Selenoproteins

Selenoproteins are a group of proteins that contain selenocysteine, the 21st amino acid. Unlike standard amino acids, selenocysteine is encoded by the UGA codon, normally a stop signal, when a specific RNA element called the SECIS (selenocysteine insertion sequence) is present in the mRNA and specialized translation factors are available. In humans, there are 25 identified selenoproteins, reflecting a conserved but differentiating role across tissues and species.

Biosynthesis and incorporation of selenocysteine differ between domains of life. In eukaryotes and archaea, a dedicated tRNA for selenocysteine (tRNA Sec) along with the SECIS element in the 3' UTR, and the Sec-specific elongation factor eEFSec and SBP2 (SECIS-binding protein 2) direct UGA to encode Sec during translation, with selenium supplied through selenophosphate. In bacteria, the process uses a distinct set of proteins, including SelB and SelA, and SECIS-like elements, but the outcome is the same: a codon normally signaling termination is reinterpreted to insert Sec.

Selenoproteins participate prominently in redox biology and metabolism. Many act as antioxidants or redox regulators, such as glutathione peroxidases and thioredoxin reductases, while others, like the deiodinases, regulate thyroid hormone activation. Selenoprotein P serves as a selenium transport protein, and other family members contribute to cellular signaling, protein folding, and mitochondrial function. The abundance and variety of selenoproteins vary among organisms and reflect evolutionary adaptation to selenium availability and oxidative stress.

Dietary selenium status influences selenoprotein synthesis; deficiency can impair antioxidant defenses and thyroid function, whereas excessive selenium can be toxic. Defects in selenoprotein synthesis or function are linked to human disorders, highlighting the biological importance of this unique class of proteins.