2.A.36 The Monovalent Cation:Proton Antiporter-1 (CPA1) Family

The CPA1 family is a large family of proteins derived from Gram-positive and Gram-negative bacteria, blue-green bacteria, archaea, yeast, plants and animals. Transporters from eukaryotes have been functionally characterized, and all of these catalyze Na+:H+ exchange. Their primary physiological functions may be in (1) cytoplasmic pH regulation, extruding the H+ generated during metabolism, and (2) salt tolerance (in plants), due to Na+ uptake into vacuoles. Bacterial homologues are also Na+:H+ antiporters, but some also catalyze Li+:H+ antiport or Ca2+:H+ antiport under some conditions (Waditee et al., 2001).  The pathophylsiology of human members of this family have been reviewed (Padan and Landau 2016).

The phylogenetic tree for the CPA1 family shows three principal clusters. The first cluster includes proteins derived exclusively from animals, and all of the functionally characterized members of the family belong to this cluster. Of the two remaining clusters, one includes all bacterial homologues while the other includes one from Arabidopsis thaliana, one from Homo sapiens and two from yeast (S. cerevisiae and S. pombe). Several organisms possess multiple paralogues; for example seven paralogues are found in C. elegans, and five are known for humans. Most of these paralogues are very similar in sequence, and they belong to the animal specific cluster.

Using the mammalian NHE1 (2.A.36.1.1), it has been found that TMSs 4 and 9 as well as the extracellular loop between TMSs 3 and 4 are important for drug (amiloride- and benzoyl guanidinium-based derivatives) sensitivities. Mutations in these regions also affect transport activities. M4 and M9 therefore contain critical sites for both drug and cation recognition.

Daxx, a death domain-associated protein, (O35613) interacts with sodium hydrogen exchanger isoform 1 (NHE1). During ischemic stress, Daxx translocates from the nucleus to the cytoplasm, where it colocalizes with NHE1. Daxx binds to the ezrin/radixin/moesin (ERM)-interacting domain of NHE1, in competition with ezrin. Ischemic insult may trigger the nucleo-cytoplasmic translocation of Daxx, following which cytoplasmic Daxx stimulates the NHE1 transporter activity and suppresses activation of the NHE1-ezrin-Akt-1 pathway (Jung et al., 2007).

One homologue, Nhe (TC #2.A.36.1.4), is a chloride-dependent Na+:H+ antiporter in which residues 1-375 of the 438 aas are identical to Nhe-1 (TC #2.A.36.1.1). The C-terminal 63 residues are unique (Sangan et al., 2002). It is found in the apical membranes of crypt cells of the rat distal colon. This protein was reported to exhibit 6 putative TMSs and is encoded by a 2.5 kb mRNA present in many tissues (Sangan et al., 2002). However, the WHAT program predicts 10 TMSs. nhe transfected fibroblasts exhibit Cl--dependent Na+-dependent intracellular pH recovery to an acid load that was blocked by 5-ethylisopropylamiloride and 5'-nitro-2-(3-phenylpropylamino)benzoate (a Cl- channel blocker).

Numerous members of the CPA1 family have been sequenced, and these proteins vary substantially in size. The bacterial proteins have 527-549 amino acyl residues while eukaryotic proteins are generally larger, varying in size from 541-894 residues. They exhibit 10-12 putative transmembrane α-helical spanners (TMSs). A proposed topological model (Wakabayashi et al., 2000) suggests that in addition to 12 TMSs, a region between TMSs 9 and 10 dips into the membrane to line the pore. However, one homologue, Nhx1 of S. cerevisiae, has an extracellular glycosylated C-terminus (Wells and Rao, 2001).

A gene encoding a Na+/H+ antiporter was cloned from the chromosome of Halobacillus dabanensis strain D-8(T) by functional complementation. Its presence enabled the antiporter-deficient E. coli strain KNabc to survive in the presence of 0.2 M NaCl or 5 mM LiCl (Yang et al. 2006). The gene was sequenced and designated as nhaH (2.A.36.6.7). NhaH has 403 residues and is 54% identical and 76% similar to the NhaG Na+/H+ antiporter of Bacillus subtilis (TC# 2.A.36.6.2). The hydropathy profile was characteristic of a membrane protein with 12 putative transmembrane domains. Everted membrane vesicles prepared from E. coli cells carrying nhaH exhibited Na+/H+ as well as Li+/H+ antiporter activity, which was pH-dependent with highest activities at pH 8.5-9.0 and at pH 8.5, respectively. nhaH confers upon E. coli KNabc cells the ability to grow under alkaline conditions (Yang et al., 2006).

The generalized transport reaction catalyzed by functionally characterized members of the CPA1 family is:

Na+ (out) + H+ (in) ⇌ Na+ (in) + H+ (out)



This family belongs to the CPA Superfamily.

 

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Xiang, M., M. Feng, S. Muend, and R. Rao. (2007). A human Na+/H+ antiporter sharing evolutionary origins with bacterial NhaA may be a candidate gene for essential hypertension. Proc. Natl. Acad. Sci. U.S.A. 104: 18677-186781.

Yan, J.J., M.Y. Chou, T. Kaneko, and P.P. Hwang. (2007). Gene expression of Na+/H+ exchanger in zebrafish H+-ATPase-rich cells during acclimation to low-Na+ and acidic environments. Am. J. Physiol. Cell Physiol. 293: C1814-1823.

Yang, L., Y. Jin, W. Huang, Q. Sun, F. Liu, and X. Huang. (2018). Full-length transcriptome sequences of ephemeral plant Arabidopsis pumila provides insight into gene expression dynamics during continuous salt stress. BMC Genomics 19: 717.

Yang, L.F., J.Q. Jiang, B.S. Zhao, B. Zhang, d.e.Q. Feng, W.D. Lu, L. Wang, and S.S. Yang. (2006). A Na+/H+ antiporter gene of the moderately halophilic bacterium Halobacillus dabanensis D-8T: cloning and molecular characterization. FEMS Microbiol. Lett. 255: 89-95.

Zou, Y.J., L.F. Yang, L. Wang, and S.S. Yang. (2008). Cloning and characterization of a Na+/H+ antiporter gene of the moderately halophilic bacterium Halobacillus aidingensis AD-6T. J Microbiol 46: 415-421.

Examples:

TC#NameOrganismal TypeExample
2.A.36.1.1

Na+:H+ antiporter 1 (Nhe-1) (Regulated by Daxx (O35613)). An integral membrane protein that regulates intracellular pH and has a large N-terminal membrane domain of 12 transmembrane segments and an intracellular C-terminal regulatory domain (Reddy et al., 2008). The dimer catalyzes antiport with 2Na+/2H+ stoichiometry (Fuster et al., 2008). Nedd4-1 and β-arrestin-1 are key regulators of Na+/H+ exchanger 1 ubiquitylation, endocytosis and function (Simonin and Fuster et al., 2010). Important in heart disease and cancer. Structural studies have been performed using NMR (Lee et al., 2011).

Animals

Nhe-1 of Rattus norvegicus

 
2.A.36.1.10Basal membrane Nhe3 AnimalsNhe3 of Aedes aegypti (Q17L17)
 
2.A.36.1.11

The Na+:H+ Exchanger, NHE1, is developmentally regulated and necessary for cell polarity (Patel and Barber, 2005).

Slime Molds

NHE1 of Dictyostelium discoideum (Q552S0)

 
2.A.36.1.12

Na+:H+ antiporter, NHX1; (vacuolar/endosomal Na+ tolerance protein).  Plays roles in ion homeostasis and vesicle trafficing (Mukherjee et al. 2006). The structures and functions of these NHX homologues have been reviewed (Dutta and Fliegel 2018).

Yeast; plants

NHX1 (YDR456w) of Saccharomyces cerevisiae

 
2.A.36.1.13

Na /H exchanger-1 (NHE1).  Stoichiometry = 1:1. TMS VI of NHE1 is a discontinuous pore-lining helix with residues Asn(227), Ile(233), and Leu(243) lining the translocation pore (Tzeng et al., 2010). (orthologous to NHE1 of rat, TC# 2.A.36.1.1). It regulates internal pH in human monocytes and is important in heart disease and cancer (Tsai et al. 2015). Structural studies have been performed using NMR and EPR (Lee et al., 2011; Nygaard et al. 2011).  Extracytoplasmic loops contribute to ion coordination and inhibitor sensitivity (Lee et al. 2012).  The regulation of NHE1 has been reviewed (Wakabayashi et al. 2013).  CD44 (LHR, MDU2, MDU3, MIC4; P16070) regulates breast cancer metastasis by regulating NHE1 expression (Chang et al. 2014).  The role of NHE1 in kidney proximal tubule functions, including pH regulation, vectorial Na+ transport, cell volume control and cell survival has been reviewed (Parker et al. 2015).  Helix M9 and the adjacent exofacial re-entrant loop 5 between M9 and M10 (EL5) are important elements involved in cation transport and inhibitor sensitivity (Jinadasa et al. 2015).  A 12 TMS topology has been confirmed (Liu et al. 2015).  Mutations  cause Lichtenstein-Knorr syndrome, an autosomal recessive condition that associates sensorineural hearing loss with cerebellar ataxia (Guissart et al. 2015). Cleaved FAS ligand (transmembrane CD95L; 1 TMS; P48023) activates NHE1 through the Akt/ROCK1 signalling pathway to stimulate cell motility (Monet et al. 2016). NHE1 may contribute to internal pH and motility of mammalian sperm (Muzzachi et al. 2018). The intracellular loop, IL5 is critical for proton sensing and ion transport (Wong et al. 2018). NHE1 and CD44 (the hyaluronan receptor with 742 aas and 2 TMSs, one at the N-terminus and one at the C-terminus (P16070)) appear to play important roles in cardiac remodeling (Suleiman et al. 2018).

Animals

SLC9A1 of Homo sapiens

 
2.A.36.1.14

Sodium/hydrogen exchanger 6 (Na+/H+ exchanger 6) (NHE-6) (Solute carrier family 9 member 6).  This Na+/H+ exchanger is encoded by an X-linked gene that is widely expressed and especially abundant in brain, heart and skeletal muscle where it is implicated in endosomal pH homeostasis and trafficking as well as maintenance of cell polarity. Several mutations in the coding region of NHE6 are linked with severe intellectual disability, autistic behavior, ataxia and other abnormalities (Ilie et al. 2014).  A christianson syndrome-linked mutation disrupts endosomal function and elicits neurodegeneration and cell death (Ilie et al. 2016).  Heterozygous female mice suffer from visuospatial memory and motor coordination deficits similar to but less severe than those observed in X-chromosome hemizygous mutant males (Sikora et al. 2016).

Animals

SLC9A6 of Homo sapiens

 
2.A.36.1.15

Sodium/hydrogen exchanger 3 (Na+/H+ exchanger 3) (NHE-3) (Solute carrier family 9 member 3) (Dominguez Rieg et al. 2016).

Animals

SLC9A3 of Homo sapiens

 
2.A.36.1.16Sodium/hydrogen exchanger 5 (Na(+)/H(+) exchanger 5) (NHE-5) (Solute carrier family 9 member 5)AnimalsSLC9A5 of Homo sapiens
 
2.A.36.1.17

Sodium/hydrogen exchanger 2 (Na+/H+ exchanger 2) (NHE-2 or NHE2) (Solute carrier family 9 member 2).  Mediates butyrate-dependent Na+ absorption (Rajendran et al. 2015).

Animals

SLC9A2 of Homo sapiens

 
2.A.36.1.18Sodium/hydrogen exchanger 4 (Na(+)/H(+) exchanger 4) (NHE-4) (Solute carrier family 9 member 4)AnimalsSLC9A4 of Homo sapiens
 
2.A.36.1.19Sodium/hydrogen exchanger 9 (Na(+)/H(+) exchanger 9) (NHE-9) (Solute carrier family 9 member 9)AnimalsSLC9A9 of Homo sapiens
 
2.A.36.1.2

Na+:H+ antiporter 3 (NHE-3 or NHE3). Regulated by Na+/H+ exchange regulatory cofactors (NHERF; O14745; TC #8.A.24.1.1) (Seidler et al., 2009). Cyclic AMP-mediated endocytosis of intestinal epithelial NHE3 requires binding to synaptotagmin 1 (Musch et al., 2010).  Decreased activity is responsible for congenital Na+ diarrhea in the human brush boarder (Janecke et al. 2015). Reduced functional expression of NHE3, and DRA contribute to Cl- and Na+ stool loss in microvillus inclusion disease (MVID) diarrhea (Kravtsov et al. 2016).

Animals

Nhe-3 of Rattus norvegicus

 
2.A.36.1.20

Endomembrane (Golgi) K+, Na+/H+ exchanger 5, NHX5, of 521 aas and 11 TMSs.  Three acidic residues are critical for transport activity as well as seedling growth, regulation of protein transport into vesicles and ionic homeostasis (Qiu 2016). NHX6 is 80% identical to NHX5 (535 aas and 11 TMSs) and serves the same function.

Plants

NHX5 of Arabidopsis thaliana (Q9SLJ7)

 
2.A.36.1.21

Sodium:proton antiporter of 468 aas and 13 TMSs, Sod2 or NHE1.  Residues within TMS 11 play important roles in transport, suggesting that this TMS forms part of the ion translocation core (Dutta et al. 2017).

NHE1 of Schizosaccharomyces pombe (Fission yeast)

 
2.A.36.1.22

Na+/H+ exchanger, beta-like, NHE, of 917 aas and 11 putative TMSs.  Involved in pH homeostasis (Li et al. 2019).

NHE of Penaeus vannamei (Pacific white shrimp)

 
2.A.36.1.23

Sodium/proton exchanger of 529 aas and 12 or 13 TMSs.  The six NHXs in grape have been bioinformatically characterized (Ayadi et al. 2019). This protein is 81% identical to the exchanger with TC# 2.A.36.1.5.

NHX6 of Vitis vinifera (wine grape)

 
2.A.36.1.3

Na+/K+:H+ antiporter, Nhe-7, present in the Golgi apparatus and endosomes. There are four isoforms, NHE6-9. They regulate the luminal pH as well as intracellular trafficking, and function in cell polarity development (Ohgaki et al., 2011). Nhe-6 (Nhe6) is associated with X-linked intellectural disability and autism when processing and trafficking is impaired (Ilie et al. 2013).

Animals

SLC9A7 of Homo sapiens

 
2.A.36.1.4Cl--dependent Na+:H+ antiporter (Nhe) (residues 1-375 are identical to Nhe-1 [TC #2.A.36.1.1]).AnimalsNhe of Rattus norvegicus
 
2.A.36.1.5Na+/K+:H+ antiporter, NHX2PlantsNHX2 of Lycopersicon esculentum (CAC83608)
 
2.A.36.1.6Zebrafish Na+:H+ antiporter NheC (Yan et al., 2007) (most similar to TC# 2.A.36.1.2, 48% identical)AnimalsNheC of Danio rerio (A3KPJ8)
 
2.A.36.1.7The basolateral intestinal Na+/H+ antiporter PBO-4 (Beg et al., 2008)Animals PBO-4 of Caenorhabditis elegans (Q21386)
 
2.A.36.1.8Na+/H+ exchanger, Nhx-2 (Pfeiffer et al., 2008) AnimalsNhx-2 of Caenorhabditis elegans (Q09432)
 
2.A.36.1.9

Human Na+/H+ Exchanger, NHE-8 or SLC9A8. Functions in intracellular pH homeostasis, cell volume regulation, and electroneutral NaCl absorption in epithelia. It attenuates Ca2+ influx in the proximal tubular epithelium (Wiebe et al. 2019).

Animals

SLC9A8 of Homo sapiens

 
Examples:

TC#NameOrganismal TypeExample
2.A.36.2.1

Putative Na+/H+ exchanger, Cpa1 (399aas; 13 TMSs)

Archaea

Cpa1 of Methanothermobacter thermautotrophicus (O26854)

 
2.A.36.2.2

The electroneutral Na+/Li+:H+ antiporter, Nha2. Catalyzes Na+:Li+ antiport; contributes to salt homeostasis. It correlates with heritable hypertension (Xiang et al., 2007) and is critical for insulin secretion (Deisl et al. 2013). Like electrogenic Na+/H+ exchangers, it has two conserved aspartyl residues in the Na+ binding site but seems to be electroneutral (Uzdavinys et al. 2017).

Animals

SLC9B2 of Homo sapiens

 
2.A.36.2.3 solute carrier family 9, subfamily B (NHA1, cation proton antiporter 1), member 1AnimalsSLC9B1 of Homo sapiens
 
Examples:

TC#NameOrganismal TypeExample
2.A.36.3.1

Putative antiporter of 549 aas (function unknown) (Verkhovskaya et al. 2001).

Bacteria

YjcE of E. coli

 
2.A.36.3.2Na+, K+, Li+, Rb+:H+ antiporter, YvgPBacteriaYvgP of Bacillus subtilis (CAB15347)
 
2.A.36.3.3Uncharacterized Na(+)/H(+) exchanger Rv2287/MT2345BacteriaRv2287 of Mycobacterium tuberculosis
 
Examples:

TC#NameOrganismal TypeExample
2.A.36.4.1[Na+ or K+]:H+ antiporter Nha1 Yeast Nha1 (YLR138w) of Saccharomyces cerevisiae
 
2.A.36.4.2

Na+:H+ antiporter, Nha2 or Sod2-22.  Exports Na+ and Li+ but not K+.  Three residues, T141 in TMS 4, A179 in TMS 5 and V375 in TMS 11, determine the cation selectivity (Kinclova-Zimmermannova et al. 2015).

Yeast

Nha2 of Zygosaccharomyces rouxii

 
2.A.36.4.3

Na+:H+ antiporter, Nha1 or Sod1.  It provides salt tolerance by removing sodium or lithium ions in exchange for protons, and TMS 4 plays an important role (Ullah et al. 2013).

Yeast

Nha1 of Schizosaccharomyces pombe

 
2.A.36.4.4The K+, Rb+ and other alkali metal cation efflux porter, Cnh1 (Kinclova-Zimmermannova and Sychrova, 2007). Transports Na+, K+, Li+ and Rb+ in several Candida species.  Confers tolerance to high salt concentrations (Krauke and Sychrova 2008).

Yeast

Cnh1 of Candida albicans (Q9P937)

 
2.A.36.4.5Probable Na(+)/H(+) antiporter C3A11.09YeastSPAC3A11.09 of Schizosaccharomyces pombe
 
Examples:

TC#NameOrganismal TypeExample
2.A.36.5.1

Low-affinity Na+ (K+, Li+ or Cs+):H+ antiporter, Nhx1. It is up-regluated in response to high salt stress conditions (Yang et al. 2018). It has the same general architecture as CHX17 of A. thaliana (TC# 2.A.37.4.2) (Sze and Chanroj 2018).

Plants

Nhx1 of Arabidopsis thaliana

 
2.A.36.5.2

Vacuolar Na+/H+ antiporter, NHX1. A class-I type NHX. Confers NaCl tolerance and therefore pumps Na+ from the cytosol to the vacuole (Jha et al., 2011).

Halophytic plants

NHX1 of Salicornia brachiata (B1PLB6)

 
2.A.36.5.3

Vacuolar Na+/H+ exchanger, DgNHX1 or NHX1, of 510 aas and 13 putative (but possibly 9 actual) TMSs. Involved in adaptation to salt stress conditions and expressed under these same conditions (Liu et al. 2013). 

Plants

NHX1 of Chrysanthemum morifolium (Florist's daisy) (Dendranthema grandiflorum)

 
2.A.36.5.4

Vacuorlar Na+/H+ exchanger, Nhx1 of 542 aas and 13 TMSs.  Involved in salt tolerance (Mishra et al. 2014).

Plants

Nhx1 of Vigna radiata (Mung bean)

 
2.A.36.5.5

Na+:H+ antiporter, Nhx1 of 470 aas and 9 TMSs. NHX1 can confer a high level of salinity tolerance when overexpressed in Brassica juncea. Verma et al. 2007 reported its functional characterization. Overexpression conferred a high level of salinity tolerance in rice. Transgenic rice plants overexpressing PgNHX1 developed more extensive root systems and completed their life cycle by setting flowers and seeds in the presence of 150 mM NaCl.

Nhx1 of Pennisetum americanum (Pearl millet) (Pennisetum glaucum)

 
2.A.36.5.6

Na+/Li+/H+ exchanger of 545 aas and 12 TMSs, NHX3.  It is localized to the tonoplast membrane where it increases salt tolerance and reduces Li+ toxicity.  TMS 11 is important in Li+ and Na+ transport (Pan et al. 2017).

NHX3 of Populus euphratica (Euphrates poplar)

 
Examples:

TC#NameOrganismal TypeExample
2.A.36.6.1Putative Na+:H+ antiporter, Nhe2 Archaea The AF0846 gene (Nhe2) of Archaeoglobus fulgidus
 
2.A.36.6.10

Na+/H+ antiporter of 403 aas and 11 predicted TMSs, NhaH. Exchanges Na+ or Li+ but not K+ for H+ (Zou et al. 2008).  Confers Na+ and Li+ tolerance.

NhaH of Halobacillus aidingensis

 
2.A.36.6.11

Na+/H+ antiporter, NhaP2 (YcgO; CvrA) of 578 aas and 13 TMSs. Involved in growth at low osmolarity, intracellular K+ maintenance, and volume regulation (Verkhovskaya et al. 2001).

NhaP2 of E. coli

 
2.A.36.6.2

Na+ (Li+):H+ antiporter NhaG (Gouda et al. 2001).  Several very similar antiporters have been isolated from uncultured bacteria from a lake in China (Wang et al. 2013).

Bacteria

NhaG of Bacillus subtilis ATCC9372

 
2.A.36.6.3

K+:H+ antiporter, KhaP2 (NhaP2). Participates in volume control under low osmorality conditions (Radchenko et al., 2006; Resch et al., 2010)

Bacteria

KhaP2 of Vibrio parahaemolyticus (Q87KV8)

 
2.A.36.6.4The K+(NH4+):H+ antiporter, NhaP (confers alkali resistance for alkaline pH homeostasis) (Wei et al., 2007)BacteriaNhaP of Alkalimonas amylolytica (Q0ZAH6)
 
2.A.36.6.5

K+:H+ antiporter NhaP2 (catalyzes K+:H+ and Na+:H+ exchange; Resch et al., 2010). (84% identical to 2.A.36.6.3). A cation binding pocket in the middle of the membrane and a pathway leading to it have been identified (Mourin et al. 2018).

Bacteria

NhaP2 of Vibrio cholerae (Q9KNM9)

 
2.A.36.6.6

Na+/H+ antiporter 1 (MjNhaP1).  NhaP1 is a dimer with 13 TMSs per monomer as revealed by electron crystalography of 2-d crystals (Goswami et al. 2011).  This structure is contrasted with that of the distantly related bacterial NhaA; these two structures are quite different in detail, but similar within the 6 TMS repeat unit. Asp234/235 of helix VIII are involved in ligand-binding, and helix X plays a role in the activation of the transporter (Kedrov et al. 2007).

Archaea

MJ0057 (NhaP1) of Methanocaldococcus jannaschii

 
2.A.36.6.7

NhaH Na+/Li+/H+ antiporter (Yang et al. 2006).

Firmicutes

NhaH of Halobacillus dabanensis (Q2XWL3)

 
2.A.36.6.8

Na+/H+ antiporter of 424 aas, NhaP, that extrudes sodium in exchange for external protons. Has weak (if any) Li+/H+ antiport activity (Kuroda et al. 2004).

NhaP of Pseudomonas aeruginosa

 
2.A.36.6.9

Na+/H+ antiporter, NhaP, of 443 aas.  Several 3-d structures are known (Wöhlert et al. 2014).  The ion is coordinated by three acidic side chains, a water molecule, a serine and a main-chain carbonyl in an unwound stretch of TMS 5 at the deepest point of a negatively charged cytoplasmic funnel. A second narrow polar channel may facilitate proton uptake from the cytoplasm. Transport activity is cooperative at pH 6 but not at pH 5, due to pH-dependent allosteric coupling of protomers through two histidines at the dimer interface (Wöhlert et al. 2014).

NhaP of Pyrococcus abyssi

 
Examples:

TC#NameOrganismal TypeExample
2.A.36.7.1

ApNhaP: a Na+:H+ antiporter at pH 5-9; a Ca2+:H+ antiporter at alkaline pH (not an Li:H+ antiporter) (Waditee et al. 2001).  When the gene for ApNhaP is expressed in the fresh water cyanobacterium, Synechococcus sp. PCC 7942, it became salt tolerant and could live in salt water (Waditee et al. 2002; ).

Cyanobacteria

ApNhaP of Aphanothece halophytica

 
2.A.36.7.10

Na+/H+ antiporter of 1145 aas and 12 TMSs, SOS1.  Suppresses salt (200 mM NaCl) sensitivity, promoting tolerance (Wu et al. 2007). 65% identical to the A. thaliana homologue (TC# 2.A.36.7.6)

SOS1 of Populus euphratica (Euphrates poplar)

 
2.A.36.7.2Low affinity (Km=8 mM) Na+(Li+):H+ antiporter, NhaS1BacteriaNhaS1 of Synechocystis sp. PCC6803
 
2.A.36.7.3

Li+/H+ antiporter, AtNHX8 (An et al., 2007).  An orthologue in Puccinellia tenuiflora (alkali grass) is up regulated under salt stress and confers tolerance to high NaCl stress (Wang et al. 2011).

Plants

NHX8 of Arabidopsis thaliana (Q3YL57)

 
2.A.36.7.4Sodium/hydrogen exchanger 11 (Na(+)/H(+) exchanger 11) (NHE-11) (Solute carrier family 9 member 11) (Solute carrier family 9 member C2)AnimalsSLC9C2 of Homo sapiens
 
2.A.36.7.5

Sodium/hydrogen exchanger 10 (Na+/H+ exchanger 10) (NHE-10) (Solute carrier family 9 member 10) (Solute carrier family 9 member C1) (Sperm-specific Na+/H+ exchanger) (sNHE).  Predicted to have 17 TMSs in a 13 +  4 TMS arrangement.  The last 4 TMSs are homologous to the 4 TMS voltage sensor of the Ca2+ channel, 1.A.1.11.7.

Animals

SLC9C1 of Homo sapiens

 
2.A.36.7.6

Dimeric Salt-Overly-Sensitive 1 (SOS1) sodium:proton exchanger 7 (NHX7) (Núñez-Ramírez et al. 2012).  The salt stress-induced SALT-OVERLY-SENSITIVE (SOS) pathway in Arabidopsis thaliana involves the perception of a calcium signal by the SOS3 and SOS3-like CALCIUM-BINDING PROTEIN8 (SCaBP8; 5.b.1.1.8) calcium sensors, which then interact with and activate the SOS2 protein kinase (9.B.106.3.4), forming a complex at the plasma membrane that activates the SOS1 Na⁺/H⁺ exchanger (Lin et al. 2014).  The involvement of SOS1 in Na+ efflux in plant roots has been reviewed (Britto and Kronzucker 2015). SOS1 appears to encode a salinity-inducible plasma membrane Na+ /H+ antiporter (Song et al. 2012).

 

Plants

SOS1 of Arabidopsis thaliana

 
2.A.36.7.7

Testis-specific sodium:proton exchanger, mtsNHE (Slc9c1) of 1175 aas and 12 - 16 TMSs.  It is present in sperm flagellae and seems to be required for optimal sperm motility, fertilization and the acrosome reaction (Liu et al. 2010).  69% identical to the human NHE, TC# 2.A.36.7.5.  It may have a 12 TMS topology, but has a long C-terminal hydrophilic domain with a segment showing 2 - 4 TMSs. 

Animals

mtsNHE of Mus musculus

 
2.A.36.7.8

Putative Na+/H+ antiporter of 1142 aas

Alveolata

Nha of Eimeria tenella (Coccidian parasite)

 
2.A.36.7.9

Sodium/proton antiporter, Nhe1 of 1690 aas

Alveolata

Nhe1 of Plasmodium falciparum

 
Examples:

TC#NameOrganismal TypeExample