The carboxyl-terminal di-lysine motif is essential for catalytic activity of UDP-glucuronosyltransferase 1A9.
Drug Metab Pharmacokinet
; 35(5): 466-474, 2020 Oct.
Article
in En
| MEDLINE
| ID: mdl-32883578
UDP-Glucuronosyltransferase (UGT) is a type I membrane protein localized to the endoplasmic reticulum (ER). UGT has a di-lysine motif (KKXX/KXKXX) in its cytoplasmic domain, which is defined as an ER retention signal. However, our previous study has revealed that UGT2B7, one of the major UGT isoform in human, localizes to the ER in a manner that is independent of this motif. In this study, we focused on another UGT isoform, UGT1A9, and investigated the role of the di-lysine motif in its ER localization, glucuronidation activity, and homo-oligomer formation. Immunofluorescence microscopy indicated that the cytoplasmic domain of UGT1A9 functioned as an ER retention signal in a chimeric protein with CD4, but UGT1A9 itself could localize to the ER in a di-lysine motif-independent manner. In addition, UGT1A9 formed homo-oligomers in the absence of the motif. However, deletion of the di-lysine motif or substitution of lysines in the motif for alanines, severely impaired glucuronidation activity of UGT1A9. This is the first study that re-defines the cytoplasmic di-lysine motif of UGT as an essential peptide for retaining glucuronidation capacity.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Glucuronosyltransferase
/
Biocatalysis
/
Lysine
Limits:
Animals
/
Humans
Language:
En
Journal:
Drug Metab Pharmacokinet
Journal subject:
FARMACOLOGIA
/
METABOLISMO
Year:
2020
Document type:
Article
Country of publication:
United kingdom