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2.A.72 The K+ Uptake Permease (KUP) Family


Proteins of the KUP/HAK/KT family include the KUP (TrkD) protein of E. coli and homologues in both Gram-positive and Gram-negative bacteria. High affinity (20 μM) K+ uptake systems (Hak1) of the yeast Debaryomyces occidentalis as well as the fungus, Neurospora crassa, and several homologues in plants have been characterized. Arabidopsis thaliana and other plants possess multiple KUP family paralogues. While many plant proteins cluster tightly together, the Hak1 proteins from yeast as well as the two Gram-positive and Gram-negative bacterial proteins are distantly related on the phylogenetic tree for the KUP family. The E. coli protein is 622 amino acyl residues long and has 12 estabilshed transmembrane spanners (440 residues) with a requisite hydrophilic, C-terminal domain of 182 residues, localized to the cytoplasmic side of the membrane (Sato et al. 2014). Deletion of most of the hydrophilic domain reduces but does not abolish KUP transport activity. The function of the C-terminal domain is not known. The E. coli KUP protein is believed to be a secondary transporter. Uptake is blocked by protonophores such as CCCP (but not arsenate), and evidence for a proton symport mechanism has been presented (Zakharyan and Trchounian, 2001). The N. crassa protein was earlier shown to be a K+:H+ symporter, establishing that the KUP family consists of secondary carriers.

The yeast high affinity (KM = 1 µM) K+ transporter Hak1 is 762 amino acyl residues long with 12 putative TMSs. Like the E. coli KUP protein, it possesses a C-terminal hydrophilic domain, probably localized to the cytoplasmic side of the membrane. Hak1 may be able to accumulate K+ 106-fold against a concentration gradient. The plant high and low affinity K+ transporters can complement K+ uptake defects in E. coli. 

TRK transporters, responsible for the  bulk of K+ accumulation in plants, fungi, and bacteria, mediate ion currents driven by the large membrane voltages (-150 to -250 mV) common to non-animal cells. Bacterial TRK proteins resemble K+ channels in their primary sequence, crystallize as membrane dimers having intramolecular K+-channel-like folding, and complex with a cytoplasmic collar formed of four RCK domains (Pardo et al. 2015). Fungal TRK proteins possess a large built-in regulatory domain and a highly conserved pair of transmembrane helices (TMSs 7 and 8, ahead of the C-terminus), postulated to facilitate intramembranal oligomerization.These fungal HAK proteins are chloride channels mediating efflux, a process suppressed by osmoprotective agents. It involve hydrophobic gating and resembles conduction by Cys-loop ligand-gated anion channels. Possibly, the tendency of hydrophobic or amphipathic transmembrane helices to self-organize into oligomers creates novel ionic pathways through membranes: hydrophobic nanopores, pathways of low selectivity governed by the chaotropic behavior of individual ionic species under the influence of membrane voltage (Pardo et al. 2015).

The generalized transport reaction for members of the KUP family is:



K+ (out) + energy → K+ (in).



This family belongs to the: APC Superfamily.

References associated with 2.A.72 family:

Bañuelos, M.A., R.D. Klein, S.J. Alexander-Bowman, and A. Rodrîguez-Navarro. (1995). A potassium transporter of the yeast Schwanniomyces occidentalis homologous to the Kup system of Escherichia coli has a high concentrative capacity. EMBO J. 14: 3021-3027. 7621817
Daras, G., S. Rigas, D. Tsitsekian, T.A. Iacovides, and P. Hatzopoulos. (2015). Potassium transporter TRH1 subunits assemble regulating root-hair elongation autonomously from the cell fate determination pathway. Plant Sci 231: 131-137. 25575998
Fu, H.-H. and S. Luan. (1998). AtKUP1: a dual-affinity K+ transporter from Arabidopsis. Plant Cell 10: 63-73. 9477572
Garciadeblas, B., J. Barrero-Gil, B. Benito, and A. Rodríguez-Navarro. (2007). Potassium transport systems in the moss Physcomitrella patens: pphak1 plants reveal the complexity of potassium uptake. Plant J. 52: 1080-1093. 17916113
Greiner T., Ramos J., Alvarez MC., Gurnon JR., Kang M., Van Etten JL., Moroni A. and Thiel G. (2011). Functional HAK/KUP/KT-like potassium transporter encoded by chlorella viruses. Plant J. 68(6):977-86. 21848655
Guo, Z.K., Q. Yang, X.Q. Wan, and P.Q. Yan. (2008). Functional characterization of a potassium transporter gene NrHAK1 in Nicotiana rustica. J Zhejiang Univ Sci B 9: 944-952. 19067462
Haro, R., L. Sainz, F. Rubio, and A. Rodríguez-Navarro. (1999). Cloning of two genes encoding potassium transporters in Neurospora crassa and expression of the corresponding cDNAs in Saccharomyces cerevisiae. Mol. Microbiol. 31: 511-520. 10027968
Kim, E.J., J.M. Kwak, N. Uozumi, and J.I. Schroeder. (1998). AtKUP1, an Arabidopsis gene encoding high-affinity potassium transport activity. Plant Cell 10: 51-62. 9477571
Nieves-Cordones, M., F. Alemán, V. Martínez, and F. Rubio. (2014). K+ uptake in plant roots. The systems involved, their regulation and parallels in other organisms. J Plant Physiol. 171: 688-695. 24810767
Pardo JP., Gonzalez-Andrade M., Allen K., Kuroda T., Slayman CL. and Rivetta A. (2015). A structural model for facultative anion channels in an oligomeric membrane protein: the yeast TRK (K(+)) system. Pflugers Arch. 467(12):2447-60. 26100673
Prista, C., J.C. González-Hernández, J. Ramos, and M.C. Loureiro-Dias. (2007). Cloning and characterization of two K+ transporters of Debaryomyces hansenii. Microbiology. 153: 3034-3043. 17768246
Pyo, Y.J., M. Gierth, J.I. Schroeder, and M.H. Cho. (2010). High-affinity K+ transport in Arabidopsis: AtHAK5 and AKT1 are vital for seedling establishment and postgermination growth under low-potassium conditions. Plant Physiol. 153: 863-875. 20413648
Rivetta, A., K.E. Allen, C.W. Slayman, and C.L. Slayman. (2013). Coordination of K+ transporters in neurospora: TRK1 is scarce and constitutive, while HAK1 is abundant and highly regulated. Eukaryot. Cell. 12: 684-696. 23475706
Sato Y., Nanatani K., Hamamoto S., Shimizu M., Takahashi M., Tabuchi-Kobayashi M., Mizutani A., Schroeder JI., Souma S. and Uozumi N. (2014). Defining membrane spanning domains and crucial membrane-localized acidic amino acid residues for K(+) transport of a Kup/HAK/KT-type Escherichia coli potassium transporter. J Biochem. 155(5):315-23. 24519967
Schleyer, M. and E.P. Bakker. (1993). Nucleotide sequence and 3'-end deletion studies indicate that the K+-uptake protein Kup from Escherichia coli is composed of a hydrophobic core linked to a large and partially essential hydrophilic C terminus. J. Bacteriol. 175: 6925-6931. 8226635
Senn, M.E., F. Rubio, M.A. Bañuelos, and A. Rodríguez-Navarro. (2001). Comparative functional features of plant potassium HvHAK1 and HvHAK2 transporters. J. Biol. Chem. 276: 44563-44569. 11562376
Trchounian, A. and H. Kobayashi. (1999). Kup is the major K+ uptake system in Escherichia coli upon hyper-osmotic stress at a low pH. FEBS Lett. 447: 144-148. 10214935
Zakharyan, E. and A. Trchounian. (2001). K+ influx by Kup in Escherichia coli is accompanied by a decrease in H+ efflux. FEMS Microbiol. Lett. 204: 61-64. 11682179