DGCR8_MOUSE
ID DGCR8_MOUSE Reviewed; 773 AA.
AC Q9EQM6;
DT 10-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2004, sequence version 2.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Microprocessor complex subunit DGCR8;
DE AltName: Full=DiGeorge syndrome critical region 8 homolog;
DE AltName: Full=Gy1;
GN Name=Dgcr8;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=12705904; DOI=10.1016/s0006-291x(03)00554-0;
RA Shiohama A., Sasaki T., Noda S., Minoshima S., Shimizu N.;
RT "Molecular cloning and expression analysis of a novel gene DGCR8 located in
RT the DiGeorge syndrome chromosomal region.";
RL Biochem. Biophys. Res. Commun. 304:184-190(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-243.
RC TISSUE=Embryo;
RA Gong L., Yeh E.T.H.;
RT "Isolation and characterization of a novel human gene deleted in DiGeorge
RT syndrome.";
RL Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=17259983; DOI=10.1038/ng1969;
RA Wang Y., Medvid R., Melton C., Jaenisch R., Blelloch R.;
RT "DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem
RT cell self-renewal.";
RL Nat. Genet. 39:380-385(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-95; SER-271; SER-275; THR-279
RP AND SER-377, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Kidney, Liver, Lung, Spleen, and
RC Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP INTERACTION WITH CPSF3; DROSHA AND ISY1.
RX PubMed=26255770; DOI=10.1016/j.cell.2015.07.008;
RA Du P., Wang L., Sliz P., Gregory R.I.;
RT "A biogenesis step upstream of microprocessor controls miR-17~92
RT expression.";
RL Cell 162:885-899(2015).
CC -!- FUNCTION: Component of the microprocessor complex that acts as a
CC RNA- and heme-binding protein that is involved in the initial step of
CC microRNA (miRNA) biogenesis (PubMed:17259983). Component of the
CC microprocessor complex that is required to process primary miRNA
CC transcripts (pri-miRNAs) to release precursor miRNA (pre-miRNA) in the
CC nucleus. Within the microprocessor complex, DGCR8 function as a
CC molecular anchor necessary for the recognition of pri-miRNA at dsRNA-
CC ssRNA junction and directs DROSHA to cleave 11 bp away form the
CC junction to release hairpin-shaped pre-miRNAs that are subsequently cut
CC by the cytoplasmic DICER to generate mature miRNAs. The heme-bound
CC DGCR8 dimer binds pri-miRNAs as a cooperative trimer (of dimers) and is
CC active in triggering pri-miRNA cleavage, whereas the heme-free DGCR8
CC monomer binds pri-miRNAs as a dimer and is much less active. Both
CC double-stranded and single-stranded regions of a pri-miRNA are required
CC for its binding. Specifically recognizes and binds N6-methyladenosine
CC (m6A)-containing pri-miRNAs, a modification required for pri-miRNAs
CC processing (By similarity). Involved in the silencing of embryonic stem
CC cell self-renewal (PubMed:17259983). {ECO:0000250|UniProtKB:Q8WYQ5,
CC ECO:0000269|PubMed:17259983}.
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:Q8WYQ5};
CC Note=Binds 1 heme group per homodimer. {ECO:0000250|UniProtKB:Q8WYQ5};
CC -!- SUBUNIT: Monomer; in absence of heme (By similarity). Homodimer; the
CC association with heme promotes its dimerization (By similarity).
CC Component of the microprocessor complex, or pri-miRNA processing
CC protein complex, which is composed of DROSHA and DGCR8
CC (PubMed:26255770). The microprocessor complex is a heterotrimer; each
CC of the two DROSHA RNase III domains binds one DGCR8 (via C-terminal
CC region) (By similarity). Interacts with ILF3, NCL and DROSHA (By
CC similarity). Interacts with CPSF3 and ISY1; this interaction is in an
CC RNA dependent manner (PubMed:26255770). Interacts with PUS10;
CC interaction promotes pri-miRNAs processing (By similarity).
CC {ECO:0000250|UniProtKB:Q8WYQ5, ECO:0000269|PubMed:26255770}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q8WYQ5}. Nucleus,
CC nucleolus {ECO:0000250|UniProtKB:Q8WYQ5}. Note=Colocalizes with
CC nucleolin and DROSHA in the nucleolus. Mostly detected in the nucleolus
CC as electron-dense granular patches around the fibrillar center (FC) and
CC granular component (GC). Also detected in the nucleoplasm as small foci
CC adjacent to splicing speckles near the chromatin structure. Localized
CC with DROSHA in GW bodies (GWBs), also known as P-bodies.
CC {ECO:0000250|UniProtKB:Q8WYQ5}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:12705904}.
CC -!- DEVELOPMENTAL STAGE: Expressed in embryonic stem cells. During embryo
CC development it is expressed in neuroepithelium of primary brain, limb
CC bud, vessels, thymus, and around the palate.
CC {ECO:0000269|PubMed:12705904, ECO:0000269|PubMed:17259983}.
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DR EMBL; AB086857; BAD06468.1; -; mRNA.
DR EMBL; BC062919; AAH62919.1; -; mRNA.
DR EMBL; BC066118; AAH66118.1; -; mRNA.
DR EMBL; AF201683; AAG35599.1; -; mRNA.
DR CCDS; CCDS28018.1; -.
DR RefSeq; NP_201581.2; NM_033324.2.
DR AlphaFoldDB; Q9EQM6; -.
DR BMRB; Q9EQM6; -.
DR SMR; Q9EQM6; -.
DR BioGRID; 220480; 7.
DR ComplexPortal; CPX-3081; Microprocessor complex.
DR CORUM; Q9EQM6; -.
DR IntAct; Q9EQM6; 1.
DR STRING; 10090.ENSMUSP00000009321; -.
DR iPTMnet; Q9EQM6; -.
DR PhosphoSitePlus; Q9EQM6; -.
DR EPD; Q9EQM6; -.
DR jPOST; Q9EQM6; -.
DR MaxQB; Q9EQM6; -.
DR PaxDb; Q9EQM6; -.
DR PeptideAtlas; Q9EQM6; -.
DR PRIDE; Q9EQM6; -.
DR ProteomicsDB; 279859; -.
DR DNASU; 94223; -.
DR Ensembl; ENSMUST00000009321; ENSMUSP00000009321; ENSMUSG00000022718.
DR GeneID; 94223; -.
DR KEGG; mmu:94223; -.
DR UCSC; uc007yne.1; mouse.
DR CTD; 54487; -.
DR MGI; MGI:2151114; Dgcr8.
DR VEuPathDB; HostDB:ENSMUSG00000022718; -.
DR eggNOG; KOG4334; Eukaryota.
DR GeneTree; ENSGT00390000015977; -.
DR HOGENOM; CLU_017211_3_0_1; -.
DR InParanoid; Q9EQM6; -.
DR OMA; QDYKADT; -.
DR OrthoDB; 855874at2759; -.
DR PhylomeDB; Q9EQM6; -.
DR TreeFam; TF324256; -.
DR BioGRID-ORCS; 94223; 21 hits in 73 CRISPR screens.
DR ChiTaRS; Dgcr8; mouse.
DR PRO; PR:Q9EQM6; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; Q9EQM6; protein.
DR Bgee; ENSMUSG00000022718; Expressed in embryonic post-anal tail and 96 other tissues.
DR ExpressionAtlas; Q9EQM6; baseline and differential.
DR Genevisible; Q9EQM6; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0070877; C:microprocessor complex; ISO:MGI.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0014069; C:postsynaptic density; IDA:MGI.
DR GO; GO:0003725; F:double-stranded RNA binding; ISO:MGI.
DR GO; GO:0020037; F:heme binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0070878; F:primary miRNA binding; IDA:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0140517; F:protein-RNA adaptor activity; ISO:MGI.
DR GO; GO:0031053; P:primary miRNA processing; ISO:MGI.
DR GO; GO:0072091; P:regulation of stem cell proliferation; IMP:MGI.
DR CDD; cd00201; WW; 1.
DR InterPro; IPR040375; DGCR8.
DR InterPro; IPR014720; dsRBD_dom.
DR InterPro; IPR001202; WW_dom.
DR InterPro; IPR036020; WW_dom_sf.
DR PANTHER; PTHR13482; PTHR13482; 1.
DR Pfam; PF00035; dsrm; 2.
DR SMART; SM00358; DSRM; 2.
DR SMART; SM00456; WW; 1.
DR SUPFAM; SSF51045; SSF51045; 1.
DR PROSITE; PS50137; DS_RBD; 1.
DR PROSITE; PS50020; WW_DOMAIN_2; 1.
PE 1: Evidence at protein level;
KW Heme; Iron; Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; RNA-binding; Ubl conjugation.
FT CHAIN 1..773
FT /note="Microprocessor complex subunit DGCR8"
FT /id="PRO_0000079879"
FT DOMAIN 301..334
FT /note="WW"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 511..578
FT /note="DRBM 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00266"
FT DOMAIN 620..685
FT /note="DRBM 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00266"
FT REGION 1..342
FT /note="Necessary for interaction with NCL"
FT /evidence="ECO:0000250"
FT REGION 1..275
FT /note="Necessary for nuclear localization and retention"
FT /evidence="ECO:0000250"
FT REGION 1..70
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 264..284
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 276..751
FT /note="Necessary for heme-binding and pri-miRNA processing"
FT /evidence="ECO:0000250"
FT REGION 363..382
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 390..409
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 701..773
FT /note="Interaction with DROSHA"
FT /evidence="ECO:0000250|UniProtKB:Q8WYQ5"
FT REGION 745..773
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 352
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:Q8WYQ5"
FT MOD_RES 35
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8WYQ5"
FT MOD_RES 92
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8WYQ5"
FT MOD_RES 95
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 271
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 275
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 279
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 373
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8WYQ5"
FT MOD_RES 377
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CROSSLNK 424
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q8WYQ5"
FT CROSSLNK 500
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q8WYQ5"
FT CROSSLNK 707
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q8WYQ5"
FT CONFLICT 241..243
FT /note="DDF -> VCW (in Ref. 3; AAG35599)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 773 AA; 86321 MW; DA837BD6017B0446 CRC64;
METYESPSPL PREPAGEAMM ENRACPFQVL PHEQSPPPPL QTSSDAEVMD VGSGGDGQSE
PPADDPFNFY GASLLSKGSF SKGRLLIDPN CSGHSPRTAR HAPAVRKFSP DLKLLKDVKI
SVSFTESCRS KDRKVLYTGV ERSTRPECGQ LLSPVSGDVH ACPFGGSVGN GVGLGGESAD
KKDEENELDQ EKRVEYAVLD ELEDFTDNLE LDEEGTGGFT AKAIVQRDRV DEEALNFSYE
DDFDNDVDAL LEEGLCAPKK RRMEEKYGGD SDHPSDGETS VQPMMTKIKT VLKSRGRPPT
EPLPDGWIMT FHNSGVPVYL HRESRVVTWS RPYFLGTGSI RKHDPPLSSI PCLHYKKMKD
NEEREQNCDL APSGEVSPVK PLGRSAELDF PLEEPDSMGG DSGSMDEKDP LGAEAAAGAL
GQVKAKVEVC KDESVDLEEF RNYLEKRFDF EQVTVKKFRT WAERRQFNRE MKRKQAESER
PILPANQKLI TLSVQDAPTK KEFVINPNGK SEVCILHEYM QRVLKVRPVY NFFECENPSE
PFGASVTIDG VTYGSGTASS KKLAKNKAAR ATLEILIPDF VKQTSEEKPK DSEELEYFNH
ISIEDSRVYE LTSKAGLLSP YQILHECLKR NHGMGDTSIK FEVVPGKNQK SEYVMACGKH
TVRGWCKNKR VGKQLASQKI LQLLHPHVKN WGSLLRMYGR ESSKMVKQET SDKSVIELQQ
YAKKNRPNLH ILSKLQEEMK RLAAEREETR KKPKMSIVAS AQPGGEPLCT VDV
