Conserved residues in all sequences are highlighted: identical, similar and unrelated residues are indicated by dark, light and white backgrounds, respectively. The red box represents the zona pellucida domain. Potential GPI-anchor residues predicted by GPI-SOM (fttp://gpi.unibe.ch/) are represented by black letters with blue background, while those suggested from sequence similarity are highlighted in light blue. Residues underlined in red represent the transmembrane domain predicted by the TMpred program (http://www.ch.embnet.org/). Letters edged in yellow represent the predicted proteolytic cleavage site. All relevant sequences of the uromodulin (THP), GP-2, and XL18 have been registered in the DDBJ/EMBL/GenBank databases with accession numbers XL18 (AAC59871), rTHP (AAB33313), hTHP (P07911), and hGP-2 (AAB19240), respectively.