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Histidine Phosphotransfer domain, involved in signalling through a two part component systems in which an autophosphorylating histidine protein kinase serves as a phosphoryl donor to a response regulator protein; the response regulator protein is modulated by phosphorylation and dephosphorylation of a conserved aspartic acid residue; two-component proteins are abundant in most eubacteria; In E. coli there are 62 two-component proteins involved in a variety of processes such as chemotaxis, osmoregulation, metabolism and transport 1; also present in both Gram positive and Gram negative pathogenic bacteria where they regulate basic housekeeping functions and control expression of toxins and other proteins important for pathogenesis; in archaea and eukaryotes, two-component pathways constitute a very small number of all signaling systems; in fungi they mediate environmental stress responses and, in pathogenic yeast, hyphal development. In Dictyostelium and in plants, they are involved in important processes such as osmoregulation, cell growth, and differentiation; to date two-component proteins have not been identified in animals; in most prokaryotic systems, the output response is effected directly by the RR, which functions as a transcription factor while in eukaryotic systems, two-component proteins are found at the beginning of signaling pathways where they interface with more conventional eukaryotic signaling strategies such as MAP kinase and cyclic nucleotide cascades
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