Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing 210016, China.
State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, Jiangsu 211166, China; Center of Pathology and Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing 211166, China.
J Proteomics. 2021 Jul 15;243:104262. doi: 10.1016/j.jprot.2021.104262. Epub 2021 May 10.
Histidine phosphorylation is critically important in a variety of cellular processes including signal transduction, cell cycle, proliferation, differentiation, and apoptosis. It is estimated to account for 6% of all phosphorylated amino acids. However, due to the acid lability of the PN bond, the study of pHis lags far behind that of pSer, pThr, and pTyr. Recently, the development and use of pHis-specific antibodies and methodologies have led to a resurgence in the study of histidine phosphorylation. Although a considerable number of pHis proteins and sites have been discovered, most of them have not been manually curated and integrated to any databases. There is a lack of a data repository for pHis, and such work is expected to help further systemic studies of pHis. Thus, we present a comprehensive resource database of histidine phosphorylation (HisPhosSite) by curating experimentally validated pHis proteins and sites and compiling putative pHis sites with ortholog search. HisPhosSite contains 776 verified pHis sites and 2702 verified pHis proteins in 38 eukaryotic and prokaryotic species and 15,378 putative pHis sites and 10,816 putative pHis proteins in 1366 species. HisPhosSite provides rich annotations of pHis sites and proteins and multiple search engines (including motif search and BLAST search) for users to locate pHis sites of interest. HisPhosSite is available at http://reprod.njmu.edu.cn/hisphossite. SIGNIFICANCE: Histidine phosphorylation is involved in a variety of cellular processes as well as cancers, and it has been proved to be more common than previously thought. The HisPhosSite database was developed to collect pHis data from published literatures with experimental evidences. Unification of the identified pHis proteins and sites will give researchers an informative resource for histidine phosphorylation. HisPhosSite has a user-friendly interface with multiple search engines for users to locate pHis sites of interest. In addition, the database provides rich structural and functional annotations. HisPhosSite will help future studies and elucidation of the functions of histidine phosphorylation.
组氨酸磷酸化在各种细胞过程中至关重要，包括信号转导、细胞周期、增殖、分化和凋亡。据估计，它占所有磷酸化氨基酸的 6%。然而，由于 PN 键的酸性不稳定性，pHis 的研究远远落后于 pSer、pThr 和 pTyr。最近，pHis 特异性抗体和方法的发展和使用导致了对组氨酸磷酸化研究的复兴。尽管已经发现了相当数量的 pHis 蛋白和位点，但其中大多数尚未经过人工整理并整合到任何数据库中。目前缺乏 pHis 的数据存储库，这项工作有望帮助进一步系统地研究 pHis。因此，我们通过整理实验验证的 pHis 蛋白和位点，并通过同源搜索编译推定的 pHis 位点，创建了一个组氨酸磷酸化（HisPhosSite）的综合资源数据库。HisPhosSite 包含 38 种真核和原核生物中的 776 个已验证的 pHis 位点和 2702 个已验证的 pHis 蛋白，以及 1366 种生物中的 15378 个推定的 pHis 位点和 10816 个推定的 pHis 蛋白。HisPhosSite 为 pHis 位点和蛋白提供了丰富的注释，并为用户提供了多种搜索引擎（包括模式搜索和 BLAST 搜索），以定位感兴趣的 pHis 位点。HisPhosSite 可在 http://reprod.njmu.edu.cn/hisphossite 上获取。意义：组氨酸磷酸化参与多种细胞过程以及癌症，并且已经证明它比以前想象的更为普遍。HisPhosSite 数据库是为了从已发表的文献中收集具有实验证据的 pHis 数据而开发的。将鉴定的 pHis 蛋白和位点统一起来，将为研究人员提供一个有关组氨酸磷酸化的信息资源。HisPhosSite 具有用户友好的界面，带有多个搜索引擎，供用户定位感兴趣的 pHis 位点。此外，该数据库还提供了丰富的结构和功能注释。HisPhosSite 将有助于未来对组氨酸磷酸化功能的研究和阐明。
