纯度 | >90%SDS-PAGE. |
种属 | Human |
靶点 | Cdk12 |
Uniprot No | Q9NYV4 |
内毒素 | < 0.01EU/μg |
表达宿主 | E.coli |
表达区间 | 800-1157aa |
氨基酸序列 | CVDVFEMIAQIGEGTYGQVYKARDHHTNDMVALKKVRLEHEKEGFPITAVREIKILRQLNHRNIVNLHEIVTDKQDAVEFRKDKGSFYLVFEYMDHDLMGLLESGMVDFNEENNASIMKQLLDGLNYCHKKNFLHRDIKCSNILMNNRGKVKLADFGLARLYNADDRERPYTNKVITLWYRPPELLLGEERYGPSIDVWSCGCILGELFVKRPLFQANAEMAQLETISKICGSPVPAVWPNVIKLPLFHTLKQKKTHRRRLREDFEFMPAPALDLLDKMLDLDPDKRITAEDALRSPWLRKINPDEMPTPQLPTWQDCHELWSKKRRRQMREQQESLPPTVIASTKYQQHGATMVGDA |
预测分子量 | 46.7 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3篇与CDK12重组蛋白相关的文献信息及摘要概括:
1. **文献名称**:CDK12 regulates DNA repair genes by suppressing intronic polyadenylation
**作者**:Davidson L, et al. (2014)
**摘要**:研究发现CDK12重组蛋白通过抑制内含子多聚腺苷酸化,维持DNA损伤修复相关基因(如BRCA1)的全长转录本表达。该机制缺陷导致同源重组修复障碍,提示CDK12可作为癌症治疗靶点。
2. **文献名称**:Structural and functional analysis of the Cdk13/Cdk12 cyclin K complex
**作者**:Greifenberg AK, et al. (2016)
**摘要**:通过重组CDK12蛋白与cyclin K的复合物结构解析,揭示其激酶活性依赖独特的N端延伸结构域,并证实其对RNA聚合酶II C端结构域磷酸化的特异性调控,为选择性抑制剂设计提供依据。
3. **文献名称**:CDK12 inhibition enhances sensitivity of BRCA-proficient cancers to PARP inhibitors
**作者**:Joshi PM, et al. (2019)
**摘要**:利用重组CDK12蛋白筛选小分子抑制剂,发现其失活可诱导BRCA1/2野生型肿瘤产生复制压力,显著增强PARP抑制剂疗效,为合成致死策略开辟新方向。
注:以上文献为代表性研究,实际检索建议通过PubMed/Google Scholar以关键词"CDK12 recombinant"+"structure/function/inhibitor"获取最新原文。
CDK12 (Cyclin-Dependent Kinase 12) is a serine/threonine kinase belonging to the CDK family, primarily involved in transcriptional regulation and genome stability maintenance. It forms a functional complex with Cyclin K to regulate RNA polymerase II (RNAPII)-mediated transcription elongation, mRNA splicing, and DNA damage response. CDK12 phosphorylates the C-terminal domain (CTD) of RNAPII, influencing the recruitment of factors critical for transcriptional termination and co-transcriptional RNA processing. Unlike other transcription-associated CDKs (e.g., CDK9), CDK12 specifically governs the expression of DNA damage response (DDR) genes, including those in the homologous recombination repair (HRR) pathway (e.g., BRCA1. ATR).
Recombinant CDK12 protein is engineered using heterologous expression systems (e.g., E. coli, mammalian cells) for in vitro studies. Its production enables mechanistic exploration of CDK12-Cyclin K interactions, substrate specificity, and regulatory roles in transcription-coupled DDR. Dysregulation of CDK12 is implicated in cancers, particularly ovarian and prostate cancers, where truncating mutations correlate with HRR deficiency and sensitivity to PARP inhibitors. Recombinant CDK12 is pivotal for screening kinase inhibitors, studying resistance mechanisms in cancer therapy, and deciphering post-translational modifications affecting its activity. Recent studies also highlight its potential as a therapeutic target, given its dual role in transcription and genome stability. However, structural complexity and functional overlap with CDK13 pose challenges in developing selective inhibitors. Research tools like recombinant CDK12 thus bridge gaps in understanding its biology and translational applications.
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