低氧响应过程中蛋白质半胱氨酸修饰调控作用的生物信息学分析  

Regulatory role of protein cysteine modifications in hypoxia-responsive process based on bioinformatics analysis

作　　者：吕志红 王盘琴 郭伟峰[2] 王振龙 程涵 LYU Zhihong;WANG Panqin;GUO Weifeng;WANG Zhenlong;CHENG Han(College of Life Sciences,Zhengzhou University,Zhengzhou 450001;School of Electrical and Informa tion Engineering,Zhengzhou University,Zhengzhou 450001)

机构地区：[1]郑州大学生命科学学院,郑州450001 [2]郑州大学电气与信息工程学院,郑州450001

出　　处：《郑州大学学报(医学版)》2025年第2期180-185,共6页Journal of Zhengzhou University(Medical Sciences)

基　　金：国家自然科学基金项目(62002329,U2004152);中原科技创新领军人才项目(224200510001);河南省自然科学基金项目(242300421401);郑州大学青年教师基础研究培育项目(JC21343016);数字医学工程国家重点实验室开放研究基金项目(2024-K07)。

摘　　要：目的:基于生物信息学探讨蛋白质半胱氨酸修饰(PCM)在低氧响应过程中的调控作用。方法:通过比对iHypoxia数据库中低氧响应蛋白的UniProt ID和CysModDB、iCysMod数据库中PCM底物的UniProt ID,筛选出能够发生PCM的低氧响应蛋白及其修饰位点,分析不同物种和不同PCM类型中以上蛋白及修饰位点的分布情况,并分析同一PCM位点上不同半胱氨酸修饰之间的相互影响。对人类发生PCM的低氧响应蛋白进行GO功能注释和KEGG通路富集分析。利用Xena Browser网站上12种常见肿瘤的体细胞突变数据筛选发生PCM的人类低氧响应蛋白上的错义突变,比较非PCM区域和PCM区域每1000个氨基酸中的突变数。利用COSMIC和DrugBank数据库比对发生PCM的低氧响应蛋白的UniProt ID与癌基因和药物靶标的UniProt ID,获取发生PCM的低氧响应蛋白分别被注释为癌基因与药物靶标的数量并进行癌基因与药物靶标富集分析。结果:共获得4种动物(人类、小鼠、大鼠和牛)1111个低氧响应蛋白的5242个PCM位点;低氧响应蛋白可发生氧化、S-亚硝基化、S-谷胱甘肽化等多种PCM,不同修饰之间存在相互影响。受PCM调控的低氧响应蛋白显著富集于与癌症等相关的信号通路中。596个低氧响应蛋白的错义突变更易于发生在PCM区域。人类发生PCM的低氧响应蛋白中有85个被注释为癌基因,340个被注释为药物靶标,且受PCM调控的低氧响应蛋白与癌基因和药物靶标高度相关(富集比例分别为8.34和4.63,P<0.01)。结论:PCM在低氧响应过程中发挥重要调控作用。Aim:To explore the regulatory role of protein cysteine modification(PCM)in hypoxia-response process based on bioinformatics analysis.Methods:By comparing the UniProt ID of hypoxia-responsive proteins in iHypoxia with the UniProt ID of PCM substrates in CysModDB and iCysMod,the hypoxia-responsive proteins capable of PCM and their modification sites were screened.The distribution of the above proteins and PCM sites in different species and different PCM types were analyzed,and the interaction of different modifications at the same PCM site was analyzed.GO functional annotation and KEGG pathway enrichment analysis were performed for hypoxia-responsive proteins with PCM in human.Somatic mutation data from 12 common cancers on the Xena Browser website was used to screen for missense mutations on human hypoxia-responsive proteins with PCM,and compared the density of mutation sites in non-PCM and PCM regions.The UniProt ID of hypoxia-responsive proteins with PCM were compared with the UniProt ID of oncogenes in COSMIC and drug targets in DrugBank,the number of hypoxia-responsive proteins with PCM annotated as oncogenes and drug targets was obtained,and enrichment analysis of oncogenes and drug targets was performed.Results:A total of 5242 PCM sites of 1111 hypoxia-responsive proteins from 4 animals(human,mouse,rat,cow)were obtained.Various PCM such as oxidation,S-nitrosylation and S-glutathionylation occured in hypoxia-responsive proteins,and there were interactions among different modifications.Hypoxia-responsive proteins regulated by PCM were significantly enriched in signaling pathways associated with cancer.Mutations of 596 hypoxia-responsive proteins were more likely to occur in the PCM region.Out of the hypoxia-responsive proteins with PCM in human,85 were annotated as oncogenes and 340 were annotated as drug targets,and the hypoxia-responsive proteins regulated by PCM were highly correlated with oncogenes and drug targets(enrichment ratio were 8.34 and 4.63,P<0.01).Conclusion:PCM plays an important role in the re

关 键 词：蛋白质半胱氨酸修饰 低氧响应蛋白 调控作用 生物信息学分析 

分 类 号：R318.04[医药卫生—生物医学工程]