Rabbit anti-Human BRD4 Polyclonal Antibody | anti-BRD4 antibody
BRD4, CT (BRD4, HUNK1, Bromodomain-containing protein 4, Protein HUNK1)
Purified by Protein A affinity chromatography.
Purified by Protein A affinity chromatography.
Dilution: ELISA: 1:1,000
Western Blot: 1:100-500
NCBI and Uniprot Product Information
NCBI Description
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 Description
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 (Ref.25). 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. Ref.7 Ref.8 Ref.15 Ref.16 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28Isoform 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. Ref.7 Ref.8 Ref.15 Ref.16 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28
Subunit structure: Interacts with p53/TP53; the interaction is direct. Interacts (via CTD region) with CDK9 and CCNT1, acting as an associated component of P-TEFb complex. Interacts with RELA (when acetylated at 'Lys-310'). Interacts (via NET domain) with WHSC1L1, JMJD6, CHD4, GLTSCR1 and ATAD5. Isoform B: interacts with NCAPD3 and SMC2. Interacts with bovine papillomavirus type 1 regulatory protein E2 and human herpes virus-8 (HHV-8) protein LANA. These interactions may serve for the tethering of viral genomes to host mitotic chromosomes allowing successful partitioning of the viral genome during cell division. Interacts with Epstein-Barr virus (EBV) protein EBNA1; this interaction facilitates transcriptional activation by EBNA1. Ref.7 Ref.8 Ref.10 Ref.11 Ref.12 Ref.16 Ref.21 Ref.26 Ref.28
Subcellular location: 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. Ref.7 Ref.22 Ref.28 Ref.31
Tissue specificity: Ubiquitously expressed. Ref.6
Domain: The NET domain mediates interaction with a number of chromatin proteins involved in transcription regulation (WHSC1L1, JMJD6, CHD4, GLTSCR1 and ATAD5) (Ref.21).The C-terminal (CTD) region mediates interaction and recruitment of CDK9 and CCNT1 subunits of the P-TEFb complex (Ref.7, Ref.8). It is also required for maintenance of higher-order chromatin structure (Ref.23).The 2 bromo domains mediate specific binding to acetylated histones via Asn-140 and Asn-433, respectively (Ref.31). The exact combination of modified histone tails required to recruit BRD4 to target genes is still unclear. The first bromo domain has high affinity for acetylated histone H4 tail, whereas the second bromo domain recognizes multiply acetylated marks in histone H3 (Ref.39). A number of specific inhibitors bind competitively to acetyl-lysine-binding residues Asn-140 and Asn-433, promoting removal from acetylated histones. Many of these inhibitors are benzodiazepine derivatives (Ref.35, Ref.37, Ref.40, Ref.41).
Post-translational modification: Phosphorylation by CK2 disrupt the intramolecular binding between the bromo domain 2 and the NPS region and promotes binding between the NPS and the BID regions, leading to activate the protein and promote binding to acetylated histones. In absence of phosphorylation, BRD4 does not localize to p53/TP53 target gene promoters, phosphorylation promoting recruitment to p53/TP53 target promoters.
Involvement in disease: 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. Ref.1 Ref.6
Miscellaneous: Some specific inhibitors of BRD4 that prevent binding to acetylated histones by binding Asn-140 and Asn-433 are promising therapeutic molecules for the treatment of leukemias. JQ1, a thieno-triazolo-1,4-diazepine derivative, and I-BET, a benzodiazepine derivative, have been tested on tumors with success (Ref.31, Ref.32, Ref.34). Treatment with GSK1210151A (I-BET151, a I-BET derivative) has strong effets on mixed lineage leukemia and promotes myeloid differentiation and leukemia stem-cell depletion (Ref.34).
Sequence similarities: Contains 2 bromo domains.Contains 1 NET domain.
Sequence caution: The sequence AAC27978.1 differs from that shown. Reason: Erroneous initiation.
Research Articles on BRD4
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Product Notes
The BRD4 brd4 (Catalog #AAA648256) is an Antibody produced from Rabbit and is intended for research purposes only. The product is available for immediate purchase. The BRD4, CT (BRD4, HUNK1, Bromodomain-containing protein 4, Protein HUNK1) reacts with Human and may cross-react with other species as described in the data sheet. AAA Biotech's BRD4 can be used in a range of immunoassay formats including, but not limited to, ELISA (EL/EIA), Western Blot (WB). Suitable for use in Western Blot, ELISA Dilution: ELISA: 1:1,000 Western Blot: 1:100-500. Researchers should empirically determine the suitability of the BRD4 brd4 for an application not listed in the data sheet. Researchers commonly develop new applications and it is an integral, important part of the investigative research process. It is sometimes possible for the material contained within the vial of "BRD4, Polyclonal Antibody" to become dispersed throughout the inside of the vial, particularly around the seal of said vial, during shipment and storage. We always suggest centrifuging these vials to consolidate all of the liquid away from the lid and to the bottom of the vial prior to opening. Please be advised that certain products may require dry ice for shipping and that, if this is the case, an additional dry ice fee may also be required.Precautions
All products in the AAA Biotech catalog are strictly for research-use only, and are absolutely not suitable for use in any sort of medical, therapeutic, prophylactic, in-vivo, or diagnostic capacity. By purchasing a product from AAA Biotech, you are explicitly certifying that said products will be properly tested and used in line with industry standard. AAA Biotech and its authorized distribution partners reserve the right to refuse to fulfill any order if we have any indication that a purchaser may be intending to use a product outside of our accepted criteria.Disclaimer
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