A mutation which disrupts the hydrophobic core of the signal peptide of bilirubin UDP-glucuronosyltransferase, an endoplasmic reticulum membrane protein, causes Crigler-Najjar type II.

Abstract:

: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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Seppen J,Steenken E,Lindhout D,Bosma PJ,Elferink RP

doi

10.1016/0014-5793(96)00677-1

subject

Has Abstract

pub_date

1996-07-29 00:00:00

pages

294-8

issue

3

eissn

0014-5793

issn

1873-3468

pii

0014579396006771

journal_volume

390

pub_type

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