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Microprocessor complex subunit DGCR8

 
Known also as: DiGeorge syndrome critical region 8

Known abbreviations: DGCR8, C22orf12, DGCRK6, LP4941

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. 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. Involved in the silencing of embryonic stem cells self-renewal.

Cofactor

Binds 1 heme group per homodimer.

Subunit structure

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 DGCR8 (heme-free or heme-bound forms) and DROSHA. The microprocessor complex may contain multiple subunit of DGCR8 and DROSHA. Interacts with ILF3, NCL and DROSHA.

Subcellular location

Nucleus. Nucleus › nucleolus.

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.

Tissue specificity

Ubiquitously expressed.

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.

 




Activities in which Microprocessor complex subunit DGCR8 is involved: Pathways in which Microprocessor complex subunit DGCR8 is involved:

NCBI GI number(s): -
Species: Homo sapiens

Links to other databases:

Database ID Link
Uniprot Q8WYQ5 Q8WYQ5
BRENDA - -
KEGG hsa:54487 hsa:54487
PFAM: PF00035
PF00035
InterPro: IPR001159
IPR014720
IPR001202
IPR001159
IPR014720
IPR001202
CATH: - -
SCOP: - -
Solved crystal structures: 1X47
2YT4
3LE4
[PDB] [details]
[PDB] [details]
[PDB] [details]


Protein sequence:
METDESPSPLPCGPAGEAVMESRARPFQALPREQSPPPPLQTSSGAEVMD
VGSGGDGQSELPAEDPFNFYGASLLSKGSFSKGRLLIDPNCSGHSPRTAR
HAPAVRKFSPDLKLLKDVKISVSFTESCRSKDRKVLYTGAERDVRAECGL
LLSPVSGDVHACPFGGSVGDGVGIGGESADKKDEENELDQEKRVEYAVLD
ELEDFTDNLELDEEGAGGFTAKAIVQRDRVDEEALNFPYEDDFDNDVDAL
LEEGLCAPKKRRTEEKYGGDSDHPSDGETSVQPMMTKIKTVLKSRGRPPT
EPLPDGWIMTFHNSGVPVYLHRESRVVTWSRPYFLGTGSIRKHDPPLSSI
PCLHYKKMKDNEEREQSSDLTPSGDVSPVKPLSRSAELEFPLDEPDSMGA
DPGPPDEKDPLGAEAAPGALGQVKAKVEVCKDESVDLEEFRSYLEKRFDF
EQVTVKKFRTWAERRQFNREMKRKQAESERPILPANQKLITLSVQDAPTK
KEFVINPNGKSEVCILHEYMQRVLKVRPVYNFFECENPSEPFGASVTIDG
VTYGSGTASSKKLAKNKAARATLEILIPDFVKQTSEEKPKDSEELEYFNH
ISIEDSRVYELTSKAGLLSPYQILHECLKRNHGMGDTSIKFEVVPGKNQK
SEYVMACGKHTVRGWCKNKRVGKQLASQKILQLLHPHVKNWGSLLRMYGR
ESSKMVKQETSDKSVIELQQYAKKNKPNLHILSKLQEEMKRLAEEREETR
KKPKMSIVASAQPGGEPLCTVDV

Microprocessor complex subunit DGCR8 (Homo sapiens) is product of expression of DGCR8 gene.

References:

Title Authors Journal Publication date (Issue) PubMed ID
Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex. Han J, Lee Y, Yeom KH, Nam JW, Heo I, Rhee JK, Sohn SY, Cho Y, Zhang BT, Kim VN Cell 2006-06-02 (125) 16751099
The Drosha-DGCR8 complex in primary microRNA processing. Han J, Lee Y, Yeom KH, Kim YK, Jin H, Kim VN Genes Dev 2004-12-15 (18) 15574589
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, K Genome Res 2004-10-01 (14) 15489334
Complete sequencing and characterization of 21,243 full-length human cDNAs. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K Nat Genet 2004-02-01 (36) 14702039
Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M Cell 2006-11-03 (127) 17081983
Initial characterization of the human central proteome. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J BMC Syst Biol 2011-01-01 (5) 21269460
The full-ORF clone resource of the German cDNA Consortium. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I BMC Genomics 2007-01-01 (8) 17974005
A quantitative atlas of mitotic phosphorylation. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP Proc Natl Acad Sci U S A 2008-08-05 (105) 18669648
Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK Sci Signal 2009-01-01 (2) 19690332
Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis. Cantin GT, Yi W, Lu B, Park SK, Xu T, Lee JD, Yates JR 3rd J Proteome Res 2008-03-01 (7) 18220336
Large-scale cDNA transfection screening for genes related to cancer development and progression. Wan D, Gong Y, Qin W, Zhang P, Li J, Wei L, Zhou X, Li H, Qiu X, Zhong F, He L, Yu J, Yao G, Jiang H, Qian L, Yu Y, Shu H, Chen X, Xu H, Guo M, Pan Z, Chen Y, Ge C, Yang S, Gu J Proc Natl Acad Sci U S A 2004-11-02 (101) 15498874
The human DiGeorge syndrome critical region gene 8 and Its D. melanogaster homolog are required for miRNA biogenesis. Landthaler M, Yalcin A, Tuschl T Curr Biol 2004-12-14 (14) 15589161
The Microprocessor complex mediates the genesis of microRNAs. Gregory RI, Yan KP, Amuthan G, Chendrimada T, Doratotaj B, Cooch N, Shiekhattar R Nature 2004-11-11 (432) 15531877
Formation of GW bodies is a consequence of microRNA genesis. Pauley KM, Eystathioy T, Jakymiw A, Hamel JC, Fritzler MJ, Chan EK EMBO Rep 2006-09-01 (7) 16906129
Heme is involved in microRNA processing. Faller M, Matsunaga M, Yin S, Loo JA, Guo F Nat Struct Mol Biol 2007-02-01 (14) 17159994
A genome annotation-driven approach to cloning the human ORFeome. Collins JE, Wright CL, Edwards CA, Davis MP, Grinham JA, Cole CG, Goward ME, Aguado B, Mallya M, Mokrab Y, Huckle EJ, Beare DM, Dunham I Genome Biol 2004-01-01 (5) 15461802
The DNA sequence of human chromosome 22. Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP, et al. Nature 1999-12-02 (402) 10591208
Crystal structure of human DGCR8 core. Sohn SY, Bae WJ, Kim JJ, Yeom KH, Kim VN, Cho Y... Nat Struct Mol Biol 2007-09-01 (14) 17704815
Molecular cloning and expression analysis of a novel gene DGCR8 located in the DiGeorge syndrome chromosomal region. Shiohama A, Sasaki T, Noda S, Minoshima S, Shimizu N... Biochem Biophys Res Commun 2003-04-25 (304) 12705904
Characterization of DGCR8/Pasha, the essential cofactor for Drosha in primary miRNA processing. Yeom KH, Lee Y, Han J, Suh MR, Kim VN... Nucleic Acids Res 2006-01-01 (34) 16963499
Nucleolar localization of DGCR8 and identification of eleven DGCR8-associated proteins. Shiohama A, Sasaki T, Noda S, Minoshima S, Shimizu N... Exp Cell Res 2007-12-10 (313) 17765891
Posttranscriptional crossregulation between Drosha and DGCR8. Han J, Pedersen JS, Kwon SC, Belair CD, Kim YK, Yeom KH, Yang WY, Haussler D, Blelloch R, Kim VN... Cell 2009-02-09 (136) 19135890
Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M... Sci Signal 2010-01-01 (3) 20068231
System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B... Sci Signal 2011-01-01 (4) 21406692



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Last modification of this entry: April 26, 2013.

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