A novel mammalian endoplasmic reticulum ubiquitin ligase homologous to the yeast Hrd1

Biochem Biophys Res Commun. 2003 Mar 28;303(1):91-7. doi: 10.1016/s0006-291x(03)00279-1.

Abstract

The yeast hHrd1 is a ubiquitin-protein ligase (E3) involved in ER-associated degradation. It was originally identified by genetic methods as an E3 of the yeast cholesterol biosynthetic enzyme HMG-CoA reductase (HMGR). We report the identification and cloning of a human homologue of Hrd1 (hHrd1). Immunofluorescence imaging confirms that the endogenous hHrd1 resides in the ER and in vitro assay demonstrates that it has a ubiquitin-ligase activity. However, the homology between the human and yeast Hrd1 is limited to the N-terminal domain of the proteins, and hHrd1 does not appear to be involved in the degradation of mammalian HMGR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Blotting, Western
  • CHO Cells
  • Cloning, Molecular
  • Cricetinae
  • Cystic Fibrosis Transmembrane Conductance Regulator / chemistry
  • DNA, Complementary / metabolism
  • Endoplasmic Reticulum / enzymology*
  • HeLa Cells
  • Humans
  • Ligases / chemistry*
  • Ligases / metabolism*
  • Microscopy, Fluorescence
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae Proteins*
  • Sequence Homology, Amino Acid
  • Time Factors
  • Tissue Distribution
  • Transfection
  • Ubiquitin / metabolism
  • Ubiquitin-Protein Ligases*

Substances

  • CFTR protein, human
  • DNA, Complementary
  • Recombinant Proteins
  • Saccharomyces cerevisiae Proteins
  • Ubiquitin
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • HRD1 protein, S cerevisiae
  • Ubiquitin-Protein Ligases
  • Ligases