Table 5.

Natural examples for domain shuffling in divergent TCS.¹

Domain	Protein	Context	Function
HisKin	Pyruvate dehydrogenase kinase	Glucose metabolism In S. cerevisiae	Inhibits the mitochondrial pyruvate dehydrogenase complex by phosphorylation of the E1 alpha subunit, thus contributing to the regulation of glucose metabolism
HisKin	Adenylate cyclase	Sporulation in some organisms	Stringent response, protein kinases are activated (PKAs)
HisKin	BCKD-kinase	Valine, leucine and isoleucine catabolic pathways in Mouse	Catalyzes the phosphorylation and inactivation of the branched-chain alpha-ketoacid dehydrogenase complex, the key regulatory enzyme of the valine, leucine and isoleucine catabolic pathways. Key enzyme that regulate the activity state of the BCKD complex
HisKin	Phytochrome A	Regulatory photoreceptor In Deinococcus	Regulatory photoreceptor which exists in two forms that are reversibly interconvertible by light: the Pr form that absorbs maximally in the red region of the spectrum and the Pfr form that absorbs maximally in the far-red region. Photoconversion of Pr to Pfr induces an array of morphogenic responses, whereas reconversion of Pfr to Pr cancels the induction of those responses. Pfr controls the expression of a number of nuclear genes including those encoding the small subunit of ribulose-bisphosphate carboxylase, chlorophyll A/B binding protein, protochlorophyllide reductase, rRNA, etc. It also controls the expression of its own gene(s) in a negative feedback fashion
Response Reg	Adventurous-gliding motility protein Z	Chemosensory system in Myxococcus	Required for adventurous-gliding motility, in response to environmental signals sensed by the frz chemosensory system. Forms ordered clusters that span the cell length and that remain stationary relative to the surface across which the cells move, serving as anchor points that allow the bacterium to move forward. Clusters disassemble at the lagging cell pol
Response Reg	Adenylate cyclase	Sporulation in some organisms	Stringent response, response regulators are activated
Response Reg	Serine/threonine-protein kinase ppk18	Schizosaccharomyces pombe	Serine/threonine-protein kinase ppk18 plays pivotal roles in cell proliferation and cell growth in response to nutrient status

Notes:

¹The table shows natural domain shuffling events where sensor domains and response regulator domains appear in different new contexts. In the three prokaryotic as well as in the eukaryotic examples only domains can be recognized but new functions are adopted.