UniProt functional annotation for Q8WYQ5



	UniProt functional annotation for Q8WYQ5

UniProt code: Q8WYQ5.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: 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). {ECO:0000250|UniProtKB:Q9EQM6, ECO:0000269|PubMed:15531877, ECO:0000269|PubMed:15574589, ECO:0000269|PubMed:15589161, ECO:0000269|PubMed:16751099, ECO:0000269|PubMed:16906129, ECO:0000269|PubMed:16963499, ECO:0000269|PubMed:17159994, ECO:0000269|PubMed:25799998, ECO:0000269|PubMed:26027739, ECO:0000269|PubMed:26748718}.

Cofactor: Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000269|PubMed:17159994}; Note=Binds 1 heme group per homodimer. {ECO:0000269|PubMed:17159994};

Subunit: 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). Interacts with CPSF3 and ISY1; this interaction is in an RNA dependent manner (By similarity). Interacts with PUS10; interaction promotes pri-miRNAs processing (PubMed:31819270). {ECO:0000250|UniProtKB:Q9EQM6, ECO:0000269|PubMed:15531877, ECO:0000269|PubMed:15574589, ECO:0000269|PubMed:15589161, ECO:0000269|PubMed:16751099, ECO:0000269|PubMed:16963499, ECO:0000269|PubMed:17159994, ECO:0000269|PubMed:17765891, ECO:0000269|PubMed:19135890, ECO:0000269|PubMed:26748718, ECO:0000269|PubMed:31819270}.

Subcellular location: Nucleus {ECO:0000269|PubMed:16906129, ECO:0000269|PubMed:16963499, ECO:0000269|PubMed:17159994, ECO:0000269|PubMed:22118463}. Nucleus, nucleolus {ECO:0000269|PubMed:17159994}. 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 (PubMed:17159994).

Tissue specificity: Ubiquitously expressed. {ECO:0000269|PubMed:12705904}.

Domain: 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.

Sequence caution: Sequence=AAO86726.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAB15165.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAB15238.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		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). {ECO:0000250\|UniProtKB:Q9EQM6, ECO:0000269\|PubMed:15531877, ECO:0000269\|PubMed:15574589, ECO:0000269\|PubMed:15589161, ECO:0000269\|PubMed:16751099, ECO:0000269\|PubMed:16906129, ECO:0000269\|PubMed:16963499, ECO:0000269\|PubMed:17159994, ECO:0000269\|PubMed:25799998, ECO:0000269\|PubMed:26027739, ECO:0000269\|PubMed:26748718}.


Cofactor:		Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000269\|PubMed:17159994}; Note=Binds 1 heme group per homodimer. {ECO:0000269\|PubMed:17159994};
Subunit:		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). Interacts with CPSF3 and ISY1; this interaction is in an RNA dependent manner (By similarity). Interacts with PUS10; interaction promotes pri-miRNAs processing (PubMed:31819270). {ECO:0000250\|UniProtKB:Q9EQM6, ECO:0000269\|PubMed:15531877, ECO:0000269\|PubMed:15574589, ECO:0000269\|PubMed:15589161, ECO:0000269\|PubMed:16751099, ECO:0000269\|PubMed:16963499, ECO:0000269\|PubMed:17159994, ECO:0000269\|PubMed:17765891, ECO:0000269\|PubMed:19135890, ECO:0000269\|PubMed:26748718, ECO:0000269\|PubMed:31819270}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:16906129, ECO:0000269\|PubMed:16963499, ECO:0000269\|PubMed:17159994, ECO:0000269\|PubMed:22118463}. Nucleus, nucleolus {ECO:0000269\|PubMed:17159994}. 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 (PubMed:17159994).
Tissue specificity:		Ubiquitously expressed. {ECO:0000269\|PubMed:12705904}.
Domain:		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.
Sequence caution:		Sequence=AAO86726.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAB15165.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAB15238.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};