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]