lmmol · Proteins

Bromodomain-containing protein 4

UniProt O60885 Organism Homo sapiens Gene BRD4, HUNK1

Also known as: BRD4, HUNK1

Function

Chromatin reader protein that recognizes and binds acetylated histones and plays a key role in transmission of epigenetic memory across cell divisions and transcription regulation. Remains associated with acetylated chromatin throughout the entire cell cycle and provides epigenetic memory for postmitotic G1 gene transcription by preserving acetylated chromatin status and maintaining high-order chromatin structure. During interphase, plays a key role in regulating the transcription of signal-inducible genes by associating with the P-TEFb complex and recruiting it to promoters. Also recruits P-TEFb complex to distal enhancers, so called anti-pause enhancers in collaboration with JMJD6. BRD4 and JMJD6 are required to form the transcriptionally active P-TEFb complex by displacing negative regulators such as HEXIM1 and 7SKsnRNA complex from P-TEFb, thereby transforming it into an active form that can then phosphorylate the C-terminal domain (CTD) of RNA polymerase II. Regulates differentiation of naive CD4(+) T-cells into T-helper Th17 by promoting recruitment of P-TEFb to promoters (By similarity). Promotes phosphorylation of 'Ser-2' of the C-terminal domain (CTD) of RNA polymerase II. According to a report, directly acts as an atypical protein kinase and mediates phosphorylation of 'Ser-2' of the C-terminal domain (CTD) of RNA polymerase II; these data however need additional evidences in vivo. In addition to acetylated histones, also recognizes and binds acetylated RELA, leading to further recruitment of the P-TEFb complex and subsequent activation of NF-kappa-B. Also acts as a regulator of p53/TP53-mediated transcription: following phosphorylation by CK2, recruited to p53/TP53 specific target promoters.

Classification

Family (Pfam)
PF17035 BET, PF17105 BRD4_CDT, PF00439 Bromodomain
InterPro
BRD4_CDT, Bromo_Brdt_I, Bromo_Brdt_II, Bromo_chromatin_reader, Bromodomain, Bromodomain-like_sf, Bromodomain_CS, NET_dom, NET_sf
Functional cluster
RNA-Polymerase II Transcription Factors

Experimental structures · PDB · 602

A predicted model is available from AlphaFold.

Gene Ontology · 36

Disease associations

Drugs targeting this protein · 6

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Literature · 56 cited papers

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