InterPro domain: IPR004536

The UGA (TGA) codon is normally a termination codon, however it is also used as a selenocysteine (Sec) codon by numerous organisms [ 1 ]. Sec is the 21st amino acid that is inserted into selenoproteins (protein that includes a selenocysteine (Se-Cys) amino acid residue). The synthesis of Sec and its incorporation into proteins requires the activity of a number of proteins, one of which is selenophosphate synthetase (SPS), also known as the SelD gene product [ 2 , 3 ]. SPS catalises the production of the selenium donor compound monoselenophosphate (MSP) from selenide and ATP. MSP is then used to synthesize Sec from seryl-tRNAs [ 4 ].

SPS was initially identified in E. coli as the product of the gene selD, one of four essential selenoprotein synthesis genes (selA-D) [ 5 ]. SelC is the tRNA itself, SelD acts as a donor of reduced selenium, SelA modifies a serine residue on SelC into selenocysteine, and SelB is a selenocysteine-specific translation elongation factor. 3' or 5' non-coding elements of mRNA have been found as probable structures for directing selenocysteine incorporation. Later, the selD homologues from eukaryotes, bacteria, and archaea were identified [ 5 ].

In mammals, two gene products, SPS1 and SPS2 are proposed to be selenophosphate synthetases. SPS1 may be involved in Sec recycling via a selenium salvage pathway, whereas SPS2 may play a role in the synthesis of selenophosphate [ 5 ]. SPS2 is a selenoprotein and could serve as an autoregulator of selenoprotein synthesis [ 6 ].

Drosophila SPS1 (UniProt: O18373) lacks selenide-dependent SPS activity due to an arginine substitution of the critical Cys (or Sec) residue in the catalytic domain of the enzyme when expressed in E. coli [ 6 ]. Drosophila SPS2 (also known as Dsps2) is a selenoprotein that contains a UGA stop codon in the catalytic centre of the enzyme, nevertheless, the read-through activity can be provided by a mammalian-like SECIS element in its 3'UTR [ 7 ].

1. Selenocysteine. Annu. Rev. Biochem. 65, 83-100
2. Identification of a novel selD homolog from eukaryotes, bacteria, and archaea: is there an autoregulatory mechanism in selenocysteine metabolism? Proc. Natl. Acad. Sci. U.S.A. 93, 15086-91
3. In vitro synthesis of selenocysteinyl-tRNA(UCA) from seryl-tRNA(UCA): involvement and characterization of the selD gene product. Proc. Natl. Acad. Sci. U.S.A. 87, 543-7
4. Selenium biochemistry. Annu. Rev. Biochem. 59, 111-27
5. Selenophosphate synthetase genes from lung adenocarcinoma cells: Sps1 for recycling L-selenocysteine and Sps2 for selenite assimilation. Proc. Natl. Acad. Sci. U.S.A. 101, 16162-7
6. SelD homolog from Drosophila lacking selenide-dependent monoselenophosphate synthetase activity. J. Mol. Biol. 274, 174-80
7. The class 2 selenophosphate synthetase gene of Drosophila contains a functional mammalian-type SECIS. EMBO Rep. 1, 441-6