人SIRT1基因启动子及蛋白的生物信息学分析  

Bioinformatics Analysis of Human SIRT1 Gene Promoter and Encoding Protein

作　　者：王道[1] 陈建林[1] 刘文彬[2] 刘丹[1] 宋甜 WANG Dao;CHEN Jianlin;LIU Wenbin;LIU Dan;SONG Tian(Department of Obstetrics and Gynecology,the Second Xiangya Hospital of Central South University,Changsha 410011,China;College of Life Sciences,Hunan Normal University,Changsha 410081,China)

机构地区：[1]中南大学湘雅二医院妇产科,长沙410011 [2]湖南师范大学生命科学学院,长沙410081

出　　处：《激光生物学报》2023年第4期368-384,共17页Acta Laser Biology Sinica

基　　金：国家自然科学基金项目(31670178);湖南省自然科学基金项目(2021JJ30918)。

摘　　要：为深入分析人SIRT1基因启动子及蛋白的结构和功能,本文采用生物信息学方法分析人SIRT1基因5′端启动子、启动子区Motif、转录因子结合位点、甲基化CpG岛、单核苷酸多态性、进化关系、理化性质、二级和三级结构、保守结构域、突变和翻译后修饰位点、互作蛋白及生物学功能。TSSW和Neural Network Promoter Prediction数据库预测其区间分别存在3个、2个启动子。MEME数据库预测启动子区存在3个Motif。EMBOSS、MethPrimer和CpG Finder数据库都发现CpG岛聚集分布于1600~2200 bp区。PROMO和AliBaba2.1数据库预测其启动子区域共同转录因子为22个。JASPAR软件获得6个与正负链相结合的转录因子。SNP Function Prediction数据库还发现不同种族等位基因频率存在差异。人SIRT1基因位于染色体10q21.3上,广泛分布在不同组织中。人SIRT1蛋白由747个氨基酸组成,属于亲水、不稳定的蛋白质,在不同物种间具有较高的保守性。结构域位于第254~489位氨基酸序列,属于SIR2超家族,主要分布在细胞核和线粒体中,二级结构主要以α-螺旋和无规则卷曲为主,相比AlphaFold2,SWISS-MODEL数据库构建的三级模型更可靠。SIRT1蛋白共含有突变位点106个、N-糖基化位点1个、磷酸化位点61个,与EP300、TP53等多种蛋白相互作用,并且参与昼夜节律过程、类固醇激素反应、细胞内受体信号等,涉及寿命调节通路、AMPK信号通路、FoxO信号通路等。本研究为了解SIRT1对炎症反应等疾病的影响及感染机制提供了参考依据。To further explore the structure and function of the promoter and protein of human SIRT1 gene,our research used bioinformatic methods to analyze 5′-end promoter,promoter Motif,transcription factor binding sites,CpG island,single-nucleotide polymorphism,phylogenetic homology,physicochemical properties,hydrophilicity/hydrophobicity,secondary/tertiary structure,conserved domain,mutation site,N-glycosylation and phosphorylation sites,interacted proteins and biological function.The number of promoters predicted by TSSW and Neural Network Promoter Prediction database was 3 and 2 respectively.There were 3 Motifs found in the promoter region by using MEME database.The CpG islands were clustered in the 1600~2200 bp,which were found by using EMBOSS,MethPrimer and CpG Finder database.PROMO and AliBaba2.1 database showed that there were 22 transcription factors in their promoter regions.And there were 6 transcription factors found that bind to the positive and negative chains by using JASPAR software.Besides,there were differences found in allele frequencies between different ethnic groups by using SNP Function Prediction database.Human SIRT1 gene is located at chromosome 10q21.3 and widely distributed in different tissues,which is a hydrophilic and unstable protein with a high conservation among different species.The domain is located at the 254~489 amino acid sequence,belonging to the SIR2 superfamily,mainly located in the nucleus and mitochondria.The secondary structure of the protein mainly containsα-helices and irregular coiling.Compared with AlphaFold2,the tertiary structure model constructed by SWISS-MODEL database was reliable.SIRT1 contained 106 mutation sites,1 N-glycosylation and 61 phosphorylation sites,which interacted with EP300,TP53 and other proteins.It also participated in circadian rhythm process,steroid hormone response,and intracellular receptor signaling etc.,which were associated with longevity regulation pathway,AMPK signaling pathway,and FoxO signaling pathway etc.This study can provide a theoretic

关 键 词：人SIRT1基因 启动子 蛋白 生物信息学 炎症 

分 类 号：Q811.4[生物学—生物工程]