A cDNA clone (HUT2) sharing 61.1% and 89.9% sequence identity with the
human erythroid (HUT11) and the rabbit (UT2) urea transporters, respe
ctively, was isolated by homology cloning from a human kidney library,
HUT2 transcripts were restricted to the kidney and the HUT2 polypepti
de was not immunoprecipitated with blood group Kidd-related antibodies
(anti-Jk3) in coupled transcription-translation assays, Functional ex
pression studies in Xenopus oocytes demonstrated that HUT2-mediated ur
ea transport was not inhibited by p-chloromercuribenzene sulfonate (pC
MBS) which, however, inhibited the urea flux mediated by HUT11. These
findings demonstrate that at least two distinct urea transporters are
present in human tissues, By in situ hybridization, the gene encoding
HUT2 has been assigned to chromosome 18q12.1-q21-1, as found previousl
y for the Kidd/urea transporter HUT11, suggesting that both genes evol
ved from duplication of a common ancestor.