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Gene Review

AQP2  -  aquaporin 2 (collecting duct)

Homo sapiens

Synonyms: ADH water channel, AQP-2, AQP-CD, Aquaporin-2, Aquaporin-CD, ...
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Disease relevance of AQP2


Psychiatry related information on AQP2


High impact information on AQP2


Chemical compound and disease context of AQP2


Biological context of AQP2

  • AQP2 vesicles and the IMCD apical membrane contain homologs of vesicle-targeting and signal transduction proteins found in neurons [15].
  • Although missense mutations in AQP1 and AQP2 proteins are known to result in recessive traits in vivo and in vitro, when E134G or T138R are co-expressed with wild-type AQP0 protein, the mutant proteins exhibit dominant negative behaviour [16].
  • Along with T126M, mutations H122S, N124S, and A125T were introduced to preserve the consensus sequence for N-linked glycosylation found in human AQP2 [17].
  • Using oocytes, externally applied TEA blocked AQP1/AQP2/AQP4 with IC50 values of 1.4, 6.2, and 9.8 microM, respectively [18].
  • The acquired form of NDI is much more common than the congenital form, is almost always less severe, and is associated with downregulation of AQP2 [19].

Anatomical context of AQP2


Associations of AQP2 with chemical compounds

  • AQP2 is exclusively expressed in the principal cells of the connecting tubule and collecting duct and is the predominant vasopressin-regulated water channel [1].
  • Together, the results suggest that the decrease in AVP-stimulated osmotic water permeability results, at least in part, in the decrease in AQP2 protein [22].
  • Similarly AQP2 mutant proteins are trapped intracellularly and cannot be expressed at the luminal membrane [19].
  • Patients who have congenital NDI and bear mutations in the AVPR2 or AQP2 genes have a "pure" NDI phenotype with loss of water but normal conservation of sodium, potassium, chloride, and calcium [23].
  • Then, AQP2 moved from EEA1-positive endosomes to the subapical AQP2-storage compartment, which is sensitive to wortmannin and LY294002 [21].

Physical interactions of AQP2


Co-localisations of AQP2

  • Washout of forskolin induced retrieval of AQP2 into the cytoplasm, and AQP2 was transiently colocalized with EEA1-positive endosomes [21].
  • TRPC3 and -C6 colocalized with aquaporin-2, but not with the Na(+)/Ca(2+) exchanger or peanut lectin [25].

Regulatory relationships of AQP2


Other interactions of AQP2


Analytical, diagnostic and therapeutic context of AQP2


  1. Aquaporins in the kidney: from molecules to medicine. Nielsen, S., Frøkiaer, J., Marples, D., Kwon, T.H., Agre, P., Knepper, M.A. Physiol. Rev. (2002) [Pubmed]
  2. Physiology and pathophysiology of renal aquaporins. Nielsen, S., Kwon, T.H., Christensen, B.M., Promeneur, D., Frøkiaer, J., Marples, D. J. Am. Soc. Nephrol. (1999) [Pubmed]
  3. The 4.5 A structure of human AQP2. Schenk, A.D., Werten, P.J., Scheuring, S., de Groot, B.L., Müller, S.A., Stahlberg, H., Philippsen, A., Engel, A. J. Mol. Biol. (2005) [Pubmed]
  4. Lithium effectively complements vasopressin V2 receptor antagonist in the treatment of hyponatraemia of SIADH rats. Kazama, I., Arata, T., Michimata, M., Hatano, R., Suzuki, M., Miyama, N., Sanada, S., Sato, A., Satomi, S., Ejima, Y., Sasaki, S., Matsubara, M. Nephrol. Dial. Transplant. (2007) [Pubmed]
  5. Development of water transport in the collecting duct. Bonilla-Felix, M. Am. J. Physiol. Renal Physiol. (2004) [Pubmed]
  6. Nephrogenic diabetes insipidus. Bichet, D.G. Advances in chronic kidney disease. (2006) [Pubmed]
  7. Low-calcium diet in hypercalciuric enuretic children restores AQP2 excretion and improves clinical symptoms. Valenti, G., Laera, A., Gouraud, S., Pace, G., Aceto, G., Penza, R., Selvaggi, F.P., Svelto, M. Am. J. Physiol. Renal Physiol. (2002) [Pubmed]
  8. Urinary aquaporin-2 excretion during early human development. Zelenina, M., Li, Y., Glorieux, I., Arnaud, C., Cristini, C., Decramer, S., Aperia, A., Casper, C. Pediatr. Nephrol. (2006) [Pubmed]
  9. Urinary excretion of aquaporin-2 in patients with diabetes insipidus. Kanno, K., Sasaki, S., Hirata, Y., Ishikawa, S., Fushimi, K., Nakanishi, S., Bichet, D.G., Marumo, F. N. Engl. J. Med. (1995) [Pubmed]
  10. Minireview: aquaporin 2 trafficking. Valenti, G., Procino, G., Tamma, G., Carmosino, M., Svelto, M. Endocrinology (2005) [Pubmed]
  11. Two distinct aquaporin-4 cDNAs isolated from medullary cone of quail kidney. Yang, Y., Cui, Y., Fan, Z., Cook, G.A., Nishimura, H. Comp. Biochem. Physiol., Part A Mol. Integr. Physiol. (2007) [Pubmed]
  12. Urinary aquaporin-2 in healthy humans and patients with liver cirrhosis and chronic heart failure during baseline conditions and after acute water load. Pedersen, R.S., Bentzen, H., Bech, J.N., Nyvad, O., Pedersen, E.B. Kidney Int. (2003) [Pubmed]
  13. Aldosterone increases urine production and decreases apical AQP2 expression in rats with diabetes insipidus. Nielsen, J., Kwon, T.H., Praetorius, J., Frøkiaer, J., Knepper, M.A., Nielsen, S. Am. J. Physiol. Renal Physiol. (2006) [Pubmed]
  14. Down-regulation of Na+ transporters and AQP2 is responsible for acyclovir-induced polyuria and hypophosphatemia. Andrade, L., Rebouças, N.A., Seguro, A.C. Kidney Int. (2004) [Pubmed]
  15. Modulation of vasopressin-elicited water transport by trafficking of aquaporin2-containing vesicles. Ward, D.T., Hammond, T.G., Harris, H.W. Annu. Rev. Physiol. (1999) [Pubmed]
  16. Functional impairment of lens aquaporin in two families with dominantly inherited cataracts. Francis, P., Chung, J.J., Yasui, M., Berry, V., Moore, A., Wyatt, M.K., Wistow, G., Bhattacharya, S.S., Agre, P. Hum. Mol. Genet. (2000) [Pubmed]
  17. Neonatal mortality in an aquaporin-2 knock-in mouse model of recessive nephrogenic diabetes insipidus. Yang, B., Gillespie, A., Carlson, E.J., Epstein, C.J., Verkman, A.S. J. Biol. Chem. (2001) [Pubmed]
  18. Quaternary ammonium compounds as water channel blockers. Specificity, potency, and site of action. Detmers, F.J., de Groot, B.L., Müller, E.M., Hinton, A., Konings, I.B., Sze, M., Flitsch, S.L., Grubmüller, H., Deen, P.M. J. Biol. Chem. (2006) [Pubmed]
  19. Nephrogenic diabetes insipidus. Bichet, D.G. Am. J. Med. (1998) [Pubmed]
  20. Patients with autosomal nephrogenic diabetes insipidus homozygous for mutations in the aquaporin 2 water-channel gene. van Lieburg, A.F., Verdijk, M.A., Knoers, V.V., van Essen, A.J., Proesmans, W., Mallmann, R., Monnens, L.A., van Oost, B.A., van Os, C.H., Deen, P.M. Am. J. Hum. Genet. (1994) [Pubmed]
  21. Aquaporin-2 is retrieved to the apical storage compartment via early endosomes and phosphatidylinositol 3-kinase-dependent pathway. Tajika, Y., Matsuzaki, T., Suzuki, T., Aoki, T., Hagiwara, H., Kuwahara, M., Sasaki, S., Takata, K. Endocrinology (2004) [Pubmed]
  22. Changes in aquaporin-2 protein contribute to the urine concentrating defect in rats fed a low-protein diet. Sands, J.M., Naruse, M., Jacobs, J.D., Wilcox, J.N., Klein, J.D. J. Clin. Invest. (1996) [Pubmed]
  23. Molecular biology of hereditary diabetes insipidus. Fujiwara, T.M., Bichet, D.G. J. Am. Soc. Nephrol. (2005) [Pubmed]
  24. The effect of anti-diuretic hormone on the endolymphatic sac of the inner ear. Kumagami, H., Loewenheim, H., Beitz, E., Wild, K., Schwartz, H., Yamashita, K., Schultz, J., Paysan, J., Zenner, H.P., Ruppersberg, J.P. Pflugers Arch. (1998) [Pubmed]
  25. Identification and localization of TRPC channels in the rat kidney. Goel, M., Sinkins, W.G., Zuo, C.D., Estacion, M., Schilling, W.P. Am. J. Physiol. Renal Physiol. (2006) [Pubmed]
  26. Recent advances in the understanding of water metabolism in heart failure. Schrier, R.W., Martin, P.Y. Adv. Exp. Med. Biol. (1998) [Pubmed]
  27. How tonicity regulates genes: story of TonEBP transcriptional activator. Jeon, U.S., Kim, J.A., Sheen, M.R., Kwon, H.M. Acta physiologica (Oxford, England) (2006) [Pubmed]
  28. Selective V2-receptor vasopressin antagonism decreases urinary aquaporin-2 excretion in patients with chronic heart failure. Martin, P.Y., Abraham, W.T., Lieming, X., Olson, B.R., Oren, R.M., Ohara, M., Schrier, R.W. J. Am. Soc. Nephrol. (1999) [Pubmed]
  29. Discovery of aquaporins: a breakthrough in research on renal water transport. van Lieburg, A.F., Knoers, N.V., Deen, P.M. Pediatr. Nephrol. (1995) [Pubmed]
  30. Altered expression of aquaporins in bullous keratopathy and Fuchs' dystrophy corneas. Kenney, M.C., Atilano, S.R., Zorapapel, N., Holguin, B., Gaster, R.N., Ljubimov, A.V. J. Histochem. Cytochem. (2004) [Pubmed]
  31. Sevoflurane anaesthesia causes a transient decrease in aquaporin-2 and impairment of urine concentration. Morita, K., Otsuka, F., Ogura, T., Takeuchi, M., Mizobuchi, S., Yamauchi, T., Makino, H., Hirakawa, M. British journal of anaesthesia. (1999) [Pubmed]
  32. Aquaporin-2 expression in the mammalian cochlea and investigation of its role in Meniere's disease. Mhatre, A.N., Jero, J., Chiappini, I., Bolasco, G., Barbara, M., Lalwani, A.K. Hear. Res. (2002) [Pubmed]
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