This subfamily includes putative UreI proton-gated urea channels and putative amide transporters (AmiS of the amidase gene cluster). Helicobacter pylori UreI (HpUreI), a proton-gated inner membrane urea channel opens in acidic pH to allow urea influx to the cytoplasm. There urea is metabolized, producing NH3 and Co2, leading to buffering of the periplasm. This action is essential for the survival of H. pylori in the stomach, and has been identified as a mechanism that could be clinically targeted to prevent various illnesses associated with infection by H. pylori. UreI and the related amide channels (AmiS) appear to function as hexamers, and have 6 predicted transmembrane segments. UreI has also been shown have a lipid "plug" in the center of the hexamer. Urea enters at the periplasmic opening of UreI and must pass 2 constriction sites, one on each side of a conserved Glu (Glu 177, H. pylori numbering), to reach the cytoplasm. Urea/thiourea selectivity is diminished by mutation of a conserved Trp to Ala or Phe in constriction site 2 (cytoplasmic). Channel functionality is greatly diminished by mutation of a conserved Trp in constriction site 1 (periplasmic) and a conserved Tyr in constriction site 2, and to a lesser extent a conserved Phe in site 1. In the cytoplasm, urease hydrolyzes urea to form ammonia and carbamate, which decomposes to carbonic acid. UreI is fully open at pH 5.0 to facilitate urea influx, but closes at neutral pH, preventing over-alkalization. Glu 177 (H. pylori numbering) is present in urea channel proteins, but absent in the related amide channels, suggesting that it plays a role in urea specificity.
Feature 1: transport channel [chemical binding site], 8 residue positions
Conserved feature residue pattern:L L F T Y W L W
Evidence:
Comment:Two constriction sites (designated site 1 and site 2) were identified in the Helicobacter pylori UreI urea channel, on either side of a conserved Glu (the urea transport residue).
Comment:For Helicobacter pylori UreI : mutation of a conserved Trp (located in constriction site 2) decreases urea:thiourea selectivity, and mutation in a conserved Trp or Phe (both located in constriction site 1), or a conserved Tyr (located in constriction site 2) inactivates or impairs transport of urea or thiourea.
Jiyao W et al.(2023). "The conserved domain database in 2023.",