Characterization of a variant of ERGIC2 transcript

ERGIC2 (formerly known as PTX1) is a gene identified by subtractive hybridization on the basis that it is expressed in normal human prostate, but not in prostate carcinoma. It is unrelated to the gene encoding pituitary homeobox protein (Ptx1 or Pitx1), which regulates pituitary hormone gene expression. Based on sequence homology with the yeast Erv41 protein, it is suggested that the ERGIC2 protein is an endoplasmic reticulum (ER) resident protein involved in protein trafficking between the ER and Golgi intermediate compartment (ERGIC) and cis-Golgi. However, studies from our laboratory and others have shown that it may have other functions. In this study, we have identified a variant ERGIC2 transcript with a four base deletion at the junction of exons 8-9, resulting in frame shift after codon #189. As a result, a truncated protein of 215 residues (24.5 kDa) is predicted as compared with the 377-residue (42.6 kDa) wild-type (WT) protein. The truncated variant ERGIC2 protein loses 45% of the luminal domain and the transmembrane domain near the C-terminus, and this effectively abrogates its function as the ERGIC-Golgi protein transport shuttle. The variant, like the WT protein, was found to upregulate the heme oxygenase 1 gene, suggesting that it may be involved in the oxidative stress pathway.