Sodium–hydrogen antiporter 3

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.^[5][6]

SLC9A3
Identifiers
Aliases	SLC9A3, NHE3, NHE-3, Sodium–hydrogen antiporter 3, DIAR8, solute carrier family 9 member A3
External IDs	OMIM: 182307; MGI: 105064; HomoloGene: 55804; GeneCards: SLC9A3; OMA:SLC9A3 - orthologs
Gene location (Human) Chr. Chromosome 5 (human)[1] Band 5p15.33 Start 470,456 bp[1] End 524,449 bp[1]
Gene location (Mouse) Chr. Chromosome 13 (mouse)[2] Band 13 C1|13 40.15 cM Start 74,269,576 bp[2] End 74,317,561 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in mucosa of transverse colon sural nerve gallbladder body of stomach gonad testicle right uterine tube human kidney appendix mucosa of esophagus Top expressed in jejunum right kidney duodenum human kidney zygote large intestine colon secondary oocyte primary oocyte proximal tubule More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding PDZ domain binding antiporter activity solute:proton antiporter activity potassium:proton antiporter activity sodium:proton antiporter activity Cellular component integral component of membrane membrane cell surface extracellular exosome plasma membrane brush border membrane brush border apical plasma membrane vesicle Biological process regulation of pH proton transmembrane transport ion transport cation transport sodium ion transport potassium ion transmembrane transport transmembrane transport regulation of intracellular pH sodium ion import across plasma membrane transport anion transmembrane transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6550 105243 Ensembl ENSG00000281861 ENSG00000066230 ENSMUSG00000036123 UniProt P48764 G3X939 RefSeq (mRNA) NM_001284351 NM_004174 NM_001081060 RefSeq (protein) NP_001271280 NP_004165 NP_001074529 Location (UCSC) Chr 5: 0.47 – 0.52 Mb Chr 13: 74.27 – 74.32 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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.^[7]

Regulation

Protein kinase C stimulates NHE3, while protein kinase A inhibits it.^[8]

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

Inhibitors

• Tenapanor^[9]

Stimulators

• Insulin^[10] stimulates NHE3 and thereby proximal tubule sodium absorption.

Interactions

Sodium–hydrogen antiporter 3 has been shown to interact with CHP.^[11]

References

1. ENSG00000066230 GRCh38: Ensembl release 89: ENSG00000281861, ENSG00000066230 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000036123 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: SLC9A3 Solute carrier family 9 (sodium/hydrogen exchanger), member 3".
6. Brant SR, Bernstein M, Wasmuth JJ, Taylor EW, McPherson JD, Li X, Walker S, Pouyssegur J, Donowitz M, Tse CM (March 1993). "Physical and genetic mapping of a human apical epithelial Na+/H+ exchanger (NHE3) isoform to chromosome 5p15.3". Genomics. 15 (3): 668–72. doi:10.1006/geno.1993.1122. PMID 8096830.
7. VI. Mechanisms of Salt & Water Reabsorption Archived February 10, 2007, at the Wayback Machine
8. 852 Walter F., PhD. Boron (2005). Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. ISBN 1-4160-2328-3. Page 852
9. Spencer AG, Labonte ED, Rosenbaum DP, Plato CF, Carreras CW, Leadbetter MR, Kozuka K, Kohler J, Koo-McCoy S, He L, Bell N, Tabora J, Joly KM, Navre M, Jacobs JW, Charmot D (2014). "Intestinal inhibition of the Na+/H+ exchanger 3 prevents cardiorenal damage in rats and inhibits Na+ uptake in humans". Sci Transl Med. 6 (227): 227ra36. doi:10.1126/scitranslmed.3007790. PMID 24622516. S2CID 10741924.
10. Klisic J, Hu MC, Nief V, Reyes L, Fuster D, Moe OW, Ambühl PM (2002). "Insulin activates Na(+)/H(+) exchanger 3: biphasic response and glucocorticoid dependence". Am J Physiol Renal Physiol. 283 (3): F532-9. doi:10.1152/ajprenal.00365.2001. PMID 12167605.
11. Inoue H, Nakamura Y, Nagita M, Takai T, Masuda M, Nakamura N, Kanazawa H (2003). "Calcineurin homologous protein isoform 2 (CHP2), Na+/H+ exchangers-binding protein, is expressed in intestinal epithelium". Biol. Pharm. Bull. 26 (2): 148–55. doi:10.1248/bpb.26.148. PMID 12576672.

Further reading

• McDonough AA, Leong PK, Yang LE (2003). "Mechanisms of pressure natriuresis: how blood pressure regulates renal sodium transport". Ann. N. Y. Acad. Sci. 986: 669–77. doi:10.1111/j.1749-6632.2003.tb07281.x. PMID 12763917. S2CID 86115595.
• Orlowski J, Kandasamy RA, Shull GE (1992). "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. doi:10.1016/S0021-9258(19)50428-8. PMID 1577762.
• Brant SR, Yun CH, Donowitz M, Tse CM (1995). "Cloning, tissue distribution, and functional analysis of the human Na+/N+ exchanger isoform, NHE3". Am. J. Physiol. 269 (1 Pt 1): C198-206. doi:10.1152/ajpcell.1995.269.1.C198. PMID 7631746.
• Colombani V, Silviani V, Marteau C, Lerique B, Cartouzou G, Gerolami A (1996). "Presence of the NHE3 isoform of the Na+/H+ exchanger in human gallbladder". Clin. Sci. 91 (2): 209–12. doi:10.1042/cs0910209. PMID 8795445.
• Dudeja PK, Rao DD, Syed I, Joshi V, Dahdal RY, Gardner C, Risk MC, Schmidt L, Bavishi D, Kim KE, Harig JM, Goldstein JL, Layden TJ, Ramaswamy K (1996). "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. doi:10.1152/ajpgi.1996.271.3.G483. PMID 8843774.
• Lin X, Barber DL (1996). "A calcineurin homologous protein inhibits GTPase-stimulated Na-H exchange". Proc. Natl. Acad. Sci. U.S.A. 93 (22): 12631–6. Bibcode:1996PNAS...9312631L. doi:10.1073/pnas.93.22.12631. PMC 38044. PMID 8901634.
• Yun CH, Lamprecht G, Forster DV, Sidor A (1998). "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. doi:10.1074/jbc.273.40.25856. PMID 9748260.
• Biemesderfer D, Nagy T, DeGray B, Aronson PS (1999). "Specific association of megalin and the Na+/H+ exchanger isoform NHE3 in the proximal tubule". J. Biol. Chem. 274 (25): 17518–24. doi:10.1074/jbc.274.25.17518. PMID 10364184.
• Mobasheri A, Golding S, Pagakis SN, Corkey K, Pocock AE, Fermor B, O'Brien MJ, Wilkins RJ, Ellory JC, Francis MJ (1998). "Expression of cation exchanger NHE and anion exchanger AE isoforms in primary human bone-derived osteoblasts". Cell Biol. Int. 22 (7–8): 551–62. doi:10.1006/cbir.1998.0299. PMID 10452823. S2CID 12201584.
• Trujillo E, Alvarez de la Rosa D, Mobasheri A, González T, Canessa CM, Martín-Vasallo P (1999). "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. PMID 10506918.
• Repishti M, Hogan DL, Pratha V, Davydova L, Donowitz M, Tse CM, Isenberg JI (2001). "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. doi:10.1152/ajpgi.2001.281.1.G159. PMID 11408268. S2CID 616434.
• Malakooti J, Memark VC, Dudeja PK, Ramaswamy K (2002). "Molecular cloning and functional analysis of the human Na(+)/H(+) exchanger NHE3 promoter". Am. J. Physiol. Gastrointest. Liver Physiol. 282 (3): G491-500. doi:10.1152/ajpgi.00273.2001. PMID 11841999. S2CID 23652274.
• Gekle M, Serrano OK, Drumm K, Mildenberger S, Freudinger R, Gassner B, Jansen HW, Christensen EI (2002). "NHE3 serves as a molecular tool for cAMP-mediated regulation of receptor-mediated endocytosis". Am. J. Physiol. Renal Physiol. 283 (3): F549-58. doi:10.1152/ajprenal.00206.2001. PMID 12167607.
• Kennedy DJ, Leibach FH, Ganapathy V, Thwaites DT (2002). "Optimal absorptive transport of the dipeptide glycylsarcosine is dependent on functional Na+/H+ exchange activity". Pflügers Arch. 445 (1): 139–46. doi:10.1007/s00424-002-0910-1. PMID 12397398. S2CID 22183032.
• Lee SH, Seok YS, Jung HH, Oh BH, Lee HM, Kwon SY, Jung KY (2002). "Expression of mRNA transcripts of the Na+/H+ and Cl-/HCO3- exchanger isoforms in human nasal mucosa". Acta Otolaryngol. 122 (8): 866–71. doi:10.1080/003655402/000028045. PMID 12542207.
• Inoue H, Nakamura Y, Nagita M, Takai T, Masuda M, Nakamura N, Kanazawa H (2003). "Calcineurin homologous protein isoform 2 (CHP2), Na+/H+ exchangers-binding protein, is expressed in intestinal epithelium". Biol. Pharm. Bull. 26 (2): 148–55. doi:10.1248/bpb.26.148. PMID 12576672.
• Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J (2003). "Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides". Nat. Biotechnol. 21 (5): 566–9. doi:10.1038/nbt810. PMID 12665801. S2CID 23783563.

External links

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