SLC9A3 Membrane Protein Introduction

Introduction of SLC9A3

Solute carrier family 9A3 (SLC9A3) is also known as sodium/hydrogen exchanger 3 (NHE-3) or sodium-hydrogen antiporter 3. It is encoded by the SLC9A3 gene in humans. SLC9A3 is differently expressed in colon, kidney and 9 other tissues. It belongs to the solute carrier family 9, and functions as a Na⁺/H⁺ antiporter. SLC9A3 is shown to be involved in pH homeostasis, and signal transduction. Mutations in SLC9A3 gene may cause congenital secretory sodium diarrhea.

Basic Information of SLC9A3
Protein Name	Sodium/hydrogen exchanger 3
Gene Name	SLC9A3
Aliases	Na(+)/H(+) exchanger 3, NHE-3, Solute carrier family 9 member 3, NHE3
Organism	Homo sapiens (Human)
UniProt ID	P48764
Transmembrane Times	10
Length (aa)	834
Sequence	MWGLGARGPDRGLLLALALGGLARAGGVEVEPGGAHGESGGFQVVTFEWAHVQDPYVIALWILVASLAKIGFHLSHKVTSVVPESALLIVLGLVLGGIVWAADHIASFTLTPTVFFFYLLPPIVLDAGYFMPNRLFFGNLGTILLYAVVGTVWNAATTGLSLYGVFLSGLMGDLQIGLLDFLLFGSLMAAVDPVAVLAVFEEVHVNEVLFIIVFGESLLNDAVTVVLYNVFESFVALGGDNVTGVDCVKGIVSFFVVSLGGTLVGVVFAFLLSLVTRFTKHVRIIEPGFVFIISYLSYLTSEMLSLSAILAITFCGICCQKYVKANISEQSATTVRYTMKMLASSAETIIFMFLGISAVNPFIWTWNTAFVLLTLVFISVYRAIGVVLQTWLLNRYRMVQLEPIDQVVLSYGGLRGAVAFALVVLLDGDKVKEKNLFVSTTIIVVFFTVIFQGLTIKPLVQWLKVKRSEHREPRLNEKLHGRAFDHILSAIEDISGQIGHNYLRDKWSHFDRKFLSRVLMRRSAQKSRDRILNVFHELNLKDAISYVAEGERRGSLAFIRSPSTDNVVNVDFTPRSSTVEASVSYLLRENVSAVCLDMQSLEQRRRSIRDAEDMVTHHTLQQYLYKPRQEYKHLYSRHELTPTEDEKQDREIFHRTMRKRLESFKSTKLGLNQNKKAAKLYKRERAQKRRNSSIPNGKLPMESPAQNFTIKEKDLELSDTEEPPNYDEEMSGGIEFLASVTKDTASDSPAGIDNPVFSPDEALDRSLLARLPPWLSPGETVVPSQRARTQIPYSPGTFCRLMPFRLSSKSVDSFLQADGPEERPPAALPESTHM

Function of SLC9A3 Membrane Protein

SLC9A3 belongs to sodium-hydrogen exchanger (NHE) protein family, which 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. SLC9A3 is an epithelial brush border sodium/hydrogen exchanger which can expel acids from the cells through an inward sodium ion gradient. Mutations in this gene can cause congenital secretory sodium diarrhea. SLC9A3 is very important for intestinal sodium absorption, and downregulation of SLC9A3 has been identified in infectious diseases and is associated with inflammatory bowel diseases (IBD)-associated diarrhea. The expression of SLC9A3 is regulated by DNA methylation. In addition, SLC9A3 has a critical functional role in dilated intercellular spaces (DIS), and SLC9A3 can be a potential therapeutic target in patients with Eosinophilic Esophagitis (EoE). Furthermore, SLC9A3 is associated with colitis through disruption of the gut microbial ecology.

Fig.1 Cellular models for luminal acidification by NHE3. (Pholpramool, 2011)

Application of SLC9A3 Membrane Protein in Literature

Wang Y.Y., et al. SLC9A3 Protein Is Critical for Acrosomal Formation in Postmeiotic Male Germ Cells. Int J Mol Sci. 2017, 19(1). PubMed ID: 29286340

This article indicates that SLC9A3 plays a critical role in acrosomal formation during spermiogenesis.
Yin J., et al. A common NHE3 single-nucleotide polymorphism has normal function and sensitivity to regulatory ligands. Am J Physiol Gastrointest Liver Physiol. 2017, 313(2): G129-G137. PubMed ID: 28495802

This article identifies a common NHE3 single-nucleotide polymorphism-NHE3-799C, and indicates that it’s enriched in Asian populations, and associated with normal function and sensitivity to regulatory ligands.
Janecke A.R., et al. Reduced sodium/proton exchanger NHE3 activity causes congenital sodium diarrhea. Hum Mol Genet. 2015, 24(23): 6614-23. PubMed ID: 26358773

This article indicates that mutations in NHE3 can lead to congenital sodium diarrhea.
Fonseca-Camarillo G. and Yamamoto-Furusho J.K. Gene expression of solute carrier family 9 (sodium/hydrogen exchanger) 3, (SLC9A3) is downregulated in patients with ulcerative colitis. Inflamm Bowel Dis. 2012, 18(6): 1197-8. PubMed ID: 22447429

This article shows that SLC9A3 is downregulated in patients with ulcerative colitis.
Ivanis G., et al. Renal expression and localization of SLC9A3 sodium/hydrogen exchanger and its possible role in acid-base regulation in freshwater rainbow trout (Oncorhynchus mykiss). Am J Physiol Regul Integr Comp Physiol. 2008, 295(3): R971-8. PubMed ID: 18667717

This article demonstrates that SLC9A3 can promote acid-base regulation through stimulating H⁺ secretion and HCO₃^- reabsorption in freshwater rainbow trout.

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Reference

Pholpramool C, et al. (2011). Role of Na⁺/H⁺ exchanger 3 in the acidification of the male reproductive tract and male fertility. Clin Exp Pharmacol Physiol. 38(7): 403-9.

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