The 5'-flanking region of the human calreticulin gene shares homology with the human GRP78, GRP94, and protein disulfide isomerase promoters

Abstract

Calreticulin (CR) is a calcium binding protein that resides in the endoplasmic and sarcoplasmic reticulum and is reactive with human Ro/SS-A autoimmune sera. We have used human CR cDNA to isolate a human 6-kilobase genomic clone that contains 529 base pairs upstream of the presumed transcription start site, 9 exons, 8 introns, and several hundred base pairs 3' of a polyadenylation sequence. Analysis of the human CR promoter region reveals a number of potential regulatory sites also found in the human GRP78, GRP94, and protein disulfide isomerase promoters, including multiple Sp1 and CCAAT consensus sequences, an AP-2 recognition sequence (absent in protein disulfide isomerase), and multiple GC-rich areas. DNA footprint and gel shift analysis on the CR 5'-flanking region demonstrates an area that is bound by protein found in human but not murine nuclear extracts. This sequence is homologous with previously determined regulatory sequences of the human GRP78 and GRP94 promoters. These data indicate that CR, GRP78, GRP94, and protein disulfide isomerase may in part have similar transcriptional regulation and suggest that their gene products while structurally distinct may have similar functions or co-functions. These observations are of additional interest as all four of these genes encode acidic proteins that localize to the endoplasmic reticulum.