| Structural highlights
Disease
SL9A6_HUMAN Christianson syndrome. The disease is caused by variants affecting the gene represented in this entry. The disease may be caused by variants affecting the gene represented in this entry.
Function
SL9A6_HUMAN 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 intracellular pH in some specialized cells, osteoclasts and stereocilia where this transporter localizes to the plasma membrane (By similarity).[UniProtKB:A1L3P4][1] [2] [3] [4] [5]
References
- ↑ Nakamura N, Tanaka S, Teko Y, Mitsui K, Kanazawa H. Four Na+/H+ exchanger isoforms are distributed to Golgi and post-Golgi compartments and are involved in organelle pH regulation. J Biol Chem. 2005 Jan 14;280(2):1561-72. doi: 10.1074/jbc.M410041200. Epub 2004 , Nov 2. PMID:15522866 doi:https://dx.doi.org/10.1074/jbc.M410041200
- ↑ Ohgaki R, Matsushita M, Kanazawa H, Ogihara S, Hoekstra D, van Ijzendoorn SC. The Na+/H+ exchanger NHE6 in the endosomal recycling system is involved in the development of apical bile canalicular surface domains in HepG2 cells. Mol Biol Cell. 2010 Apr 1;21(7):1293-304. doi: 10.1091/mbc.e09-09-0767. Epub 2010 , Feb 3. PMID:20130086 doi:https://dx.doi.org/10.1091/mbc.e09-09-0767
- ↑ Lucien F, Pelletier PP, Lavoie RR, Lacroix JM, Roy S, Parent JL, Arsenault D, Harper K, Dubois CM. Hypoxia-induced mobilization of NHE6 to the plasma membrane triggers endosome hyperacidification and chemoresistance. Nat Commun. 2017 Jun 21;8:15884. PMID:28635961 doi:10.1038/ncomms15884
- ↑ Ouyang Q, Joesch-Cohen L, Mishra S, Riaz HA, Schmidt M, Morrow EM. Functional Assessment In Vivo of the Mouse Homolog of the Human Ala-9-Ser NHE6 Variant. eNeuro. 2019 Dec 4;6(6):ENEURO.0046-19.2019. PMID:31676550 doi:10.1523/ENEURO.0046-19.2019
- ↑ Ilie A, Boucher A, Park J, Berghuis AM, McKinney RA, Orlowski J. Assorted dysfunctions of endosomal alkali cation/proton exchanger SLC9A6 variants linked to Christianson syndrome. J Biol Chem. 2020 May 15;295(20):7075-7095. PMID:32277048 doi:10.1074/jbc.RA120.012614
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