Biology:Sodium–hydrogen antiporter 3

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

Sodium–hydrogen antiporter 3 also known as sodium–hydrogen exchanger 3 (NHE3) or solute carrier family 9 member 3 (SLC9A3) is a protein that in humans is encoded by the SLC9A3 gene.

SLC9A3 is a sodium–hydrogen antiporter. It is found on the apical side of the epithelial cells of the proximal tubule of the nephron of the kidney, in the apical membrane of enterocytes of the intestine, as well as the basolateral side of both duodenal and pancreatic cells responsible for the release of HCO−3 into the duodenal lumen. It is primarily responsible for maintaining the balance of sodium. It is also indirectly linked to buffering of blood pH. The NHE3 antiporter imports one sodium ion into the cytosol of a tubule cell as it ejects one hydrogen ion from the cell into the lumen of the proximal tubule. The sodium within the tubule cell may then be retained by the body rather than excreted in the urine. The NHE3 antiporter indirectly contributes to blood buffering capacity because hydrogen ions that are ejected are the products of the carbonic anhydrase enzyme, which also makes bicarbonate.

Regulation

Protein kinase C stimulates NHE3, while protein kinase A inhibits it.

There is a specific protein functioning as an NHE3 regulator, Sodium-hydrogen antiporter 3 regulator 1.

Inhibitors

• Tenapanor

Stimulators

• Insulin stimulates NHE3 and thereby proximal tubule sodium absorption.

Interactions

Sodium–hydrogen antiporter 3 has been shown to interact with CHP.

Further reading

• "Mechanisms of pressure natriuresis: how blood pressure regulates renal sodium transport". Ann. N. Y. Acad. Sci. 986: 669–77. 2003. doi:10.1111/j.1749-6632.2003.tb07281.x. PMID 12763917. 
• "Molecular cloning of putative members of the Na/H exchanger gene family. cDNA cloning, deduced amino acid sequence, and mRNA tissue expression of the rat Na/H exchanger NHE-1 and two structurally related proteins". J. Biol. Chem. 267 (13): 9331–9. 1992. doi:10.1016/S0021-9258(19)50428-8. PMID 1577762. 
• "Cloning, tissue distribution, and functional analysis of the human Na+/N+ exchanger isoform, NHE3". Am. J. Physiol. 269 (1 Pt 1): C198-206. 1995. doi:10.1152/ajpcell.1995.269.1.C198. PMID 7631746. 
• "Presence of the NHE3 isoform of the Na+/H+ exchanger in human gallbladder". Clin. Sci. 91 (2): 209–12. 1996. doi:10.1042/cs0910209. PMID 8795445. 
• "Intestinal distribution of human Na+/H+ exchanger isoforms NHE-1, NHE-2, and NHE-3 mRNA". Am. J. Physiol. 271 (3 Pt 1): G483-93. 1996. doi:10.1152/ajpgi.1996.271.3.G483. PMID 8843774. 
• "A calcineurin homologous protein inhibits GTPase-stimulated Na-H exchange". Proc. Natl. Acad. Sci. U.S.A. 93 (22): 12631–6. 1996. doi:10.1073/pnas.93.22.12631. PMID 8901634. Bibcode: 1996PNAS...9312631L. 
• "NHE3 kinase A regulatory protein E3KARP binds the epithelial brush border Na+/H+ exchanger NHE3 and the cytoskeletal protein ezrin". J. Biol. Chem. 273 (40): 25856–63. 1998. doi:10.1074/jbc.273.40.25856. PMID 9748260. 
• "Specific association of megalin and the Na+/H+ exchanger isoform NHE3 in the proximal tubule". J. Biol. Chem. 274 (25): 17518–24. 1999. doi:10.1074/jbc.274.25.17518. PMID 10364184. 
• "Expression of cation exchanger NHE and anion exchanger AE isoforms in primary human bone-derived osteoblasts". Cell Biol. Int. 22 (7–8): 551–62. 1998. doi:10.1006/cbir.1998.0299. PMID 10452823. 
• "Sodium transport systems in human chondrocytes. II. Expression of ENaC, Na+/K+/2Cl- cotransporter and Na+/H+ exchangers in healthy and arthritic chondrocytes". Histol. Histopathol. 14 (4): 1023–31. 1999. PMID 10506918. 
• "Human duodenal mucosal brush border Na(+)/H(+) exchangers NHE2 and NHE3 alter net bicarbonate movement". Am. J. Physiol. Gastrointest. Liver Physiol. 281 (1): G159-63. 2001. doi:10.1152/ajpgi.2001.281.1.G159. PMID 11408268. 
• "Molecular cloning and functional analysis of the human Na(+)/H(+) exchanger NHE3 promoter". Am. J. Physiol. Gastrointest. Liver Physiol. 282 (3): G491-500. 2002. doi:10.1152/ajpgi.00273.2001. PMID 11841999. 
• "NHE3 serves as a molecular tool for cAMP-mediated regulation of receptor-mediated endocytosis". Am. J. Physiol. Renal Physiol. 283 (3): F549-58. 2002. doi:10.1152/ajprenal.00206.2001. PMID 12167607. 
• "Optimal absorptive transport of the dipeptide glycylsarcosine is dependent on functional Na+/H+ exchange activity". Pflügers Arch. 445 (1): 139–46. 2002. doi:10.1007/s00424-002-0910-1. PMID 12397398. 
• "Expression of mRNA transcripts of the Na+/H+ and Cl-/HCO3- exchanger isoforms in human nasal mucosa". Acta Otolaryngol. 122 (8): 866–71. 2002. doi:10.1080/003655402/000028045. PMID 12542207. 
• "Calcineurin homologous protein isoform 2 (CHP2), Na+/H+ exchangers-binding protein, is expressed in intestinal epithelium". Biol. Pharm. Bull. 26 (2): 148–55. 2003. doi:10.1248/bpb.26.148. PMID 12576672. 
• "Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides". Nat. Biotechnol. 21 (5): 566–9. 2003. doi:10.1038/nbt810. PMID 12665801. 

External links

• Sodium-Hydrogen+Exchanger at the US National Library of Medicine Medical Subject Headings (MeSH)