| Type: | Family | Name: | Uncharacterised protein family, CYTH/CHAD/HD-like domain-containing |
| Description: | This group includes uncharacterised proteins with CYTH and CHAD domains, and a central HD-like domain.The N-terminal domain of the members of is distantly related to thermophilic adenylate cyclases (class 2) () and to mammalian thiamine triphosphatases (), and belongs to the CYTH domain superfamily (), which also includes , , and others []. CYTH domain proteins may play a central role in the interface between nucleotide and polyphosphate metabolism []. Based on the conservation of catalytic residues, CYTH domains are likely to chelate two divalent cations and exhibit a reaction mechanism that is dependent on two metal ions, analogous to nucleotide cyclases, polymerases, and certain phosphoesterases []. It has also been suggested that the experimentally characterised members of the CYTH domain superfamily, namely, adenylyl cyclase and thiamine triphosphatase, are secondary derivatives of proteins that performed an ancient role in polyphosphate and nucleotide metabolism [].The C-terminal CHAD domain () is an alpha-helical domain that is found fused to the CYTH domain or is encoded by genes occurring in the same operon as those encoding CYTH domains (e.g., , stand-alone CHAD). Therefore, it is predicted to be functionally associated with CYTH adenylate cyclases []. While there is no experimental evidence as to the function of the CHAD domain, and no clear functional prediction can be made for it, the conserved histidines and other charged residues could form a strongly polar surface that could either participate in metal chelation, or act as phosphoacceptors [].Apart from these two domains, members of this group have a unique central domain. It is distantly related to the HD-type metal dependent phosphohydrolase domain (), but there is no indication as to its function.Related families include , and , , , , . | Short Name: | UPF_CYTH/CHAD/HD-like |
