ERp72, an abundant luminal endoplasmic reticulum protein, contains three copies of the active site sequences of protein disulfide isomerase

• Published in: The Journal of biological chemistry 1990-01, Vol.265 (2), p.1094-1101
• Main Authors: MAZZARELLA, R. A, MYTHILI SRINIVASAN, HAUGEJORDEN, S. M, GREEN, M
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Base Sequence; Binding Sites; Biological and medical sciences; DNA - genetics; Electrophoresis, Polyacrylamide Gel; Endoplasmic Reticulum - metabolism; Fundamental and applied biological sciences. Psychology; Gene Expression; genes; Genes. Genome; Isomerases - genetics; Membrane Glycoproteins - genetics; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Mutation; protein disulfide-isomerase; Protein Disulfide-Isomerases; Transfection
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/s0021-9258(19)40163-4

We have cloned, sequenced, and expressed full length cDNA clones encoding two abundant, luminal endoplasmic reticulum proteins (ERp), ERp59/PDI and ERp72. ERp59/PDI has been identified as the microsomal enzyme protein disulfide isomerase (PDI). An analysis of the amino acid sequence of ERp72 showed that it shared sequence identity with ERp59/PDI at three discrete regions, having three copies of the sequences that are thought to be the CGHC-containing active sites of ERp59/PDI. Thus, ERp72 appears to be a newly described member of the family of CGHC-containing proteins. ERp59/PDI has the sequence KDEL at its COOH terminus while ERp72 has the related sequence KEEL. Removal of the KDEL of ERp59/PDI or the KEEL of ERp72 by in vitro mutagenesis techniques and subsequent analysis of the mutants in transient expression assays, showed that both sequences are endoplasmic reticulum retention signals for their respective proteins. The most dramatic difference in secretion between the wild type and the mutant forms of the protein was seen in the case of ERp72.