Bromodomain-containing protein 3

BRD3
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2E7N, 2NXB, 2OO1, 2YW5, 3S91, 3S92, 5HFR, 5A7C, 5HJC
Identifiers
Aliases	BRD3, ORFX, RING3L, bromodomain containing 3
External IDs	OMIM: 601541; MGI: 1914632; HomoloGene: 81801; GeneCards: BRD3; OMA:BRD3 - orthologs
Gene location (Human)
Chr.	Chromosome 9 (human)
End	134,068,535 bp
Gene location (Mouse)
Chr.	Chromosome 2 (mouse)
End	27,397,674 bp
RNA expression pattern
	Top expressed in
	nipple; ; internal globus pallidus; ; optic nerve; ; oocyte; ; inferior ganglion of vagus nerve; ; pylorus; ; secondary oocyte; ; ventral tegmental area; ; dorsal motor nucleus of vagus nerve; ; external globus pallidus;
	Top expressed in
	genital tubercle; ; tail of embryo; ; Rostral migratory stream; ; cortex of thymus; ; ganglionic eminence; ; cumulus cell; ; ventricular zone; ; granulocyte; ; maxillary prominence; ; mandibular prominence;
	More reference expression data
	; ;
	More reference expression data
Gene ontology
Molecular function	protein binding; chromatin binding; lysine-acetylated histone binding;
Cellular component	nucleus;
Biological process	regulation of transcription, DNA-templated; regulation of transcription by RNA polymerase II; transcription, DNA-templated; chromatin organization;
	Sources:Amigo / QuickGO
Orthologs
	8019
	67382
	ENSG00000169925
	ENSMUSG00000026918
	Q15059
	Q8K2F0
	NM_007371
	NM_001113573; NM_001113574; NM_023336
	NP_031397; NP_031397.1
	NP_001107045; NP_001107046; NP_075825
	Wikidata
View/Edit Human	View/Edit Mouse

Bromodomain-containing protein 3 (BRD3) also known as RING3-like protein (RING3L) is a protein that in humans is encoded by the BRD3 gene.^[5]^[6]^[7] This gene was identified based on its homology to the gene encoding the RING3 (BRD2) protein, a serine/threonine kinase. The gene maps to 9q34, a region which contains several major histocompatibility complex (MHC) genes.

Structure

BRD3 is a member of the Bromodomain and Extra-Terminal motif (BET) protein family. Like other BET family members it contains two tandem homologous bromodomains and an "Extra-Terminal" motif.

BRD3, similar to BRD2, does not have a long C-terminal domain as BET family proteins BRD4 and BRDT do.^[8]

Function

Like other BET protein family members, BRD3 associates with acetylated lysine residues on histones and transcription factors.^[9]^[10]

BRD3 has been implicated in nucleosome remodeling in the context of transcription.^[11] In addition, BRD3 has been shown to interact with RNA molecules and form protein-RNA aggregates.^[12]

BRD2 and BRD3 perform overlapping cellular functions.^[13]

Clinical significance

Chromosomal translocation of BRD3 with the NUT gene has been implicated in NUT midline carcinoma.^[14] BRD3-NUT driven cancers are histopathologically indistinguishable from BRD4-NUT driven cancers, likely because these translocations involve the N-terminal portion bromodomain-containing portion of these proteins which are highly conserved.

Depletion of BRD3 slows growth in cancer models including prostate cancer and medulloblastoma. The effect of BRD3 depletion is milder than that of other BET proteins BRD2 and BRD4 when each is tested in isolation.^[15]^[16] BET inhibitors target highly conserved BET bromodomains and displace BRD2, BRD3, and BRD4 from chromatin simultaneously. Functional redundancy between BRD2 and BRD3 suggests that their simultaneous disruption of these proteins may be more important than is appreciated by depletion of these proteins individually.^[17]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000169925 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000026918 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Nomura N, Nagase T, Miyajima N, Sazuka T, Tanaka A, Sato S, Seki N, Kawarabayasi Y, Ishikawa K, Tabata S (Dec 1995). "Prediction of the coding sequences of unidentified human genes. II. The coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of cDNA clones from human cell line KG-1". DNA Research. 1 (5): 223–9. doi:10.1093/dnares/1.5.223. PMID 7584044.
^ Thorpe KL, Abdulla S, Kaufman J, Trowsdale J, Beck S (Oct 1996). "Phylogeny and structure of the RING3 gene". Immunogenetics. 44 (5): 391–6. doi:10.1007/BF02602785. PMID 8781126. S2CID 44613743.
^ "Entrez Gene: BRD3 bromodomain containing 3".
^ Belkina AC, Denis GV (Jul 2012). "BET domain co-regulators in obesity, inflammation and cancer". Nature Reviews. Cancer. 12 (7): 465–77. doi:10.1038/nrc3256. PMC 3934568. PMID 22722403.
^ Gamsjaeger R, Webb SR, Lamonica JM, Billin A, Blobel GA, Mackay JP (Jul 2011). "Structural basis and specificity of acetylated transcription factor GATA1 recognition by BET family bromodomain protein Brd3". Molecular and Cellular Biology. 31 (13): 2632–40. doi:10.1128/MCB.05413-11. PMC 3133386. PMID 21555453.
^ Lamonica JM, Deng W, Kadauke S, Campbell AE, Gamsjaeger R, Wang H, Cheng Y, Billin AN, Hardison RC, Mackay JP, Blobel GA (May 2011). "Bromodomain protein Brd3 associates with acetylated GATA1 to promote its chromatin occupancy at erythroid target genes". Proceedings of the National Academy of Sciences of the United States of America. 108 (22): E159-68. doi:10.1073/pnas.1102140108. PMC 3107332. PMID 21536911.
^ LeRoy G, Rickards B, Flint SJ (Apr 2008). "The double bromodomain proteins Brd2 and Brd3 couple histone acetylation to transcription". Molecular Cell. 30 (1): 51–60. doi:10.1016/j.molcel.2008.01.018. PMC 2387119. PMID 18406326.
^ Daneshvar K, Ardehali MB, Klein IA, Hsieh FK, Kratkiewicz AJ, Mahpour A; et al. (2020). "lncRNA DIGIT and BRD3 protein form phase-separated condensates to regulate endoderm differentiation". Nat Cell Biol. 22 (10): 1211–1222. doi:10.1038/s41556-020-0572-2. PMC 8008247. PMID 32895492.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ Stonestrom AJ, Hsu SC, Jahn KS, Huang P, Keller CA, Giardine BM, Kadauke S, Campbell AE, Evans P, Hardison RC, Blobel GA (Feb 2015). "Functions of BET proteins in erythroid gene expression". Blood. 125 (18): 2825–34. doi:10.1182/blood-2014-10-607309. PMC 4424630. PMID 25696920.
^ French CA (2012). "Pathogenesis of NUT midline carcinoma". Annual Review of Pathology. 7: 247–65. doi:10.1146/annurev-pathol-011811-132438. PMID 22017582.
^ Asangani IA, Dommeti VL, Wang X, Malik R, Cieslik M, Yang R, Escara-Wilke J, Wilder-Romans K, Dhanireddy S, Engelke C, Iyer MK, Jing X, Wu YM, Cao X, Qin ZS, Wang S, Feng FY, Chinnaiyan AM (Jun 2014). "Therapeutic targeting of BET bromodomain proteins in castration-resistant prostate cancer". Nature. 510 (7504): 278–82. Bibcode:2014Natur.510..278A. doi:10.1038/nature13229. PMC 4075966. PMID 24759320.
^ Tang Y, Gholamin S, Schubert S, Willardson MI, Lee A, Bandopadhayay P, Bergthold G, Masoud S, Nguyen B, Vue N, Balansay B, Yu F, Oh S, Woo P, Chen S, Ponnuswami A, Monje M, Atwood SX, Whitson RJ, Mitra S, Cheshier SH, Qi J, Beroukhim R, Tang JY, Wechsler-Reya R, Oro AE, Link BA, Bradner JE, Cho YJ (Jul 2014). "Epigenetic targeting of Hedgehog pathway transcriptional output through BET bromodomain inhibition" (PDF). Nature Medicine. 20 (7): 732–40. doi:10.1038/nm.3613. PMC 4108909. PMID 24973920.
^ Stonestrom AJ, Hsu SC, Jahn KS, Huang P, Keller CA, Giardine BM, Kadauke S, Campbell AE, Evans P, Hardison RC, Blobel GA (Apr 2015). "Functions of BET proteins in erythroid gene expression". Blood. 125 (18): 2825–34. doi:10.1182/blood-2014-10-607309. PMC 4424630. PMID 25696920.

External links

Human BRD3 genome location and BRD3 gene details page in the UCSC Genome Browser.

Structure

Function

Clinical significance

References

External links

Further reading