Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Egasyn is localized within the lumen of the endoplasmic reticulum (ER) where it complexes with and thus causes sequestration of a considerable portion of beta-glucuronidase. Egasyn has an HTEL sequence at its carboxyl terminus rather than the KDEL sequence that serves as a retention signal for many ER lumenal proteins. To determine whether the HTEL sequence acts as an ER retention signal and/or functions in complex formation, HTEL-deleted egasyn was expressed in mammalian cell lines. The majority of HTEL-deleted egasyn was secreted, while wild type egasyn was retained in the ER. Furthermore, the egasyn HTEL sequence, when added to the carboxyl termini of two secretory proteins, mouse esterase, Es-N, and rat alpha 1-acid glycoprotein (AGP), caused retention of both proteins within the ER, demonstrating that the HTEL sequence is both necessary and sufficient for retention of egasyn and, by extension, the egasyn-glucuronidase complex within the ER. Other carboxyl terminal tetrapeptides including HIEL and HVEL, naturally occurring in other ER lumenal proteins, were also sufficient for ER retention of AGP, while HTEHT and HTEHK were inefficient in ER retention. The HTEL sequence, in contrast, is not required for egasyn-glucuronidase complex formation. Further, the complex is apparently unstable outside the ER since it was not visible in the medium of cells transfected with egasyn lacking the HTEL sequence despite abundant secretion of this egasyn. These results show that it is possible to localize proteins within the lumen of the ER if they form complexes with ER lumenal proteins containing an intrinsic ER retention sequence.
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PMID:The signal for retention of the egasyn-glucuronidase complex within the endoplasmic reticulum. 834 16

The expression and androgen regulation of beta-glucuronidase molecular forms were examined in mouse epididymis, liver, and kidney. Two-dimensional polyacrylamide gel electrophoresis performed under nondenaturing conditions showed that, compared to liver and kidney, which contain four microsomal (M1-M4) and a major lysosomal (L) form of beta-glucuronidase, the epididymis revealed regional differences and tissue specificity in the expression of the various molecular forms of the enzyme. Only the lysosomal form (pI 5.4-6.1) is present in the caput epididymidis while the corpus/cauda contains the lysosomal form, the free X form (pI 5.9-6.3) and the four microsomal forms (X form complexed with egasyn). Mutant mice that lack egasyn have no microsomal forms in the distal epididymis. In epididymal fluid, the lysosomal form is found throughout the epididymis, whereas the X form appears only in the corpus/cauda epididymidis. Sodium dodecyl Sulfate (SDS)-gel electrophoresis and western blot analysis of immunoprecipitated beta-glucuronidase revealed only one band corresponding to the L form (apparent molecular weight 74 kDa) in the caput epididymidis and two bands in the corpus/cauda (apparent molecular weights 73 and 75 kDa), corresponding to L and X forms, respectively. Castration of mice led to the suppression of the regional differences in the appearance of X and M forms in the epididymis. Testosterone supplementation to castrated mice restored the characteristic electrophoretic pattern of beta-glucuronidase in the caput epididymidis. In the liver and kidney, castration has no effect on the expression of the molecular forms, whereas androgen treatment induced the X form in the kidney. Histochemical localization of beta-glucuronidase confirmed the region specificity seen in the epididymis and in addition revealed cell specificity in the expression of beta-glucuronidase. These results indicate that beta-glucuronidase shows tissue specificity and, in the case of the epididymis, region and cell specificity. In addition, the enzyme in the different tissues responds differentially to androgens.
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PMID:Androgen regulation of molecular forms of beta-D-glucuronidase in the mouse epididymis: comparison with liver and kidney. 879 10

Egasyn is an accessory protein of beta-glucuronidase (beta-G) in the liver microsomes. Liver microsomal beta-G is stabilized within the luminal site of the microsomal vesicles by complexation with egasyn which is one of the carboxylesterase isozymes. We investigated the effects of organophosphorus compounds (OPs) such as insecticides on the dissociation of egasyn-beta-glucuronidase (EG) complex. The EG complex was easily dissociated by administration of OPs, i.e. fenitrothion, EPN, phenthionate, and bis-beta-nitrophenyl phosphate (BNPP), and resulting beta-G dissociated was released into blood, leading to the rapid and transient increase of plasma beta-G level with a concomitant decrease of liver microsomal beta-G level. In a case of phenthionate treatment, less increase in plasma beta-G level was observed, as compared with those of other OPs. This may be explained by the fact that phenthionate was easily hydrolyzed by carboxylesterase. Similarly, carbamate insecticides such as carbaryl caused rapid increase of plasma beta-G level. In contrast, no significant increase of plasma beta-G level was observed when pyrethroid insecticides were administered to rats. This is due to the fact that pyrethroids such as phenthrin and allethrin were easily hydrolyzed by A-esterase as well as carboxylesterase. On the other hand, addition of OPs to the incubation mixture containing liver microsomes caused the release of beta-G from microsomes to the medium. From these in vivo and in vitro data, it is concluded that increase of the plasma beta-G level after OP administration is much more sensitive biomarker than cholinesterase inhibition to acute intoxication of OPs and carbamates.
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PMID:Toxicological significance in the cleavage of esterase-beta-glucuronidase complex in liver microsomes by organophosphorus compounds. 1042 85

Lysosomal beta-glucuronidase shows a dual localization in mouse liver, where a significant fraction is retained in the endoplasmic reticulum (ER) by interaction with an ER-resident carboxyl esterase called egasyn. This interaction of mouse egasyn (mEg) with murine beta-glucuronidase (mGUSB) involves binding of the C-terminal 8 residues of the mGUSB to the carboxylesterase active site of the mEg. We isolated the recombinant human homologue of the mouse egasyn cDNA and found that it too binds human beta-glucuronidase (hGUSB). However, the binding appears not to involve the active site of the human egasyn (hEg) and does not involve the C-terminal 18 amino acids of hGUSB. The full-length cDNA encoding hEg was isolated from a human liver cDNA library using full-length mEg cDNA as a probe. The 1941-bp cDNA differs by only a few bases from two previously reported cDNAs for human liver carboxylesterase, allowing the anti-human carboxylesterase antiserum to be used for immunoprecipitation of human egasyn. The cDNA expressed bis-p-nitrophenyl phosphate (BPNP)-inhibitable esterase activity in COS cells. When expressed in COS cells, it is localized to the ER. The intracellular hEg coimmunoprecipitated with full-length hGUSB and with a truncated hGUSB missing the C-terminal 18-amino-acid residue when extracts of COS cells expressing both proteins were treated with anti-hGUSB antibody. It did not coimmunoprecipitate with mGUSB from extracts of coexpressing COS cells. Unlike mEg, hEg was not released from the hEg-GUSB complex with BPNP. Thus, hEg resembles mEg in that it binds hGUSB. However, it differs from mEg in that (i) it does not appear to use the esterase active site for binding since treatment with BPNP did not release hEg from hGUSB and (ii) it does not use the C terminus of GUSB for binding, since a C-terminal truncated hGUSB (the C-terminal 18 amino acids are removed) bound as well as nontruncated hGUSB. Evidence is presented that an internal segment of 51 amino acids between 228 and 279 residues contributes to binding of hGUSB by hEg.
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PMID:Human egasyn binds beta-glucuronidase but neither the esterase active site of egasyn nor the C terminus of beta-glucuronidase is involved in their interaction. 1056 16

Egasyn-beta-glucuronidase complex is located at the luminal site of liver microsomal endoplasmic reticulum. When organophosphorus insecticides (OP) are incorporated into the liver microsomes, they become tightly bound to egasyn, a carboxylesterase isozyme, and subsequently, beta-glucuronidase (BG) is dissociated and released into blood. Consequently, the increase in plasma BG activity becomes a good biomarker of OP exposure. Thus, the single administration of EPN (O-ethyl O-p-nitrophenylphenylphosphonothioate), acephate and chlorpyrifos increased plasma BG activity in approximately 100-fold the control level in rats. The increase in plasma BG activity after OP exposure is a much more sensitive biomarker of acute OP exposure than acetylcholinesterase (AChE) inhibition.
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PMID:Extremely sensitive biomarker of acute organophosphorus insecticide exposure. 1600 1


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