Abstract:
Two-component systems (TCS) are important types of machinery allowing for efficient signal recognition and transmission in
bacterial cells. The majority of TCSs utilized by bacteria is composed of a sensor histidine kinase (HK) and a cognate response
regulator (RR). In the present study,we report two newly predicted protein domains—both to be included in the next release of the
Pfamdatabase: Response_reg_2 (PF19192) andHEF_HK(PF19191)—in bacteriawhich exhibit high structural similarity, respectively,
with typical domains of RRs and HKs. Additionally, the genes encoding for the novel predicted domains exhibit a 91.6% linkage
observed across 644 genomic regions recovered from 628 different bacterial strains. The remarkable adjacent colocalization between
genes carrying Response_reg_2 and HEF_HK in addition to their conserved structural features, which are highly similar to
those fromwell-known HKs and RRs, raises the possibility of Response_reg_2 and HEF_HK constituting a new TCS in bacteria. The
genomic regions inwhich these predicted two-component systems-like are located additionally exhibit an overrepresented presence
of restriction–modification (R–M) systems especially the type II R–M. Among these, there is a conspicuous presence of C-5 cytosinespecific
DNAmethylaseswhichmay indicate a functional associationwith the newly discovered domains. The solid presence of R–M
systems and the presence of theGHKL family domain HATPase_c_3 across most of the HEF_HK-containing genes are also indicative
that these genes are evolutionarily related to the paraMORC family of ATPases.
