Figure 1.

Synthesis and co-translational incorporation of selenocysteine in humans. The cycle, which is conserved in archaea and eukaryotes, begins with a mischarging reaction in which seryl-tRNA synthetase attaches L-serine (L-Ser) to a non-cognate tRNA^Sec. A specific kinase, O-phosphoseryl-tRNA^Sec kinase (PSTK), phosphorylates the seryl group yielding a phosphoseryl (Sep)-tRNA^Sec intermediate. In the terminal synthetic reaction, O-phosphoseryl-tRNA^Sec:selenocysteinyl-tRNA^Sec synthase (SepSecS), catalyzes conversion of Sep-tRNA^Sec into selenocysteinyl (Sec)-tRNA^Sec by a mechanism that requires selenophosphate and a co-factor pyridoxal phosphate (PLP). Selenophosphate, the main selenium donor in man, is a product of the catalytic activity of selenophosphate synthetase (SPS2). Human SPS2 is a selenoenzymes that utilizes as a reaction substrate the final product of selenoprotein/selenocysteine degradation, selenide, and adenosine triphosphate (ATP). Finally, Sec-tRNA^Sec is targeted and delivered to the ribosome by a specialized elongation factor – EFsec. An auxiliary protein factor, SECIS-binding protein 2 (SBP2), is required for decoding of the selenocysteine UGA codon in all vertebrates, whereas a shorter ortholog is functional in invertebrates. Selenocysteine (green sphere) is inserted into the nascent protein (orange spheres) in response to a specific UGA codon. SECIS, an in-cis element in the selenoprotein mRNA located in the 3′-UTR, forms a stem loop structure and is required for decoding of the selenocysteine UGA codon. In bacteria, a single enzyme, SelA, converts Ser-tRNA^Sec to Sec-tRNA^Sec, elongation factor SelB binds directly to SECIS, which is, in turn, a part of the coding sequence.