selenoprotein

Selenoproteins are a class of proteins that contain the amino acid selenocysteine (Sec), the 21st amino acid, incorporated into polypeptides at UGA codons through a specialized recoding mechanism rather than as a standard stop signal. In humans and many other organisms, about 25 selenoproteins are encoded in the genome, reflecting the essential yet tightly regulated role of selenium in biology.

The insertion of Sec requires a unique set of molecular components and RNA elements. In eukaryotes, a SECIS element located in the 3’ untranslated region of the mRNA directs the recoding of UGA from a stop signal to Sec, with the help of the Sec incorporation machinery including SBP2, eEFSec, and SepSecS, and the supply of selenophosphate. The Sec tRNA is initially charged with serine and then converted to Sec. In bacteria, a related but distinct system uses SelA to convert Ser-tRNASec to Sec-tRNASec and SelB to guide insertion at UGA with a bacterial SECIS element.

Notable selenoproteins include glutathione peroxidases (antioxidant enzymes), thioredoxin reductases, iodothyronine deiodinases (thyroid hormone metabolism), and selenophosphate synthetase. Selenoprotein P is a secreted, selenium-rich protein thought to participate in selenium transport.

Functionally, selenoproteins contribute to redox balance and protection against oxidative stress, and Sec often enhances catalytic efficiency under physiological conditions. Selenium status influences selenoprotein expression; deficiency can lead to disorders such as cardiomyopathy (historically linked to Keshan disease) and increased oxidative damage, while excessive selenium can be toxic. The presence of selenoproteins varies across lineages, reflecting evolutionary loss or retention of Sec usage in response to selenium availability and ecological niche.