TP53BP1

Tumor protein p53 binding protein 1

PDB rendering based on 1gzh.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
1GZH, 1KZY, 1XNI, 2G3R, 2IG0, 2LVM, 3LGF, 3LGL, 3LH0

Identifiers

Symbols

TP53BP1 ; 53BP1; p202

External IDs

OMIM: 605230 MGI: 1351320 HomoloGene: 4137 GeneCards: TP53BP1 Gene

Gene ontology
Molecular function	• RNA polymerase II activating transcription factor binding • RNA polymerase II transcription cofactor activity • p53 binding • damaged DNA binding • protein binding • methylated histone binding • telomeric DNA binding
Cellular component	• condensed chromosome kinetochore • chromosome, telomeric region • nucleus • nucleoplasm • replication fork • cytoplasm
Biological process	• double-strand break repair via homologous recombination • DNA repair • double-strand break repair • transcription from RNA polymerase II promoter • cellular response to DNA damage stimulus • positive regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • positive regulation of sequence-specific DNA binding transcription factor activity
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 15:
43.7 – 43.8 Mb

Chr 2:
121.19 – 121.27 Mb

PubMed search

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.^[1]^[2]^[3]

Clinical significance

53BP1 is underexpressed in most cases of triple-negative breast cancer.^[4]

Interactions

53BP1 has been shown to interact with Histone H4 dimethylated or monomethylated at Lysine 20,^[5] Replication protein A1,^[6] RPA2,^[6] E2F1,^[7] Ataxia telangiectasia mutated,^[8]^[9] p53,^[1]^[10]^[11]^[12]^[13]^[14]^[15] PAXIP1,^[16]^[17] DYNLL1,^[13] H2AFX^[8]^[9]^[11] and Bloom syndrome protein.^[11]

References

↑ 1.0 1.1 Iwabuchi K, Bartel PL, Li B, Marraccino R, Fields S (Jul 1994). "Two cellular proteins that bind to wild-type but not mutant p53". Proc Natl Acad Sci U S A 91 (13): 6098–102. doi:10.1073/pnas.91.13.6098. PMC 44145. PMID 8016121.
↑ Iwabuchi K, Li B, Massa HF, Trask BJ, Date T, Fields S (Nov 1998). "Stimulation of p53-mediated transcriptional activation by the p53-binding proteins, 53BP1 and 53BP2". J Biol Chem 273 (40): 26061–8. doi:10.1074/jbc.273.40.26061. PMID 9748285.
↑ "Entrez Gene: TP53BP1 tumor protein p53 binding protein 1".
↑ 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 (June 2010). "53BP1 loss rescues BRCA1 deficiency and is associated with triple-negative and BRCA-mutated breast cancers". Nat. Struct. Mol. Biol. 17 (6): 688–95. doi:10.1038/nsmb.1831. PMC 2912507. PMID 20453858.
↑ Botuyan, Maria Victoria; Lee Joseph; Ward Irene M; Kim Ja-Eun; Thompson James R; Chen Junjie; Mer Georges (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. doi:10.1016/j.cell.2006.10.043. ISSN 0092-8674. PMC 1804291. PMID 17190600.
↑ 6.0 6.1 Yoo, E; Kim Byung U; Lee Seung Youn; Cho Chae Hyun; Chung Jay H; Lee Chang-Hun (Aug 2005). "53BP1 is associated with replication protein A and is required for RPA2 hyperphosphorylation following DNA damage". Oncogene (England) 24 (35): 5423–30. doi:10.1038/sj.onc.1208710. ISSN 0950-9232. PMID 15856006.
↑ Choubey, D; Li S J; Datta B; Gutterman J U; Lengyel P (Oct 1996). "Inhibition of E2F-mediated transcription by p202". EMBO J. (ENGLAND) 15 (20): 5668–78. ISSN 0261-4189. PMC 452311. PMID 8896460.
↑ 8.0 8.1 Fernandez-Capetillo, Oscar; Chen Hua-Tang, Celeste Arkady, Ward Irene, Romanienko Peter J, Morales Julio C, Naka Kazuhito, Xia Zhenfang, Camerini-Otero R Daniel, Motoyama Noboru, Carpenter Phillip B, Bonner William M, Chen Junjie, Nussenzweig André (Dec 2002). "DNA damage-induced G2-M checkpoint activation by histone H2AX and 53BP1". Nat. Cell Biol. (England) 4 (12): 993–7. doi:10.1038/ncb884. ISSN 1465-7392. PMID 12447390.
↑ 9.0 9.1 Ward, Irene M; Minn Kay; Jorda Katherine G; Chen Junjie (May 2003). "Accumulation of checkpoint protein 53BP1 at DNA breaks involves its binding to phosphorylated histone H2AX". J. Biol. Chem. (United States) 278 (22): 19579–82. doi:10.1074/jbc.C300117200. ISSN 0021-9258. PMID 12697768.
↑ Derbyshire, Dean J; Basu Balaku P; Serpell Louise C; Joo Woo S; Date Takayasu; Iwabuchi Kuniyoshi; Doherty Aidan J (Jul 2002). "Crystal structure of human 53BP1 BRCT domains bound to p53 tumour suppressor". EMBO J. (England) 21 (14): 3863–72. doi:10.1093/emboj/cdf383. ISSN 0261-4189. PMC 126127. PMID 12110597.
↑ 11.0 11.1 11.2 Sengupta, Sagar; Robles Ana I, Linke Steven P, Sinogeeva Natasha I, Zhang Ran, Pedeux Remy, Ward Irene M, Celeste Arkady, Nussenzweig André, Chen Junjie, Halazonetis Thanos D, Harris Curtis C (Sep 2004). "Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest". J. Cell Biol. (United States) 166 (6): 801–13. doi:10.1083/jcb.200405128. ISSN 0021-9525. PMC 2172115. PMID 15364958.
↑ Ekblad, Caroline M S; Friedler Assaf; Veprintsev Dmitry; Weinberg Richard L; Itzhaki Laura S (Mar 2004). "Comparison of BRCT domains of BRCA1 and 53BP1: A biophysical analysis". Protein Sci. (United States) 13 (3): 617–25. doi:10.1110/ps.03461404. ISSN 0961-8368. PMC 2286730. PMID 14978302.
↑ 13.0 13.1 Lo, Kevin W-H; Kan Ho-Man; Chan Ling-Nga; Xu Wei-Guang; Wang Ke-Peng; Wu Zhenguo; Sheng Morgan; Zhang Mingjie (Mar 2005). "The 8-kDa dynein light chain binds to p53-binding protein 1 and mediates DNA damage-induced p53 nuclear accumulation". J. Biol. Chem. (United States) 280 (9): 8172–9. doi:10.1074/jbc.M411408200. ISSN 0021-9258. PMID 15611139.
↑ Joo, Woo S; Jeffrey Philip D; Cantor Sharon B; Finnin Michael S; Livingston David M; Pavletich Nikola P (Mar 2002). "Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure". Genes Dev. (United States) 16 (5): 583–93. doi:10.1101/gad.959202. ISSN 0890-9369. PMC 155350. PMID 11877378.
↑ Derbyshire, Dean J; Basu Balaku P; Date Takayasu; Iwabuchi Kuniyoshi; Doherty Aidan J (Oct 2002). "Purification, crystallization and preliminary X-ray analysis of the BRCT domains of human 53BP1 bound to the p53 tumour suppressor". Acta Crystallogr. D Biol. Crystallogr. (Denmark) 58 (Pt 10 Pt 2): 1826–9. doi:10.1107/S0907444902010910. ISSN 0907-4449. PMID 12351827.
↑ Jowsey, Paul A; Doherty Aidan J; Rouse John (Dec 2004). "Human PTIP facilitates ATM-mediated activation of p53 and promotes cellular resistance to ionizing radiation". J. Biol. Chem. (United States) 279 (53): 55562–9. doi:10.1074/jbc.M411021200. ISSN 0021-9258. PMID 15456759.
↑ Manke, Isaac A; Lowery Drew M; Nguyen Anhco; Yaffe Michael B (Oct 2003). "BRCT repeats as phosphopeptide-binding modules involved in protein targeting". Science (United States) 302 (5645): 636–9. doi:10.1126/science.1088877. PMID 14576432.

Choubey D, Lengyel P (1995). "Binding of an interferon-inducible protein (p202) to the retinoblastoma protein". J. Biol. Chem. 270 (11): 6134–40. doi:10.1074/jbc.270.11.6134. PMID 7890747.
Choubey D; Li SJ; Datta B et al. (1996). "Inhibition of E2F-mediated transcription by p202". EMBO J. 15 (20): 5668–78. PMC 452311. PMID 8896460.
Datta B; Li B; Choubey D et al. (1996). "p202, an interferon-inducible modulator of transcription, inhibits transcriptional activation by the p53 tumor suppressor protein, and a segment from the p53-binding protein 1 that binds to p202 overcomes this inhibition". J. Biol. Chem. 271 (44): 27544–55. doi:10.1074/jbc.271.44.27544. PMID 8910340.
Wen Y; Yan DH; Spohn B et al. (2000). "Tumor suppression and sensitization to tumor necrosis factor alpha-induced apoptosis by an interferon-inducible protein, p202, in breast cancer cells". Cancer Res. 60 (1): 42–6. PMID 10646849.
Xia Z, Morales JC, Dunphy WG, Carpenter PB (2001). "Negative cell cycle regulation and DNA damage-inducible phosphorylation of the BRCT protein 53BP1". J. Biol. Chem. 276 (4): 2708–18. doi:10.1074/jbc.M007665200. PMID 11042216.
Joo WS; Jeffrey PD; Cantor SB et al. (2002). "Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure". Genes Dev. 16 (5): 583–93. doi:10.1101/gad.959202. PMC 155350. PMID 11877378.
Derbyshire DJ; Basu BP; Serpell LC et al. (2002). "Crystal structure of human 53BP1 BRCT domains bound to p53 tumour suppressor". EMBO J. 21 (14): 3863–72. doi:10.1093/emboj/cdf383. PMC 126127. PMID 12110597.
Lai H; Lin L; Nadji M et al. (2002). "Mutations in the p53 tumor suppressor gene and early onset breast cancer". Cancer Biol. Ther. 1 (1): 31–6. doi:10.4161/cbt.1.1.37. PMID 12170762.
Derbyshire DJ; Basu BP; Date T et al. (2003). "Purification, crystallization and preliminary X-ray analysis of the BRCT domains of human 53BP1 bound to the p53 tumour suppressor". Acta Crystallogr. D Biol. Crystallogr. 58 (Pt 10 Pt 2): 1826–9. doi:10.1107/S0907444902010910. PMID 12351827.
Wang B, Matsuoka S, Carpenter PB, Elledge SJ (2002). "53BP1, a mediator of the DNA damage checkpoint". Science 298 (5597): 1435–8. doi:10.1126/science.1076182. PMID 12364621.
Richie CT; Peterson C; Lu T et al. (2003). "hSnm1 Colocalizes and Physically Associates with 53BP1 before and after DNA Damage". Mol. Cell. Biol. 22 (24): 8635–47. doi:10.1128/MCB.22.24.8635-8647.2002. PMC 139863. PMID 12446782.
DiTullio RA; Mochan TA; Venere M et al. (2003). "53BP1 functions in an ATM-dependent checkpoint pathway that is constitutively activated in human cancer". Nat. Cell Biol. 4 (12): 998–1002. doi:10.1038/ncb892. PMID 12447382.
Fernandez-Capetillo O; Chen HT; Celeste A et al. (2003). "DNA damage-induced G2-M checkpoint activation by histone H2AX and 53BP1". Nat. Cell Biol. 4 (12): 993–7. doi:10.1038/ncb884. PMID 12447390.
Strausberg RL; Feingold EA; Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Peng A, Chen PL (2003). "NFBD1, like 53BP1, is an early and redundant transducer mediating Chk2 phosphorylation in response to DNA damage". J. Biol. Chem. 278 (11): 8873–6. doi:10.1074/jbc.C300001200. PMID 12551934.
Stewart GS; Wang B; Bignell CR et al. (2003). "MDC1 is a mediator of the mammalian DNA damage checkpoint". Nature 421 (6926): 961–6. doi:10.1038/nature01446. PMID 12607005.
Yan DH; Abramian A; Li Z et al. (2003). "P202, an interferon-inducible protein, inhibits E2F1-mediated apoptosis in prostate cancer cells". Biochem. Biophys. Res. Commun. 303 (1): 219–22. doi:10.1016/S0006-291X(03)00320-6. PMID 12646190.
Kao GD; McKenna WG; Guenther MG et al. (2003). "Histone deacetylase 4 interacts with 53BP1 to mediate the DNA damage response". J. Cell Biol. 160 (7): 1017–27. doi:10.1083/jcb.200209065. PMC 2172769. PMID 12668657.

PDB gallery

1gzh: CRYSTAL STRUCTURE OF THE BRCT DOMAINS OF HUMAN 53BP1 BOUND TO THE P53 TUMOR SUPPRESSOR

1kzy: Crystal Structure of the 53bp1 BRCT Region Complexed to Tumor Suppressor P53

1ssf: Solution structure of the mouse 53BP1 fragment (residues 1463-1617)

1xni: Tandem Tudor Domain of 53BP1

2g3r: Crystal Structure of 53BP1 tandem tudor domains at 1.2 A resolution

2ig0: Structure of 53BP1/methylated histone peptide complex

TP53BP1

Clinical significance

Interactions

References

Further reading