Mahmood Malik Siddique, Afzal Maryam, Batool Hina, Saif Amara, Aqdas Tahreem, Ashraf Naeem Mahmood, Saleem Mahjabeen
School of Biochemistry & Biotechnology, University of the Punjab, Lahore, Pakistan.
Department of Biochemistry, NUR International University, Lahore, Pakistan.
Bioinform Biol Insights. 2022 Aug 9;16:11779322221115547. doi: 10.1177/11779322221115547. eCollection 2022.
gene encodes a phospholysine phosphohistidine inorganic pyrophosphate phosphatase, which functions as a tumor-suppressor protein. The tumor suppression by this protein has been confirmed in various cancers, including hepatocellular carcinoma (HCC). downregulation promotes cell growth and proliferation by modulating the signaling pathway. This study identifies potentially deleterious missense single nucleotide variants (SNVs) associated with the gene using multiple computational tools based on different algorithms. A total of 4 destabilizing mutants are identified as , and , from the conserved region of the phosphatase. The 3-dimensional (3D) modeling and structural comparison of variants with the native protein reveals significant structural and conformational variations after mutations, suggesting disruption in the function of phospholysine phosphohistidine inorganic pyrophosphate phosphatase. The identified mutations might, therefore, participate in the cause of HCC.
基因编码一种磷酸赖氨酸磷酸组氨酸无机焦磷酸磷酸酶，其作为一种肿瘤抑制蛋白发挥作用。该蛋白的肿瘤抑制作用已在包括肝细胞癌（HCC）在内的多种癌症中得到证实。其下调通过调节信号通路促进细胞生长和增殖。本研究使用基于不同算法的多种计算工具，鉴定了与该基因相关的潜在有害错义单核苷酸变异（SNV）。从磷酸酶的保守区域总共鉴定出4个不稳定突变体，分别为 、 和 。变异体与天然蛋白的三维（3D）建模和结构比较显示，突变后存在显著的结构和构象变化，表明磷酸赖氨酸磷酸组氨酸无机焦磷酸磷酸酶的功能受到破坏。因此，所鉴定的突变可能参与了肝细胞癌的病因。
