The proteins of the Trk family are derived from Gram-negative and Gram-positive bacteria, yeast and plants. The proteins of E. coli K12 (TrkH and TrkG) as well as several yeast and plant proteins have been functionally and topologically characterized. While TrkH is generally present in E. coli and other enteric bacteria, TrkG is encoded by a foreign gene located within the prophage rac region of the E. coli K12 chromosome. TrkG is not present in several other E. coli strains. The sizes of the Trk family members vary from 423 residues to 1235 residues. The bacterial proteins are of 423-558 residues, the Triticum aestivum protein is 533 residues, and the yeast proteins vary between 841 and 1241 residues. These proteins possess 8 putative transmembrane ?-helical spanners. An 8 TMS topology with N- and C-termini on the inside, has been established for AtHKT1 of A. thaliana (Kato et al., 2001) and Trk2 of S. cerevisiae (Zeng et al., 2004). This folding pattern resembles quadruplicated primitive K⁺ channels of the VIC superfamily (TC #1.A.1) instead of typical 12 TMS carriers. As homology has been established between Trk carriers and VIC family channels, the latter were presumably the precursors of the former.

The phylogenetic tree reveals that the proteins cluster according to phylogeny of the source organism with (1) the Gram-negative bacterial Trk proteins, (2) the Gram-negative and Gram-positive bacterial Ktr proteins, (3) the yeast proteins and (4) the plant proteins comprising four distinct clusters (Saier et al., 1999). S. cerevisiae possesses two paralogues, high- and low-affinity K⁺ transporters.

The KtrAB system of Vibrio alginolyticus consists of a cytoplasmic NAD-binding regulatory subunit, KtrA, shared by several other K⁺ transporters and channels, and an integral membrane protein, KtrB, which is very similar to NtpJ of E. hirae and distantly related to TrkH of E. coli (Nakamura et al., 1998b). All of these systems may be multicomponent. However, the integral membrane constituents have been proposed to exhibit a basic structure of four consecutive M1-P-loop-M2 motifs analogous to the KcsA K⁺ channel of Streptomyces lividans (see TC #1.A.1). Two homologues of the V. alginolyticus KtrAB are found in B. subtilis. Both systems catalyze K⁺ uptake but with differing Kms: 1 mM for KtrAB and 10 mM for KtrCD (Holtmann et al., 2003).

The E. coli TrkH and TrkG proteins are complexed to two peripheral membrane proteins, TrkA, an NAD⁺-binding protein, and TrkE, an ATP-binding protein. The peripheral membrane proteins are thought to function in regulation rather than energy coupling. TrkE maps to the sapABCDF operon which encodes an ABC transporter (TC #3.A.1.5.5), and the SapD ATP binding cassette (ABC) protein of E. coli can stimulate K⁺ uptake via either Trk^H or Trk^G (Harms et al., 2001). Therefore, SapD is probably TrkE. ATP binding to SapD, rather than ATP hydrolysis, appears to activate. Thus, the pmf drives transport while ATP binding activates transport. At least one other ATP-activating protein is probably present in the E. coli cell (Harms et al., 2001).

Both yeast transport systems are believed to function by K⁺:H⁺ symport, but the wheat protein functions by K⁺:Na⁺ symport. It is possible that some of these proteins can function by a channel-type mechanism.

The generalized transport reaction catalyzed by the Trk family members is therefore probably:

K⁺ (out) + H⁺ (out) K⁺ (in) + H⁺ (in).