Tchem BRD4 Bromodomain-containing protein 4

Protein Summary

Description

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: BRD4 is 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. 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 (PubMed:22509028). 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. Isoform B: Acts as a chromatin insulator in the DNA damage response pathway. Inhibits DNA damage response signaling by recruiting the condensin-2 complex to acetylated histones, leading to chromatin structure remodeling, insulating the region from DNA damage response by limiting spreading of histone H2AFX/H2A.x phosphorylation. The protein encoded by this gene is homologous to the murine protein MCAP, which associates with chromosomes during mitosis, and to the human RING3 protein, a serine/threonine kinase. Each of these proteins contains two bromodomains, a conserved sequence motif which may be involved in chromatin targeting. This gene has been implicated as the chromosome 19 target of translocation t(15;19)(q13;p13.1), which defines an upper respiratory tract carcinoma in young people. Two alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• O60885
• O60433
• Q4G0X8
• Q86YS8
• Q96PD3

Gene Name

• BRD4

Ensembl ID

• ENST00000263377
• ENSP00000263377
• ENSG00000141867
• ENST00000360016
• ENSP00000353112
• ENST00000371835
• ENSP00000360901

Symbol

• HUNK1
• CAP
• MCAP
• HUNK1
• HUNKI

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
viral protein	1
virus	1
biological process	0.94
co-expressed gene	0.93
interacting protein	0.84

Protein Classes

DTO Classes

Protein / Epigenetic Regulator / Reader / Bromodomain / Bromodomain-containing Protein 4

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1188.82   (req: < 5)

Gene RIFs: 353   (req: <= 3)

Antibodies: 374   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1188.82   (req: >= 5)

Gene RIFs: 353   (req: > 3)

Antibodies: 374   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 20

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 2604

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 6