A NEW HUMAN SELENIUM-CONTAINING PROTEIN - PURIFICATION, CHARACTERIZATION, AND CDNA SEQUENCE

Selenium which occurs in proteins as the amino acid, selenocysteine, i s essential for numerous biological processes and for human health. A prominent Se-75-labeled protein detected in human T-cells migrated as a 15-kDa band by SDS-polyacrylamide gel electrophoresis. This protein subunit was purified and subjected to tryptic digestion and peptide se quence analyses. Sequences of tryptic peptides derived from the protei n corresponded to a human placental gene sequence containing an open r eading frame of 162 residues and a readthrough in-frame TGA codon. Thr ee different peptide sequences of the 15-kDa protein corresponded to a nucleotide sequence located downstream of this codon, suggesting that the T-cell 15-kDa selenoprotein contains a selenocysteine residue enc oded by TGA. Post-translational processing of the N-terminal portion o f the predicted gene product to give the 15-kDa protein was suggested on the basis of molecular mass, amino acid analysis, and immunoblot as says of the purified protein. The 3'-untranslated region (UTR) of the gene encoding the 15-kDa protein contained a sequence that is very sim ilar to the canonical selenocysteine-inserting sequence element. Compu ter analysis of transcript map data bases indicated that this gene was located on human chromosome 1. Its coding sequence showed no homology to known protein-encoding genes. The 15-kDa protein gene was expresse d as mRNA in a wide range of tissues, with increased levels in the thy roid, parathyroid, and prostate-derived cells as evidenced by searches of partial cDNA sequences in public data bases. Genes corresponding t o the 15-kDa selenocysteine containing protein were found in mice and rats, while the corresponding genes in Caenorhabditis elegans and Brug ia malayi contained a cysteine codon in place of TGA The discovery of a new human selenoprotein provides an additional example of the role o f selenium in mammalian systems.