Slc9a1
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 (By similarity). 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. In addition, can transport lithium Li(+) and functions also as a Na(+)/Li(+) antiporter. SLC9A1 also functions in membrane anchoring and organization of scaffolding complexes that coordinate signaling inputs (By similarity).
Involvement in disease
Defects in Slc9a1 is the cause of slow-wave epilepsy (swe) phenotype (PubMed:9335342). Mutant mice display slow-wave epilepsy, with a neurological syndrome including ataxia and a unique epilepsy phenotype consisting of 3/sec absence and tonic-clonic seizures. Mutants show selective neuronal death in the cerebellum and brainstem. Mice display also several other significant abnormalities in growth and development, and less than half of the mutant homozygous animals survived to weaning. Most died by 35-40 days (PubMed:9335342).
Post-translational modifications
O-glycosylated.
Ubiquitinated, leading to its degradation by the proteasome. Ubiquitination is reduced by CHP1.
Palmitoylated; may play a major role in SLC9A1 regulation.
Phosphorylation at Thr-784 increases SLC9A1 activity. Specifically dephosphorylated at Thr-784 by PPP3CA that negatively regulates SLC9A1 activity. Phosphorylation at Ser-652 by AKT1 reduces SLC9A1 binding to CALM1.
Sequence Similarities
Belongs to the monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family.
Tissue Specificity
Expressed in kidney, brain and stomach.
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
Nhe1, Sodium/hydrogen exchanger 1, Na(+)/H(+) exchanger 1, Solute carrier family 9 member 1, NHE-1