Structures of the Human Gene for the Protein Disulfide Isomerase-Related Polypeptide ERp60 and a Processed Gene and Assignment of These Genes to 15q15 and 1q21

Abstract

ERp60 (also known as ERp61 or GRP58) is an isoform of protein disulfide isomerase (PDI) that has two thioredoxin-like domainsaanda′ in positions corresponding to those of domainsaanda′ in the PDI polypeptide and shows a significant amino acid sequence similarity to PDI in almost all parts. We report here that the human ERp60 gene is about 18 kb in size and consists of 13 exons. No distinct correlation was found between its exon–intron organization and the modular structure of the ERp60 polypeptide, nor were any similarities in exon–intron organization found between the human ERp60, PDI, and thioredoxin genes. The 5′ flanking region of the ERp60 gene has no TATAA box or CCAAT motif but contains several potential binding sites for transcription factors. The highest levels of expression of the ERp60 mRNA were found by Northern blotting in the liver, placenta, lung, pancreas, and kidney, and the lowest in the heart, skeletal muscle, and brain. We also isolated an intronless ERp60 gene that probably represents a pseudogene. The ERp60 gene was mapped by fluorescencein situhybridization to 15q15 and the processed gene to 1q21, so that neither was located on the same chromosome as the human PDI and thioredoxin genes.