CRISPR-associated Rossmann Fold (CARF) and SMODS-associated and fused to various effector domains (SAVED) are key components of cyclic oligonucleotide-based antiphage signaling systems (CBASS) that sense cyclic oligonucleotides and transmit the signal to an effector inducing cell dormancy or death. Most of the CARFs are components of a CBASS built into type III CRISPR–Cas systems, where the CARF domain binds cyclic oligoA (cOA) synthesized by Cas10 polymerase-cyclase and allosterically activates the effector, typically a promiscuous ribonuclease. Additionally, this signaling pathway includes a ring nuclease, often also a CARF domain (either the sensor itself or a specialized enzyme) that cleaves cOA and mitigates dormancy or death induction. We present a comprehensive census of CARF and SAVED domains in bacteria and archaea, and their sequence- and structure-based classification. There are 10 major families of CARF domains and multiple smaller groups that differ in structural features, association with distinct effectors, and presence or absence of the ring nuclease activity. By comparative genome analysis, we predict specific functions of CARF and SAVED domains and partition the CARF domains into those with both sensor and ring nuclease functions, and sensor-only ones. Several families of ring nucleases functionally associated with sensor-only CARF domains are also predicted.

中文翻译：

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CARF域超家族的进化和功能分类，是原核抗病毒防御中的关键传感器。

CRISPR相关罗斯曼折叠（CARF）和小号MODS-一个ssociated和融合至v arious È ffector d omains（保存）是关键部件Ç yclic寡核苷酸b ASED一个ntiphage小号ignaling小号感应环状寡核苷酸并将信号传递至效应子的系统（CBASS），诱导细胞休眠或死亡。大多数CARF是内置在III型CRISPR–Cas系统中的CBASS的组件，其中CARF域结合由Cas10聚合酶-环化酶合成的环状寡聚腺苷酸（cOA），并变构激活效应物，通常是混杂的核糖核酸酶。另外，该信号传导途径包括环状核酸酶，通常也是裂解cOA并减轻休眠或死亡诱导的CARF域（传感器本身或专门的酶）。我们目前对细菌和古细菌中的CARF和SAVED域进行了全面的人口普查，并对其进行了基于序列和结构的分类。有10个主要的CARF域家族和多个较小的组，它们的结构特征不同，与不同的效应子相关，是否存在环核酸酶活性。通过比较基因组分析，我们预测了CARF和SAVED域的特定功能，并将CARF域划分为具有传感器和环核酸酶功能的区域，以及仅具有传感器功能的区域。还预测了在功能上与仅传感器的CARF域相关的环核酸酶的几个家族。