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A mutation which disrupts the hydrophobic core of the signal peptide of bilirubin UDP‐glucuronosyltransferase, an endoplasmic reticulum membrane protein, causes Crigler‐Najjar type IIs
Author(s) -
Seppen Jurgen,
Steenken Edmee,
Lindhout Dick,
Bosma Piter J.,
Oude Elferink Ronald P.J.
Publication year - 1996
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(96)00677-1
Subject(s) - endoplasmic reticulum , mutant , wild type , chemistry , microsome , mutant protein , signal peptide , arginine , biochemistry , mutation , microbiology and biotechnology , in vitro , leucine , biology , gene , peptide sequence , amino acid
Crigler‐Najjar (CN) disease is caused by a deficiency of the hepatic enzyme, bilirubin UDP‐glucuronosyltransferase (B‐UGT). We have found two CN type II patients, who were homozygous for a leucine to arginine transition at position 15 of B‐UGT1. This mutation is expected to disrupt the hydrophobic core of the signal peptide of B‐UGT1. Wild type and mutant B‐UGT cDNAs were transfected in COS cells. Mutant and wild type mRNA were formed in equal amounts. The mutant protein was expressed with 0.5% efficiency, as compared to wild type. Mutant and wild type mRNAs were translated in vitro. Wild type transferase is processed by microsomes, no processing of the mutant protein was observed.