ArticleThe Biochemical journal2004
Proline residues in transmembrane segment IV are critical for activity, expression and targeting of the Na+/H+ exchanger isoform 1.
Article in The Biochemical journal, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 89 citations in OpenAlex.
- Characterization of Critical Amino Acids in the Transport and Selectivity of the Plant NaInternational journal of molecular sciences · 2025Article
- Allosteric links between the hydrophilic N-terminus and transmembrane core of human NaProtein science : a publication of the Protein Society · 2022Article
- Amino Acids 785, 787 of the NaInternational journal of molecular sciences · 2021Article
- Intracellular pH regulation: characterization and functional investigation of HBMC molecular and cell biology · 2021Article
- Role of Genetic Mutations of the NaMolecular and cellular biochemistry · 2021Review
- Amino Acids 563-566 of the NaInternational journal of molecular sciences · 2020Article
- Si permeability of a deficient Lsi1 aquaporin in tobacco can be enhanced through a conserved residue substitution.Plant direct · 2019Article
- Functional Analysis of Conserved Transmembrane Charged Residues and a Yeast Specific Extracellular Loop of the Plasma Membrane NaScientific reports · 2019Article
- Transmembrane Segment XI of the NaScientific reports · 2017Article
- Na+/H+ exchanger NHE1 regulation modulates metastatic potential and epithelial-mesenchymal transition of triple-negative breast cancer cells.Oncotarget · 2016Article
- Expression and characterization of the SOS1 Arabidopsis salt tolerance protein.Molecular and cellular biochemistry · 2016Article
- Stop Codon Polymorphisms in the Human SLC9A1 Gene Disrupt or Compromise Na+/H+ Exchanger Function.PloS one · 2016Article
- Determinants of Cation Permeation and Drug Sensitivity in Predicted Transmembrane Helix 9 and Adjoining Exofacial Re-entrant Loop 5 of Na+/H+ Exchanger NHE1.The Journal of biological chemistry · 2015Article
- A novel human mutation in the SLC9A1 gene results in abolition of Na+/H+ exchanger activity.PloS one · 2015Article
- Functional role and analysis of cysteine residues of the salt tolerance protein Sod2.Molecular and cellular biochemistry · 2014Article
- Structural and functional analysis of transmembrane segment IV of the salt tolerance protein Sod2.The Journal of biological chemistry · 2013Article
- Statistical analyses and computational prediction of helical kinks in membrane proteins.Journal of computer-aided molecular design · 2012Article
- Gender-specific effects of exercise on cardiac pathology in Na(+)/H(+) exchanger overexpressing mice.Molecular and cellular biochemistry · 2012Article
- Elevated expression of activated Na(+)/H(+) exchanger protein induces hypertrophy in isolated rat neonatal ventricular cardiomyocytes.Molecular and cellular biochemistry · 2011Article
- B-Raf associates with and activates the NHE1 isoform of the Na+/H+ exchanger.The Journal of biological chemistry · 2011Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
NHE1 (Na+/H+ exchanger isoform 1) is a ubiquitously expressed integral membrane protein that regulates intracellular pH in mammalian cells. Proline residues within transmembrane segments have unusual properties, acting as helix breakers and increasing flexibility of membrane segments, since they lack an amide hydrogen. We examined the importance of three conserved proline residues in TM IV (transmembrane segment IV) of NHE1. Pro167 and Pro168 were mutated to Gly, Ala or Cys, and Pro178 was mutated to Ala. Pro168 and Pro178 mutant proteins were expressed at levels similar to wild-type NHE1 and were targeted to the plasma membrane. However, the mutants P167G (Pro167-->Gly), P167A and P167C were expressed at lower levels compared with wild-type NHE1, and a significant portion of P167G and P167C were retained intracellularly, possibly indicating induced changes in the structure of TM IV. P167G, P167C, P168A and P168C mutations abolished NHE activity, and P167A and P168G mutations caused markedly decreased activity. In contrast, the activity of the P178A mutant was not significantly different from that of wild-type NHE1. The results indicate that both Pro167 and Pro168 in TM IV of NHE1 are required for normal NHE activity. In addition, mutation of Pro167 affects the expression and membrane targeting of the exchanger. Thus both Pro167 and Pro168 are strictly required for NHE function and may play critical roles in the structure of TM IV of the NHE.
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