Puente Xose S, López-Otín Carlos
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, 33006-Oviedo, Spain.
Genome Res. 2004 Apr;14(4):609-22. doi: 10.1101/gr.1946304.
Proteases perform important roles in multiple biological and pathological processes. The availability of the rat genome sequence has facilitated the analysis of the complete protease repertoire or degradome of this model organism. The rat degradome consists of at least 626 proteases and homologs, which are distributed into 24 aspartic, 160 cysteine, 192 metallo, 221 serine, and 29 threonine proteases. This distribution is similar to that of the mouse degradome but is more complex than that of the human degradome composed of 561 proteases and homologs. This increased complexity of rat proteases mainly derives from the expansion of several families, including placental cathepsins, testases, kallikreins, and hematopoietic serine proteases, involved in reproductive or immunological functions. These protease families have also evolved differently in rat and mouse and may contribute to explain some functional differences between these closely related species. Likewise, genomic analysis of rat protease inhibitors has shown some differences with mouse protease inhibitors and the expansion of families of cysteine and serine protease inhibitors in rodents with respect to human. These comparative analyses may provide new views on the functional diversity of proteases and inhibitors and contribute to the development of innovative strategies for treating proteolysis diseases.
蛋白酶在多种生物学和病理过程中发挥着重要作用。大鼠基因组序列的可得性促进了对这种模式生物完整蛋白酶库或降解组的分析。大鼠降解组至少由626种蛋白酶和同源物组成，它们被分为24种天冬氨酸蛋白酶、160种半胱氨酸蛋白酶、192种金属蛋白酶、221种丝氨酸蛋白酶和29种苏氨酸蛋白酶。这种分布与小鼠降解组的分布相似，但比由561种蛋白酶和同源物组成的人类降解组更为复杂。大鼠蛋白酶这种增加的复杂性主要源于几个家族的扩张，包括参与生殖或免疫功能的胎盘组织蛋白酶、睾丸蛋白酶、激肽释放酶和造血丝氨酸蛋白酶。这些蛋白酶家族在大鼠和小鼠中也有不同的进化，可能有助于解释这些密切相关物种之间的一些功能差异。同样，对大鼠蛋白酶抑制剂的基因组分析显示，其与小鼠蛋白酶抑制剂存在一些差异，并且啮齿动物中半胱氨酸和丝氨酸蛋白酶抑制剂家族相对于人类有所扩张。这些比较分析可能为蛋白酶和抑制剂的功能多样性提供新的见解，并有助于开发治疗蛋白水解疾病的创新策略。
