The Journal of Membrane Biology

, Volume 212, Issue 2, pp 109–117

Genomic Organization of the Mammalian SLC14a2 Urea Transporter Genes



Urea transporters encoded by the UT-A gene play fundamental roles in the kidney and possibly other tissues. Knowledge of the genomic organization of the mouse, rat and human UT-A genes has enabled the engineering of transgenic and knockout animals and these have helped refine our understanding of the role of UT-A proteins. This review summarizes the published work that has accrued on the structure and regulation of these genes. It also documents a novel cDNA, human UT-A3, which has enabled a major refinement of the human UT-A gene structure. This and other information contained in this review should prove useful for future comparative genomic analysis, studies addressing gene regulation and for the engineering of transgenic and knockout animal strains.


Membrane proteins UT-A Kidney Genomic analysis 


  1. Bagnasco S.M., Peng T., Janech M.G., Karakashian A., Sands J.M. 2001. Cloning and characterization of the human urea transporter UT-A1 and mapping of the human Slc14a2 gene. Am. J. Physiol. 281:F400–F406Google Scholar
  2. Bagnasco S.M., Peng T., Nakayama Y., Sands J.M. 2000. Differential expression of individual UT-A urea transporter isoforms in rat kidney. J. Am. Soc. Nephrol. 11:1980–1986PubMedGoogle Scholar
  3. Fenton R.A., Chou C.L., Stewart G.S., Smith C.P., Knepper M.A. 2004. Urinary concentrating defect in mice with selective deletion of phloretin-sensitive urea transporters in the renal collecting duct. Proc. Natl. Acad. Sci. USA 101:7469–7474PubMedCrossRefGoogle Scholar
  4. Fenton R.A., Cooper G.J., Morris I.D., Smith C.P. 2002a. Coordinated expression of UT-A and UT-B urea transporters in rat testis. Am. J. Physiol. 282:C1492–C1501Google Scholar
  5. Fenton R.A., Cottingham C.A., Stewart G.S., Howorth A., Hewitt J.A., Smith C.P. 2002b. Structure and characterization of the mouse UT-A gene (Slc14a2). Am. J. Physiol. 282:F630–F638Google Scholar
  6. Fenton R.A., Flynn A., Shodeinde A., Smith C.P., Schnermann J., Knepper M.A. 2005a. Renal phenotype of UT-A urea transporter knockout mice. J. Am. Soc. Nephrol. 16:1583–1592CrossRefGoogle Scholar
  7. Fenton R.A., Hewitt J.E., Howorth A., Cottingham C.A., Smith C.P. 1999. The murine urea transporter genes Slc14a1 and Slc14a2 occur in tandem on chromosome 18. Cytogenet. Cell Genet. 87:95–96PubMedCrossRefGoogle Scholar
  8. Fenton R.A., Howorth A., Cooper G.J., Meccariello R., Morris I.D., Smith C.P. 2000. Molecular characterization of a novel UT-A urea transporter isoform (UT-A5) in testis. Am. J. Physiol. 279:C1425–C1431Google Scholar
  9. Fenton R.A., Shodeinde A., Knepper M.A. 2005b. The UT-A urea transporter promoter, UT-Aα, targets principal cells of the renal inner medullary collecting duct. Am. J. Physiol. 290:F188–F195Google Scholar
  10. Fenton R.A., Stewart G.S., Carpenter B., Howorth A., Potter E.A., Cooper G.J., Smith C.P. 2002c. Characterization of mouse urea transporters UT-A1 and UT-A2. Am. J. Physiol. 283:F817–F825Google Scholar
  11. Karakashian A., Timmer R.T., Klein J.D., Gunn R.B., Sands J.M., Bagnasco S.M. 1999. Cloning and characterization of two new isoforms of the rat kidney urea transporter: UT-A3 and UT-A4. J. Am. Soc. Nephrol. 10:230–237PubMedGoogle Scholar
  12. Mistry A.C., Chen G., Kato A., Nag K., Sands J.M., Hirose S. 2005. A novel type of urea transporter, UT-C, is highly expressed in proximal tubule of seawater eel kidney. Am. J. Physiol. 288:F455–F465CrossRefGoogle Scholar
  13. Nakayama Y., Naruse M., Karakashian A., Peng T., Sands J.M., Bagnasco S.M. 2001. Cloning of the rat Slc14a2 gene and genomic organization of the UT-A urea transporter. Biochim. Biophys. Acta 1518:19–26PubMedGoogle Scholar
  14. Nakayama Y., Peng T., Sands J.M., Bagnasco S.M. 1999. Both cAMP and tonicity increase the activity of the rat UT-A2 promoter. J. Am. Soc. Nephrol. 10:21ACrossRefGoogle Scholar
  15. Nakayama Y., Peng T., Sands J.M., Bagnasco S.M. 2000. The TonE/TonEBP pathway mediates tonicity-responsive regulation of UT-A urea transporter expression. J. Biol. Chem. 275:38275–38280PubMedCrossRefGoogle Scholar
  16. Peng T., Sands J.M., Bagnasco S.M. 2002. Glucocorticoids inhibit transcription and expression of the UT-A urea transporter gene. Am. J. Physiol. 282:F853–F858Google Scholar
  17. Sands J.M. 2003. Mammalian urea transporters. Annu. Rev. Physiol. 65:543–566PubMedCrossRefGoogle Scholar
  18. Shayakul C., Steel A., Hediger M.A. 1996. Molecular cloning and characterization of the vasopressin-regulated urea transporter of rat kidney collecting ducts. J. Clin. Invest. 98:2580–2587PubMedGoogle Scholar
  19. Shayakul C., Tsukaguchi H., Berger U.V., Hediger M.A. 2001. Molecular characterization of a novel urea transporter from kidney inner medullary collecting ducts. Am. J. Physiol. 280:F487–F494Google Scholar
  20. Smith C.P., Lee W.S., Martial S., Knepper M.A., You G., Sands J.M., Hediger M.A. 1995. Cloning and regulation of expression of the rat kidney urea transporter (rUT2). J. Clin. Invest. 96:1556–1563PubMedCrossRefGoogle Scholar
  21. Smith C.P., Potter E.A., Fenton R.A., Stewart G.S. 2004. Characterization of a human colonic cDNA encoding a structurally novel urea transporter, hUT-A6. Am. J. Physiol. 287:C1087–C1093CrossRefGoogle Scholar
  22. Stewart G.S., Fenton R.A., Thevenod F., Smith C.P. 2004. Urea movement across mouse colonic plasma membranes is mediated by UT-A urea transporters. Gastroenterology 126:765–773PubMedCrossRefGoogle Scholar
  23. Uchida S., Sohara E., Rai T., Ikawa M., Okabe M., Sasaki S. 2005. Impaired urea accumulation in the inner medulla of mice lacking the urea transporter UT-A2. Mol. Cell Biol. 25:7357–7363PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2007

Authors and Affiliations

  1. 1.Faculty of Life SciencesThe University of ManchesterManchesterUK
  2. 2.The Water and Salt Research Center, Institute of AnatomyUniveristy of AarhusAarhusDenmark

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