Mammalian selenium-containing proteins identified thus far contain selenium in 
the form of a selenocysteine residue encoded by UGA. These proteins lack common 
amino acid sequence motifs, but 3'-untranslated regions of selenoprotein genes 
contain a common stem-loop structure, selenocysteine insertion sequence (SECIS) 
element, that is necessary for decoding UGA as selenocysteine rather than a stop 
signal. We describe here a computer program, SECISearch, that identifies 
mammalian selenoprotein genes by recognizing SECIS elements on the basis of 
their primary and secondary structures and free energy requirements. When 
SECISearch was applied to search human dbEST, two new mammalian selenoproteins, 
designated SelT and SelR, were identified. We determined their cDNA sequences 
and expressed them in a monkey cell line as fusion proteins with a green 
fluorescent protein. Incorporation of selenium into new proteins was confirmed 
by metabolic labeling with (75)Se, and expression of SelT was additionally 
documented in immunoblot assays. SelT and SelR did not have homology to 
previously characterized proteins, but their putative homologs were detected in 
various organisms. SelR homologs were present in every organism characterized by 
complete genome sequencing. The data suggest applicability of SECISearch for 
identification of new selenoprotein genes in nucleotide data bases.