title: The SLC14 gene family of urea transporters.
abstract: Carrier-mediated urea transport allows rapid urea movement across the cell membrane, which is particularly important in the process of urinary concentration and for rapid urea equilibrium in non-renal tissues. Urea transporters mediate passive urea uptake that is inhibited by phloretin and urea analogues. Facilitated urea transporters are divided into two classes: (1) the renal tubular/testicular type of urea transporter, UT-A1 to -A5, encoded by alternative splicing of the SLC14A2 gene, and (2) the erythrocyte urea transporter UT-B1 encoded by the SLC14A1 gene. The primary structure of urea transporters is unique, consisting of two extended, hydrophobic, membrane-spanning domains and an extracellular glycosylated-connecting loop. UT-A1 is the result of a gene duplication of this two-halves-structure, and the duplicated portions are linked together by a large intracellular hydrophilic loop, carrying several putative protein kinase A (PKA) and -C (PKC) phosphorylation sites. UT-A1 is located in the apical membrane of the kidney inner medullary collecting duct cells, where it is stimulated acutely by cAMP-mediated phosphorylation in response to the antidiuretic hormone vasopressin. Vasopressin also up-regulates UT-A2 mRNA/protein expression in the descending thin limb of the loops of Henle. UT-A1 and UT-A2 are regulated independently and respond differently to changes in dietary protein content. UT-A3 and UT-A4 are located in the rat kidney medulla and UT-A5 in the mouse testis. The widely expressed UT-B participates in urea recycling in the descending vasa recta, as demonstrated by a relatively mild "urea-selective" urinary concentrating defect in transgenic UT-B null mice and individuals with the Jk(null) blood group.
authors.affiliation: Renal Unit, Department of Medicine, Siriraj Hospital, Mahidol University, 2 Prannok Rd, Bangkoknoi, Bangkok 10700, Thailand. sinka@mahidol.ac.th
authors.forename: Chairat
authors.initials: C
authors.lastname: Shayakul
authors.forename: Matthias A
authors.initials: MA
authors.lastname: Hediger
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology; D007668:Kidney / Q000502:physiology; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D005810:Multigene Family / Q000502:physiology; D014508:Urea / Q000378:metabolism*; D000096982:Urea Transporters
chemical_list: D026901:Membrane Transport Proteins; D014508:Urea; D000096982:Urea Transporters