SLC9A6 Membrane Protein Introduction

Introduction of SLC9A6

Solute carrier family 9A6 (SLC9A6) is also known as sodium-hydrogen antiporter 6 (NHE-6) or sodium/hydrogen exchanger 6. SLC9A6 is encoded by the SLC9A6 gene in humans, which is ubiquitously expressed in the brain, adrenal, and 23 other tissues. The SLC9A6 gene is conserved in Rhesus monkey, chicken, chimpanzee, dog, rat, zebrafish, fruit fly, mouse, mosquito, cow, C.elegans, and frog. It belongs to the solute carrier family 9, and functions as a Na⁺/H⁺ antiporter. SLC9A6 is documented to be involved in pH homeostasis, and signal transduction.

Basic Information of SLC9A6
Protein Name	Sodium/hydrogen exchanger 6
Gene Name	SLC9A6
Aliases	Na(+)/H(+) exchanger 6, KIAA0267, NHE6
Organism	Homo sapiens (Human)
UniProt ID	Q92581
Transmembrane Times	13
Length (aa)	669
Sequence	MARRGWRRAPLRRGVGSSPRARRLMRPLWLLLAVGVFDWAGASDGGGGEARAMDEEIVSEKQAEESHRQDSANLLIFILLLTLTILTIWLFKHRRARFLHETGLAMIYGLLVGLVLRYGIHVPSDVNNVTLSCEVQSSPTTLLVTFDPEVFFNILLPPIIFYAGYSLKRRHFFRNLGSILAYAFLGTAISCFVIGSIMYGCVTLMKVTGQLAGDFYFTDCLLFGAIVSATDPVTVLAIFHELQVDVELYALLFGESVLNDAVAIVLSSSIVAYQPAGDNSHTFDVTAMFKSIGIFLGIFSGSFAMGAATGVVTALVTKFTKLREFQLLETGLFFLMSWSTFLLAEAWGFTGVVAVLFCGITQAHYTYNNLSTESQHRTKQLFELLNFLAENFIFSYMGLTLFTFQNHVFNPTFVVGAFVAIFLGRAANIYPLSLLLNLGRRSKIGSNFQHMMMFAGLRGAMAFALAIRDTATYARQMMFSTTLLIVFFTVWVFGGGTTAMLSCLHIRVGVDSDQEHLGVPENERRTTKAESAWLFRMWYNFDHNYLKPLLTHSGPPLTTTLPACCGPIARCLTSPQAYENQEQLKDDDSDLILNDGDISLTYGDSTVNTEPATSSAPRRFMGNSSEDALDRELAFGDHELVIRGTRLVLPMDDSEPPLNLLDNTRHGPA

Function of SLC9A6 Membrane Protein

As a proton exchanger and transporter, SLC9A6 mediates the sodium-ion transport by exchanging intracellular hydrogen ions to external sodium ions and plays an important role in cell pH regulation and cell volume. As a member of SLC9A family, SLC9A6 is associated with Nef internalization into M2 macrophages. The relocalization of SLC9A6 from endosomes to plasma membrane is related to endosome hyperacidification. In addition, SLC9A6 is identified in the choroid plexus and it may be involved in pH modulation of the CSF. SLC9A6 expression is down-regulated in Caco-2 cells via the mechanisms of rotavirus-induced diarrhea. Moreover, SLC9A6 is associated with recycling endosomal function and neuronal degeneration and cell death. SLC9A6 is also functionally associated with Alzheimer disease via endosomal pH modulation and amyloid precursor protein. Furthermore, SLC9A6 plays a critical role in endosome hyperacidification and chemoresistance.

Fig.1 Model for endosomal pH regulation of Aβ production by NHE6. (Prasad, 2015)

Application of SLC9A6 Membrane Protein in Literature

Damkier H.H., et al. The murine choroid plexus epithelium expresses the 2Cl^-/H⁺ exchanger ClC-7 and Na⁺/H⁺ exchanger NHE6 in the luminal membrane domain. Am J Physiol Cell Physiol. 2018, 314(4): C439-C448. PubMed ID: 29351414

This article indicates that SLC9A6 is identified in the choroid plexus for the first time, and it may be involved in pH modulation of the CSF.
Lucien F., et al. Hypoxia-induced mobilization of NHE6 to the plasma membrane triggers endosome hyperacidification and chemoresistance. Nat Commun. 2017, 8: 15884. PubMed ID: 28635961

This article shows that NHE6 plays a critical role in endosome hyperacidification and chemoresistance.
Chen H., et al. Human rotavirus strain Wa downregulates NHE1 and NHE6 expressions in rotavirus-infected Caco-2 cells. Virus Genes. 2017, 53(3): 367-376. PubMed ID: 28289928

This article indicates that SLC9A6 expression is down-regulated in Caco-2 cells via the mechanisms of rotavirus-induced diarrhea.
Ilie A., et al. A Christianson syndrome-linked deletion mutation (∆(287)ES(288)) in SLC9A6 disrupts recycling endosomal function and elicits neurodegeneration and cell death. Mol Neurodegener. 2016, 11(1): 63. PubMed ID: 27590723

This article shows that functional deficiency caused by the mutation in SLC9A6 is associated with recycling endosomal function and neuronal degeneration and cell death.
Prasad H. and Rao R. The Na⁺/H⁺ exchanger NHE6 modulates endosomal pH to control processing of amyloid precursor protein in a cell culture model of Alzheimer disease. J Biol Chem. 2015, 290(9): 5311-27. PubMed ID: 25561733

This article demonstrates that SLC9A6 is functionally associated with Alzheimer disease via endosomal pH modulation and amyloid precursor protein.

SLC9A6 Preparation Options

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Reference

Prasad H and Rao R. (2015). The Na⁺/H⁺ exchanger NHE6 modulates endosomal pH to control processing of amyloid precursor protein in a cell culture model of Alzheimer disease. J Biol Chem. 290(9): 5311-27.

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