PDF(Pubmed)
Abstract：
Phosphohistidine (pHis) is a reversible protein post-translational modification (PTM) that is currently poorly understood. The P-N bond in pHis is heat and acid-sensitive, making it more challenging to study than the canonical phosphoamino acids pSer, pThr, and pTyr. As advancements in the development of tools to study pHis have been made, the roles of pHis in cells are slowly being revealed. To date, a handful of enzymes responsible for controlling this modification have been identified, including the histidine kinases NME1 and NME2, as well as the phosphohistidine phosphatases PHPT1, LHPP, and PGAM5. These tools have also identified the substrates of these enzymes, granting new insights into previously unknown regulatory mechanisms. Here, we discuss the cellular function of pHis and how it is regulated on known pHis-containing proteins, as well as cellular mechanisms that regulate the activity of the pHis kinases and phosphatases themselves. We further discuss the role of the pHis kinases and phosphatases as potential tumor promoters or suppressors. Finally, we give an overview of various tools and methods currently used to study pHis biology. Given their breadth of functions, unraveling the role of pHis in mammalian systems promises radical new insights into existing and unexplored areas of cell biology.
摘要：
磷酸组氨酸（pHis）是一种可逆的蛋白质翻译后修饰（PTM），目前尚不清楚。PHis中的P-N键对热和酸敏感，使研究比规范的磷酸氨基酸pSer更具挑战性，pThr,和pTyr。随着研究phis的工具开发的进步，PHis在细胞中的作用正在慢慢被揭示。迄今为止,已经确定了几种负责控制这种修饰的酶，包括组氨酸激酶NME1和NME2，以及磷酸组氨酸磷酸酶PHPT1，LHPP，pgam5这些工具还确定了这些酶的底物，为以前未知的监管机制提供新的见解。这里,我们讨论了pHis的细胞功能以及它是如何在已知的含pHis的蛋白质上调节的，以及调节pHis激酶和磷酸酶本身活性的细胞机制。我们进一步讨论了pHis激酶和磷酸酶作为潜在的肿瘤启动子或抑制剂的作用。最后,我们概述了目前用于研究phis生物学的各种工具和方法。鉴于它们的功能广度，揭示pHis在哺乳动物系统中的作用有望对现有和未开发的细胞生物学领域产生根本性的新见解。
