前列腺相关基因4的生物信息学分析

Bioinformatics analysis of prostate-associated gene 4

目的 采用多种生物预测软件分析人前列腺相关基因4(prostate-associated gene 4,PAGE4)的结构、功能。方法用ProtParam在线工具分析PAGE4的理化性质,利用NetPhos 3.1 Server、NetOGlyc 4.0 Server、NetNGlyc 1.0 Server与cBioPortal数据库预测PAGE4的磷酸化、糖基化及突变位点。通过TMHMM Server 2.0、SignalP 5.0 Server和PSORTⅡPrediction工具分别预测PAGE4蛋白的跨膜区域、信号肽及亚细胞定位。采用SOPMA、SWISS-MODEL及DisProt无序蛋白数据库分析PAGE4的蛋白结构域。STRING、Target Scan、miRDB以及DIANA-microT在线数据库用于预测PAGE4的互相作用蛋白和潜在microRNA调控分子。结果 生物信息学分析结果显示PAGE4蛋白的分子式为C459H743N147O171S3,分子量为11 153.01,共有氨基酸102个。PAGE4是一种亲水蛋白,定位于细胞内,为非分泌蛋白,不存在跨膜区及信号肽,蛋白序列中存在一个核定位信号。亚细胞定位分析显示,PAGE4主要定位于线粒体,细胞骨架及细胞核。PAGE4存在10个磷酸化位点,但不存在糖基化位点。PAGE4的二级结构主要为无规则卷曲,而无三级结构。PAGE4蛋白无序性约为100%,为天然无序蛋白。PAGE4与同源域相互作用蛋白激酶1(homeodomain-interacting protein kinase 1,HIPK1)、双特异性蛋白激酶(dual specificity protein kinase, CLK2)等10个分子存在潜在互作关系,hsa-miR-371a-5p、hsa-miR-6505-3p、hsa-miR-3919、hsa-miR-3123与hsa-miR-4704-3p可能调控PAGE4的表达。结论 PAGE4是一种亲水、无序、非分泌的胞内蛋白,存在磷酸化位点与突变位点,可以与多种蛋白和microRNA分子相互作用。分析PAGE4的结构功能特点,可以为PAGE4生物学功能及致病分子机制的深入研究提供理论依据。

Objective To analyze the structure and function of human prostate-associated gene 4(PAGE4) by bioinformatics software. Methods The physicochemical properties of PAGE4 were analyzed by the ProtParam tool. The phosphorylation, glycosylation and mutation sites of PAGE4 were predicted by NetPhos 3.1 Server, NetOGlyc 4.0 Server, NetNGlyc 1.0 Server and cBioPortal database. The transmembrane region, signal peptide, and subcellular localization of PAGE4 protein were predicted by TMHMM Server 2.0, SignalP 5.0 Server, and PSORT Ⅱ Prediction, respectively. The protein domain of PAGE4 was analyzed by SOPMA, SWISS-MODEL and DisProt. Online databases such as STRING, Target Scan, miRDB, and DIANA-microT were usedto predict the interacting proteins of PAGE4 and the potential upstream microRNAs. Results The bioinformatics analysisshowed that the molecular formula of PAGE4 was C459 H743 N147 O171 S3, the molecular weight was 11,153.01, and PAGE4 contained 102 amino acids. PAGE4 was a hydrophilic protein, which was localized in cells. It was a non-secretory protein withouta transmembrane region and signal peptide. There was a nuclear localization signal in the protein sequence. Subcellular localizationanalysis displayed that PAGE4 was mainly located in mitochondria, cytoskeleton, and nucleus. PAGE4 had 10 phosphorylationsites, but no glycosylation site was found. The secondary structure of PAGE4 was mainly irregular curl, and there was no tertiarystructure in PAGE4. PAGE4 protein disorder was about 100%, which was a natural disorder protein. PAGE4 had a potentialinteraction with 10 molecules such as homeodomain-interacting protein kinase 1( HIPK1) and dual specificity protein kinase(CLK2). hsa-miR-371 a-5 p, hsa-miR-6505-3 p, hsa-miR-3919, hsa-miR-3123 and hsa-miR-4704-3 p might regulate theexpression of PAGE4. Conclusion PAGE4 is a hydrophilic, disordered and non-secretory intracellular protein withphosphorylation sites and mutation sites, which can interact with a variety of proteins and microRNAs. Analyzing the structural andfunctional characteristics of PAGE4 can provide a theoretical basis for the in-depth study of biological function and pathogenicmolecular mechanism of PAGE4.