Pycsar (pyrimidine cyclase system for antiphage resistance) provides immunity against bacteriophage. The pyrimidine cyclase (PycC) synthesizes cyclic nucleotides in response to infection; these serve as specific second messenger signals. The signal activates the adjacent effector, leading to bacterial cell death and abortive phage infection. A clade E Pycsar system. The pyrimidine cyclase gene of a two-gene Pycsar system, generates cyclic CMP (cCMP) from CTP in response to bacteriophage infection. Has little to no activity on ATP, GTP or UTP. Expression of this and adjacent effector EcPycTM (AC P0DV25) confers resistance to bacteriophage P1 and T5; expression of this gene alone does not confer resistance. When cells expressing the Pycsar system are infected by phage T5 at low multiplicity of infection (0.2 MOI) the culture survives, at 2.0 MOI bacteria enter growth arrest. The same cells enter growth arrest after exposure to 250 uM cCMP but not cUMP; thus the effector protein responds only to the cNMP produced by its cognate NTP cyclase. Some of the cells treated with cCMP have abnormal membrane protrusions. CTP = 3',5'-cyclic CMP + diphosphate Cannot be replaced by Mg(2+). In E.coli strain MG1655 transformed with both genes cCMP appears between 15 and 30 minutes after infection with phage T5 (at protein level). No cCMP accumulates in uninfected cells. Optimum pH is 7.5-9.0. Homodimer. Has an N-terminal nucleotide cyclase domain and a C-terminal nucleotide sensor domain (AGS-C); removal of the latter leads to loss of phage P1 and T5 resistance. T5 phage that escape Pycsar have mutated major capsid protein pb8 (D20, AC Q6QGD8); infection with these phage elicits less cCMP production. Ectopic expression of the capsid protein in addition to both Pycsar genes does not induce effector-mediated toxicity, suggesting another factor is necessary. Belongs to the adenylyl cyclase class-4/guanylyl cyclase family. Pyrimidine cyclase subfamily.