InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: BRD4

Summary

InnateDB Protein

IDBP-34502.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

BRD4

Protein Name

bromodomain containing 4

Synonyms

CAP; HUNK1; HUNKI; MCAP;

Species

Homo sapiens

Ensembl Protein

ENSP00000263377

InnateDB Gene

IDBG-34500 (BRD4)

Protein Structure

UniProt Annotation

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: 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. {ECO:0000269PubMed:22509028}.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.

Subcellular Localization

Nucleus. Chromosome. Note=Associates with acetylated chromatin. Released from chromatin upon deacetylation of histones that can be triggered by different signals such as activation of the JNK pathway or nocodazole treatment.

Disease Associations

Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein. {ECO:0000269PubMed:11733348, ECO:0000269PubMed:12543779}.

Tissue Specificity

Ubiquitously expressed. {ECO:0000269PubMed:12543779}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 103 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.

Experimentally validated
Total	103 [view]
Protein-Protein	83 [view]
Protein-DNA	19 [view]
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	1 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0002039	p53 binding
GO:0003677	DNA binding
GO:0003682	chromatin binding
GO:0005515	protein binding
GO:0070577	lysine-acetylated histone binding

Biological Process

GO:0000083	regulation of transcription involved in G1/S transition of mitotic cell cycle
GO:0001833	inner cell mass cell proliferation
GO:0006338	chromatin remodeling
GO:0006351	transcription, DNA-templated
GO:0006468	protein phosphorylation
GO:0006974	cellular response to DNA damage stimulus
GO:0007059	chromosome segregation
GO:0010971	positive regulation of G2/M transition of mitotic cell cycle
GO:0016032	viral process
GO:0032968	positive regulation of transcription elongation from RNA polymerase II promoter
GO:0043123	positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043388	positive regulation of DNA binding
GO:0043983	histone H4-K12 acetylation
GO:0044154	histone H3-K14 acetylation
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0050727	regulation of inflammatory response
GO:1901407	regulation of phosphorylation of RNA polymerase II C-terminal domain
GO:2000002	negative regulation of DNA damage checkpoint

Cellular Component

GO:0000790	nuclear chromatin
GO:0000794	condensed nuclear chromosome
GO:0005634	nucleus
GO:0005694	chromosome
GO:0005737	cytoplasm
GO:0008024	positive transcription elongation factor complex b