THE BETA-GLUCURONIDASE PROPEPTIDE CONTAINS A SERPIN-RELATED OCTAMER NECESSARY FOR COMPLEX-FORMATION WITH EGASYN ESTERASE AND FOR RETENTION WITHIN THE ENDOPLASMIC-RETICULUM

beta-Glucuronidase is retained within the endoplasmic reticulum (ER) v ia complex formation with esterase-22 (egasyn), which in turn has a CO OH-terminal HTEL ER retention sequence. To identify the regions of glu curonidase that interact with egasyn, complex formation was assayed in COS cells cotransfected with egasyn cDNA and with either deletion con structs of glucuronidase or with constructs containing specific glucur onidase propeptide sequences appended to the carboxyl terminus of a ra t secretory protein alpha 1-acid glycoprotein. The region of glucuroni dase essential for complex formation is a linear octamer sequence at t he COOH terminus of the propeptide. A portion of this octamer is simil ar to a sequence near the reactive site of serpins. This and associate d data indicate that an interaction related to that between serine pro teinases and their serpin inhibitors retains beta-glucuronidase within the ER. Further, attachment of this octamer sequence provides an alte rnative method of targeting proteins to the ER lumen of any cell that contains egasyn. These and related results demonstrate that complex fo rmation with esterases/proteinases within the ER is important in the s ubcellular targeting and/or processing of certain proteins.