Bromodomain-containing protein 2
Also known as: BRD2, KIAA9001, RING3
Function
Chromatin reader protein that specifically recognizes and binds histone H4 acetylated at 'Lys-5' and 'Lys-12' (H4K5ac and H4K12ac, respectively), 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. Plays a key role in genome compartmentalization via its association with CTCF and cohesin: recruited to chromatin by CTCF and promotes formation of topologically associating domains (TADs) via its ability to bind acetylated histones, contributing to CTCF boundary formation and enhancer insulation. Also recognizes and binds acetylated non-histone proteins, such as STAT3. Involved in inflammatory response by regulating differentiation of naive CD4(+) T-cells into T-helper Th17: recognizes and binds STAT3 acetylated at 'Lys-87', promoting STAT3 recruitment to chromatin. In addition to acetylated lysines, also recognizes and binds lysine residues on histones that are both methylated and acetylated on the same side chain to form N6-acetyl-N6-methyllysine (Kacme), an epigenetic mark of active chromatin associated with increased transcriptional initiation. Specifically binds histone H4 acetyl-methylated at 'Lys-5' and 'Lys-12' (H4K5acme and H4K12acme, respectively).
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
- Homeobox & Zinc-Finger Transcription Factors
Experimental structures · PDB · 166
- 1X0J X-ray 1.80A
- 2DVQ X-ray 2.04A
- 2DVR X-ray 2.30A
- 2DVS X-ray 2.04A
- 2DVV X-ray 1.80A
- 2E3K X-ray 2.30A
- 2G4A NMR
- 2YDW X-ray 1.90A
- 2YEK X-ray 1.98A
- 3AQA X-ray 2.30A
- 3ONI X-ray 1.61A
- 4A9E X-ray 1.91A
- … and 154 more
A predicted model is available from AlphaFold.
Gene Ontology · 20
- GO:0000785 chromatin
- GO:0005737 cytoplasm
- GO:0016607 nuclear speck
- GO:0005654 nucleoplasm
- GO:0005634 nucleus
- GO:0140033 acetylation-dependent protein binding
- GO:0003682 chromatin binding
- GO:0042393 histone binding
- GO:0140015 histone H3K14ac reader activity
- GO:0140011 histone H4K12ac reader activity
- GO:0140012 histone H4K5ac reader activity
- GO:0004674 protein serine/threonine kinase activity
- GO:0140588 chromatin looping
- GO:0006338 chromatin remodeling
- GO:0006351 DNA-templated transcription
- GO:0006334 nucleosome assembly
- GO:2000330 positive regulation of T-helper 17 cell lineage commitment
- GO:0071168 protein localization to chromatin
- GO:0006357 regulation of transcription by RNA polymerase II
- GO:0007283 spermatogenesis
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 2 1.00
- Bromodomain-containing protein 2 1.00
- Bromodomain-containing protein 2 0.99
- Bromodomain-containing protein 2 0.99
- Bromodomain-containing protein 3 0.89
- Bromodomain-containing protein 3 0.88
- Bromodomain testis-specific protein 0.83
- Bromodomain-containing protein 4A 0.83
- Bromodomain-containing protein 4 0.82
- Bromodomain-containing protein 4B 0.81
- Bromodomain testis-specific protein 0.77
- Bromodomain testis-specific protein 0.74
Co-cited proteins · studied together in the literature
- Bromodomain-containing protein 3 4 shared papers
- Protein LANA1 1 shared papers
- Bromodomain-containing protein 4 3 shared papers
- Bromodomain-containing protein 2 1 shared papers
- Bromodomain-containing protein 4 1 shared papers
- Histone-lysine N-methyltransferase set5 1 shared papers
- Histone H4 1 shared papers
- Histone H4 1 shared papers
- Histone H4 1 shared papers
- Signal transducer and activator of transcription 3 1 shared papers
- Histone H4 1 shared papers
- Histone acetyltransferase p300 1 shared papers
Literature · 27 cited papers
- Acetyl-methyllysine marks chromatin at active transcription start sites. Nature · 2023
- BRD2 compartmentalizes the accessible genome. Nat. Genet. · 2022
- 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
- Distinct roles of Brd2 and Brd4 in potentiating the transcriptional program for th17 cell differentiation. Mol. Cell · 2017
- 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
- System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci. Signal. · 2011
- Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
- Selective inhibition of BET bromodomains. Nature · 2010
- Structural implications for K5/K12-di-acetylated histone H4 recognition by the second bromodomain of BRD2. FEBS Lett. · 2010
- … and 15 more in the literature graph