人肿瘤关联钙信号转导因子2的生物信息学分析

Bioinformatic analysis of the structure and function of human TACSTD2

目的人肿瘤关联钙信号转导因子2(TACSTD2)在肿瘤形成过程中的促癌作用越来越受到重视。文中旨在采用生物信息学方法预测TACSTD2的分子结构和生物学功能,为进一步研究TACSTD2的功能提供借鉴。方法获取人源性TACSTD2基因mRNA和蛋白氨基酸序列,利用生物信息学方法分析TACSTD2蛋白开放阅读框(ORF)、理化性质、信号肽、亚细胞定位,预测TACSTD2蛋白的跨膜结构、二级结构、三级结构、结构域、蛋白修饰位点,最后预测TACSTD2蛋白的互作蛋白并进行相关的通路分析,及TACSTD2在人不同正常组织和肿瘤组织中的mRNA和蛋白表达水平。结果TACSTD2的mR⁃NA序列得到的ORF有12个,最长的ORF是ORF1,共972bp,可编码323个氨基酸。TACSTD2蛋白亲水性的氨基酸要多于疏水性的氨基酸,表明TACSTD2蛋白属于亲水性蛋白。TACSTD2是一种高度保守的碱性分泌蛋白,在胞质内外均有跨膜区。TACSTD2氨基酸序列存在核定位信号(nuclear localization signal,NLS),提示TACSTD2可定位于细胞核。TACSTD2蛋白主要分布在细胞质膜、细胞外、细胞核以及细胞质。二级结构预测结果表明,TACSTD2蛋白主要为环状结构,其次为螺旋结构。TACSTD2蛋白有15个丝氨酸修饰位点,17个苏氨酸修饰位点,8个酪氨酸修饰位点。TACSTD2与Claudin(CLDN)家族蛋白存在蛋白互作。TACSTD2参与以下信号通路:细胞表面受体信号通路、视觉感知细胞增殖、上皮细胞迁移的负调控、上皮细胞增殖的调节、对刺激的反应等。与正常组织比较,TACSTD2的mRNA在宫颈癌、肺癌、甲状腺癌、子宫癌、肝癌、结直肠癌中等肿瘤组织高表达。结论TACSTD2在多种恶性肿瘤中高表达,可通过细胞表面受体信号参与恶性肿瘤细胞的增殖、迁移、粘附等过程,为进一步研究TACSTD2的功能提供借鉴。

Objective The role of human tumor⁃related calcium signal transductor 2(TACSTD2)in promoting tumorigenesis has been noticed recently.We predicted the molecular structure and biological function of TACSTD2 by bioinformatic methods,in order to provide reference for further study of TACSTD2.Methods The homo sapiens TACSTD2 mRNA and protein amino acid sequences were obtained from the National Center for Biotechnology Information(NCBI)database.The bioinformatic methods were used to analyze the open reading frame(ORF)of TACSTD2,physicochemical properties,signal peptide and protein localization,subcellular localiza⁃tion,and prediction of transmembrane structure and secondary structure,tertiary structure,potential protein modification sites,do⁃mains,protein modification sites proteins,protein interacting with TACSTD2,biological functions of TACSTD2,and expression of TAC⁃STD2 in human normal tissues and certain tumor types.Results According to the mRNA sequence of TACSTD2,there are 12 ORFs,and the longest is ORF1,with a total of 972bp,encoding 323 amino acids.The hydrophilic amino acid of TACSTD2 is more than that of hydrophobic amino acid,indicating that TACSTD2 belongs to hydro⁃philic protein.TACSTD2 is a highly conserved alkaline secreted pro⁃tein with a transmembrane region both inside and outside the cytoplasm.The presence of nuclear localization signal(NLS)in the amino acid sequence of TACSTD2 suggests that TACSTD2 can locate in cell nucleus.TACSTD2 mainly distribute in cytoplasmic membrane,extracellular,nucleus and cytoplasm.The secondary structure prediction results showed that the main structure of TACSTD2 was ran⁃dom coil,followed by aαhelix.TACSTD2 has 15 serine modification sites,17 threonine modification sites,and 8 tyrosine modification sites.The TACSTD2 has protein interactions with Claudin(CLDN)protein family;and participating in signaling pathway such as cell surface receptor,cell proliferation,negative regulation of epithelial cell migration,and so on.Comparing with normal human tissues,its mRNA expression is up⁃regulated in most tumor types such as cervical cancer,lung cancer,thyroid cancer,uterine cancer,liver cancer,colorectal cancer.Conclusion According to the analysis of the structure and function of TACSTD2,TACSTD2 is highly⁃ex⁃pression in multiple malignancies.It can participate in the process of proliferation,migration and adhesion of malignant tumor cells through cell surface receptor signaling pathways.This study provide reference for the further research about the function of TACSTD2.