TOP2B

Topoisomerase (DNA) II beta 180kDa

Human Topoisomerase Iibeta in complex with DNA (gold spheres). PDB entry 4j3n[1]
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
SymbolsTOP2B ; TOPIIB; top2beta
External IDsOMIM: 126431 MGI: 98791 HomoloGene: 134711 ChEMBL: 3396 GeneCards: TOP2B Gene
EC number5.99.1.3
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez715521974
EnsemblENSG00000077097ENSMUSG00000017485
UniProtQ02880Q64511
RefSeq (mRNA)NM_001068NM_009409
RefSeq (protein)NP_001059NP_033435
Location (UCSC)Chr 3:
25.64 – 25.71 Mb
Chr 14:
16.37 – 16.43 Mb
PubMed search

DNA topoisomerase 2-beta is an enzyme that in humans is encoded by the TOP2B gene.[2][3]

This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during transcription. This nuclear enzyme is involved in processes such as chromosome condensation, chromatid separation, and the relief of torsional stress that occurs during DNA transcription and replication. It catalyzes the transient breaking and rejoining of two strands of duplex DNA which allows the strands to pass through one another, thus altering the topology of DNA. Two forms of this enzyme exist as likely products of a gene duplication event. The gene encoding this form, beta, is localized to chromosome 3 and the alpha form is localized to chromosome 17. The gene encoding this enzyme functions as the target for several anticancer agents, for example mitoxantrone, and a variety of mutations in this gene have been associated with the development of drug resistance. Reduced activity of this enzyme may also play a role in ataxia-telangiectasia. Alternative splicing of this gene results in two transcript variants; however, the second variant has not yet been fully described.[4]

Interactions

TOP2B has been shown to interact with BAZ1B,[5] HDAC1,[6][7] Histone deacetylase 2,[6] T-cell surface glycoprotein CD3 epsilon chain,[8] Small ubiquitin-related modifier 1[9] and P53.[10]

References

  1. Wu, C. -C.; Li, Y. -C.; Wang, Y. -R.; Li, T. -K.; Chan, N. -L. (2013). "On the structural basis and design guidelines for type II topoisomerase-targeting anticancer drugs". Nucleic Acids Research 41 (22): 10630–10640. doi:10.1093/nar/gkt828. PMID 24038465.
  2. Tan KB, Dorman TE, Falls KM, Chung TD, Mirabelli CK, Crooke ST, Mao J (January 1992). "Topoisomerase II alpha and topoisomerase II beta genes: characterization and mapping to human chromosomes 17 and 3, respectively". Cancer Res 52 (1): 231–4. PMID 1309226.
  3. Jenkins JR, Ayton P, Jones T, Davies SL, Simmons DL, Harris AL, Sheer D, Hickson ID (January 1993). "Isolation of cDNA clones encoding the beta isozyme of human DNA topoisomerase II and localisation of the gene to chromosome 3p24". Nucleic Acids Res 20 (21): 5587–92. doi:10.1093/nar/20.21.5587. PMC 334390. PMID 1333583.
  4. "Entrez Gene: TOP2B topoisomerase (DNA) II beta 180kDa".
  5. Kitagawa, Hirochika; Fujiki Ryoji, Yoshimura Kimihiro, Mezaki Yoshihiro, Uematsu Yoshikatsu, Matsui Daisuke, Ogawa Satoko, Unno Kiyoe, Okubo Mataichi, Tokita Akifumi, Nakagawa Takeya, Ito Takashi, Ishimi Yukio, Nagasawa Hiromichi, Matsumoto Toshio, Yanagisawa Junn, Kato Shigeaki (June 2003). "The chromatin-remodeling complex WINAC targets a nuclear receptor to promoters and is impaired in Williams syndrome". Cell (United States) 113 (7): 905–17. doi:10.1016/S0092-8674(03)00436-7. ISSN 0092-8674. PMID 12837248.
  6. 6.0 6.1 Tsai, S C; Valkov N; Yang W M; Gump J; Sullivan D; Seto E (November 2000). "Histone deacetylase interacts directly with DNA topoisomerase II". Nat. Genet. (UNITED STATES) 26 (3): 349–53. doi:10.1038/81671. ISSN 1061-4036. PMID 11062478.
  7. Johnson, C A; Padget K; Austin C A; Turner B M (February 2001). "Deacetylase activity associates with topoisomerase II and is necessary for etoposide-induced apoptosis". J. Biol. Chem. (United States) 276 (7): 4539–42. doi:10.1074/jbc.C000824200. ISSN 0021-9258. PMID 11136718.
  8. Nakano, H; Yamazaki T; Miyatake S; Nozaki N; Kikuchi A; Saito T (March 1996). "Specific interaction of topoisomerase II beta and the CD3 epsilon chain of the T cell receptor complex". J. Biol. Chem. (UNITED STATES) 271 (11): 6483–9. doi:10.1074/jbc.271.11.6483. ISSN 0021-9258. PMID 8626450.
  9. Mao, Y; Desai S D; Liu L F (August 2000). "SUMO-1 conjugation to human DNA topoisomerase II isozymes". J. Biol. Chem. (UNITED STATES) 275 (34): 26066–73. doi:10.1074/jbc.M001831200. ISSN 0021-9258. PMID 10862613.
  10. Cowell, I G; Okorokov A L; Cutts S A; Padget K; Bell M; Milner J; Austin C A (February 2000). "Human topoisomerase IIalpha and IIbeta interact with the C-terminal region of p53". Exp. Cell Res. (UNITED STATES) 255 (1): 86–94. doi:10.1006/excr.1999.4772. ISSN 0014-4827. PMID 10666337.

Further reading