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. There are 10 members of the KUP (HAK) family in sugar beets (Beta vulgaris) and the results suggest that the BvHAK gene family plays important roles in the response of sugar beet to salt stress (Yang et al. 2022). Cyclic di-AMP traps proton-coupled K+ transporters of the KUP family in an inward-occluded conformation (Fuss et al. 2023).

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.  Plant genomes contain large numbers of HAK/KUP/KT transporters, and they show diverse roles in K+ uptake and translocation, salt tolerance and osmotic potential regulation, as well as in controlling root morphology and shoot phenotyping (Li et al. 2018). HAK/KUP/KT transporters can be phosphorylated by CIPK-CBL complexes for activating K+ uptake and probably signaling (Li et al. 2018).

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).

Plant HAK/KUP/KT family members function as plasma membrane (PM) H+/K+ symporters and modulate chemiosmotically-driven polar auxin transport (PAT). Yang et al. 2020 showed that inactivation of OsHAK5 (TC# 2.A.72.3.9) in rice decreased rootward and shootward PAT, tiller number, and the length of both lateral roots and root hairs, while OsHAK5 overexpression had the opposite effect, irrespective of the K+ supply. Inhibitors of ATP-binding-cassette type-B transporters, NPA and BUM, abolished the OsHAK5-overexpression effect on PAT. The mechanistic basis of these changes included the OsHAK5-mediated decrease of transmembrane potential (depolarization), increase of extracellular pH, and increase of PM-ATPase activity. Thus, dual roles of OsHAK5 in altering cellular chemiosmotic gradients (generated continuously by PM H+-ATPase) and regulating ATP-dependent auxin transport. Both functions may underlie the prominent effect of OsHAK5 on rice architecture (Yang et al. 2020).

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

K+ (out) + Na+ or H+ (out) → K+ (in) + Na+ or H+ (in).

This family belongs to the APC Superfamily.



Azeem, F., R. Zameer, M.A. Rehman Rashid, I. Rasul, S. Ul-Allah, M.H. Siddique, S. Fiaz, A. Raza, A. Younas, A. Rasool, M.A. Ali, S. Anwar, and M.H. Siddiqui. (2021). Genome-wide analysis of potassium transport genes in Gossypium raimondii suggest a role of GrHAK/KUP/KT8, GrAKT2.1 and GrAKT1.1 in response to abiotic stress. Plant Physiol. Biochem 170: 110-122. [Epub: Ahead of Print]

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.

Cai, K., H. Gao, X. Wu, S. Zhang, Z. Han, X. Chen, G. Zhang, and F. Zeng. (2019). The Ability to Regulate Transmembrane Potassium Transport in Root Is Critical for Drought Tolerance in Barley. Int J Mol Sci 20:.

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.

Fu, H.-H. and S. Luan. (1998). AtKUP1: a dual-affinity K+ transporter from Arabidopsis. Plant Cell 10: 63-73.

Fuss, M.F., J.P. Wieferig, R.A. Corey, Y. Hellmich, I. Tascón, J.S. Sousa, P.J. Stansfeld, J. Vonck, and I. Hänelt. (2023). Cyclic di-AMP traps proton-coupled K transporters of the KUP family in an inward-occluded conformation. Nat Commun 14: 3683.

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.

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.

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.

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.

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.

Li, W., G. Xu, A. Alli, and L. Yu. (2018). Plant HAK/KUP/KT K transporters: Function and regulation. Semin Cell Dev Biol 74: 133-141.

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.

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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.

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.

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.

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.

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.

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.

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Yang, T., H. Feng, S. Zhang, H. Xiao, Q. Hu, G. Chen, W. Xuan, N. Moran, A. Murphy, L. Yu, and G. Xu. (2020). The Potassium Transporter OsHAK5 Alters Rice Architecture via ATP-Dependent Transmembrane Auxin Fluxes. Plant Commun 1: 100052.

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TC#NameOrganismal TypeExample

Low affinity K+ uptake permease, KUP or TrkD.  It has 12 established TMSs with four transmembrane acidic residues important for K+ uptake (Sato et al. 2014).


KUP of E. coli (P63183)


Probable potassium transport system protein Kup


Kup of Methanosarcina acetivorans


Probable potassium transport system protein, Kup 1 of 670 aas

Kup1 of Lactococcus lactis


TC#NameOrganismal TypeExample
2.A.72.2.1K+ uptake permease Yeast Hak1 of Debaryomyces (Schwanniomyces) occidentalis
2.A.72.2.2The K+ uptake transporter, DhHAK1 (expressed when K+ starved) (Prista et al., 2007)YeastDhHAK1 of Debaryomyces hansenii (Q0G848)

TC#NameOrganismal TypeExample

High affinity K+ transporter, KUP1 of 712 aas and 13 -15 TMSs. This protein and KUP2 in barely may play a role in drought resistance (Cai et al. 2019).  HAK/KUP/KT8, GrAKT2.1 and GrAKT1.1 potassium channels may function in response to abiotic stress in Gossypium raimondii (Azeem et al. 2021).



AtKUP1 of Arabidopsis thaliana


Tiny root hair-1 K+ transporter (TRH1) of 775 aas, also called K+ transporter-3 (POT3; KT3) or KUP4.  It regulates root hair elongation (Daras et al. 2015).


TRH1 of Arabidopsis thaliana (Mouse-ear cress)


K+ transporter, HAK1 of 777 aas and 13 TMSs (Guo et al. 2008). Also capable of anion channel activity at high voltages as those found in plants, fungi and bacteria, but not animal cells, possibly using to a new route formed by oligomerization (Pardo et al. 2015).


HAK1 of Nicotiana rustica (Aztec tobacco)


KUP9 (POT9) potassium ion transporter of 807 aas and 14 TMSs.  It is up-regluated upon salt stress (Yang et al. 2018).

KUP9 of Arabidopsis thaliana (Mouse-ear cress)


K+:H+ symporter, HAK1. Hak1p is produced at high levels but is down regluated by extracellular K and by expression of Trk1 (2.A.38.2.2) (Rivetta et al. 2013).


Hak1 of Neurospora crassa


High affinity K+ uptake transporter, Hak1, of 775 aas and 12 TMSs.  It is involved in drought resistance and is influenced by the H+-ATPases, HA1 and HA2 (see TC# 3.A.3.3.9) (Cai et al. 2019).


Hak1 of Hordeum vulgare

2.A.72.3.4Low affinity, Na+-sensitive K+ uptake transporter (vacuolar ?)PlantsHak2 of Hordeum vulgare
2.A.72.3.5Dominant K+ uptake porter, Hak1 (47% identical to 3.A.72.3.4; 822aas) (Garciadeblas et al., 2007)


Hak1 of Physcomitrella patens (A5PH39)


High affinity K+ transporter, HAKCV (expressed at an early stage during viral infection) (Greiner et al., 2011).


HAKCV of Paramecium bursaria Chlorella virus (A7J6G4)

2.A.72.3.7Potassium transporter 1 (OsHAK1)


HAK1 of Oryza sativa subsp. japonica
2.A.72.3.8Potassium transporter 2 (AtKT2) (AtKUP2) (AtPOT2)PlantsPOT2 of Arabidopsis thaliana

High affinity potassium transporter 5, HAK5 (Nieves-Cordones et al. 2014).  It is essential for seed development and postgermination growth in low potassium (Pyo et al. 2010) and probably plays a role in drought resistance (Cai et al. 2019). In rice, it alters the cell architecture via ATP-dependent transmembrane auxin transport (Yang et al. 2020).


Hak5 of Arabidopsis thaliana