| 纯度 | >90%SDS-PAGE. |
| 种属 | Human |
| 靶点 | TOPBP1 |
| Uniprot No | Q7Z2Z1 |
| 内毒素 | < 0.01EU/μg |
| 表达宿主 | E.coli |
| 表达区间 | 1-1910aa |
| 氨基酸序列 | MACCHKVMLLLDTAGGAARHSRVRRAALRLLTYLSCRFGLARVHWAFKFFDSQGARSRPSRVSDFRELGSRSWEDFEEELEARLEDRAHLPGPAPRATHTHGALMETLLDYQWDRPEITSPTKPILRSSGRRLLDVESEAKEAEAALGGLVNAVFLLAPCPHSQRELLQFVSGCEAQAQRLPPTPKQVMEKLLPKRVREVMVARKITFYWVDTTEWSKLWESPDHLGYWTVCELLHHGGGTVLPSESFSWDFAQAGEMLLRSGIKLSSEPHLSPWISMLPTDATLNRLLYNSPEYEASFPRMEGMLFLPVEAGKEIQETWTVTLEPLAMHQRHFQKPVRIFLKGSVAQWSLPTSSTLGTDSWMLGSPEESTATQRLLFQQLVSRLTAEELHLVADVDPGEGRPPITGVISPLSASAMILTVCRTKEAEFQRHVLQTAVADSPRDTASLFSDVVDSILNQTHDSLADTASAASPVPEWAQQELGHTTPWSPAVVEKWFPFCNISGASSDLMESFGLLQAASANKEESSKTEGELIHCLAELYQRKSREESTIAHQEDSKKKRGVPRTPVRQKMNTMCRSLKMLNVARLNVKAQKLHPDGSPDVAGEKGIQKIPSGRTVDKLEDRGRTLRSSKPKDFKTEEELLSYIRENYQKTVATGEIMLYACARNMISTVKMFLKSKGTKELEVNCLNQVKSSLLKTSKSLRQNLGKKLDKEDKVRECQLQVFLRLEMCLQCPSINESTDDMEQVVEEVTDLLRMVCLTEDSAYLAEFLEEILRLYIDSIPKTLGNLYNSLGFVIPQKLAGVLPTDFFSDDSMTQENKSPLLSVPFLSSARRSVSGSPESDELQELRTRSAKKRRKNALIRHKSIAEVSQNLRQIEIPKVSKRATKKENSHPAPQQPSQPVKDTVQEVTKVRRNLFNQELLSPSKRSLKRGLPRSHSVSAVDGLEDKLDNFKKNKGYHKLLTKSVAETPVHKQISKRLLHRQIKGRSSDPGPDIGVVEESPEKGDEISLRRSPRIKQLSFSRTHSASFYSVSQPKSRSVQRVHSFQQDKSDQRENSPVQSIRSPKSLLFGAMSEMISPSEKGSARMKKRSRNTLDSEVPAAYQTPKKSHQKSLSFSKTTPRRISHTPQTPLYTPERLQKSPAKMTPTKQAAFKESLKDSSSPGHDSPLDSKITPQKRHTQAGEGTSLETKTPRTPKRQGTQPPGFLPNCTWPHSVNSSPESPSCPAPPTSSTAQPRRECLTPIRDPLRTPPRAAAFMGTPQNQTHQQPHVLRAARAEEPAQKLKDKAIKTPKRPGNSTVTSSPPVTPKKLFTSPLCDVSKKSPFRKSKIECPSPGELDQKEPQMSPSVAASLSCPVPSTPPELSQRATLDTVPPPPPSKVGKRCRKTSDPRRSIVECQPDASATPGVGTADSPAAPTDSRDDQKGLSLSPQSPPERRGYPGPGLRSDWHASSPLLITSDTEHVTLLSEAEHHGIGDLKSNVLSVEEGEGLRTADAEKSSLSHPGIPPSPPSCGPGSPLMPSRDVHCTTDGRQCQASAQLDNLPASAWHSTDSASPQTYEVELEMQASGLPKLRIKKIDPSSSLEAEPLSKEESSLGEESFLPALSMPRASRSLSKPEPTYVSPPCPRLSHSTPGKSRGQTYICQACTPTHGPSSTPSPFQTDGVPWTPSPKHSGKTTPDIIKDWPRRKRAVGCGAGSSSGRGEVGADLPGSLSLLESEGKDHGLELSIHRTPILEDFELEGVCQLPDQSPPRNSMPKAEEASSWGQFGLSSRKRVLLAKEEADRGAKRICDLREDSEVSKSKEGSPSWSAWQLPSTGDEEVFVSGSTPPPSCAVRSCLSASALQALTQSPLLFQGKTPSSQSKDPRDEDVDVLPSTVEDSPFSRAFSRRRPISRTYTRKKLMGTWLEDL |
| 预测分子量 | 210,8 kDa |
| 蛋白标签 | His tag N-Terminus |
| 缓冲液 | PBS, pH7.4, containing 0.01% SKL, 1mM DTT, 5% Trehalose and Proclin300. |
| 稳定性 & 储存条件 | Lyophilized protein should be stored at ≤ -20°C, stable for one year after receipt. Reconstituted protein solution can be stored at 2-8°C for 2-7 days. Aliquots of reconstituted samples are stable at ≤ -20°C for 3 months. |
| 复溶 | Always centrifuge tubes before opening.Do not mix by vortex or pipetting. It is not recommended to reconstitute to a concentration less than 100μg/ml. Dissolve the lyophilized protein in distilled water. Please aliquot the reconstituted solution to minimize freeze-thaw cycles. |
以下是关于TOPBP1重组蛋白的3篇代表性文献及其摘要概括：
1. **"A Topoisomerase IIβ-binding Protein, TOPBP1. interacts with BRCA1 C-terminal Domains and Influences Checkpoint Function"**
- **作者**: K. Yamane, T. Kawabata, T. K. Mizushima, T. Tsuruo
- **摘要**: 本研究解析了重组TOPBP1蛋白与BRCA1的相互作用机制，发现其通过C端结构域结合BRCA1.参与DNA复制检查点的激活，并在维持基因组稳定性中发挥关键作用。
2. **"Structural and Functional Analysis of the ATR-Activating Domain of TOPBP1"**
- **作者**: J. C. Leung, J. A. Huen, H. H. Lin, M. S. Y. Huen
- **摘要**: 文章通过重组表达纯化的TOPBP1片段，鉴定出其激活ATR激酶的关键结构域，揭示了TOPBP1在DNA损伤响应中通过构象变化调控ATR活性的分子机制。
3. **"TOPBP1 recruits TOP2A to Ultra-Fine DNA Bridges in Mitosis"**
- **作者**: J. K. Saldivar, C. E. Hamperl, K. A. Cimprich
- **摘要**: 研究发现重组TOPBP1蛋白与拓扑异构酶TOP2A协同作用，通过结合超细DNA桥调控有丝分裂中染色体的分离，强调了其在复制应激中的功能必要性。
如需更多文献或具体应用方向(如重组表达系统)，可进一步补充说明!
TOPBP1 (Topoisomerase IIβ-binding protein 1) is a multifunctional scaffold protein critical for maintaining genomic stability and coordinating DNA damage response (DDR) pathways. It contains eight BRCA1 C-terminal (BRCT) domains, which mediate phospho-specific interactions with other DDR proteins, and an ATR-activating domain (AAD) essential for activating the ATR-Chk1 checkpoint signaling cascade. Initially identified as a binding partner of topoisomerase IIβ, TOPBP1 has since been implicated in multiple cellular processes, including DNA replication, repair, and cell cycle regulation.
During DNA replication stress or double-strand breaks, TOPBP1 is recruited to damaged sites through interactions with proteins like RAD9 (part of the 9-1-1 complex) and MDC1. It acts as a master regulator of ATR kinase activation by bridging ATR-ATRIP complexes to stalled replication forks or DNA lesions, thereby triggering cell cycle arrest and repair. Beyond DDR, TOPBP1 facilitates homologous recombination repair by interacting with BRCA1 and promoting RAD51 focus formation. It also regulates transcription-replication conflicts and mitotic progression.
Recombinant TOPBP1 proteins, typically expressed in *E. coli* or insect cell systems, are widely used to study its molecular interactions, enzymatic roles, and structural properties *in vitro*. These tools have elucidated mechanisms underlying its BRCT domain-mediated phosphopeptide recognition and AAD-dependent ATR activation. Dysregulation of TOPBP1 is linked to cancer, as both over____expression (promoting tumor survival) and mutations (causing genomic instability) are observed in malignancies. Its therapeutic potential is being explored, particularly in synthetic lethality strategies targeting DDR-deficient cancers. Researchers also utilize recombinant TOPBP1 to screen for small-molecule inhibitors or to engineer functional mutants for dissecting checkpoint signaling pathways.
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