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Article

Amino Acids 563–566 of the Na+/H+ Exchanger Isoform 1 C-Terminal Cytosolic Tail Prevent Protein Degradation and Stabilize Protein Expression and Activity

1
Department of Biochemistry, University Alberta, Edmonton, AB T6G 2H7, Canada
2
Department of Biotechnology, Thapar Institute of Engineering and Technology Patiala, Patiala 147004, Punjab, India
3
Medical Biochemistry and Molecular Biology, Saarland University, 66421 Homburg, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(5), 1737; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21051737
Received: 21 January 2020 / Revised: 28 February 2020 / Accepted: 29 February 2020 / Published: 3 March 2020
(This article belongs to the Special Issue Structure and Function of Membrane Proteins)
Isoform one of the mammalian Na+/H+ exchanger is a plasma membrane protein that is ubiquitously present in humans. It regulates intracellular pH through the removal of one intracellular proton in exchange for a single extracellular sodium. It consists of a 500 amino acid membrane domain plus a 315 amino acid, C-terminal tail. We examined amino acids of the C-terminal tail that are important in the targeting and activity of the protein. A previous study demonstrated that stop codon polymorphisms can result in decreased activity, expression, targeting and enhanced protein degradation. Here, we determine elements that are critical in these anomalies. A series of progressive deletions of the C-terminal tail demonstrated a progressive decrease in activity and targeting, though these remained until a final drop off with the deletion of amino acids 563–566. The deletion of the 562LIAGERS568 sequence or the alteration to the 562LAAAARS568 sequence caused the decreased protein expression, aberrant targeting, reduced activity and enhanced degradation of the Na+/H+ exchanger (NHE1) protein. The 562LIAGERS568 sequence bound to other regions of the C-terminal cytosolic domain. We suggest this region is necessary for the activity, targeting, stability, and expression of the NHE1 protein. The results define a new sequence that is important in maintenance of NHE1 protein levels and activity. View Full-Text
Keywords: membrane protein; Na+/H+ exchanger; pH regulation; protein degradation; protein stability membrane protein; Na+/H+ exchanger; pH regulation; protein degradation; protein stability
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MDPI and ACS Style

Li, X.; Dutta, D.; Jung, M.; Zimmermann, R.; Fliegel, L. Amino Acids 563–566 of the Na+/H+ Exchanger Isoform 1 C-Terminal Cytosolic Tail Prevent Protein Degradation and Stabilize Protein Expression and Activity. Int. J. Mol. Sci. 2020, 21, 1737. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21051737

AMA Style

Li X, Dutta D, Jung M, Zimmermann R, Fliegel L. Amino Acids 563–566 of the Na+/H+ Exchanger Isoform 1 C-Terminal Cytosolic Tail Prevent Protein Degradation and Stabilize Protein Expression and Activity. International Journal of Molecular Sciences. 2020; 21(5):1737. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21051737

Chicago/Turabian Style

Li, Xiuju, Debajyoti Dutta, Martin Jung, Richard Zimmermann, and Larry Fliegel. 2020. "Amino Acids 563–566 of the Na+/H+ Exchanger Isoform 1 C-Terminal Cytosolic Tail Prevent Protein Degradation and Stabilize Protein Expression and Activity" International Journal of Molecular Sciences 21, no. 5: 1737. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21051737

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