BRD4

BRD4
Available structures PDB Human UniProt search: PDBe RCSB List of PDB id codes 2I8N, 2LSP, 2MJV, 2OSS, 2OUO, 2YEL, 2YEM, 3MXF, 3P5O, 3SVF, 3SVG, 3U5J, 3U5K, 3U5L, 3UVW, 3UVX, 3UVY, 3UW9, 3ZYU, 4A9L, 4BJX, 4BW1, 4BW2, 4BW3, 4BW4, 4C66, 4C67, 4CFK, 4CFL, 4CL9, 4CLB, 4DON, 4E96, 4F3I, 4GPJ, 4HBV, 4HBW, 4HBX, 4HBY, 4HXK, 4HXL, 4HXM, 4HXN, 4HXO, 4HXP, 4HXR, 4HXS, 4IOO, 4IOQ, 4IOR, 4J0R, 4J0S, 4J3I, 4KV1, 4KV4, 4LR6, 4LRG, 4LYI, 4LYS, 4LYW, 4LZR, 4LZS, 4MEN, 4MEO, 4MEP, 4MEQ, 4MR3, 4MR4, 4NQM, 4NR8, 4NUC, 4NUD, 4NUE, 4O70, 4O71, 4O72, 4O74, 4O75, 4O76, 4O77, 4O78, 4O7A, 4O7B, 4O7C, 4O7E, 4O7F, 4OGI, 4OGJ, 4PCE, 4PCI, 4PS5, 4QB3, 4QR3, 4QR4, 4QR5, 4QZS, 4UIX, 4UIZ, 4UYD, 4WIV, 4XY9, 4XYA, 4Z1Q, 4Z1S, 4Z93, 5A5S, 5A85, 5BT4, 5D3T, 5D3S, 5D3H, 5D3J, 5CTL, 4WHW, 5D3R, 4X2I, 5CPE, 5CRZ, 4YH3, 4ZC9, 5EI4, 5D3P, 5CQT, 5D3L, 5EIS, 5CRM, 5D0C, 5EGU, 5CP5, 5D25, 5CY9, 5COI, 5D26, 4YH4, 5CS8, 5ACY, 5DX4, 5D24, 5HM0, 5HLS, 2N3K, 5JWM, 5DLX, 2NCZ, 2NNU, 5DW2, 2ND1, 4ZW1, 5CFW, 2ND0, 5DLZ
Identifiers
Aliases	BRD4, CAP, HUNK1, HUNKI, MCAP, bromodomain containing 4
External IDs	OMIM: 608749 HomoloGene: 137685 GeneCards: BRD4
Gene location (Human) Chr. Chromosome 19 (human) Band 19p13.12 Start 15,235,519 bp End 15,332,545 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in sural nerve nipple internal globus pallidus pylorus secondary oocyte cardia renal medulla vena cava entorhinal cortex saphenous vein n/a More reference expression data BioGPS More reference expression data
Gene ontology Molecular function p53 binding chromatin binding protein binding lysine-acetylated histone binding RNA polymerase II complex binding RNA polymerase II CTD heptapeptide repeat kinase activity enzyme binding RNA polymerase II C-terminal domain binding P-TEFb complex binding Cellular component nucleoplasm chromosome condensed nuclear chromosome nucleus cytosol Biological process chromatin remodeling regulation of transcription, DNA-templated negative regulation of DNA damage checkpoint regulation of transcription involved in G1/S transition of mitotic cell cycle transcription, DNA-templated cellular response to DNA damage stimulus regulation of inflammatory response positive regulation of I-kappaB kinase/NF-kappaB signaling positive regulation of G2/M transition of mitotic cell cycle regulation of phosphorylation of RNA polymerase II C-terminal domain viral process positive regulation of transcription elongation from RNA polymerase II promoter positive regulation of transcription by RNA polymerase II chromatin organization protein phosphorylation positive regulation of transcription, DNA-templated positive regulation of histone H3-K36 trimethylation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 23476 n/a Ensembl ENSG00000141867 n/a UniProt O60885 n/a RefSeq (mRNA) NM_014299 NM_058243 NM_001330384 NM_001379291 NM_001379292 n/a RefSeq (protein) NP_001317313 NP_055114 NP_490597 NP_001366220 NP_001366221 n/a Location (UCSC) Chr 19: 15.24 – 15.33 Mb n/a PubMed search n/a
Wikidata
View/Edit Human

Bromodomain-containing protein 4 is a protein that in humans is encoded by the BRD4 gene.

BRD4 is a member of the BET (bromodomain and extra terminal domain) family, which also includes BRD2, BRD3, and BRDT. BRD4, similar to other BET family members, contains two bromodomains that recognize acetylated lysine residues. BRD4 also has an extended C-terminal domain with little sequence homology to other BET family members.

Structure

The two bromodomains in BRD4, termed BD1 and BD2, consist of 4 alpha-helices linked by 2 loops. The ET domain structure is made up of 3 alpha-helices and a loop. The C-terminal domain of BRD4 has been implicated in promoting gene transcription through interaction with the transcription elongation factor P-TEFb and RNA polymerase II.

Function

The protein encoded by this gene is homologous to the murine protein MCAP, which associates with chromosomes during mitosis, and to the human BRD2 (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 the NUT midline carcinoma. Two alternatively spliced transcript variants have been described.

Role in cancer

Most cases of NUT midline carcinoma involve translocation of the BRD4 gene with NUT genes. BRD4 is often required for expression of Myc and other "tumor driving" oncogenes in hematologic cancers including multiple myeloma, acute myelogenous leukemia and acute lymphoblastic leukaemia.

BRD4 is a major target of BET inhibitors, a class of pharmaceutical drugs currently being evaluated in clinical trials.

Interactions

Notably, BRD4 interacts with P-TEFb via its P-TEFb interaction domain (PID), thereby stimulating its kinase activity and stimulating its phosphorylation of the carboxy-terminal domain (CTD) of RNA polymerase II. Recent review.

BRD4 has been shown to interact with GATA1,JMJD6,RFC2,RFC3,RFC1,RFC4 and RFC5.

BRD4 has also been implicated in binding with the diacetylated Twist protein, and the disruption of this interaction has been shown to suppress tumorigenesis in basal-like breast cancer.

BRD4 has also been shown to interact with a variety of inhibitors, such as MS417; inhibition of BRD4 with MS417 has been shown to down-regulate NF-κB activity seen in HIV-associated kidney disease. BRD4 also interacts with apabetalone (RVX-208), which is being evaluated for treatment of atherosclerosis and cardiovascular disease.

External links

• Human BRD4 genome location and BRD4 gene details page in the UCSC Genome Browser.

Further reading