ArticleThe Biochemical journal2006
Evidence for allosteric regulation of pH-sensitive System A (SNAT2) and System N (SNAT5) amino acid transporter activity involving a conserved histidine residue.
Article in The Biochemical journal, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 47 citations in OpenAlex.
- Combined walking exercise and alkali therapy in patients with CKD4-5 regulates intramuscular free amino acid pools and ubiquitin E3 ligase expression.European journal of applied physiology · 2013Trial
- pH-mediated activation of the lysosomal arginine sensor SLC38A9.FEBS letters · 2026Article
- Molecular mechanisms and evolutionary adaptations of transporters for photosynthates and specialized metabolites in plants.Plant cell reports · 2026Review
- pH-dependent regulation in SLC38A9.bioRxiv : the preprint server for biology · 2025Article
- Amino Acid Sensing by Transceptors: Exploring Substrate-Induced Regulation of Amino Acid Transporters and Transporter Expression.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Sodium-Dependent Neutral Amino Acid Transporter 2 Can Serve as a Tertiary Carrier for l-Type Amino Acid Transporter 1-Utilizing Prodrugs.Molecular pharmaceutics · 2023Article
- Low pH up-regulates interleukin-6 mRNA in L6-G8C5 rat skeletal muscle cells independent of pH sensing by SNAT2(SLC38A2) transporters.FASEB bioAdvances · 2022Article
- Reduction of Rapid Proliferating Tumour Cell Lines by Inhibition of the Specific Glycine Transporter GLYT1.Biomedicines · 2021Article
- Dexamethasone acutely suppresses the anabolic SNAT2/SLC38A2 amino acid transporter protein in L6-G8C5 rat skeletal muscle cells.FASEB bioAdvances · 2021Article
- Interplay of Carbonic Anhydrase IX With Amino Acid and Acid/Base Transporters in the Hypoxic Tumor Microenvironment.Frontiers in cell and developmental biology · 2020Review
- Effects of Sodium and Amino Acid Substrate Availability upon the Expression and Stability of the SNAT2 (SLC38A2) Amino Acid Transporter.Frontiers in pharmacology · 2018Article
- The neuronal and astrocytic protein SLC38A10 transports glutamine, glutamate, and aspartate, suggesting a role in neurotransmission.FEBS open bio · 2017Article
- Identification of a Disulfide Bridge in Sodium-Coupled Neutral Amino Acid Transporter 2(SNAT2) by Chemical Modification.PloS one · 2016Article
- Mechanism of Fine-tuning pH Sensors in Proprotein Convertases: IDENTIFICATION OF A pH-SENSING HISTIDINE PAIR IN THE PROPEPTIDE OF PROPROTEIN CONVERTASE 1/3.The Journal of biological chemistry · 2015Article
- Characterization and Regulation of the Amino Acid Transporter SNAT2 in the Small Intestine of Piglets.PloS one · 2015Article
- Glutamate metabolism and HIV-associated neurocognitive disorders.Journal of neurovirology · 2014Review
- The SLC38 family of sodium-amino acid co-transporters.Pflugers Archiv : European journal of physiology · 2014Review
- Article
- Capturing cooperative interactions with the PSI-MI format.Database : the journal of biological databases and curation · 2013Article
- Considering protonation as a posttranslational modification regulating protein structure and function.Annual review of biophysics · 2013Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
System A and N amino acid transporters are key effectors of movement of amino acids across the plasma membrane of mammalian cells. These Na+-dependent transporters of the SLC38 gene family are highly sensitive to changes in pH within the physiological range, with transport markedly depressed at pH 7.0. We have investigated the possible role of histidine residues in the transporter proteins in determining this pH-sensitivity. The histidine-modifying agent DEPC (diethyl pyrocarbonate) markedly reduces the pH-sensitivity of SNAT2 and SNAT5 transporters (representative isoforms of System A and N respectively, overexpressed in Xenopus oocytes) in a concentration-dependent manner but does not completely inactivate transport activity. These effects of DEPC were reversed by hydroxylamine and partially blocked in the presence of excess amino acid substrate. DEPC treatment also blocked a reduction in apparent affinity for Na+ (K0.5Na+) of the SNAT2 transporter at low external pH. Mutation of the highly conserved C-terminal histidine residue to alanine in either SNAT2 (H504A) or SNAT5 (H471A) produced a transport phenotype exhibiting reduced, DEPC-resistant pH-sensitivity with no change in K0.5Na+ at low external pH. We suggest that the pH-sensitivity of these structurally related transporters results at least partly from a common allosteric mechanism influencing Na+ binding, which involves an H+-modifier site associated with C-terminal histidine residues.
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Registered trials
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