TOPBP1

Topoisomerase (DNA) II binding protein 1

Rendering of TOPBP1 from PDB 1WF6
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
SymbolsTOPBP1 ; TOP2BP1
External IDsOMIM: 607760 MGI: 1920018 HomoloGene: 38262 ChEMBL: 3175 GeneCards: TOPBP1 Gene
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez11073235559
EnsemblENSG00000163781ENSMUSG00000032555
UniProtQ92547Q6ZQF0
RefSeq (mRNA)NM_007027NM_176979
RefSeq (protein)NP_008958NP_795953
Location (UCSC)Chr 3:
133.32 – 133.38 Mb
Chr 9:
103.31 – 103.35 Mb
PubMed search

DNA topoisomerase 2-binding protein 1 is an enzyme that in humans is encoded by the TOPBP1 gene.[1][2][3]

This gene encodes a binding protein which interacts with the C-terminal region of topoisomerase II beta. This interaction suggests a supportive role for this protein in the catalytic reactions of topoisomerase II beta through transient breakages of DNA strands.[3]

Interactions

TOPBP1 has been shown to interact with RAD9A,[4] E2F1,[5][6] Promyelocytic leukemia protein,[7] ZBTB17[8] and UBR5.[9]

Clinical relevance

This gene may be involved in the development of ovarian and breast cancer.[10]

Mutations in TOPBP1 cause Idiopathic pulmonary arterial hypertension .[11]

References

  1. Yamane K, Kawabata M, Tsuruo T (February 1998). "A DNA-topoisomerase-II-binding protein with eight repeating regions similar to DNA-repair enzymes and to a cell-cycle regulator". Eur J Biochem 250 (3): 794–9. doi:10.1111/j.1432-1033.1997.00794.x. PMID 9461304.
  2. Nagase T, Seki N, Ishikawa K, Ohira M, Kawarabayasi Y, Ohara O, Tanaka A, Kotani H, Miyajima N, Nomura N (May 1997). "Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain". DNA Res 3 (5): 321–9, 341–54. doi:10.1093/dnares/3.5.321. PMID 9039502.
  3. 3.0 3.1 "Entrez Gene: TOPBP1 topoisomerase (DNA) II binding protein 1".
  4. Mäkiniemi, M; Hillukkala T, Tuusa J, Reini K, Vaara M, Huang D, Pospiech H, Majuri I, Westerling T, Mäkelä T P, Syväoja J E (August 2001). "BRCT domain-containing protein TopBP1 functions in DNA replication and damage response". J. Biol. Chem. (United States) 276 (32): 30399–406. doi:10.1074/jbc.M102245200. ISSN 0021-9258. PMID 11395493.
  5. Liu, Kang; Lin Fang-Tsyr; Ruppert J Michael; Lin Weei-Chin (May 2003). "Regulation of E2F1 by BRCT domain-containing protein TopBP1". Mol. Cell. Biol. (United States) 23 (9): 3287–304. doi:10.1128/MCB.23.9.3287-3304.2003. ISSN 0270-7306. PMC 153207. PMID 12697828.
  6. Yu, Xiaochun; Chini Claudia Christiano Silva; He Miao; Mer Georges; Chen Junjie (October 2003). "The BRCT domain is a phospho-protein binding domain". Science (United States) 302 (5645): 639–42. doi:10.1126/science.1088753. PMID 14576433.
  7. Xu, Zhi-Xiang; Timanova-Atanasova Anna, Zhao Rui-Xun, Chang Kun-Sang (June 2003). "PML colocalizes with and stabilizes the DNA damage response protein TopBP1". Mol. Cell. Biol. (United States) 23 (12): 4247–56. doi:10.1128/MCB.23.12.4247-4256.2003. ISSN 0270-7306. PMC 156140. PMID 12773567.
  8. Herold, Steffi; Wanzel Michael; Beuger Vincent; Frohme Carsten; Beul Dorothee; Hillukkala Tomi; Syvaoja Juhani; Saluz Hans-Peter; Haenel Frank; Eilers Martin (September 2002). "Negative regulation of the mammalian UV response by Myc through association with Miz-1". Mol. Cell (United States) 10 (3): 509–21. doi:10.1016/S1097-2765(02)00633-0. ISSN 1097-2765. PMID 12408820.
  9. Honda, Yoshiomi; Tojo Masahide; Matsuzaki Kazuhito; Anan Tadashi; Matsumoto Mitsuhiro; Ando Masayuki; Saya Hideyuki; Nakao Mitsuyoshi (February 2002). "Cooperation of HECT-domain ubiquitin ligase hHYD and DNA topoisomerase II-binding protein for DNA damage response". J. Biol. Chem. (United States) 277 (5): 3599–605. doi:10.1074/jbc.M104347200. ISSN 0021-9258. PMID 11714696.
  10. Forma E, Wójcik-Krowiranda K, Bieńkiewicz A, Bryś M (2013) Molecular basis of gynecological oncology - TopBP1 protein as the guardian of genome integrity. Ginekol Pol 84(5):373-376
  11. De Jesus Perez, V. A.; Yuan, K; Lyuksyutova, M. A.; Dewey, F; Orcholski, M. E.; Shuffle, E. M.; Mathur, M; Yancy Jr, L; Rojas, V; Li, C. G.; Cao, A; Alastalo, T. P.; Khazeni, N; Cimprich, K. A.; Butte, A. J.; Ashley, E; Zamanian, R. T. (2014). "Whole Exome Sequencing Reveals Topbp1 As a Novel Gene in Idiopathic Pulmonary Arterial Hypertension". American Journal of Respiratory and Critical Care Medicine 189 (10): 140404073105009. doi:10.1164/rccm.201310-1749OC. PMID 24702692.

Further reading