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Gene Review

BRD2  -  bromodomain containing 2

Homo sapiens

Synonyms: Bromodomain-containing protein 2, D6S113E, FSH, FSRG1, KIAA9001, ...
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Disease relevance of BRD2


Psychiatry related information on BRD2

  • Correlations between NAT variables and neuropsychological tests suggest the executive control deficits associated with VaD may contribute to specific action difficulties, such as distractor interference and inefficient, error-prone action on complex tasks [5].
  • While the groups did not differ in dementia severity or overall impairment on the NAT, the VaD group committed more errors (3.3 vs. 1.6, p = 02) [5].
  • This study examines differences between individuals diagnosed with vascular dementia (VaD; n = 25) versus Alzheimer's disease (AD; n = 23) on the Naturalistic Action Test (NAT; Schwartz et al., 2003), a performance-based measure that includes three tasks of increasing complexity [5].
  • The purpose of this study was to determine whether polymorphisms in the human NAT genes influence susceptibility to Alzheimer's disease [6].

High impact information on BRD2


Chemical compound and disease context of BRD2

  • NAT was identified recently in Mycobacterium tuberculosis and is a candidate for modulating the response to isoniazid [9].
  • A new platelet alloantigen, termed CA, has recently been implicated in a case of neonatal alloimmune thrombocytopenia (NATP) in a Filipino family in Canada. Maternal anti-CA serum reacted with glycoprotein (GP) IIIa and maintained its reactivity after removal of high mannose carbohydrate residues from GPIIIa [10].
  • In this report, we demonstrate an interaction between subtilisin NAT (formerly designated BSP, or nattokinase), a profibrinolytic serine proteinase from Bacillus subtilis, and plasminogen activator inhibitor 1 (PAI-1) [11].
  • Conjugation of primary amino and hydroxylamino groups with acetate, catalyzed by acetyl CoA-dependent arylamine acetyltransferase (NAT) enzymes, may play an important role in the intricate series of metabolic pathways that produce or prevent toxicity following exposure to homo- and heterocyclic arylamine and hydrazine xenobiotics [12].
  • The NAT activities of Klebsiella pneumoniae were inhibited by ibuprofen in a dose-dependent manner both in vitro and in vivo [13].

Biological context of BRD2


Anatomical context of BRD2


Associations of BRD2 with chemical compounds

  • High-molecular-mass complexes (1 to 2 MDa) sharing several subunits but apparently differing in others include the TRAP/SMCC, NAT, DRIP, ARC, and human Mediator complexes [21].
  • These data strongly suggest that defective arylamine N-acetylation in the rabbit model is caused by a gene deletion resulting in an absence of specific mRNA and NAT enzyme protein [22].
  • The first three-dimensional structure of a member of the NAT family identifies a catalytic triad consisting of aspartate, histidine and cysteine proposed to form the activation mechanism [9].
  • Arylamine N:-acetyltransferase (NAT) was first identified as the inactivator of the anti-tubercular drug isoniazid [9].
  • We explored the feasibility of allele-specific oligonucleotide probe typing for PIA antigens to determine the risk of second or subsequent fetuses in families where one infant had a diagnosis of anti-PIA1-mediated NATP [4].

Other interactions of BRD2

  • RING3 and ORFX are found to be ubiquitously expressed in human adult and foetal tissues [23].
  • DNA sequencing of this clone and predicted amino acids showed more than 93% homology to RING3 kinase, a member of a newly described family of bromodomain-containing proteins that transactivates in the nucleus the promoters of a number of the E2F family of transcription factors [19].
  • The class II region of the human MHC contains all of the known class II genes: as well as antigen processing components and only one gene not obviously associated with the immune system, RING3 [24].
  • Association of BRD2 polymorphisms with photoparoxysmal response [25].
  • We present a dense STR/linkage disequilibrium(LD)/gene map between the RING3 and HLA-B loci, reference allelic sizes on the most prevalent HLA haplotypes and their allelic frequencies in pedigree founders [26].

Analytical, diagnostic and therapeutic context of BRD2

  • Northern blot analysis showed that the NAT gene was expressed with a 4-kb transcript in all of tissues examined so far [16].
  • Tissue was fixed for immunohistochemistry with specific NAT antibodies [27].
  • Here, we report that synthetic gallosilicate molecular sieves with the NAT topology and Si/Ga ratios close to but slightly higher than 1.50 undergo an in situ transformation under their crystallization conditions [28].
  • The potential effect of the NAT genotypes in individual susceptibility to lung cancer was examined in a hospital based case-control study consisting of 392 Caucasian lung cancer patients [152 adenocarcinomas, 173 squamous cell carcinomas (SCC) and 67 other primary lung tumours] and 351 controls [29].
  • CONCLUSIONS: This case suggests that, at least in some newly infected individuals, the HCV viral load can fluctuate dramatically prior to seroconversion, and that NAT, even on individual samples, will not totally prevent HCV transmission [30].


  1. Kaposi's Sarcoma-Associated Herpesvirus LANA-1 Interacts with the Short Variant of BRD4 and Releases Cells from a BRD4- and BRD2/RING3-Induced G1 Cell Cycle Arrest. Ottinger, M., Christalla, T., Nathan, K., Brinkmann, M.M., Viejo-Borbolla, A., Schulz, T.F. J. Virol. (2006) [Pubmed]
  2. E mu-BRD2 transgenic mice develop B-cell lymphoma and leukemia. Greenwald, R.J., Tumang, J.R., Sinha, A., Currier, N., Cardiff, R.D., Rothstein, T.L., Faller, D.V., Denis, G.V. Blood (2004) [Pubmed]
  3. Failure of routine HIV-1 tests in a case involving transmission with preseroconversion blood components during the infectious window period. Ling, A.E., Robbins, K.E., Brown, T.M., Dunmire, V., Thoe, S.Y., Wong, S.Y., Leo, Y.S., Teo, D., Gallarda, J., Phelps, B., Chamberland, M.E., Busch, M.P., Folks, T.M., Kalish, M.L. JAMA (2000) [Pubmed]
  4. Prenatal diagnosis of neonatal alloimmune thrombocytopenia using allele-specific oligonucleotide probes. McFarland, J.G., Aster, R.H., Bussel, J.B., Gianopoulos, J.G., Derbes, R.S., Newman, P.J. Blood (1991) [Pubmed]
  5. Everyday action in dementia: evidence for differential deficits in Alzheimer's disease versus subcortical vascular dementia. Giovannetti, T., Schmidt, K.S., Gallo, J.L., Sestito, N., Libon, D.J. Journal of the International Neuropsychological Society : JINS. (2006) [Pubmed]
  6. NAT gene polymorphisms and susceptibility to Alzheimer's disease: identification of a novel NAT1 allelic variant. Johnson, N., Bell, P., Jonovska, V., Budge, M., Sim, E. BMC Med. Genet. (2004) [Pubmed]
  7. Composite co-activator ARC mediates chromatin-directed transcriptional activation. Näär, A.M., Beaurang, P.A., Zhou, S., Abraham, S., Solomon, W., Tjian, R. Nature (1999) [Pubmed]
  8. BRD2 (RING3) is a probable major susceptibility gene for common juvenile myoclonic epilepsy. Pal, D.K., Evgrafov, O.V., Tabares, P., Zhang, F., Durner, M., Greenberg, D.A. Am. J. Hum. Genet. (2003) [Pubmed]
  9. An update on genetic, structural and functional studies of arylamine N-acetyltransferases in eucaryotes and procaryotes. Sim, E., Payton, M., Noble, M., Minchin, R. Hum. Mol. Genet. (2000) [Pubmed]
  10. Amino acid 489 is encoded by a mutational "hot spot" on the beta 3 integrin chain: the CA/TU human platelet alloantigen system. Wang, R., McFarland, J.G., Kekomaki, R., Newman, P.J. Blood (1993) [Pubmed]
  11. The profibrinolytic enzyme subtilisin NAT purified from Bacillus subtilis Cleaves and inactivates plasminogen activator inhibitor type 1. Urano, T., Ihara, H., Umemura, K., Suzuki, Y., Oike, M., Akita, S., Tsukamoto, Y., Suzuki, I., Takada, A. J. Biol. Chem. (2001) [Pubmed]
  12. Human acetyltransferase polymorphisms. Grant, D.M., Hughes, N.C., Janezic, S.A., Goodfellow, G.H., Chen, H.J., Gaedigk, A., Yu, V.L., Grewal, R. Mutat. Res. (1997) [Pubmed]
  13. Ibuprofen inhibits arylamine N-acetyltransferase activity in the bacteria Klebsiella pneumoniae. Chung, J.G., Lo, H.H., Hsieh, S.E., Yen, Y.S. Curr. Microbiol. (1997) [Pubmed]
  14. Crystal Structure of the Human BRD2 Bromodomain: INSIGHTS INTO DIMERIZATION AND RECOGNITION OF ACETYLATED HISTONE H4. Nakamura, Y., Umehara, T., Nakano, K., Jang, M.K., Shirouzu, M., Morita, S., Uda-Tochio, H., Hamana, H., Terada, T., Adachi, N., Matsumoto, T., Tanaka, A., Horikoshi, M., Ozato, K., Padmanabhan, B., Yokoyama, S. J. Biol. Chem. (2007) [Pubmed]
  15. RING3 kinase transactivates promoters of cell cycle regulatory genes through E2F. Denis, G.V., Vaziri, C., Guo, N., Faller, D.V. Cell Growth Differ. (2000) [Pubmed]
  16. Orientation of HLA-DNA gene and identification of a CpG island-associated gene adjacent to DNA in human major histocompatibility complex class II region. Okamoto, N., Ando, A., Kawai, J., Yoshiwara, T., Tsuji, K., Inoko, H. Hum. Immunol. (1991) [Pubmed]
  17. Phylogeny and structure of the RING3 gene. Thorpe, K.L., Abdulla, S., Kaufman, J., Trowsdale, J., Beck, S. Immunogenetics (1996) [Pubmed]
  18. A homologue of the Drosophila female sterile homeotic (fsh) gene in the class II region of the human MHC. Beck, S., Hanson, I., Kelly, A., Pappin, D.J., Trowsdale, J. DNA Seq. (1992) [Pubmed]
  19. Identification and cloning of an 85-kDa protein homologous to RING3 that is upregulated in proliferating endothelial cells. BelAiba, R.S., Baril, P., Chebloune, Y., Tabone, E., Boukerche, H. Eur. J. Biochem. (2001) [Pubmed]
  20. Activation-induced nuclear translocation of RING3. Guo, N., Faller, D.V., Denis, G.V. J. Cell. Sci. (2000) [Pubmed]
  21. Characterization of mediator complexes from HeLa cell nuclear extract. Wang, G., Cantin, G.T., Stevens, J.L., Berk, A.J. Mol. Cell. Biol. (2001) [Pubmed]
  22. N-acetylation pharmacogenetics: a gene deletion causes absence of arylamine N-acetyltransferase in liver of slow acetylator rabbits. Blum, M., Grant, D.M., Demierre, A., Meyer, U.A. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  23. Chromosomal localization, gene structure and transcription pattern of the ORFX gene, a homologue of the MHC-linked RING3 gene. Thorpe, K.L., Gorman, P., Thomas, C., Sheer, D., Trowsdale, J., Beck, S. Gene (1997) [Pubmed]
  24. Organisation and functions of class II genes and molecules. Beck, S., Belich, M., Gruneberg, U., Jackson, A., Kelly, A., Sanseau, P., Sanderson, F., Trowsdale, J., Van Ham, M. DNA Seq. (1996) [Pubmed]
  25. Association of BRD2 polymorphisms with photoparoxysmal response. Lorenz, S., Taylor, K.P., Gehrmann, A., Becker, T., Muhle, H., Gresch, M., Tauer, U., Sander, T., Stephani, U. Neurosci. Lett. (2006) [Pubmed]
  26. Short tandem repeat (STR) haplotypes in HLA: an integrated 50-kb STR/linkage disequilibrium/gene map between the RING3 and HLA-B genes and identification of STR haplotype diversification in the class III region. Vorechovsky, I., Kralovicova, J., Laycock, M.D., Webster, A.D., Marsh, S.G., Madrigal, A., Hammarström, L. Eur. J. Hum. Genet. (2001) [Pubmed]
  27. Expression of arylamine N-acetyltransferase in human intestine. Hickman, D., Pope, J., Patil, S.D., Fakis, G., Smelt, V., Stanley, L.A., Payton, M., Unadkat, J.D., Sim, E. Gut (1998) [Pubmed]
  28. In situ disorder-order transformation in synthetic gallosilicate zeolites with the NAT topology. Hong, S.B., Lee, S.H., Shin, C.H., Woo, A.J., Alvarez, L.J., Zicovich-Wilson, C.M., Camblor, M.A. J. Am. Chem. Soc. (2004) [Pubmed]
  29. Relevance of N-acetyltransferase 1 and 2 (NAT1, NAT2) genetic polymorphisms in non-small cell lung cancer susceptibility. Wikman, H., Thiel, S., Jäger, B., Schmezer, P., Spiegelhalder, B., Edler, L., Dienemann, H., Kayser, K., Schulz, V., Drings, P., Bartsch, H., Risch, A. Pharmacogenetics (2001) [Pubmed]
  30. Fluctuation of HCV viral load before seroconversion in a healthy volunteer blood donor. Fang, C.T., Tobler, L.H., Haesche, C., Busch, M.P., Phelps, B., Leparc, G. Transfusion (2003) [Pubmed]
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