The propeptide of beta-glucuronidase. Further evidence of its involvement in compartmentalization of beta-glucuronidase and sequence similarity with portions of the reactive site region of the serpin superfamily.
A significant portion of murine hepatocyte beta-glucuronidase is maintained within the endoplasmic reticulum (ER) by complex formation with the esterase active site of the protein egasyn. The carboxyl-terminal propeptide of the precursor form of glucuronidase appears important in localization of glucuronidase to the ER since a naturally occurring mutation in it is associated with decreased levels of ER glucuronidase. A sequence similarity was noted between the carboxyl-terminal propeptide and portions of the conserved sequences of the reactive site region of members of the serpin (serine proteinase inhibitor) superfamily. Also, previous studies had shown that a synthetic peptide, corresponding to the propeptide region, was a specific and potent inhibitor of the esterase activity of purified egasyn. Taken together, these results suggest that (a) the egasyn-glucuronidase system may use a novel mechanism related to that of serine proteinases and their inhibitors in complex formation and in subsequent localization of glucuronidase within the ER and that (b) a possible function of ER glucuronidase is to modulate the esterase activity of egasyn.
Roswell Park Cancer Institute, Molecular and Cellular Biology Department, Buffalo, New York 14263.
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Li
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Takeuchi
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Manly
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Chapman
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Swank
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004721:Endoplasmic Reticulum / Q000201:enzymology; D004792:Enzyme Precursors / Q000235:genetics*; D005966:Glucuronidase / Q000235:genetics*; D007668:Kidney / Q000201:enzymology*; D008099:Liver / Q000201:enzymology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D005810:Multigene Family; D009154:Mutation; D016133:Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D015843:Serpins / Q000235:genetics*
D004792:Enzyme Precursors; D015843:Serpins; D005966:Glucuronidase