TP53BP1

TP53BP1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesTP53BP1, 53BP1, p202, p53BP1, TP53, TDRD30, tumor protein p53 binding protein 1
External IDsMGI: 1351320 HomoloGene: 4137 GeneCards: TP53BP1
Gene location (Human)
Chr.Chromosome 15 (human)[1]
BandNo data availableStart43,403,061 bp[1]
End43,510,728 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

7158

27223

Ensembl

ENSG00000067369

ENSMUSG00000043909

UniProt

Q12888

P70399

RefSeq (mRNA)

NM_001141979
NM_001141980
NM_005657

NM_001290830
NM_013735

RefSeq (protein)

NP_001135451
NP_001135452
NP_005648

NP_001277759
NP_038763

Location (UCSC)Chr 15: 43.4 – 43.51 MbChr 15: 121.19 – 121.27 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Tumor suppressor p53-binding protein 1 also known as p53-binding protein 1 or 53BP1 is a protein that in humans is encoded by the TP53BP1 gene.[5][6][7]

Clinical significance

53BP1 is underexpressed in most cases of triple-negative breast cancer.[8]

DNA repair

DNA double-strand breaks (DSBs) are cytotoxic damages that can be repaired either by the homologous recombinational repair (HR) pathway or by the non-homologous end-joining (NHEJ) pathway. NHEJ, although faster than HR, is less accurate. The early divergent step between the two pathways is end resection, and this step is regulated by numerous factors. In particular, BRCA1 and 53BP1 play a role in determining the balance between the two pathways.[9][10] 53BP1 restricts resection and promotes NHEJ.

Interactions

53BP1 has been shown to physically interact with:

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000067369 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000043909 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:".
  4. ↑ "Mouse PubMed Reference:".
  5. ↑ Iwabuchi K, Bartel PL, Li B, Marraccino R, Fields S (Jun 1994). "Two cellular proteins that bind to wild-type but not mutant p53". Proceedings of the National Academy of Sciences of the United States of America. 91 (13): 6098–102. PMC 44145 Freely accessible. PMID 8016121. doi:10.1073/pnas.91.13.6098.
  6. ↑ Iwabuchi K, Li B, Massa HF, Trask BJ, Date T, Fields S (Oct 1998). "Stimulation of p53-mediated transcriptional activation by the p53-binding proteins, 53BP1 and 53BP2". The Journal of Biological Chemistry. 273 (40): 26061–8. PMID 9748285. doi:10.1074/jbc.273.40.26061.
  7. ↑ "Entrez Gene: TP53BP1 tumor protein p53 binding protein 1".
  8. ↑ Bouwman P, Aly A, Escandell JM, Pieterse M, Bartkova J, van der Gulden H, Hiddingh S, Thanasoula M, Kulkarni A, Yang Q, Haffty BG, Tommiska J, Blomqvist C, Drapkin R, Adams DJ, Nevanlinna H, Bartek J, Tarsounas M, Ganesan S, Jonkers J (Jun 2010). "53BP1 loss rescues BRCA1 deficiency and is associated with triple-negative and BRCA-mutated breast cancers". Nature Structural & Molecular Biology. 17 (6): 688–95. PMC 2912507 Freely accessible. PMID 20453858. doi:10.1038/nsmb.1831.
  9. ↑ Panier S, Boulton SJ (2014). "Double-strand break repair: 53BP1 comes into focus". Nat. Rev. Mol. Cell Biol. 15 (1): 7–18. PMID 24326623. doi:10.1038/nrm3719.
  10. ↑ Li J, Xu X (2016). "DNA double-strand break repair: a tale of pathway choices". Acta Biochim. Biophys. Sin. (Shanghai). 48 (7): 641–6. PMID 27217474. doi:10.1093/abbs/gmw045.
  11. ↑ Botuyan MV, Lee J, Ward IM, Kim JE, Thompson JR, Chen J, Mer G (Dec 2006). "Structural basis for the methylation state-specific recognition of histone H4-K20 by 53BP1 and Crb2 in DNA repair". Cell. 127 (7): 1361–73. PMC 1804291 Freely accessible. PMID 17190600. doi:10.1016/j.cell.2006.10.043.
  12. ↑ Derbyshire DJ, Basu BP, Serpell LC, Joo WS, Date T, Iwabuchi K, Doherty AJ (Jul 2002). "Crystal structure of human 53BP1 BRCT domains bound to p53 tumour suppressor". The EMBO Journal. 21 (14): 3863–72. PMC 126127 Freely accessible. PMID 12110597. doi:10.1093/emboj/cdf383.
  13. ↑ Ekblad CM, Friedler A, Veprintsev D, Weinberg RL, Itzhaki LS (Mar 2004). "Comparison of BRCT domains of BRCA1 and 53BP1: a biophysical analysis". Protein Science. 13 (3): 617–25. PMC 2286730 Freely accessible. PMID 14978302. doi:10.1110/ps.03461404.
  14. ↑ Joo WS, Jeffrey PD, Cantor SB, Finnin MS, Livingston DM, Pavletich NP (Mar 2002). "Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure". Genes & Development. 16 (5): 583–93. PMC 155350 Freely accessible. PMID 11877378. doi:10.1101/gad.959202.
  15. ↑ Derbyshire DJ, Basu BP, Date T, Iwabuchi K, Doherty AJ (Oct 2002). "Purification, crystallization and preliminary X-ray analysis of the BRCT domains of human 53BP1 bound to the p53 tumour suppressor". Acta Crystallographica Section D. 58 (Pt 10 Pt 2): 1826–9. PMID 12351827. doi:10.1107/S0907444902010910.
  16. ↑ Lo KW, Kan HM, Chan LN, Xu WG, Wang KP, Wu Z, Sheng M, Zhang M (Mar 2005). "The 8-kDa dynein light chain binds to p53-binding protein 1 and mediates DNA damage-induced p53 nuclear accumulation". The Journal of Biological Chemistry. 280 (9): 8172–9. PMID 15611139. doi:10.1074/jbc.M411408200.

Further reading

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