摘要
GFPT2作为己糖胺代谢重要的转录因子,在动物的多种疾病发生发展中起着重要作用。利用生物信息学方法对GFPT2蛋白的组分、功能、正选择位点及其分子进化进行了详细的分析。结果表明:13条不同物种氨基酸序列组分分析显示亮氨酸占比最高为9.86%,含量最低的氨基酸为色氨酸(0.15%),平均长度为664.8。系统进化树和结构域显示人和猴子的亲缘性最近,其次是大鼠、小鼠,所有氨基酸均包含两个SIS保守结构域。混合效应-演化模型(mixed effects model of evolution,MEME)和固定效应(fixed effects likelihood,REL)方法共发现8个正选择位点。基因本体论(gene ontology,GO)功能富集分析发现GFPT2主要参与GFPT酶活性、蛋白结合、碳水化合物衍生物结合方面发挥作用等生物学过程。京都基因与基因组百科全书(Kyoto encyclopedia of gene and genomes,KEGG)分析显示差异基因主要参与氨基糖和核苷酸糖代谢,丙氨酸、天冬氨酸和谷氨酸代谢,胰岛素抵抗3条信号通路。并且筛选到与GFPT2相互作用的10个基因:GFPT1、GLUL、GNPDA1、GNPNAT1、GPI、HK1、MPI、PPAT、AMDHD2、CAD。研究结果可以为GFPT2分子功能的深层次研究提供一定的借鉴作用,对进一步探究由己糖胺代谢导致的代谢异常及心血管疾病治疗具有重要的现实意义。
As an important transcription factor of hexosamine metabolism,GFPT2 plays an important role in the occurrence and development of animal diseases.The components,functions,positive selection sites and molecular evolution of GFPT2 protein were analyzed in detail by bioinformatics methods.The results show that the highest proportion of leucine is 9.86%,and the lowest content is tryptophan(0.15%).The average length is 664.8.Phylogenetic tree and domains show that human and monkey have the closest genetic relationship,followed by rats and mice.All amino acids contain two SIS conserved domains.Eight positive selection sites are found by mixed effects model of evolution(MEME)and fixed effects likelihood(REL)methods.Gene ontology(GO)functional enrichment analysis show that GFPT2 is mainly involved in GFPT enzyme activity,protein binding,carbohydrate derivative binding and other biological processes.Kyoto encyclopedia of gene and genomes(KEGG)analysis show that the differentially expressed genes are mainly involved in amino sugar and nucleotide sugar metabolism,alanine,aspartate and glutamic acid metabolism,and insulin resistance.Ten genes interacting with GFPT2 are screened:GFPT1,GLUL,GNPDA1,GNPNAT1,GPI,HK1,MPI,PPAT,AMDHD2,CAD.The results can provide a reference for the further study of the molecular function of GFPT2,and have important practical significance for further exploring the metabolism caused by hexosamine metabolism and the treatment of cardiovascular diseases.
作者
魏思昂
丁志文
冯焱
WEI Si-ang;DING Zhi-wen;FENG Yan(College of Life Science, Shanxi Agricultural University, Taigu 030801, China;Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China)
出处
《科学技术与工程》
北大核心
2021年第21期8814-8821,共8页
Science Technology and Engineering
基金
山西省回国留学项目(2017-067)
国家自然科学基金(81700256)。
