Extensive Protein-Protein Interactions Involving UDP-glucuronosyltransferase (UGT) 2B7 in Human Liver Microsomes

UDP-glucuronosyltransferase (UGT) 2B7 is a membrane protein that catalyzes glucuronidation of endogenous and exogenous substrates. Because UGTs are expressed in the endoplasmic reticulum (ER), their substrates and metabolites need to be transported through the ER membrane. However, insight into the...

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Bibliographic Details
Published in:DRUG METABOLISM AND PHARMACOKINETICS 2014, Vol.29 (3), p.259-265
Main Authors: Fujiwara, Ryoichi, Itoh, Tomoo
Format: Article
Language:English
Subjects:
CYP3A4
Glucuronosyltransferase - metabolism
Humans
Immunoprecipitation
Liver - enzymology
Liver - metabolism
Metabolome
metabolosome
Microsomes, Liver - enzymology
Microsomes, Liver - metabolism
Protein Interaction Domains and Motifs - physiology
protein-protein interactions
UDP-glucuronosyltransferase
UGT2B7
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Summary:UDP-glucuronosyltransferase (UGT) 2B7 is a membrane protein that catalyzes glucuronidation of endogenous and exogenous substrates. Because UGTs are expressed in the endoplasmic reticulum (ER), their substrates and metabolites need to be transported through the ER membrane. However, insight into the mechanism underlying the transport of substrates/metabolites of UGTs through the ER membrane has not been elucidated. Metabolosome is a functional unit of metabolism consisting of multiple metabolism-related proteins. UGTs might form a metabolosome to facilitate the transport of their substrates and/or metabolites through the ER membrane. In the present study, therefore, extensive protein-protein interactions involving UGT2B7 were determined by a shotgun analysis of immunoprecipitate. Our shotgun analysis revealed that 92 proteins were immunoprecipitated with anti-UGT2B7 antibody in human liver microsomes. We further determined that 42 proteins out of the 92 proteins were specifically immunoprecipitated with the anti-UGT2B7 antibody. In addition to UGT2B7, other microsomal enzymes such as UGT1A, CYP3A4, CYP1A2, and a monoamine oxidase, were included in the list of proteins immuno-precipitated with the anti-UGT2B7 antibody, suggesting that these proteins might form a metabolosome to regulate their functions in the liver. Further analyses are needed to elucidate the roles of those proteins in the enzymatic activity of human UGTs.
ISSN:1347-4367
1880-0920
DOI:10.2133/dmpk.DMPK-13-RG-096