https://ror.org/00kybxq39 Department of Biochemistry and Functional Genomics, Université de Sherbrooke, Sherbrooke, Canada.
https://ror.org/00kybxq39 Department of Informatics, Université de Sherbrooke, Sherbrooke, Canada.
Life Sci Alliance. 2024 Nov 12;8(2). doi: 10.26508/lsa.202402910. Print 2025 Feb.
Proteogenomics has enabled the detection of novel proteins encoded in noncanonical or alternative open reading frames (altORFs) in genes already coding a reference protein. Reanalysis of proteomic and ribo-seq data revealed that the p53-induced death domain-containing protein (or ) gene encodes a second 171 amino acid protein, altPIDD1, in addition to the known 910-amino acid-long PIDD1 protein. The two ORFs overlap almost completely, and the translation initiation site of altPIDD1 is located upstream of PIDD1. AltPIDD1 has more translational and protein level evidence than PIDD1 across various cell lines and tissues. In HEK293 cells, the altPIDD1 to PIDD1 ratio is 40 to 1, as measured with isotope-labeled (heavy) peptides and targeted proteomics. AltPIDD1 localizes to cytoskeletal structures labeled with phalloidin and interacts with cytoskeletal proteins. Unlike most noncanonical proteins, altPIDD1 is not evolutionarily young but emerged in placental mammals. Overall, we identify as a dual-coding gene, with altPIDD1, not the annotated protein, being the primary product of translation.
蛋白质基因组学使得在已经编码参考蛋白的基因中检测到非规范或替代开放阅读框（altORFs）编码的新型蛋白质成为可能。对蛋白质组学和核糖核酸测序数据的重新分析表明，p53 诱导的死亡结构域蛋白（或 ）基因除了已知的 910 个氨基酸长的 PIDD1 蛋白外，还编码第二个 171 个氨基酸的蛋白质，altPIDD1。两个 ORF 几乎完全重叠，altPIDD1 的翻译起始位点位于 PIDD1 的上游。在各种细胞系和组织中，altPIDD1 的翻译和蛋白水平证据比 PIDD1 更多。在 HEK293 细胞中，用同位素标记的（重）肽和靶向蛋白质组学测量，altPIDD1 与 PIDD1 的比值为 40 比 1。AltPIDD1 定位于用鬼笔环肽标记的细胞骨架结构上，并与细胞骨架蛋白相互作用。与大多数非规范蛋白不同，altPIDD1 不是年轻的进化产物，而是在胎盘哺乳动物中出现的。总的来说，我们将 鉴定为一个双编码基因，altPIDD1 是翻译的主要产物，而不是注释蛋白。
