The 15 kDa selenoprotein, also known as SEP15, is one of the more than 25 selenoproteins identified in humans. Selenoproteins are unique proteins that incorporate the amino acid selenocysteine, which is known for its role in redox regulation and antioxidant defense mechanisms. SEP15 has garnered significant interest due to its potential implications in human health and disease, particularly in cancer biology.
The SEP15 gene is located on human chromosome 1 at position p31 . This gene spans approximately 51 kilobases and consists of five exons . The protein encoded by this gene is composed of 162 amino acids and contains a single selenocysteine residue at position 93 . The selenocysteine insertion sequence (SECIS) element, which is essential for the incorporation of selenocysteine into the protein, is found in the 3′-untranslated region (UTR) of its mRNA .
SEP15 is an endoplasmic reticulum (ER)-resident protein and is involved in the quality control of protein folding . It associates with UDP-glucose:glycoprotein glucosyltransferase (UGTR), a protein that plays a crucial role in the proper folding of glycoproteins . SEP15 is believed to function as an oxidoreductase, contributing to redox regulation within the ER .
The expression of SEP15, like many other selenoproteins, is regulated by the selenium status of the organism . Under conditions of low selenium, the expression of inducible selenoproteins such as SEP15 is reduced, while essential housekeeping selenoproteins maintain their expression . SEP15 is expressed in a wide range of tissues, with the highest levels observed in the liver, kidney, testes, thyroid, and prostate .
SEP15 has been implicated in cancer biology due to its differential expression in normal and malignant tissues . Polymorphisms in the SEP15 gene have been linked to an increased risk of several types of cancer . The gene’s location on chromosome 1p31, a region often deleted or mutated in various cancers, further supports its potential role in cancer etiology . SEP15’s involvement in the chemopreventive effects of dietary selenium is also a subject of ongoing research .