A 4-selenocysteine, 2-selenocysteine insertion sequence (SECIS) element methionine sulfoxide reductase from Metridium senile reveals a non-catalytic function of selenocysteines

J Biol Chem. 2011 May 27;286(21):18747-55. doi: 10.1074/jbc.M111.229807. Epub 2011 Mar 10.


Selenocysteine (Sec) residues occur in thiol oxidoreductase families, and functionally characterized selenoenzymes typically have a single Sec residue used directly for redox catalysis. However, how new Sec residues evolve and whether non-catalytic Sec residues exist in proteins is not known. Here, we computationally identified several genes with multiple Sec insertion sequence (SECIS) elements, one of which was a methionine-R-sulfoxide reductase (MsrB) homolog from Metridium senile that has four in-frame UGA codons and two nearly identical SECIS elements. One of the UGA codons corresponded to the conserved catalytic Sec or Cys in MsrBs, whereas the three other UGA codons evolved recently and had no homologs with Sec or Cys in these positions. Metabolic (75)Se labeling showed that all four in-frame UGA codons supported Sec insertion and that both SECIS elements were functional and collaborated in Sec insertion at each UGA codon. Interestingly, recombinant M. senile MsrB bound iron, and further analyses suggested the possibility of binding an iron-sulfur cluster by the protein. These data show that Sec residues may appear transiently in genes containing SECIS elements and be adapted for non-catalytic functions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Catalysis
  • Codon*
  • Iron / metabolism
  • Methionine Sulfoxide Reductases / genetics
  • Methionine Sulfoxide Reductases / metabolism*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sea Anemones / enzymology*
  • Selenocysteine / genetics
  • Selenocysteine / metabolism*


  • Codon
  • Recombinant Proteins
  • Selenocysteine
  • Iron
  • Methionine Sulfoxide Reductases
  • methionine sulfoxide reductase