Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.31 (beta-glucuronidase)
7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The accumulation of the relatively large amounts of beta-glucuronidase in microsomal fractions of normal mice depends on formation of complexes with the protein egasyn. Unexpectedly, it was found that the egasyn gene also affects the processing of beta-glucuronidase, which is segregated to lysosomes. In egasyn-positive mice lysosomal beta-glucuronidase from liver has a mean pI of 5.9 with a minor proportion at pI 5.4, whereas in egasyn-negative mice the proportion of the two lysosomal forms is reversed. Combined experiments measuring susceptibility to neuraminidase and to endoglycosidase H and specific binding to Ricinus communis lectin-agarose columns showed that the alterations in isoelectric point were associated with a decrease in complex oligosaccharides of lysosomal beta-glucuronidase in egasyn-positive mice. Since this alteration occurs not only in a congenic strain carrying the Eg0 gene but also in several other inbred strains that are homozygous for this gene, it is considered to be a genuine effect of the Eg gene rather than other genes that might regulate oligosaccharide processing. Also, the alteration is likely to be a result of direct physical interaction of the egasyn protein and lysosomal beta-glucuronidase, since a second lysosomal enzyme, beta-galactosidase, which does not form complexes with egasyn, is unaffected. The results suggest a model in which egasyn not only causes accumulation of beta-glucuronidase in the microsomal compartment but also acts upon the precursor to lysosomal beta-glucuronidase to alter its interaction with trans-Golgi-apparatus processing enzymes.
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PMID:The egasyn gene affects the processing of oligosaccharides of lysosomal beta-glucuronidase in liver. 310 73

Three differently modified forms of beta-glucuronidase are known to exist: a microsomal enzyme form (M) existing in tissues where egasyn, a second microsomal protein, is present; and an acidic (La; complex-type oligosaccharide) and a basic (Lb; non-complex type oligosaccharide) lysosomal form which occur in all mouse tissues. Lb predominates in tissues containing microsomal beta-glucuronidase, La in those lacking it. In pulse-labelling experiments using mouse strain C57BL/6 liver containing egasyn (Eg+/Eg+) and microsomal enzyme, about half of the newly synthesized beta-glucuronidase was processed to the microsomal enzyme form, which was evidently further processed to Lb, and about half directly to La. In contrast, in liver of the congenic line C57BL/6.YBR Es-1b Eg0 that lacks egasyn (Eg0/Eg0) and microsomal enzyme, most of the labelled beta-glucuronidase was processed to La, and only a minor portion to Lb. Newly synthesized enzyme appeared first in microsomal, then in light and heavy lysosomal fractions of Eg+/Eg+ liver. In Eg0/Eg0 liver, no labelled enzyme was measurable in the microsomes, but it appeared rapidly in both types of lysosomes. Taken together these findings indicate that the microsomal enzyme form serves as a precursor of Lb, and that La is synthesized independently. The apparent half-life of La is only two-thirds that of Lb; this fact accounts for the reduced beta-glucuronidase activity in Eg0/Eg0 liver, which contains La as the predominant form.
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PMID:Egasyn affects the processing of beta-glucuronidase in mouse liver. 321 27

We report biochemical, immunological, and genetic studies which demonstrate that an accessory protein with the essential features of mouse egasyn is complexed with and stabilizes a portion of beta-glucuronidase in microsomes of rat liver. The accessory protein exists as a complex with beta-glucuronidase since it coprecipitates with beta-glucuronidase after treatment of extracts with a specific beta-glucuronidase antibody. The two proteins are associated by noncovalent bonds since they are easily dissociated at elevated temperatures. Only 20-25% of total liver accessory protein is complexed with microsomal beta-glucuronidase. The remainder exists as a free form. The molecular weight of the accessory protein is 61 to 63 kDa depending upon the rat strain of origin. This protein, like mouse egasyn, has esterase catalytic activity and is concentrated in microsomes. The accessory protein is genetically polymorphic with at least four alleles. Combined biochemical and genetic evidence indicates it is identical with esterase-3 of the rat. Also, both mouse egasyn and rat esterase-3 react with antisera to egasyn and to rat esterase-3, indicating they are homologous proteins. Several inbred rat strains lack microsomal beta-glucuronidase. The same strains lack the accessory protein, suggesting that stabilization of beta-glucuronidase in rat microsomes requires egasyn.
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PMID:An accessory protein identical to mouse egasyn is complexed with rat microsomal beta-glucuronidase and is identical to rat esterase-3. 329 29

Organophosphorous compounds, which are potent inhibitors of egasyn-esterase activity, caused a rapid dissociation of the high molecular weight egasyn-microsomal beta-glucuronidase complex when administered in vivo or when added in vitro to microsomal suspensions. The dissociation was relatively specific to phosphodiester inhibitors of the esterase active site. Also, the egasyn-esterase active site was inaccessible to substrates and to inhibitors when egasyn was complexed to beta-glucuronidase. Dissociation of the egasyn-microsomal beta-glucuronidase complex in vivo by organophosphorous compounds was followed by massive and rapid secretion of microsomal beta-glucuronidase, but not egasyn, into plasma. These experiments implicate the egasyn-esterase active site in attachment of microsomal beta-glucuronidase to egasyn by a novel mechanism that, in turn, compartmentalizes beta-glucuronidase within the endoplasmic reticulum.
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PMID:Involvement of the esterase active site of egasyn in compartmentalization of beta-glucuronidase within the endoplasmic reticulum. 359 74

Mouse liver beta-glucuronidase is stabilized within microsomal vesicles by complexation with the accessory protein egasyn. The location of the beta-glucuronidase-egasyn complex and free egasyn within microsomal vesicles was investigated. Surprisingly, it was found that neither the complex nor free egasyn are intrinsic membrane components. Rather, both are either free within the vesicle lumen or only weakly bound to the inside of the vesicle membrane. This conclusion was derived from release studies using low concentrations of Triton X-100 or controlled sonication. Both the intact complex and free egasyn were released in parallel with lumenal proteins, not with intrinsic membrane components. Also, beta-glucuronidase was protected from digestion by proteinase K by the membrane of microsomal vesicles. The hydrophilic nature of both the complex and free egasyn was confirmed by phase separation experiments with the detergent Triton X-114. Egasyn is one of an unusual group of esterases that, despite being located within the lumen or only weakly bound to the lumenal surface of the endoplasmic reticulum, do not enter the secretory pathway.
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PMID:Lumenal location of the microsomal beta-glucuronidase-egasyn complex. 366 91

Recent experiments have demonstrated that egasyn not only sequesters beta-glucuronidase in microsomes by forming high molecular weight complexes with beta-glucuronidase, but also has carboxyl esterase activity. We have found several new phenotypes of egasyn-esterase after electrophoresis and isoelectric focusing of liver homogenates and purified egasyn of inbred and wild mouse strains. Several phenotypes corresponded in relative mobility and relative isoelectric point among inbred strains to that recently reported for esterase-22 by Eisenhardt and von Deimling [(1982). Comp. Biochem. Physiol. 73B:719]. This genetic evidence, plus a wide variety of comparative biochemical and physiological data, indicates that egasyn is identical to esterase-22. Both parental types of egasyn isozymes are expressed in heterozygous F1 progeny, suggesting that alterations in the egasyn structural gene are responsible for the altered isoelectric points. Also, egasyn is a monomer since no new esterase bands appear in F1 progeny. The variants in isoelectric point of egasyn map at or near the egasyn (Eg) gene within the esterases of cluster 1 near Es-9 on chromosome 8.
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PMID:Identity of esterase-22 and egasyn, the protein which complexes with microsomal beta-glucuronidase. 372 27

The glycoprotein egasyn complexes with and stabilizes precursor beta-glucuronidase in microsomes of several mouse organs. Several observations indicate egasyn is, in addition, an esterase. Liver homogenates of egasyn-positive strains have specific electrophoretically separable esterases which are absent in egasyn-negative mice. These esterases react with anti-egasyn serum. A specific esterase was likewise complexed with immunopurified microsomal beta-glucuronidase. The esterases were, like egasyn and microsomal beta-glucuronidase, concentrated in the microsomal subcellular fraction. Egasyn which is not bound to beta-glucuronidase, which represents 80-90% of total liver egasyn, is not complexed with other liver proteins. Egasyn, therefore, specifically stabilizes beta-glucuronidase in microsomes. The esterase activity is inhibited by bis-p-nitrophenyl phosphate indicating it is a carboxyl esterase. Several possible functions of egasyn-esterase activity are discussed.
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PMID:Egasyn, a protein which determines the subcellular distribution of beta-glucuronidase, has esterase activity. 406 95

The ability of TPA to induce stable phenotypic changes that normally serve as markers of differentiation was examined in the four human non-T, non-B cell lines, NALL-1, NALM-16, REH and KM-3. In all four lines, noncytotoxic concentrations of the phorbol ester caused an extensive reduction in the number of cells expressing cALL surface antigen and terminal deoxynucleotidyl transferase. The disappearance of these markers correlated with the loss of cell proliferation. In one of the cell lines, NALL-1, TPA treatment gave rise to a significant increase in Ia-like antigen and antigen T-101, markers which represent more advanced stages of cell maturation. However, surface or cytoplasmic immunoglobins, indicators of mature B cells, were not detectable. Antigen 3A1, specific for myeloid and for T cells, antigen Leu-4, specific for T cells and antigen CM1, specific for monocytes, were also absent. In all cell lines, exposure to TPA resulted in an approximately two-fold increase in acid phosphatase and beta-glucuronidase activity. The emergence of these phenotype changes was not altered upon repeated washing of the TPA-treated cells. These results demonstrate that while TPA is capable of inducing various non-T, non-B cell lines to differentiate to a limited degree, differences exist between the lines in the extent to which they can mature towards the B-cell stage.
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PMID:Differentiation-associated changes in human non-T, non-B leukemia cell lines after treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA). 671 62

beta-Glucuronidase is retained within the endoplasmic reticulum (ER) via complex formation with esterase-22 (egasyn), which in turn has a COOH-terminal HTEL ER retention sequence. To identify the regions of glucuronidase that interact with egasyn, complex formation was assayed in COS cells cotransfected with egasyn cDNA and with either deletion constructs of glucuronidase or with constructs containing specific glucuronidase propeptide sequences appended to the carboxyl terminus of a rat secretory protein alpha 1-acid glycoprotein. The region of glucuronidase essential for complex formation is a linear octamer sequence at the COOH terminus of the propeptide. A portion of this octamer is similar to a sequence near the reactive site of serpins. This and associated data indicate that an interaction related to that between serine proteinases and their serpin inhibitors retains beta-glucuronidase within the ER. Further, attachment of this octamer sequence provides an alternative method of targeting proteins to the ER lumen of any cell that contains egasyn. These and related results demonstrate that complex formation with esterases/proteinases within the ER is important in the subcellular targeting and/or processing of certain proteins.
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PMID:The beta-glucuronidase propeptide contains a serpin-related octamer necessary for complex formation with egasyn esterase and for retention within the endoplasmic reticulum. 774 42

Commercially available Wistar rats are genetically heterogeneous with respect to acid beta-D-glucuronidase (EC 3.2.1.31) in liver tissue: Of 43 rats studied, 27 animals exhibited only approximately 40% catalytic activity of the remaining group. Analysis by subcellular and density gradient fractionation, and polyacrylamide gel electrophoresis techniques showed that livers with high activity exhibit a dual enzyme distribution in lysosomes (app. 76%) and endoplasmic reticulum (named "microsomal enzyme form"; app. 24%), whereas those with low activity not only lack the microsomal enzyme form - presumably due to the absence of egasyn - but also display reduced lysosomal enzyme activity.
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PMID:Heterogeneity of Wistar rats with respect to acid beta-D-glucuronidase (EC 3.2.1.31) in liver. 795 Oct 44


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