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Sodium/hydrogen exchanger 1

Domain

The C-terminal intracellular domain is subject to extensive post-translational modifications and binding partner interactions which regulate transporter activity, scaffolding functions, downstream events and localization.

Function

Electroneutral Na(+) /H(+) antiporter that extrudes Na(+) in exchange for external protons driven by the inward sodium ion chemical gradient, protecting cells from acidification that occurs from metabolism (PubMed:11350981, PubMed:11532004, PubMed:14680478, PubMed:15035633, PubMed:15677483, PubMed:17073455, PubMed:17493937, PubMed:22020933, PubMed:27650500, PubMed:32130622, PubMed:7110335, PubMed:7603840). Exchanges intracellular H(+) ions for extracellular Na(+) in 1:1 stoichiometry (By similarity). Plays a key role in maintening intracellular pH neutral and cell volume, and thus is important for cell growth, proliferation, migration and survival (PubMed:12947095, PubMed:15096511, PubMed:22020933, PubMed:8901634). In addition, can transport lithium Li(+) and functions also as a Na(+)/Li(+) antiporter (PubMed:7603840). SLC9A1 also functions in membrane anchoring and organization of scaffolding complexes that coordinate signaling inputs (PubMed:15096511).

Involvement in disease

Lichtenstein-Knorr syndrome

LIKNS

An autosomal recessive neurologic disorder characterized by progressive cerebellar ataxia and severe progressive sensorineural hearing loss.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

O-glycosylated.

Ubiquitinated, leading to its degradation by the proteasome. Ubiquitination is reduced by CHP1.

Phosphorylation at Thr-779 increases SLC9A1 activity. Specifically dephosphorylated at Thr-779 by PPP3CA that negatively regulates SLC9A1 activity (PubMed:31375679). Phosphorylation at Ser-648 by AKT1 reduces SLC9A1 binding to CALM1 (PubMed:18757828).

Palmitoylated; may play a major role in SLC9A1 regulation.

Sequence similarities

Belongs to the monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family.

Tissue specificity

Kidney and intestine.

Cellular localization

  • Cell membrane
  • Multi-pass membrane protein
  • Basolateral cell membrane
  • Multi-pass membrane protein
  • Localized basolaterally in every epithelial cell, except in the choroid plexus where SLC9A1 is expressed luminally.

Alternative names

APNH1, NHE1, SLC9A1, Sodium/hydrogen exchanger 1, APNH, Na(+)/H(+) exchanger 1, Solute carrier family 9 member 1, NHE-1

Target type

Proteins

Primary research area

Oncology

Molecular weight

90763Da

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