Sodium–hydrogen antiporter 3

Solute carrier family 9, subfamily A (NHE3, cation proton antiporter 3), member 3
Identifiers
Symbols	SLC9A3 ; NHE3
External IDs	OMIM: 182307 MGI: 105064 HomoloGene: 55804 ChEMBL: 3273 GeneCards: SLC9A3 Gene
Gene ontology Molecular function • protein binding • sodium:proton antiporter activity • PDZ domain binding Cellular component • plasma membrane • brush border • cell surface • integral component of membrane • apical plasma membrane • brush border membrane • extracellular exosome Biological process • regulation of sodium ion transport • ion transport • regulation of pH • receptor-mediated endocytosis • circadian rhythm • sodium ion transmembrane transport • response to glucocorticoid • transmembrane transport • hydrogen ion transmembrane transport Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	6550	105243
Ensembl	ENSG00000066230	ENSMUSG00000036123
UniProt	P48764	G3X939
RefSeq (mRNA)	NM_001284351	NM_001081060
RefSeq (protein)	NP_001271280	NP_001074529
Location (UCSC)	Chr 5: 0.47 – 0.52 Mb	Chr 13: 74.12 – 74.17 Mb
PubMed search

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.^[1][2]

SLC9A3 is a sodium–hydrogen antiporter. It is found in the tubulus proximal of the nephron of the kidney and in the apical membrane of enterocytes of the intestine. It is primarily responsible for maintaining the balance of sodium.^[3]

Regulation

Protein kinase C stimulates NHE3, while protein kinase A inhibits it.^[4]

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

Inhibitors

• Tenapanor^[5]

Stimulators

• Insulin^[6] stimulates NHE3 and thereby proximal tubule sodium absorption.

Interactions

Sodium–hydrogen antiporter 3 has been shown to interact with CHP.^[7]

References

1. "Entrez Gene: SLC9A3 Solute carrier family 9 (sodium/hydrogen exchanger), member 3".
2. 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.
3. VI. Mechanisms of Salt & Water Reabsorption
4. 852 Walter F., PhD. Boron (2005). Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. ISBN 1-4160-2328-3. Page 852
5. 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.
6. 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 (283): 532ra539. doi:10.1152/ajprenal.00365.2001. PMID 12167605.
7. 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.
• 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. 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. 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. 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. 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. 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.
• 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. PMID 11408268.
• 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.
• 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". Pflugers Arch. 445 (1): 139–46. doi:10.1007/s00424-002-0910-1. PMID 12397398.
• 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.

External links

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