Jez J M, Flynn T G, Penning T M
Department of Biochemistry & Biophysics, University of Pennsylvania Medical School, Philadelphia 19104, U.S.A.
Biochem Pharmacol. 1997 Sep 15;54(6):639-47. doi: 10.1016/s0006-2952(97)84253-0.
The aldo-keto reductases (AKRs) represent a growing oxidoreductase superfamily. Forty proteins have been identified and characterized as AKRs, and an additional fourteen genes may encode proteins related to the superfamily. Found in eukaryotes and prokaryotes, the AKRs metabolize a wide range of substrates, including aliphatic aldehydes, monosaccharides, steroids, prostaglandins, and xenobiotics. This broad substrate specificity has caused problems in naming these proteins. Enzymes capable of these reactions have been referred to as aldehyde reductase (ALR1), aldose reductase (ALR2), and carbonyl reductase (ALR3); however, ALR3 is not a member of the AKR superfamily. Also, some AKRs have multiple names based upon substrate specificity. For example, human 3alpha-hydroxysteroid dehydrogenase (3apha-HSD) type I is also known as dihydrodiol dehydrogenase 4 and chlordecone reductase. To address these issues, we propose a new nomenclature system for the AKR superfamily based on amino acid sequence identities. Cluster analysis of the AKRs shows seven distinct families at the 40% amino acid identity level. The largest family (AKR1) contains the aldose reductases, aldehyde reductases, and HSDs. Other families include the prokaryotic AKRs, the plant chalcone reductases, the Shaker channels, and the ethoxyquin-inducible aflatoxin B1 aldehyde reductase. At the level of 60% amino acid identity, subfamilies are discernible. For example, the AKR1 family includes five subfamilies: (A) aldehyde reductases (mammalian); (B) aldose reductases; (C) HSDs; (D) delta4-3-ketosteroid-5beta-reductases; and (E) aldehyde reductases (plant). This cluster analysis forms the basis for our nomenclature system. Recommendations for naming an aldo-keto reductase include the root symbol "AKR," an Arabic number designating the family, a letter indicating the subfamily when multiple subfamilies exist, and an Arabic numeral representing the unique protein sequence. For example, human aldehyde reductase would be assigned as AKR1A1. Our nomenclature is both systematic and expandable, thereby allowing assignment of consistent designations for newly identified members of the superfamily.
醛酮还原酶（AKRs）是一个不断扩大的氧化还原酶超家族。已鉴定并表征了40种蛋白质为AKRs，另外还有14个基因可能编码与该超家族相关的蛋白质。AKRs存在于真核生物和原核生物中，可代谢多种底物，包括脂肪醛、单糖、类固醇、前列腺素和外源性物质。这种广泛的底物特异性给这些蛋白质的命名带来了问题。能够进行这些反应的酶被称为醛还原酶（ALR1）、醛糖还原酶（ALR2）和羰基还原酶（ALR3）；然而，ALR3不是AKR超家族的成员。此外，一些AKRs根据底物特异性有多个名称。例如，人类I型3α-羟基类固醇脱氢酶（3α-HSD）也被称为二氢二醇脱氢酶4和十氯酮还原酶。为了解决这些问题，我们基于氨基酸序列同一性提出了一种新的AKR超家族命名系统。对AKRs的聚类分析显示，在氨基酸同一性水平为40%时可分为七个不同的家族。最大的家族（AKR1）包含醛糖还原酶、醛还原酶和羟基类固醇脱氢酶。其他家族包括原核生物AKRs、植物查耳酮还原酶、Shaker通道和乙氧喹啉诱导的黄曲霉毒素B1醛还原酶。在氨基酸同一性水平为60%时，可以区分亚家族。例如，AKR1家族包括五个亚家族：（A）醛还原酶（哺乳动物）；（B）醛糖还原酶；（C）羟基类固醇脱氢酶；（D）δ4-3-酮类固醇-5β-还原酶；和（E）醛还原酶（植物）。这种聚类分析构成了我们命名系统的基础。醛酮还原酶命名的建议包括根符号“AKR”、表示家族的阿拉伯数字、存在多个亚家族时表示亚家族的字母以及代表独特蛋白质序列的阿拉伯数字。例如，人类醛还原酶将被指定为AKR1A1。我们的命名法既系统又可扩展，从而能够为超家族新鉴定的成员指定一致的名称。
