Functional in silico analysis of a non-synonymous SNP located in the coding region of the FASN gene in Korean native cattle

Hong-Sik Kong, Yoonseok Lee
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Abstract

Bovine fatty acid synthase, an enzyme encoded by the FASN gene in cattle, is a multi-enzyme protein that catalyses fatty acid synthesis. This cytosolic enzyme catalyzes the synthesis of palmitate from acetylcoenzyme A and malonyl-coenzyme A in the presence of nicotinamide adenine dinucleotide phosphate (NADPH). However, there is no previous verification study that each allele of SNPs related to lipid synthesis were impact on protein function in Korean native cattle and nsSNPs for the FASN gene have not yet been verified by computer analysis. Given the role of the FASN gene in beef quality traits in cattle, the study aimed to use computational analysis to narrow down the candidate nsSNPs for FASN that may affect protein structure and/or function, which may play an important role in lipid synthesis. These results predicted that the g.16039 T>C nsSNP at position R1957Y of FASN was functionally 'Deleterious' and 'PROBABLY DAMAGING' in non-synonymous SNP functional analysis, and the g.16039 T>C and g.17924 A>G nsSNPs at positions R1957Y and T2266A decrease the stability of a FASN protein and have two PTM sites for proteolytic cleavage and amidation. In addition, the R1957Y and T2266A variants of FASN were shown to have a direct effect on altering the protein structure. Therefore, we suggested that our results could be used as fundamental data for further studies related to functional verification of nsSNPs based on bovine cells.
位于韩国本土牛FASN基因编码区域的非同义SNP的功能硅分析
牛脂肪酸合成酶是一种催化脂肪酸合成的多酶蛋白,由牛FASN基因编码。这种胞质酶在烟酰胺腺嘌呤二核苷酸磷酸(NADPH)存在下催化乙酰辅酶A和丙二酰辅酶A合成棕榈酸酯。然而,目前尚无验证性研究表明,与脂质合成相关的snp的每个等位基因都对韩国土牛的蛋白质功能有影响,FASN基因的nssnp也尚未通过计算机分析得到验证。鉴于FASN基因在牛肉质性状中的作用,本研究旨在通过计算分析来缩小FASN可能影响蛋白质结构和/或功能的候选nssnp,这些nssnp可能在脂质合成中发挥重要作用。这些结果预示着g.16039在非同义SNP功能分析中,FASN R1957Y位置的T>C nsSNP在功能上是“有害的”和“可能有害的”,g.16039T>C和g.17924R1957Y和T2266A位置的nsSNPs降低了FASN蛋白的稳定性,并且具有两个用于蛋白水解裂解和酰胺化的PTM位点。此外,FASN的R1957Y和T2266A变体被证明对改变蛋白质结构有直接影响。因此,我们认为我们的结果可以作为进一步研究基于牛细胞的nssnp功能验证的基础数据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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