The majority of the protein members of the first four of these families exhibit a probable 10 transmembrane spanner (TMS) topology that arose from a tandemly duplicated 5 TMS unit.
The N- and C-termini are believed to be in the cytoplasm of bacterial cells, and the same may be true of most other members as well.
The other two families [sensor histidine kinase (SHK) and kinase/phosphatase/synthetase/hydrolase (KPSH)] have a single 5 TMS unit preceded by an N-terminal TMS and followed by a hydrophilic sensor histidine kinase domain (the SHK family) or catalytic domains resembling sensor kinase, phosphatase, cyclic di-guanylate (GMP) synthetase and cyclic di-GMP hydrolase catalytic domains, as well as various non-catalytic domains (the KPSH family).
Because functional data are not available for the transmembrane domains of members of the SHK and KPSH families, it is not known if these transporter-like domains retain transport activity or have evolved exclusive functions in molecular reception and signal transmission.
They could serve merely to anchor the catalytic domains to the membrane.