| Structural highlights
Disease
SL9A9_HUMAN A chromosomal aberration involving SLC9A9 has been found in a family with early-onset behavioral/developmental disorder with features of attention deficit-hyperactivity disorder and intellectual disability. Inversion inv(3)(p14:q21). The inversion disrupts DOCK3 and SLC9A9.[1] Disease susceptibility is associated with variants affecting the gene represented in this entry.
Function
SL9A9_HUMAN Endosomal Na(+), K(+)/H(+) antiporter. Mediates the electroneutral exchange of endosomal luminal H(+) for a cytosolic Na(+) or K(+) (Probable). By facilitating proton efflux, SLC9A9 counteracts the acidity generated by vacuolar (V)-ATPase, thereby limiting luminal acidification. Regulates organellar pH and consequently, e.g., endosome maturation and endocytic trafficking of plasma membrane receptors and neurotransporters (PubMed:15522866, PubMed:24065030, PubMed:28130443). Promotes the recycling of transferrin receptors back to the cell surface to facilitate additional iron uptake in the brain (PubMed:28130443). Regulates synaptic transmission by regulating the luminal pH of axonal endosomes (By similarity). Regulates phagosome lumenal pH, thus affecting phagosome maturation, and consequently, microbicidal activity in macrophages (By similarity). Can also be active at the cell surface of specialized cells, e.g., in the inner ear hair bundles uses the high K(+) of the endolymph to regulate intracellular pH (By similarity).[UniProtKB:Q8BZ00][2] [3] [4] [5]
References
- ↑ de Silva MG, Elliott K, Dahl HH, Fitzpatrick E, Wilcox S, Delatycki M, Williamson R, Efron D, Lynch M, Forrest S. Disruption of a novel member of a sodium/hydrogen exchanger family and DOCK3 is associated with an attention deficit hyperactivity disorder-like phenotype. J Med Genet. 2003 Oct;40(10):733-40. doi: 10.1136/jmg.40.10.733. PMID:14569117 doi:https://dx.doi.org/10.1136/jmg.40.10.733
- ↑ 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
- ↑ Kondapalli KC, Hack A, Schushan M, Landau M, Ben-Tal N, Rao R. Functional evaluation of autism-associated mutations in NHE9. Nat Commun. 2013;4:2510. doi: 10.1038/ncomms3510. PMID:24065030 doi:https://dx.doi.org/10.1038/ncomms3510
- ↑ Beydoun R, Hamood MA, Gomez Zubieta DM, Kondapalli KC. Na(+)/H(+) Exchanger 9 Regulates Iron Mobilization at the Blood-Brain Barrier in Response to Iron Starvation. J Biol Chem. 2017 Mar 10;292(10):4293-4301. doi: 10.1074/jbc.M116.769240. Epub , 2017 Jan 27. PMID:28130443 doi:https://dx.doi.org/10.1074/jbc.M116.769240
- ↑ 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
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