Large-scale DNA sequencing, coupled with in silico gene trapping, is a robust approach to identifying unknown genes in selected genomic regions. Using this approach we have isolated a novel human gene, PROSC (for proline synthetase co-transcribed [bacterial homolog]), from human chromosome 8p11.2, and its mouse counterpart. The human PROSC gene spanned 17 kb of genomic DNA; its cDNA was 2530 bp long, with 8 exons that included an open reading frame of 825 bp (275 amino acids). The mouse cDNA (Prosc), 1995 bp long, was predicted to encode 274 amino acids. PROSC is ubiquitously expressed in human tissues and has been highly conserved among divergent species from bacteria to mammals, suggesting its important cellular function. The gene product is likely to be a soluble cytoplasmic protein, but its function remains to be determined.