Property Summary

NCBI Gene PubMed Count 84
PubMed Score 107.75
PubTator Score 91.20

Knowledge Summary


No data available


  Differential Expression (9)

Disease log2 FC p
Waldenstrons macroglobulinemia 1.298 1.6e-02
malignant mesothelioma 1.600 3.6e-07
group 3 medulloblastoma 1.200 5.9e-03
non-small cell lung cancer 1.085 1.6e-15
intraductal papillary-mucinous neoplasm ... 1.300 2.7e-03
lung cancer 1.900 4.6e-04
colon cancer 1.100 6.3e-03
diabetes mellitus -1.100 1.3e-03
ovarian cancer 1.500 5.2e-04

Protein-protein Interaction (3)

Gene RIF (67)

26811421 TOPBP1 physically binds PLK1 and promotes PLK1 kinase-mediated phosphorylation of RAD51 at serine 14, a modification required for RAD51 recruitment to chromatin.
26695634 The innate immune regulator STAT-5 is shown to regulate transcription of the ATR binding factor TopBP1, and this is critical for the induction of the ATR pathway in human papillomavirus-infected keratinocytes.
26283799 TopBP1 maintains genome integrity in mitosis by controlling chromatin recruitment of SLX4 and by facilitating unscheduled DNA synthesis.
25916852 Findings demonstrate that TopBP1 and ATR are able to inhibit the synthesis of rRNA and to activate nucleolar stress pathway.
25794620 TopBP1 interacts with BLM to maintain genome stability but is dispensable for preventing BLM degradation.Crucial residues mediating TopBP1-MDC1 interactions identified.
25762097 TOPBP1 has a role in recruiting TOP2A to ultra-fine anaphase bridges to aid in their resolution
25694599 The results suggest that interactions between TopBP1 and E2 and between Brd4 and E2 are required to correctly initiate human papillomavirus 16 DNA replication but are not required for continuing DNA replication.
25454945 Studies identify the SIRT1-TopBP1 axis as a key signaling mode in the regulation of the metabolic checkpoint and the DNA damage checkpoint.
25301947 Phosphorylation of BRIT1 protein coordinates TopBP1 protein recruitment and amplifies ATR signaling in cell DNA damage.
25216549 Functional analyses indicat that the expression TopBP1 and Claspin positively affects the survival of brain cancer cells after exposure to radiation.
24702692 TopBP1 deficiency may increase susceptibility to small vessel loss in IPAH.
24346708 High TopBP1 mRNA and protein expression is associated with endometrial cancer.
24239288 BLM was ubiquitinated by E3 ligase MIB1 and degraded in G1 cells but was stabilized by TopBP1 in S phase cells.
24081328 Akt can switch the TopBP1 function from checkpoint activation to transcriptional regulation by regulating its quaternary structure.
23908141 Polymorphism in TOPBP1 gene is associated with pancreatic cancer.
23891287 Different modes of phosphopeptide binding by TOPBP1 BRCT domains in the DNA damage response.
23819404 Recent findings suggest TopBP1 to be a breast and ovarian cancer susceptibility gene.[review]
23685152 amino acid residues 741-885 are necessary for oligomerization of TopBP1 for centrosomal localization
23383325 Rad9, Rad17, TopBP1 and claspin play essential roles in heat-induced activation of ATR kinase and heat tolerance.
23277395 our results showed that rs115160714 polymorphism can increase breast cancer risk and is associated with changes in TopBP1 expression.
22973044 An interaction between human papillomavirus 16 E2 and TopBP1 is required for optimum viral DNA replication and episomal genome establishment
22925454 the affinity of Rad9 to TopBP1 correlates with the activation of the cellular DNA damage response and survival after DNA damage in HeLa cells.
22708334 TopBP1 is likely to be involved in hereditary predisposition to breast and/or ovarian cancer
22544570 data suggest that decreased level of TopBP1 mRNA and increased level of TopBP1 protein might be associated with progression of hereditary breast cancer
22213094 Localisation of TopBP1 at DNA damage sites was noticed as early as 5 s following damage induction, whereas p54(nrb) and PSF localised there after 20 s.
21930790 findings show TopBP1 interacts with p53 hot spot mutants and NF-YA and promotes mutant p53 and p300 recruitment to NF-Y target gene promoters; TopBP1 mediates mutant p53 gain of function in cancer
21502314 Tethering DNA damage checkpoint mediator proteins topoisomerase IIbeta-binding protein 1 (TopBP1) and Claspin to DNA activates ataxia-telangiectasia mutated and RAD3-related (ATR) phosphorylation of checkpoint kinase 1 (Chk1).
21482717 The specific TopBP1-MDC1 interaction was mediated by the fifth BRCT domain of TopBP1 and the Ser-Asp-Thr repeats of MDC1. TopBP1 accumulation at stalled replication forks was promoted by the H2AX/MDC1 signaling cascade.
21291884 These results suggest that the localization of TopBP1 to the mitotic centrosomes is necessary for proper mitotic progression.
21149450 TopBP1 deficiency in untransformed mouse and human primary cells induces cellular senescence rather than apoptosis. These results indicate that TopBP1 is essential for cell proliferation and maintenance of chromosomal integrity.
21127055 Molecular basis of BACH1/FANCJ recognition by TopBP1 in DNA replication checkpoint control.
21108795 There is no evidence for the TOPBP1*Arg309Cys variant to confer an increased risk for breast cancer in the German population.
20858457 the crystal structure of the TopBP1N-terminal region (residues 1-290) at 2.4A resolution was reported.
20724438 the crystal structure of the N-terminal region of human TopBP1, reveals an unexpected triple-BRCT domain structure.
20566845 Data provide insights into how Ad modulates ATR signaling pathways by promoting TOPBP1 degradation during infection.
20545769 The phosphorylation at both serine residues occurs in vivo and is required for the efficient interaction with TopBP1 in vitro.
20159562 The interaction between TopBP1 and BACH1 is required for the extension of single-stranded DNA regions and RPA loading following replication stress, which is a prerequisite for the subsequent activation of replication checkpoint.
20056645 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
20029092 proliferating cell nuclear antigen, ATR, TopBP1, and Chk1 are recruited to chromatin in a MutLalpha- and MutSalpha-dependent fashion after N-methyl-N'-nitro-N-nitrosoguanidine treatment.
19690177 Observational study of gene-disease association. (HuGE Navigator)
19584272 Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
19289498 Results suggest that a physiological level of TopBP1 is essential for normal G(1)/S transition, but a pathological level of TopBP1 in cancer may perturb p53 function and contribute to an aggressive tumor behavior.
19177012 PML, TopBP1, NBS1 or ATM-induced activation of phosphorylation of Chk2 participates in the DNA damage-elicited pro-apoptotic cascade that leads to the demise of Env-elicited syncytia
19164952 PML, TopBP1, NBS1 or ATM-induced activation of phosphorylation of Chk2 participates in the DNA damage-elicited pro-apoptotic cascade that leads to the demise of Env-elicited syncytia
19097996 HCLK2 functions in the same pathway as TopBP1 but that the two proteins regulate different steps in ATR activation.
19023333 PML, TopBP1, NBS1 or ATM-induced activation of phosphorylation of Chk2 participates in the DNA damage-elicited pro-apoptotic cascade that leads to the demise of Env-elicited syncytia
18923429 Miz1 and Myc affect the activity of the Atr checkpoint through their effect on TopBP1 chromatin association and stability.
18519640 Cellular complementation experiments demonstrate that TopBP1-mediated ATR activation is required for checkpoint signaling and cellular viability
18006695 Observational study of gene-disease association. (HuGE Navigator)
17913746 Interaction between SPBP and TopBP1 was found to be mediated by the ePHD domain of SPBP and the BRCT6 domain of TopBP1.
17887956 human TopBP1 is involved in the formation of the initiation complex of replication in human cells and is required for the recruitment of Cdc45 to origins of DNA replication
17765870 Together, these results suggested that TopBP1 might be a mediator of DNA damage signaling from NBS1 to ATR and promote homologous recombination repair.
17448016 This report demonstrates aberrant expression of the TopBP1 protein in breast carcinoma. We propose TOPBP1 as a breast cancer susceptibility gene.
17293600 TopBP1 necessary for the G(1)/S transition: one for activating cyclin E/CDK2 kinase and the other for loading replication components onto chromatin to initiate DNA synthesis.
17287259 findings show colocalization of TopBP1 and papillomavirus type 16 E2 on chromatin at late stages of mitosis, suggesting that TopBP1 could be the mitotic chromatin receptor for HPV16 E2
16984230 A study evaluating several chromatin modification domains encoded by TopBP1, and the implications of these findings are discussed in the context of the DNA damage response and the understanding of TopBP1 function is presented.
16930991 Observational study of gene-disease association. (HuGE Navigator)
16880517 These results suggest that while TopBP1 is a general regulator of ATR, Claspin operates downstream of TopBP1 to selectively regulate the Chk1-controlled branch of the genotoxic stress response.
16831524 Cooperative regulation of the TopBP1 promoter by Egr-1 and E2F.
16530042 Data show that recombinant TopBP1 induces a large increase in the kinase activity of both Xenopus and human ATR-ATRIP.
16314514 TopBP1 plays a critical role in the maintenance of genomic stability during normal S phase as well as following genotoxic stress.
15961388 TopBP1 is a c-Abl-interacting protein and a repressor for c-Abl expression
15195143 transcription of human MCM10 and TopBP1 is activated by transcription factors E2F1-3, but not by factors E2F4-7
12941802 hRad9/hHus1/hRad1 complex acts as a checkpoint sensor during S phase by rapidly localizing to sites of DNA damage and transducing checkpoint responses by facilitating proper localization of downstream checkpoint proteins, including TopBP1.
12810625 Both TopBP1 and BRCA1 specifically regulate the G(2)-M checkpoint, partially compensating each function.
12773567 TopBP1 is regulated by PML by association and stabilization of the protein in response to IR-induced DNA damage
11934899 interaction between the human papillomavirus 16 transcription/replication factor E2 and the DNA damage response protein TopBP1

AA Sequence


Text Mined References (94)

PMID Year Title
26811421 2016 TOPBP1 regulates RAD51 phosphorylation and chromatin loading and determines PARP inhibitor sensitivity.
26695634 2015 STAT-5 Regulates Transcription of the Topoisomerase II?-Binding Protein 1 (TopBP1) Gene To Activate the ATR Pathway and Promote Human Papillomavirus Replication.
26283799 2015 TopBP1 is required at mitosis to reduce transmission of DNA damage to G1 daughter cells.
25933514 2015 Human DNA helicase B interacts with the replication initiation protein Cdc45 and facilitates Cdc45 binding onto chromatin.
25916852 2015 High levels of TopBP1 induce ATR-dependent shut-down of rRNA transcription and nucleolar segregation.
25794620 2015 TopBP1 interacts with BLM to maintain genome stability but is dispensable for preventing BLM degradation.
25762097 2015 TOPBP1 recruits TOP2A to ultra-fine anaphase bridges to aid in their resolution.
25694599 2015 Evidence supporting a role for TopBP1 and Brd4 in the initiation but not continuation of human papillomavirus 16 E1/E2-mediated DNA replication.
25454945 2014 A divergent role of the SIRT1-TopBP1 axis in regulating metabolic checkpoint and DNA damage checkpoint.
25301947 2014 Phosphorylation of the BRCA1 C terminus (BRCT) repeat inhibitor of hTERT (BRIT1) protein coordinates TopBP1 protein recruitment and amplifies ataxia telangiectasia-mutated and Rad3-related (ATR) Signaling.
25216549 2014 TopBP1 and Claspin contribute to the radioresistance of lung cancer brain metastases.
24702692 2014 Whole-exome sequencing reveals TopBP1 as a novel gene in idiopathic pulmonary arterial hypertension.
24346708 2014 Topoisomerase II? binding protein 1 c.*229C>T (rs115160714) gene polymorphism and endometrial cancer risk.
24239288 2013 TopBP1 controls BLM protein level to maintain genome stability.
24081328 2013 Akt switches TopBP1 function from checkpoint activation to transcriptional regulation through phosphoserine binding-mediated oligomerization.
23908141 2013 Interaction of polymorphisms in mitotic regulator genes with cigarette smoking and pancreatic cancer risk.
23891287 2013 Structural insights into recognition of MDC1 by TopBP1 in DNA replication checkpoint control.
23819404 2013 [Molecular basis of gynecological oncology - TopBP1 protein as the guardian of genome integrity].
23685152 2013 Oligomerization of TopBP1 is necessary for the localization of TopBP1 to mitotic centrosomes.
23383325 2013 Rad9, Rad17, TopBP1 and claspin play essential roles in heat-induced activation of ATR kinase and heat tolerance.
23277395 2013 Association between the c.*229C>T polymorphism of the topoisomerase II? binding protein 1 (TopBP1) gene and breast cancer.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
22973044 2012 An interaction between human papillomavirus 16 E2 and TopBP1 is required for optimum viral DNA replication and episomal genome establishment.
22925454 2012 Two serine phosphorylation sites in the C-terminus of Rad9 are critical for 9-1-1 binding to TopBP1 and activation of the DNA damage checkpoint response in HeLa cells.
22708334 2012 [Molecular basis of gynecological oncology--TopBP1 protein and its participation in the transcription process].
22544570 2012 Expression of TopBP1 in hereditary breast cancer.
22213094 2012 Proteomic identification of PSF and p54(nrb) as TopBP1-interacting proteins.
21930790 2011 TopBP1 mediates mutant p53 gain of function through NF-Y and p63/p73.
21659603 2011 A DNA damage response screen identifies RHINO, a 9-1-1 and TopBP1 interacting protein required for ATR signaling.
21502314 2011 Tethering DNA damage checkpoint mediator proteins topoisomerase IIbeta-binding protein 1 (TopBP1) and Claspin to DNA activates ataxia-telangiectasia mutated and RAD3-related (ATR) phosphorylation of checkpoint kinase 1 (Chk1).
21482717 2011 MDC1 collaborates with TopBP1 in DNA replication checkpoint control.
21291884 2011 Human TopBP1 localization to the mitotic centrosome mediates mitotic progression.
21269460 2011 Initial characterization of the human central proteome.
21149450 2011 TopBP1 deficiency causes an early embryonic lethality and induces cellular senescence in primary cells.
21127055 2011 Molecular basis of BACH1/FANCJ recognition by TopBP1 in DNA replication checkpoint control.
21108795 2010 TOPBP1 missense variant Arg309Cys and breast cancer in a German hospital-based case-control study.
20858457 2010 Crystal structure of the N-terminal region of human Topoisomerase II? binding protein 1.
20724438 2011 Structure and function of the Rad9-binding region of the DNA-damage checkpoint adaptor TopBP1.
20566845 2010 Adenovirus 12 E4orf6 inhibits ATR activation by promoting TOPBP1 degradation.
20545769 2010 Casein kinase 2-dependent phosphorylation of human Rad9 mediates the interaction between human Rad9-Hus1-Rad1 complex and TopBP1.
20159562 2010 BACH1/FANCJ acts with TopBP1 and participates early in DNA replication checkpoint control.
20080954 2010 A vertebrate gene, ticrr, is an essential checkpoint and replication regulator.
20068231 2010 Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.
20056645 2010 Association of mitotic regulation pathway polymorphisms with pancreatic cancer risk and outcome.
20029092 2010 Interactions of human mismatch repair proteins MutSalpha and MutLalpha with proteins of the ATR-Chk1 pathway.
19937654 2010 Insights from the crystal structure of the sixth BRCT domain of topoisomerase IIbeta binding protein 1.
19690332 2009 Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.
19690177 2009 Polymorphic variants in hereditary pancreatic cancer genes are not associated with pancreatic cancer risk.
19584272 2009 Modification of ovarian cancer risk by BRCA1/2-interacting genes in a multicenter cohort of BRCA1/2 mutation carriers.
19289498 2009 Regulation of p53 by TopBP1: a potential mechanism for p53 inactivation in cancer.
19097996 2009 HCLK2 is required for activity of the DNA damage response kinase ATR.
19084217 2009 Variants in TF and HFE explain approximately 40% of genetic variation in serum-transferrin levels.
18923429 2008 Miz1 and HectH9 regulate the stability of the checkpoint protein, TopBP1.
18669648 2008 A quantitative atlas of mitotic phosphorylation.
18519640 2008 TopBP1 activates ATR through ATRIP and a PIKK regulatory domain.
18006695 2008 Scan of 977 nonsynonymous SNPs in CLL4 trial patients for the identification of genetic variants influencing prognosis.
17913746 2007 The ePHD protein SPBP interacts with TopBP1 and together they co-operate to stimulate Ets1-mediated transcription.
17887956 2008 Characterization of the interaction between the human DNA topoisomerase IIbeta-binding protein 1 (TopBP1) and the cell division cycle 45 (Cdc45) protein.
17765870 2007 TopBP1 associates with NBS1 and is involved in homologous recombination repair.
17525332 2007 ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage.
17448016 2007 Aberrant expression of TopBP1 in breast cancer.
17293600 2007 Human TopBP1 participates in cyclin E/CDK2 activation and preinitiation complex assembly during G1/S transition.
17287259 2007 TopBP1 regulates human papillomavirus type 16 E2 interaction with chromatin.
17006541 2006 Regulation of TopBP1 oligomerization by Akt/PKB for cell survival.
16984230 2006 TopBP1 contains a transcriptional activation domain suppressed by two adjacent BRCT domains.
16964243 2006 A probability-based approach for high-throughput protein phosphorylation analysis and site localization.
16930991 2006 Identification of a common polymorphism in the TopBP1 gene associated with hereditary susceptibility to breast and ovarian cancer.
16880517 2006 Claspin operates downstream of TopBP1 to direct ATR signaling towards Chk1 activation.
16831524 2006 The transcription factor Egr-1 is a regulator of the human TopBP1 gene.
16641997 2006 The DNA sequence, annotation and analysis of human chromosome 3.
16530042 2006 TopBP1 activates the ATR-ATRIP complex.
16314514 2005 Human TopBP1 ensures genome integrity during normal S phase.
15961388 2005 Identification of TopBP1 as a c-Abl-interacting protein and a repressor for c-Abl expression.
15635413 2005 Nucleolar proteome dynamics.
15195143 2004 Expression of MCM10 and TopBP1 is regulated by cell proliferation and UV irradiation via the E2F transcription factor.
15188402 2004 Proteins associated with type II bone morphogenetic protein receptor (BMPR-II) and identified by two-dimensional gel electrophoresis and mass spectrometry.
15138768 2004 TopBP1 localises to centrosomes in mitosis and to chromosome cores in meiosis.
15075294 2004 TopBP1 recruits Brg1/Brm to repress E2F1-induced apoptosis, a novel pRb-independent and E2F1-specific control for cell survival.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14576432 2003 BRCT repeats as phosphopeptide-binding modules involved in protein targeting.
12941802 2003 hRad9 rapidly binds DNA containing double-strand breaks and is required for damage-dependent topoisomerase II beta binding protein 1 focus formation.
12810625 2003 Both DNA topoisomerase II-binding protein 1 and BRCA1 regulate the G2-M cell cycle checkpoint.
12773567 2003 PML colocalizes with and stabilizes the DNA damage response protein TopBP1.
12697828 2003 Regulation of E2F1 by BRCT domain-containing protein TopBP1.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12421765 2002 Protein-protein interactions between large proteins: two-hybrid screening using a functionally classified library composed of long cDNAs.
12408820 2002 Negative regulation of the mammalian UV response by Myc through association with Miz-1.
11756551 2002 A DNA damage-regulated BRCT-containing protein, TopBP1, is required for cell survival.
11714696 2002 Cooperation of HECT-domain ubiquitin ligase hHYD and DNA topoisomerase II-binding protein for DNA damage response.
11395493 2001 BRCT domain-containing protein TopBP1 functions in DNA replication and damage response.
10931686 2000 Keratinocytes exposed to ultraviolet radiation reveal three down-regulated genes with potential function in differentiation and cell cycle control.
10498869 1999 Conserved BRCT regions of TopBP1 and of the tumor suppressor BRCA1 bind strand breaks and termini of DNA.
9461304 1997 A DNA-topoisomerase-II-binding protein with eight repeating regions similar to DNA-repair enzymes and to a cell-cycle regulator.
9039502 1996 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.