Sodium–hydrogen antiporter 3

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Solute carrier family 9, subfamily A (NHE3, cation proton antiporter 3), member 3
Symbols SLC9A3 ; NHE3
External IDs OMIM182307 MGI105064 HomoloGene55804 ChEMBL: 3273 GeneCards: SLC9A3 Gene
RNA expression pattern
PBB GE SLC9A3 207212 at tn.png
More reference expression data
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 [1] [2]

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 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]


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.



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


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


  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 et al. (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 et al. (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 et al. (2002). "Insulin activates Na(+)/H(+) exchanger 3: biphasic response and glucocorticoid dependence". Am J Physiol Renal Physiol (283): 532ra539. PMID 12167605. 
  7. ^ Inoue H, Nakamura Y, Nagita M, Takai T, Masuda M, Nakamura N et al. (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[edit]

  • 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 et al. (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 et al. (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 et al. (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 et al. (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 et al. (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 et al. (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 et al. (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. 

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