Bromodomain-containing protein 3

UniProt Q15059 Organism Homo sapiens Gene BRD3, KIAA0043, RING3L

Also known as: BRD3, KIAA0043, RING3L

Function

Chromatin reader that recognizes and binds acetylated histones, thereby controlling gene expression and remodeling chromatin structures. Recruits transcription factors and coactivators to target gene sites, and activates RNA polymerase II machinery for transcriptional elongation. In vitro, binds acetylated lysine residues on the N-terminus of histone H2A, H2B, H3 and H4. Involved in endoderm differentiation via its association with long non-coding RNA (lncRNA) DIGIT: BRD3 undergoes liquid-liquid phase separation upon binding to lncRNA DIGIT, promoting binding to histone H3 acetylated at 'Lys-18' (H3K18ac) to induce endoderm gene expression. Also binds non-histones acetylated proteins, such as GATA1 and GATA2: regulates transcription by promoting the binding of the transcription factor GATA1 to its targets (By similarity).

Classification

Family (Pfam): PF17035 BET, PF00439 Bromodomain
InterPro: Bromo_Brdt_I, Bromo_Brdt_II, Bromo_chromatin_reader, Bromodomain, Bromodomain-like_sf, Bromodomain_CS, NET_dom, NET_sf
Functional cluster: RRM RNA-Binding & Protein Kinases

Experimental structures · PDB · 41

2E7N NMR
2NXB X-ray 1.40A
2OO1 X-ray 1.70A
2YW5 NMR
3S91 X-ray 2.06A
3S92 X-ray 1.36A
5A7C X-ray 1.90A
5HFR X-ray 1.70A
5HJC X-ray 2.60A
6BGG NMR
6BGH NMR
6I41 X-ray 1.90A
… and 29 more

A predicted model is available from AlphaFold.

Gene Ontology · 19

Drugs targeting this protein · 6

MOLIBRESIB inhibitor
APABETALONE inhibitor
BIRABRESIB inhibitor
RO-6870810 inhibitor
EZOBRESIB inhibitor
PELABRESIB inhibitor

Related proteins · sequence + function similarity

Bromodomain-containing protein 3 0.99
Bromodomain-containing protein 2 0.89
Bromodomain-containing protein 2 0.89
Bromodomain-containing protein 2 0.89
Bromodomain-containing protein 2 0.88
Bromodomain-containing protein 2 0.88
Bromodomain-containing protein 4A 0.84
Bromodomain-containing protein 4B 0.83
Bromodomain-containing protein 4 0.82
Bromodomain-containing protein 4 0.82
Bromodomain-containing protein 4 0.82
Bromodomain-containing protein bet-1 0.79

Co-cited proteins · studied together in the literature

Bromodomain-containing protein 2 4 shared papers
Bromodomain-containing protein 3 1 shared papers
Kelch domain-containing protein 2 1 shared papers
NUT family member 1 1 shared papers
Histone-lysine N-methyltransferase NSD3 2 shared papers
Bromodomain-containing protein 4 4 shared papers
Actin-histidine N-methyltransferase 1 shared papers
Protein ENL 1 shared papers
Gag-Pol polyprotein 1 shared papers
Protein AF-9 1 shared papers
ATP-dependent chromatin remodeler CHD4 1 shared papers
SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4 1 shared papers

Literature · 25 cited papers

A common binding motif in the ET domain of BRD3 forms polymorphic structural interfaces with host and viral proteins. Structure · 2021
lncRNA DIGIT and BRD3 protein form phase-separated condensates to regulate endoderm differentiation. Nat. Cell Biol. · 2020
Selective targeting of BD1 and BD2 of the BET proteins in cancer and immunoinflammation. Science · 2020
Selective inhibition of the BD2 bromodomain of BET proteins in prostate cancer. Nature · 2020
The BRD3 ET domain recognizes a short peptide motif through a mechanism that is conserved across chromatin remodelers and transcriptional regulators. J. Biol. Chem. · 2018
Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat. Struct. Mol. Biol. · 2017
Molecular coupling of histone crotonylation and active transcription by AF9 YEATS domain. Mol. Cell · 2016
Screen identifies bromodomain protein ZMYND8 in chromatin recognition of transcription-associated DNA damage that promotes homologous recombination. Genes Dev. · 2015
An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
Histone recognition and large-scale structural analysis of the human bromodomain family. Cell · 2012
System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci. Signal. · 2011
… and 13 more in the literature graph

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