Protein posttranslational modification is an indispensable regulatory element that can fine-tune protein functions and regulate diverse cellular processes. Lysine 2-hydroxyisobutyrylation (Khib) is a protein posttranslational modification that was recently identified and is thought to play a role in a wide variety of active cellular functions. In this report, for the first time, we comparatively studied the 2-hydroxyisobutyrylation proteome in peripheral blood mononuclear cells from a biopsy-proven immunoglobulin A nephropathy (IgAN) group and a normal control group based on liquid chromatography-tandem mass spectrometry. Altogether, 7405 proteins were identified and added to a Khib library. Of these proteins, we identified 111 with upregulated expression and 83 with downregulated expression. Furthermore, we identified 428 Khib modification sites on 290 Khib-modified proteins, including 171 sites with increased modification on 122 Khib-modified proteins and 257 specific sites with reduced modification on 168 Khib-modified proteins. Importantly, the abundance of lipocalin 2 was increased in the differentially expressed proteins, and a KEGG-based functional enrichment analysis showed that Khib proteins clustered in the IL-17 signaling pathway and phagosome category, which may have important associations with IgAN. Our data enlighten our understanding of Khib in IgAN and indicate that Khib may have important regulatory roles in IgAN.

中文翻译：

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IgA肾病中赖氨酸2-羟基异丁酰化的定量蛋白质组学分析

蛋白质翻译后修饰是必不可少的调节元件，可以调节蛋白质功能并调节多种细胞过程。赖氨酸2-羟基异丁酰化（Khib）是一种蛋白质翻译后修饰，最近被发现，被认为在多种活跃的细胞功能中起作用。在本报告中，我们首次基于液相色谱-串联质谱法对活检证实的免疫球蛋白A肾病（IgAN）组和正常对照组的外周血单核细胞中的2-羟基异丁酰化蛋白质组进行了比较研究。总共鉴定出7405种蛋白质并将其添加到Khib文库中。在这些蛋白质中，我们鉴定了111个表达上调的蛋白和83个表达下调的蛋白。此外，我们在290个Khib修饰蛋白上鉴定了428个Khib修饰位点，包括171个在122 Khib修饰蛋白上具有增加修饰的位点和257个在168 Khib修饰蛋白上具有减少修饰的特异性位点。重要的是，差异表达蛋白中脂环蛋白2的丰度增加，并且基于KEGG的功能富集分析显示，Khib蛋白聚集在IL-17信号传导途径和吞噬体类别中，这可能与IgAN具有重要的关联。我们的数据启发了我们对IgAN中的Khib的理解，并表明Khib在​​IgAN中可能具有重要的调控作用。差异表达的蛋白质中脂质运载蛋白2的丰度增加，并且基于KEGG的功能富集分析显示，Khib蛋白聚集在IL-17信号通路和吞噬体类别中，这可能与IgAN具有重要的关联。我们的数据启发了我们对IgAN中的Khib的理解，并表明Khib在​​IgAN中可能具有重要的调控作用。差异表达的蛋白质中脂质运载蛋白2的丰度增加，并且基于KEGG的功能富集分析显示，Khib蛋白聚集在IL-17信号通路和吞噬体类别中，这可能与IgAN具有重要的关联。我们的数据启发了我们对IgAN中的Khib的理解，并表明Khib在​​IgAN中可能具有重要的调控作用。