SLC9A5 Membrane Protein Introduction

Introduction of SLC9A5

Solute carrier family 9A5 (SLC9A5) is also known as sodium-hydrogen antiporter 5 (NHE-5) or sodium/hydrogen exchanger 5. SLC9A5 is encoded by the SLC9A5 gene in humans. It’s biased expressed in spleen, testis and 7 other tissues. The SLC9A5 gene is conserved in Rhesus monkey, dog, chimpanzee, cow, chicken, mouse, rat, zebrafish, mosquito, fruit fly, and frog. It belongs to the solute carrier family 9, and functions as a Na⁺/H⁺ antiporter. SLC9A5 is involved in cellular pH homeostasis, and signal transduction.

Basic Information of SLC9A5
Protein Name	Sodium/hydrogen exchanger 5
Gene Name	SLC9A5
Aliases	Na(+)/H(+) exchanger 5, Solute carrier family 9 member 5, NHE5
Organism	Homo sapiens (Human)
UniProt ID	Q14940
Transmembrane Times	12
Length (aa)	896
Sequence	MLRAALSLLALPLAGAAEEPTQKPESPGEPPPGLELFRWQWHEVEAPYLVALWILVASLAKIVFHLSRKVTSLVPESCLLILLGLVLGGIVLAVAKKAEYQLEPGTFFLFLLPPIVLDSGYFMPSRLFFDNLGAILTYAVVGTLWNAFTTGAALWGLQQAGLVAPRVQAGLLDFLLFGSLISAVDPVAVLAVFEEVHVNETLFIIVFGESLLNDAVTVVLYKVCNSFVEMGSANVQATDYLKGVASLFVVSLGGAAVGLVFAFLLALTTRFTKRVRIIEPLLVFLLAYAAYLTAEMASLSAILAVTMCGLGCKKYVEANISHKSRTTVKYTMKTLASCAETVIFMLLGISAVDSSKWAWDSGLVLGTLIFILFFRALGVVLQTWVLNQFRLVPLDKIDQVVMSYGGLRGAVAFALVILLDRTKVPAKDYFVATTIVVVFFTVIVQGLTIKPLVKWLKVKRSEHHKPTLNQELHEHTFDHILAAVEDVVGHHGYHYWRDRWEQFDKKYLSQLLMRRSAYRIRDQIWDVYYRLNIRDAISFVDQGGHVLSSTGLTLPSMPSRNSVAETSVTNLLRESGSGACLDLQVIDTVRSGRDREDAVMHHLLCGGLYKPRRRYKASCSRHFISEDAQERQDKEVFQQNMKRRLESFKSTKHNICFTKSKPRPRKTGRRKKDGVANAEATNGKHRGLGFQDTAAVILTVESEEEEEESDSSETEKEDDEGIIFVARATSEVLQEGKVSGSLEVCPSPRIIPPSPTCAEKELPWKSGQGDLAVYVSSETTKIVPVDMQTGWNQSISSLESLASPPCNQAPILTCLPPHPRGTEEPQVPLHLPSDPRSSFAFPPSLAKAGRSRSESSADLPQQQELQPLMGHKDHTHLSPGTATSHWCIQFNRGSRL

Function of SLC9A5 Membrane Protein

SLC9A5 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, SLC9A5 expression might be affected by clinical exposure to NSAIDs and this may lead to transport modulation and barrier function. SLC9A5 has a regulatory role in neuronal signaling through proton movement and in synaptic transmission. In addition, SLC9A5 is functionally associated with endosomal acidification, modulating TrkA cell-surface targeting, NGF-induced neurotrophin signaling and possibly neuronal differentiation. SLC9A5 can interact with AMPK to modulate the pH homeostasis of hippocampal neurons. Moreover, NHE5 deficiency impairs cell migration and leads to loss of cell polarity. Furthermore, SLC9A5 plays a functional role in regulating learning and memory in mice, and this implies that SLC9A5 can be a potential therapeutic target for improving cognition.

Fig.1 Model of endosomal and synaptic functions of NHE5. (Diering, 2014)

Application of SLC9A5 Membrane Protein in Literature

Chen X., et al. Nhe5 deficiency enhances learning and memory via upregulating Bdnf/TrkB signaling in mice. Am J Med Genet B Neuropsychiatr Genet. 2017, 174(8): 828-838. PubMed ID: 28981195

This article indicates that SLC9A5 plays a functional role in regulating learning and memory in mice, and this implies that SLC9A5 can be a potential therapeutic target for improving cognition.
Fan S.H., et al. Endosomal Na⁺/H⁺ exchanger NHE5 influences MET recycling and cell migration. Mol Biol Cell. 2016, 27(4): 702-15. PubMed ID: 26700318

This article shows that NHE5 deficiency impairs cell migration and leads to loss of cell polarity.
Jinadasa T., et al. Activation of AMP-activated protein kinase regulates hippocampal neuronal pH by recruiting Na(+)/H(+) exchanger NHE5 to the cell surface. J Biol Chem. 2014, 289(30): 20879-97. PubMed ID: 24936055

This article indicates that SLC9A5 can interact with AMPK to modulate the pH homeostasis of hippocampal neurons.
Diering G.H. and Numata M. Endosomal pH in neuronal signaling and synaptic transmission: role of Na(+)/H(+) exchanger NHE5. Front Physiol. 2014, 4: 412. PubMed ID: 24454292

This article shows that NHE5 has a regulatory role in neuronal signaling through proton movement and in synaptic transmission.
Diering G.H., et al. Endosomal acidification by Na⁺/H⁺ exchanger NHE5 regulates TrkA cell-surface targeting and NGF-induced PI3K signaling. Mol Biol Cell. 2013, 24(21): 3435-48. PubMed ID: 24006492

This article demonstrates that SLC9A5 is functionally associated with endosomal acidification, modulating TrkA cell-surface targeting, NGF-induced neurotrophin signaling and possibly neuronal differentiation.

SLC9A5 Preparation Options

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Reference

Diering G H and Numata M. (2014). Endosomal pH in neuronal signaling and synaptic transmission: role of Na(+)/H(+) exchanger NHE5. Front Physiol. 4: 412.

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