Role of the carboxyl terminal stop transfer sequence of UGT1A6 membrane protein in ER targeting and translocation of upstream lumenal domain.
We investigated the role of the stop transfer sequence of human UGT1A6 in ER assembly and enzyme activity. We found that this sequence was able to address and translocate the upstream lumenal domain into microsomal membranes in vitro co- and posttranslationally. The signal activity of this sequence was further demonstrated in HeLa cells by its ability to target and maintain the CD4 protein deleted from both the N-terminal signal peptide and C-terminal transmembrane domain into the ER. We showed that total or partial deletion of the stop transfer sequence of UGT1A6 severely impaired enzyme activity highlighting its importance in both membrane assembly and function.
Ouzzine
M
M
UMR 7561 CNRS-Université Henri Poincaré Nancy I, Faculté de Médecine, BP 184, 54505 Vanoeuvre-lès-Nancy, France. ouzzine@medecine.uhp-nancy.fr
Barré
L
L
Netter
P
P
Magdalou
J
J
Fournel-Gigleux
S
S
D024506:5' Flanking Region / Q000235:genetics; D000595:Amino Acid Sequence; D004721:Endoplasmic Reticulum / Q000201:enzymology / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000737:chemistry* / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D008969:Molecular Sequence Data; D010843:Pichia / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D021382:Protein Sorting Signals / Q000502:physiology*; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D017384:Sequence Deletion / Q000235:genetics
D008565:Membrane Proteins; D021382:Protein Sorting Signals; C110655:UDP-glucuronosyltransferase, UGT1A6; D014453:Glucuronosyltransferase