DGCR8_BOVIN
ID DGCR8_BOVIN Reviewed; 760 AA.
AC A6QR44;
DT 22-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT 21-AUG-2007, sequence version 1.
DT 03-AUG-2022, entry version 88.
DE RecName: Full=Microprocessor complex subunit DGCR8;
DE AltName: Full=DiGeorge syndrome critical region 8 homolog;
GN Name=DGCR8;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Hippocampus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JUL-2007) to the EMBL/GenBank/DDBJ databases.
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. Component of the microprocessor complex
CC that is required to process primary miRNA transcripts (pri-miRNAs) to
CC release precursor miRNA (pre-miRNA) in the nucleus. Within the
CC microprocessor complex, DGCR8 function as a molecular anchor necessary
CC for the recognition of pri-miRNA at dsRNA-ssRNA junction and directs
CC DROSHA to cleave 11 bp away form the junction to release hairpin-shaped
CC pre-miRNAs that are subsequently cut by the cytoplasmic DICER to
CC generate mature miRNAs. The heme-bound DGCR8 dimer binds pri-miRNAs as
CC a cooperative trimer (of dimers) and is active in triggering pri-miRNA
CC cleavage, whereas the heme-free DGCR8 monomer binds pri-miRNAs as a
CC dimer and is much less active. Both double-stranded and single-stranded
CC regions of a pri-miRNA are required for its binding. Specifically
CC recognizes and binds N6-methyladenosine (m6A)-containing pri-miRNAs, a
CC modification required for pri-miRNAs processing (By similarity).
CC Involved in the silencing of embryonic stem cell self-renewal (By
CC similarity). {ECO:0000250|UniProtKB:Q8WYQ5,
CC ECO:0000250|UniProtKB:Q9EQM6}.
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. Homodimer; the association with
CC heme promotes its dimerization. Component of the microprocessor
CC complex, or pri-miRNA processing protein complex, which is composed of
CC DROSHA and DGCR8. The microprocessor complex is a heterotrimer; each of
CC the two DROSHA RNase III domains binds one DGCR8 (via C-terminal
CC region). Interacts with ILF3, NCL and DROSHA. Interacts with CPSF3 and
CC ISY1; this interaction is in an RNA dependent manner (By similarity).
CC Interacts with PUS10; interaction promotes pri-miRNAs processing.
CC {ECO:0000250|UniProtKB:Q8WYQ5, ECO:0000250|UniProtKB:Q9EQM6}.
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 ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; BC150109; AAI50110.1; -; mRNA.
DR RefSeq; NP_001094674.1; NM_001101204.1.
DR AlphaFoldDB; A6QR44; -.
DR BMRB; A6QR44; -.
DR SMR; A6QR44; -.
DR STRING; 9913.ENSBTAP00000026474; -.
DR PaxDb; A6QR44; -.
DR PRIDE; A6QR44; -.
DR Ensembl; ENSBTAT00000026474; ENSBTAP00000026474; ENSBTAG00000019869.
DR GeneID; 540254; -.
DR KEGG; bta:540254; -.
DR CTD; 54487; -.
DR VEuPathDB; HostDB:ENSBTAG00000019869; -.
DR VGNC; VGNC:28023; DGCR8.
DR eggNOG; KOG4334; Eukaryota.
DR GeneTree; ENSGT00390000015977; -.
DR HOGENOM; CLU_017211_3_0_1; -.
DR InParanoid; A6QR44; -.
DR OrthoDB; 855874at2759; -.
DR TreeFam; TF324256; -.
DR Proteomes; UP000009136; Chromosome 17.
DR Bgee; ENSBTAG00000019869; Expressed in ruminant reticulum and 108 other tissues.
DR ExpressionAtlas; A6QR44; baseline.
DR GO; GO:0070877; C:microprocessor complex; IBA:GO_Central.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0003725; F:double-stranded RNA binding; IBA:GO_Central.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0042802; F:identical protein binding; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0070878; F:primary miRNA binding; IBA:GO_Central.
DR GO; GO:0031053; P:primary miRNA processing; IBA:GO_Central.
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 2: Evidence at transcript level;
KW Heme; Iron; Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; RNA-binding; Ubl conjugation.
FT CHAIN 1..760
FT /note="Microprocessor complex subunit DGCR8"
FT /id="PRO_0000384373"
FT DOMAIN 301..334
FT /note="WW"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 498..565
FT /note="DRBM 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00266"
FT DOMAIN 606..673
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..71
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 263..284
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 276..738
FT /note="Necessary for heme-binding and pri-miRNA processing"
FT /evidence="ECO:0000250"
FT REGION 361..405
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 688..760
FT /note="Interaction with DROSHA"
FT /evidence="ECO:0000250|UniProtKB:Q8WYQ5"
FT REGION 731..760
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 372..386
FT /note="Pro residues"
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:0000250|UniProtKB:Q8WYQ5"
FT MOD_RES 271
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8WYQ5"
FT MOD_RES 275
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8WYQ5"
FT MOD_RES 279
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9EQM6"
FT CROSSLNK 411
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q8WYQ5"
FT CROSSLNK 487
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q8WYQ5"
FT CROSSLNK 694
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q8WYQ5"
SQ SEQUENCE 760 AA; 84383 MW; 3964EDB2A595F5CF CRC64;
METCGSPSPL PREPAGGVAM EDRARPLRAL PRGQSPPPPL QTSSDAEVMD VGSGGDGQAE
PPAEDPLNFY GASLLSKGSS SKARLLVDPN CSGHSPRTAR HAPAVRKFSP DLKLLKDVKI
SVSFTESCRS EDRKVLYTGA ERDVRAECGL ALSPVIGDVH AGPFGGSVGN GVGAGGESAG
KRDEEHELDQ EKRVEYAVLD ELEDFTDNLE LDEEGAGGFT AKAIVQRDRV DEEALNFSYE
DDFDNDVDAL LEEGLCAPKK RRMEEKYGGD SDHPSDGETS VQPMMTKIKT VLKSRGRPPT
EPLPDGWIMT FHNSGVPVYL HRESRVVTWS RPYFLGTGSI RKHGPPLTSI PCLHYRKMKD
SEERERAAGI APPEPELPPD EPDPLGTDAG PPDEKDPLGA EAAPGALGQV KAKVEVCKDE
SVDLEEFRNY LEKRFDFEQV TVKKFRTWAE RRQFNREMKR KQAESERPIL PANQKLITLS
VQDAPTKKEF VINPNGKSEV CILHEYMQRV LKVRPVYSFF ECENPSEPFG ASVTIDGVTY
GSGTASSKKL AKNKAARATL EILIPDFVKQ TSEEKPRDSE ELEYFNHISI EDSRVYELTS
KAGLLSPYQI LHECLKRNHG MGDTSIKFEV VPGKNQKSEY VMACGKHTVR GWCKNKRVGK
QLASQKILQL LHPHVKNWGS LLRMYGRESS KMVKQETSDK SVIELQQFAR KNKPNLHILS
KLQEEMRRLA EEREETRKKP KMSIVASAQP GGEPLCTVDV
