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Anti-CRISPR type I subtype E5 AcrIE5 (also known as AcrE5) is an anti-CRISPR (Acr) protein that was discovered via guilt-by association (GBA) approach, which is based on the strong co-occurrence and clustering of acr and anti-CRISPR associated (aca) genes through proximity and homology searches. These anti-CRISPR gene clusters all contain a conserved putative promoter region at their 5' end and a conserved aca gene at their 3' end. Type I-E and I-F acr genes are located at the same position in the genomes of a large group of related phages, and they are found in a variety of combinations and arrangements. The type I-E CRISPR-Cas system Csy is a crRNA-guided surveillance complex, composed of a crRNA and eleven Cas proteins (one Cse1, two Cse2, one Cas5, six Cas7 and one Cas6e), which recruits a nuclease-helicase protein Cas3 for target degradation. CRISPR-Cas immune systems are used by certain prokaryotes and archaea to resist the invasion of foreign nucleic acids such as phages or plasmids. Anti-CRISPRs are small proteins which are the natural inhibitors for CRISPR-Cas systems; encoded on bacterial and archaeal viruses, they allow the virus to evade host CRISPR-Cas systems. The CRISPR-Cas-mediated adaptive immune response can be divided into three steps, including the acquisition of spacer derived from invading nucleic acids, crRNA processing, and target degradation. Theoretically, Acr proteins could suppress any step to disrupt the CRISPR-Cas system. Acr proteins are diverse with no common sequence or structural motif which inhibit a wide range of CRISPR-Cas systems with various inhibition mechanisms. CRISPR-Cas systems are divided into two classes (1 and 2) and six types (class 1: types I, III and IV; class 2: types II, V and VI). Class 1 systems utilize RNA-guided complexes consisting of multiple Cas proteins as the effector proteins to recognize and cleave target DNA. Type I CRISPR-Cas systems are the most widespread in nature, and the Cas protein composition of the employed CRISPR ribonucleoprotein (crRNP) complexes differs between seven subtypes (A to F, U). Acr families are named for their type and subtype which are numbered sequentially as they are discovered.
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