Protein: TP53-binding protein 1 (53BP1) (p53-binding protein 1) (p53BP1) (Q12888)
Organism: Homo sapiens (Human)
Function: Double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis. Plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs and specifically counteracting the function of the homologous recombination (HR) repair protein BRCA1. In response to DSBs, phosphorylation by ATM promotes interaction with RIF1 and dissociation from NUDT16L1/TIRR, leading to recruitment to DSBs sites. Recruited to DSBs sites by recognizing and binding histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) and histone H4 dimethylated at 'Lys-20' (H4K20me2), two histone marks that are present at DSBs sites. Required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs. Participates in the repair and the orientation of the broken DNA ends during CSR (By similarity). In contrast, it is not required for classic NHEJ and V(D)J recombination (By similarity). Promotes NHEJ of dysfunctional telomeres via interaction with PAXIP1.
Subcellular location: Nucleus {ECO:0000269|PubMed:11331310, ECO:0000269|PubMed:15525939, ECO:0000269|PubMed:16294045, ECO:0000269|PubMed:16294047, ECO:0000269|PubMed:17190600, ECO:0000269|PubMed:19176521, ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:28241136, ECO:0000269|PubMed:9748285}. Chromosome {ECO:0000269|PubMed:12824158, ECO:0000269|PubMed:15525939, ECO:0000269|PubMed:17190600, ECO:0000269|PubMed:23333306, ECO:0000269|PubMed:23760478, ECO:0000269|PubMed:24703952, ECO:0000269|PubMed:28241136, ECO:0000269|PubMed:31135337, ECO:0000269|PubMed:37696958}. Chromosome, centromere, kinetochore {ECO:0000250|UniProtKB:P70399}. Note=Localizes to the nucleus in absence of DNA damage (PubMed:28241136). Following DNA damage, recruited to sites of DNA damage, such as double stand breaks (DSBs): recognizes and binds histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) and histone H4 dimethylated at 'Lys-20' (H4K20me2), two histone marks that are present at DSBs sites (PubMed:17190600, PubMed:23333306, PubMed:23760478, PubMed:24703952, PubMed:28241136, PubMed:31135337, PubMed:37696958). Associated with kinetochores during mitosis (By similarity). {ECO:0000250|UniProtKB:P70399, ECO:0000269|PubMed:17190600, ECO:0000269|PubMed:23333306, ECO:0000269|PubMed:23760478, ECO:0000269|PubMed:28241136, ECO:0000269|PubMed:37696958}.
Sequence: MDPTGSQLDSDFSQQDTPCLIIEDSQPESQVLEDDSGSHFSMLSRHLPNLQTHKENPVLDVVSNPEQTAGEERGDGNSGFNEHLKENKVADPVDSSNLDTCGSISQVIEQLPQPNRTSSVLGMSVESAPAVEEEKGEELEQKEKEKEEDTSGNTTHSLGAEDTASSQLGFGVLELSQSQDVEENTVPYEVDKEQLQSVTTNSGYTRLSDVDANTAIKHEEQSNEDIPIAEQSSKDIPVTAQPSKDVHVVKEQNPPPARSEDMPFSPKASVAAMEAKEQLSAQELMESGLQIQKSPEPEVLSTQEDLFDQSNKTVSSDGCSTPSREEGGCSLASTPATTLHLLQLSGQRSLVQDSLSTNSSDLVAPSPDAFRSTPFIVPSSPTEQEGRQDKPMDTSVLSEEGGEPFQKKLQSGEPVELENPPLLPESTVSPQASTPISQSTPVFPPGSLPIPSQPQFSHDIFIPSPSLEEQSNDGKKDGDMHSSSLTVECSKTSEIEPKNSPEDLGLSLTGDSCKLMLSTSEYSQSPKMESLSSHRIDEDGENTQIEDTEPMSPVLNSKFVPAENDSILMNPAQDGEVQLSQNDDKTKGDDTDTRDDISILATGCKGREETVAEDVCIDLTCDSGSQAVPSPATRSEALSSVLDQEEAMEIKEHHPEEGSSGSEVEEIPETPCESQGEELKEENMESVPLHLSLTETQSQGLCLQKEMPKKECSEAMEVETSVISIDSPQKLAILDQELEHKEQEAWEEATSEDSSVVIVDVKEPSPRVDVSCEPLEGVEKCSDSQSWEDIAPEIEPCAENRLDTKEEKSVEYEGDLKSGTAETEPVEQDSSQPSLPLVRADDPLRLDQELQQPQTQEKTSNSLTEDSKMANAKQLSSDAEAQKLGKPSAHASQSFCESSSETPFHFTLPKEGDIIPPLTGATPPLIGHLKLEPKRHSTPIGISNYPESTIATSDVMSESMVETHDPILGSGKGDSGAAPDVDDKLCLRMKLVSPETEASEESLQFNLEKPATGERKNGSTAVAESVASPQKTMSVLSCICEARQENEARSEDPPTTPIRGNLLHFPSSQGEEEKEKLEGDHTIRQSQQPMKPISPVKDPVSPASQKMVIQGPSSPQGEAMVTDVLEDQKEGRSTNKENPSKALIERPSQNNIGIQTMECSLRVPETVSAATQTIKNVCEQGTSTVDQNFGKQDATVQTERGSGEKPVSAPGDDTESLHSQGEEEFDMPQPPHGHVLHRHMRTIREVRTLVTRVITDVYYVDGTEVERKVTEETEEPIVECQECETEVSPSQTGGSSGDLGDISSFSSKASSLHRTSSGTSLSAMHSSGSSGKGAGPLRGKTSGTEPADFALPSSRGGPGKLSPRKGVSQTGTPVCEEDGDAGLGIRQGGKAPVTPRGRGRRGRPPSRTTGTRETAVPGPLGIEDISPNLSPDDKSFSRVVPRVPDSTRRTDVGAGALRRSDSPEIPFQAAAGPSDGLDASSPGNSFVGLRVVAKWSSNGYFYSGKITRDVGAGKYKLLFDDGYECDVLGKDILLCDPIPLDTEVTALSEDEYFSAGVVKGHRKESGELYYSIEKEGQRKWYKRMAVILSLEQGNRLREQYGLGPYEAVTPLTKAADISLDNLVEGKRKRRSNVSSPATPTASSSSSTTPTRKITESPRASMGVLSGKRKLITSEEERSPAKRGRKSATVKPGAVGAGEFVSPCESGDNTGEPSALEEQRGPLPLNKTLFLGYAFLLTMATTSDKLASRSKLPDGPTGSSEEEEEFLEIPPFNKQYTESQLRAGAGYILEDFNEAQCNTAYQCLLIADQHCRTRKYFLCLASGIPCVSHVWVHDSCHANQLQNYRNYLLPAGYSLEEQRILDWQPRENPFQNLKVLLVSDQQQNFLELWSEILMTGGAASVKQHHSSAHNKDIALGVFDVVVTDPSCPASVLKCAEALQLPVVSQEWVIQCLIVGERIGFKQHPKYKHDYVSH
InterPro domains: - IPR015125: Tumour suppressor p53-binding protein-1, Tudor domain (domain) [1483-1604]
- IPR047250: TP53-binding protein 1-like, second BRCT domain (domain) [1868-1954]
- IPR047249: TP53-binding protein 1-like, first BRCT domain (domain) [1728-1839]
- IPR047252: TP53-binding protein 1-like (family) [263-1972]
- IPR014722: Large ribosomal subunit protein uL2, domain 2 (homologous_superfamily) [1539-1603]
- IPR001357: BRCT domain (domain) [1661-1964]
- IPR036420: BRCT domain superfamily (homologous_superfamily) [1715-1971]
Interaction partners: - Serine-protein kinase ATM
- Histone H4
- PAX-interacting protein 1
- Histone H2AX
- Breast cancer type 1 susceptibility protein
- Cellular tumor antigen p53
- Mediator of DNA damage checkpoint protein 1
- Histone H2A type 2-A
- DNA topoisomerase 2-binding protein 1
- Ubiquitin carboxyl-terminal hydrolase 28
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:1901363 (heterocyclic compound binding), GO:0097159 (organic cyclic compound binding), GO:0005515 (protein binding), GO:0003676 (nucleic acid binding), GO:0042393 (histone binding), GO:0140030 (modification-dependent protein binding), GO:0035064 (methylated histone binding), GO:0003677 (DNA binding), GO:0140034 (methylation-dependent protein binding), GO:0003684 (damaged DNA binding), GO:0043565 (sequence-specific DNA binding), GO:0042162 (telomeric DNA binding)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0019222 (regulation of metabolic process), GO:0048584 (positive regulation of response to stimulus), GO:0051240 (positive regulation of multicellular organismal process), GO:0002684 (positive regulation of immune system process), GO:0006807 (nitrogen compound metabolic process), GO:0002682 (regulation of immune system process), GO:0051239 (regulation of multicellular organismal process), GO:0071704 (organic substance metabolic process), GO:0009892 (negative regulation of metabolic process), GO:0050793 (regulation of developmental process), GO:0044237 (cellular metabolic process), GO:0050794 (regulation of cellular process), GO:0048583 (regulation of response to stimulus), GO:0009893 (positive regulation of metabolic process), GO:0051716 (cellular response to stimulus), GO:0006950 (response to stress), GO:0051094 (positive regulation of developmental process), GO:0048523 (negative regulation of cellular process), GO:0048585 (negative regulation of response to stimulus), GO:0044238 (primary metabolic process), GO:0048522 (positive regulation of cellular process), GO:0045830 (positive regulation of isotype switching), GO:0051172 (negative regulation of nitrogen compound metabolic process), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0046483 (heterocycle metabolic process), GO:0080134 (regulation of response to stress), GO:0080135 (regulation of cellular response to stress), GO:0060255 (regulation of macromolecule metabolic process), GO:0002700 (regulation of production of molecular mediator of immune response), GO:0002694 (regulation of leukocyte activation), GO:0006725 (cellular aromatic compound metabolic process), GO:0034641 (cellular nitrogen compound metabolic process), GO:0031324 (negative regulation of cellular metabolic process), GO:0043170 (macromolecule metabolic process), GO:0050867 (positive regulation of cell activation), GO:0002696 (positive regulation of leukocyte activation), GO:2001021 (negative regulation of response to DNA damage stimulus), GO:1901360 (organic cyclic compound metabolic process), GO:0050776 (regulation of immune response), GO:0006139 (nucleobase-containing compound metabolic process), GO:0031325 (positive regulation of cellular metabolic process), GO:0002702 (positive regulation of production of molecular mediator of immune response), GO:0002697 (regulation of immune effector process), GO:0033554 (cellular response to stress), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0009889 (regulation of biosynthetic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0051173 (positive regulation of nitrogen compound metabolic process), GO:0050778 (positive regulation of immune response), GO:0031323 (regulation of cellular metabolic process), GO:0002699 (positive regulation of immune effector process), GO:0080090 (regulation of primary metabolic process), GO:0044260 (cellular macromolecule metabolic process), GO:0050865 (regulation of cell activation), GO:0010556 (regulation of macromolecule biosynthetic process), GO:0051052 (regulation of DNA metabolic process), GO:0002703 (regulation of leukocyte mediated immunity), GO:0051054 (positive regulation of DNA metabolic process), GO:0006974 (cellular response to DNA damage stimulus), GO:0010628 (positive regulation of gene expression), GO:0002705 (positive regulation of leukocyte mediated immunity), GO:0045738 (negative regulation of DNA repair), GO:0002639 (positive regulation of immunoglobulin production), GO:2001020 (regulation of response to DNA damage stimulus), GO:0010468 (regulation of gene expression), GO:0045935 (positive regulation of nucleobase-containing compound metabolic process), GO:0051053 (negative regulation of DNA metabolic process), GO:0051251 (positive regulation of lymphocyte activation), GO:0090304 (nucleic acid metabolic process), GO:0031326 (regulation of cellular biosynthetic process), GO:0002821 (positive regulation of adaptive immune response), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0006259 (DNA metabolic process), GO:0002637 (regulation of immunoglobulin production), GO:0051252 (regulation of RNA metabolic process), GO:0045934 (negative regulation of nucleobase-containing compound metabolic process), GO:0002819 (regulation of adaptive immune response), GO:0051249 (regulation of lymphocyte activation), GO:0045191 (regulation of isotype switching), GO:0000018 (regulation of DNA recombination), GO:0002822 (regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains), GO:0045911 (positive regulation of DNA recombination), GO:0002824 (positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains), GO:0002708 (positive regulation of lymphocyte mediated immunity), GO:0006282 (regulation of DNA repair), GO:2000780 (negative regulation of double-strand break repair), GO:2001141 (regulation of RNA biosynthetic process), GO:0006355 (regulation of DNA-templated transcription), GO:0006281 (DNA repair), GO:0045910 (negative regulation of DNA recombination), GO:0002706 (regulation of lymphocyte mediated immunity), GO:0050864 (regulation of B cell activation), GO:0050871 (positive regulation of B cell activation), GO:2000779 (regulation of double-strand break repair), GO:0002714 (positive regulation of B cell mediated immunity), GO:1903506 (regulation of nucleic acid-templated transcription), GO:0002712 (regulation of B cell mediated immunity), GO:0010569 (regulation of double-strand break repair via homologous recombination), GO:2000042 (negative regulation of double-strand break repair via homologous recombination), GO:0006302 (double-strand break repair), GO:0002889 (regulation of immunoglobulin mediated immune response), GO:0002891 (positive regulation of immunoglobulin mediated immune response), GO:0006303 (double-strand break repair via nonhomologous end joining)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0031974 (membrane-enclosed lumen), GO:0016604 (nuclear body), GO:0005654 (nucleoplasm), GO:0043233 (organelle lumen), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0070013 (intracellular organelle lumen), GO:0031981 (nuclear lumen), GO:0005634 (nucleus)