SLC9A6
Function
Endosomal Na(+), K(+)/H(+) antiporter (PubMed:15522866, PubMed:28635961, PubMed:31676550, PubMed:32277048). Mediates the electroneutral exchange of endosomal luminal H(+) for a cytosolic Na(+) or K(+). By facilitating proton efflux, SLC9A6 counteracts the acidity generated by vacuolar (V)-ATPase, thereby limiting luminal acidification. Responsible for alkalizing and maintaining the endosomal pH, and consequently in, e.g., endosome maturation and trafficking of recycling endosomal cargo (PubMed:15522866, PubMed:28635961, PubMed:31676550, PubMed:32277048). Plays a critical role during neurodevelopment by regulating synaptic development and plasticity (By similarity). Implicated in the maintenance of cell polarity in a manner that is dependent on its ability to modulate intravesicular pH (PubMed:20130086). Regulates intracelular pH in some specialized cells, osteoclasts and stereocilia where this transporter localizes to the plasma membrane (By similarity).
Involvement in disease
Intellectual developmental disorder, X-linked, syndromic, Christianson type
MRXSCH
A syndrome characterized by profound intellectual disability, epilepsy, ataxia, and microcephaly. It shows phenotypic overlap with Angelman syndrome.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Ubiquitinated (in vitro).
Glycosylated.
Sequence Similarities
Belongs to the monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family.
Tissue Specificity
Ubiquitous. High expression in brain, skeletal muscle, and heart, but is also detected at lower levels in most other tissues.
Cellular localization
- Endosome membrane
- Multi-pass membrane protein
- Recycling endosome membrane
- Multi-pass membrane protein
- Early endosome membrane
- Multi-pass membrane protein
- Late endosome membrane
- Multi-pass membrane protein
- Cell membrane
- Multi-pass membrane protein
- Present predominantly in the recycling compartments including early and recycling endosomes, but undergoes plasma membrane localization during vesicular recycling, which is enhanced upon certain stimuli, such as hypoxia (PubMed:11940519, PubMed:28635961, PubMed:30296617). Has a major plasmalemmal distribution in a few specialized cells, such as in vestibular hair bundles and osteoblasts (By similarity).
Alternative names
KIAA0267, NHE6, SLC9A6, Sodium/hydrogen exchanger 6, Na(+)/H(+) exchanger 6, Solute carrier family 9 member 6, NHE-6