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The 15 kDa selenoprotein (Sepl5) is one of several recently identified selenoproteins. It contains a single selenocysteine residue in the middle of a 162-amino acid open reading frame and has no detectable homology to known proteins. The human Sepl5 gene spans 5 1 kb, has 5 exons and is located on chromosome 1 at position p3 1. The gene contains two single nucleotide polymorphisms in the 3'-untranslated region (3'-UTR) including one in the SECIS element, that are distributed differently between Caucasians and African Americans. Sep15 localizes to the endoplasmic reticulum where it is tightly bound to UDP-glucose:glycoprotein glucosyltransferase, a protein involved in the quality control of protein folding. Sepl5 may be involved in the chemopreventive effect of dietary selenium. This hypothesis is based on its differential expression in normal and malignant tissues, the distribution and functional consequences of natural polymorphisms within its gene, and the location of the Sepl5 gene in a region that is often altered in a variety of cancers.