<p>Two-component signal transduction systems enable bacteria to sense, respond, and adapt to a wide range of environments, stressors, and growth conditions [<cite idref="PUB00042804"/>]. Some bacteria can contain up to as many as 200 two-component systems that need tight regulation to prevent unwanted cross-talk [<cite idref="PUB00042805"/>]. These pathways have been adapted to response to a wide variety of stimuli, including nutrients, cellular redox state, changes in osmolarity, quorum signals, antibiotics, and more [<cite idref="PUB00010651"/>]. Two-component systems are comprised of a sensor histidine kinase (HK) and its cognate response regulator (RR) [<cite idref="PUB00011096"/>]. The HK catalyses its own auto-phosphorylation followed by the transfer of the phosphoryl group to the receiver domain on RR; phosphorylation of the RR usually activates an attached output domain, which can then effect changes in cellular physiology, often by regulating gene expression. Some HK are bifunctional, catalysing both the phosphorylation and dephosphorylation of their cognate RR. The input stimuli can regulate either the kinase or phosphatase activity of the bifunctional HK.</p><p>A variant of the two-component system is the phospho-relay system. Here a hybrid HK auto-phosphorylates and then transfers the phosphoryl group to an internal receiver domain, rather than to a separate RR protein. The phosphoryl group is then shuttled to histidine phosphotransferase (HPT) and subsequently to a terminal RR, which can evoke the desired response [<cite idref="PUB00042806"/>, <cite idref="PUB00042807"/>].</p><p>This entry represents Nitrogen regulatory protein C (NtrC), which is a bacterial enhancer-binding protein that activates the transcription of genes encoding enzymes required for nitrogen metabolism. It is phosphorylated by NtrB and interacts with sigma-54. One of the best studied examples is its activation of the gene glnA, which encodes the enzyme glutamine synthetase [<cite idref="PUB00029212"/>].NtrC is composed of three domains [<cite idref="PUB00034429"/>, <cite idref="PUB00034430"/>]. The 124 residue N-terminal domain is homologous to receiver domains of other response regulator proteins in two-component signal transduction systems [<cite idref="PUB00034431"/>, <cite idref="PUB00004626"/>]. The 240 residue central domain of NtrC is homologous to a domain found in all activators of the sigma-54 RNA polymerase holoenzyme [<cite idref="PUB00011159"/>, <cite idref="PUB00001740"/>]. The C-terminal domain has been indicated to contain the determinants necessary for both DNA-binding and dimerization of full-length NtrC.</p>