Wagner Carina, Hois Victoria, Taschler Ulrike, Schupp Michael, Lass Achim
Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria.
Division of Endocrinology and Diabetology, Medical University of Graz, 8036 Graz, Austria.
Metabolites. 2022 Jun 2;12(6):516. doi: 10.3390/metabo12060516.
KIAA1363, annotated as neutral cholesterol ester hydrolase 1 (NCEH1), is a member of the arylacetamide deacetylase (AADAC) protein family. The name-giving enzyme, AADAC, is known to hydrolyze amide and ester bonds of a number of xenobiotic substances, as well as clinical drugs and of endogenous lipid substrates such as diglycerides, respectively. Similarly, KIAA1363, annotated as the first AADAC-like protein, exhibits enzymatic activities for a diverse substrate range including the xenobiotic insecticide chlorpyrifos oxon and endogenous substrates, acetyl monoalkylglycerol ether, cholesterol ester, and retinyl ester. Two independent knockout mouse models have been generated and characterized. However, apart from reduced acetyl monoalkylglycerol ether and cholesterol ester hydrolase activity in specific tissues and cell types, no gross-phenotype has been reported. This raises the question of its physiological role and whether it functions as drug detoxifying enzyme and/or as hydrolase/lipase of endogenous substrates. This review delineates the current knowledge about the structure, function and of the physiological role of KIAA1363, as evident from the phenotypical changes inflicted by pharmacological inhibition or by silencing as well as knockout of KIAA1363 gene expression in cells, as well as mouse models, respectively.
KIAA1363，被注释为中性胆固醇酯水解酶1（NCEH1），是芳基乙酰胺脱乙酰酶（AADAC）蛋白家族的成员。该家族的命名酶AADAC分别已知可水解多种外源性物质、临床药物以及内源性脂质底物（如甘油二酯）的酰胺键和酯键。同样，被注释为首个类似AADAC蛋白的KIAA1363，对多种底物具有酶活性，包括外源性杀虫剂毒死蜱氧磷以及内源性底物乙酰单烷基甘油醚、胆固醇酯和视黄酯。已经构建并表征了两种独立的基因敲除小鼠模型。然而，除了特定组织和细胞类型中乙酰单烷基甘油醚和胆固醇酯水解酶活性降低外，尚未报道明显的表型。这就引发了关于其生理作用的问题，以及它是否作为药物解毒酶和/或内源性底物的水解酶/脂肪酶发挥作用。本综述阐述了目前关于KIAA1363的结构、功能和生理作用的知识，这些知识分别来自于药理学抑制、细胞以及小鼠模型中KIAA1363基因表达的沉默和敲除所导致的表型变化。
