Abstract
UDP is generated in the lumen of the endoplasmic reticulum (ER) as a product of the UDP-glucose-dependent glycoprotein reglucosylation in the calnexin/calreticulin cycle. We describe here the identification, purification and characterization of an ER enzyme that hydrolyzes UDP to UMP. This nucleoside diphosphatase is a ubiquitously expressed, soluble 45 kDa glycoprotein devoid of transmembrane domains and KDEL-related ER localization sequences. It requires divalent cations for activity and hydrolyzes UDP, GDP and IDP but not any other nucleoside di-, mono- or triphosphates, nor thiamine pyrophosphate. By eliminating UDP, which is an inhibitory product of the UDP-Glc:glycoprotein glucosyltransferase, it is likely to promote reglucosylation reactions involved in glycoprotein folding and quality control in the ER.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acid Anhydride Hydrolases / chemistry
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Acid Anhydride Hydrolases / genetics
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Acid Anhydride Hydrolases / isolation & purification
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Acid Anhydride Hydrolases / metabolism*
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Amino Acid Sequence
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Animals
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Base Sequence
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Carbohydrate Metabolism*
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Cations, Divalent / pharmacology
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Cattle
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Cell Line
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Cloning, Molecular
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Endoplasmic Reticulum / enzymology*
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Endoplasmic Reticulum / metabolism
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Glycoproteins / metabolism*
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Glycosylation
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Glycosyltransferases / antagonists & inhibitors
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Glycosyltransferases / metabolism
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Golgi Apparatus / enzymology
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Humans
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Hydrolysis / drug effects
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Liver / cytology
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Liver / enzymology
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Liver / metabolism
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Mice
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Molecular Sequence Data
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Nucleotides / metabolism*
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Nucleotides / pharmacology
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Substrate Specificity
Substances
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Cations, Divalent
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Glycoproteins
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Nucleotides
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Glycosyltransferases
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Acid Anhydride Hydrolases
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nucleoside-diphosphatase