSMUSP00000144275; ENSMUSG00000106687.
ENSMUST00000202260; ENSMUSP00000144454; ENSMUSG00000106687.
GeneIDi94223.
KEGGimmu:94223.
UCSCiuc007yne.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB086857 mRNA. Translation: BAD06468.1.
BC062919 mRNA. Translation: AAH62919.1.
BC066118 mRNA. Translation: AAH66118.1.
AF201683 mRNA. Translation: AAG35599.1.
CCDSiCCDS28018.1.
RefSeqiNP_201581.2. NM_033324.2.
UniGeneiMm.447352.
Mm.482156.

3D structure databases

ProteinModelPortaliQ9EQM6.
SMRiQ9EQM6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi220480. 1 interactor.
IntActiQ9EQM6. 1 interactor.
STRINGi10090.ENSMUSP00000009321.

PTM databases

iPTMnetiQ9EQM6.
PhosphoSitePlusiQ9EQM6.

Proteomic databases

EPDiQ9EQM6.
MaxQBiQ9EQM6.
PaxDbiQ9EQM6.
PeptideAtlasiQ9EQM6.
PRIDEiQ9EQM6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000009321; ENSMUSP00000009321; ENSMUSG00000022718.
ENSMUST00000115633; ENSMUSP00000111296; ENSMUSG00000022718.
ENSMUST00000201668; ENSMUSP00000144275; ENSMUSG00000106687.
ENSMUST00000202260; ENSMUSP00000144454; ENSMUSG00000106687.
GeneIDi94223.
KEGGimmu:94223.
UCSCiuc007yne.1. mouse.

Organism-specific databases

CTDi54487.
MGIiMGI:2151114. Dgcr8.

Phylogenomic databases

eggNOGiKOG4334. Eukaryota.
ENOG410XS9I. LUCA.
GeneTreeiENSGT00390000015977.
HOGENOMiHOG000232104.
HOVERGENiHBG051344.
InParanoidiQ9EQM6.
KOiK18419.
OMAiMETYESP.
OrthoDBiEOG091G09GA.
PhylomeDBiQ9EQM6.
TreeFamiTF324256.

Enzyme and pathway databases

ReactomeiR-MMU-203927. MicroRNA (miRNA) biogenesis.

Miscellaneous databases

PROiQ9EQM6.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000022718.
GenevisibleiQ9EQM6. MM.

Family and domain databases

Gene3Di3.30.160.20. 1 hit.
InterProiIPR014720. dsRBD_dom.
IPR001202. WW_dom.
[Graphical view]
PfamiPF00035. dsrm. 2 hits.
[Graphical view]
SMARTiSM00358. DSRM. 2 hits.
SM00456. WW. 1 hit.
[Graphical view]
SUPFAMiSSF51045. SSF51045. 1 hit.
PROSITEiPS50137. DS_RBD. 1 hit.
PS50020. WW_DOMAIN_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiDGCR8_MOUSE
AccessioniPrimary (citable) accession number: Q9EQM6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 10, 2002
Last sequence update: July 19, 2004
Last modified: November 2, 2016
This is version 116 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.