The ubiquitous proteins with FIC (filamentation induced by cyclic AMP) domains use a conserved enzymatic machinery to modulate the activity of various target proteins by posttranslational modification, typically AMPylation. Following intensive study of the general properties of FIC domain catalysis, diverse molecular activities and biological functions of these remarkably versatile proteins are now being revealed. Here, we review the biological diversity of FIC domain proteins and summarize the underlying structure-function relationships. The original and most abundant genuine bacterial FIC domain proteins are toxins that use diverse molecular activities to interfere with bacterial physiology in various, yet ill-defined, biological contexts. Host-targeted virulence factors have evolved repeatedly out of this pool by exaptation of the enzymatic FIC domain machinery for the manipulation of host cell signaling in favor of bacterial pathogens. The single human FIC domain protein HypE (FICD) has a specific function in the regulation of protein stress responses.

中文翻译：

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FIC域蛋白的生物多样性和分子可塑性

具有FIC（由环AMP诱导的细丝化）结构域的普遍存在的蛋白使用保守的酶机制通过翻译后修饰（通常是AMPylation）来调节各种靶蛋白的活性。在深入研究FIC结构域催化的一般特性之后，这些显着多功能的蛋白质的各种分子活性和生物学功能现在被揭示出来。在这里，我们审查FIC域蛋白的生物学多样性，并总结了潜在的结构-功能关系。原始且最丰富的真正细菌FIC结构域蛋白是毒素，它们在各种但不确定的生物学环境中使用多种分子活性来干扰细菌生理。宿主靶向的毒力因子已通过从酶FIC结构域机器中脱颖而出，从该池中反复进化出来，以操纵有利于细菌病原体的宿主细胞信号转导。单个人FIC域蛋白HypE（FICD）在调节蛋白应激反应中具有特定功能。