Selenocysteine metabolism

Selenocysteine (SEC; one letter abbreviation: U) is the 21st amino acid encoded by the UGA codon. This amino acid is rare, and when present in proteins, these are called selenoproteins. Selenocysteine is similar to cysteine and the sulphur residue is replaced by a selenium residue. Selenocysteine have lower pKa and higher reduction potential than cysteine providing the enzymes’ redox centres with increased catalytic efficiency [1]. As UGA is a stop codon, UGA coding Selenocysteine is identified with a stem-loop structure called SElenoCysteine Insertion sequence (SECIS). SECIS is present in the 3’ untranslated region of selenoprotein genes [2]. The four nucleotide AUGA segment of eukaryotic canonical SECIS element is previously considered invariant. In addition to it, noncanonical SECIS element with GGGA sequence was identified in Toxoplasma gondii and Neospora caninum. The analysis of EST sequences of T. gondii and N. caninum by Novoselov et al has suggested the presence of selenoprotein homologs of Sel S, Sel W, Sel T, Sel K and Sel Q in T. gondii and the first three in N. caninum [3]. Of these, Sel Q, Sel K and Sel S are identified in T. gondii gene models in ToxoDB. Although Sel T is not present in T. gondii gene models, it is present in N. caninum. The comparison of gene models in ToxoDB to the predicted protein sequences in [3] showed that these selenocysteine-specific UGA codons are either considered as stop codons (TGME49_116600, TGME49_073770, TGME49_112640) or as part of intron (NCLIV_041980) in gene models.


The four-nucleotide segment AUGA/GGGA of SECIS is important for the interaction with SECIS binding protein, SBP2, which is essential for the selenocysteine incorporation and translation of selenoprotein mRNAs [4, 5]. The SBP protein is not identified in either T. gondii or Plasmodium falciparum genomes. The UGA codon of selenocysteine is decoded by a specific elongation factor SelB in eubacteria and its mammalian homolog mSelB was also identified [6, 7]. SPB forms a complex with Selenocysteine-specific elongation factor and the SEC-specific tRNA and the interaction of this complex is essential for encoding UGA codon with selenocysteine [8]. Both tRNASEC and SEC-specific elongation factors are present in P. falciparum and T. gondii. Two other factors which regulate selenoprotein expression are soluble liver antigen (SLA) and SECp43. SLA has been demonstrated to be involved in interaction with tRNASEC [9] and selenophosphate synthase I (SPS1, also known as selenium, water dikinase) [10]. SECp43 interacts with all these factors including SLA and involved in regulation of cellular localisation of SLA and tRNASEC [9, 10]. SLA is present in genomes of Plasmodium species and T. gondii and Neospora caninum.


As selenoprotein biosynthesis is a metabolic capability present in both P. falciparum and T. gondii, Selenocysteine biosynthesis pathway is also present in MPMP. The enzymes which are involved in the catalysis of selenate to selenide are not identified in P. falciparum. The analysis of KEGG database suggested that most of the reactions are spontaneous and the two enzyme catalysed reactions involved in the conversion of slenate to 3’-phosphoadenylyl selenate are catalysed by the enzymatic activities of and These enzymes catalyse the conversion of sulfate to 3’-phosphoadenylyl sulfate and can also catalyse the above mentioned reactions. The ortholog of human bifunctional enzyme is also present in T. gondii genome.


Protein EC Number Gene id Protein localisation Localisation data source
NADPH-thioredoxin reductase TGME49_309730 Cytosol Previous publication; GO annotation
Bifunctional sulfate adenylyltransferase/adenylyl-sulfate kinase; TGME49_282230    
Selenide, water dikinase TGME49_280560 Mitochondrion Previous publication
L-seryl-tRNA(Sec) selenium transferase Missing in annotation    
Selenocysteine lyase TGME49_216170    
Ser-tRNA ligase TGME49_251690 Apicoplast Previous publication
Ser-tRNA ligase TGME49_271625 Apicoplast Apiloc
Selenocysteine-specific elongation factor none TGME49_216960 Plasma membrane Previous publication
Soluble liver antigen (SLA/LP) none TGME49_315170 Nucleus Previous publication
SECIS binding protein none Missing in annotation    


  Genes annotated as tRNA-Sec in Toxoplasma gondii genome





Genes encoding selenoproteins present in the T. gondii genome


Selenoprotein Gene
SELQ TGME49_273770
SELK TGME49_316600
SELW Missing in annotation
SELS TGME49_312640
SELT Missing in annotation


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Sources of metabolites


Substrate Source pathways
Selenate Host