A novel mammalian endoplasmic reticulum ubiquitin ligase homologous to the yeast Hrd1.
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.
Nadav
Eran
E
Department of Biochemistry, George S. Wise Faculty of Life sciences, Tel Aviv University, Tel Aviv 69978, Israel. nadavera@post.tau.ac.il
Shmueli
Ayelet
A
Barr
Haim
H
Gonen
Hedva
H
Ciechanover
Aaron
A
Reiss
Yuval
Y
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D016466:CHO Cells; D003001:Cloning, Molecular; D006224:Cricetinae; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000737:chemistry; D018076:DNA, Complementary / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D006367:HeLa Cells; D006801:Humans; D008025:Ligases / Q000737:chemistry* / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D014018:Tissue Distribution; D014162:Transfection; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases
C505032:CFTR protein, human; D018076:DNA, Complementary; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C104621:HRD1 protein, S cerevisiae; D044767:Ubiquitin-Protein Ligases; D008025:Ligases