The product of the oncogene PTTG, pituitary tumor transforming gene, is a human homolog of the anaphase-inhibitor vertebrate protein, securin. PTTG contains a basic amino-terminal domain and an acidic carboxy-terminal domain, which acts as a transactivation domain when fused to a heterologous DNA binding domain. Human PTTG is overexpressed in Jurkat and is also detected in human thymus, testis and placenta. PTTG is mainly expressed in the cytoplasm and is also partially localized to the nucleus. Vertebrate PTTG regulates the separin Esp1, which promotes chromatid separation, to overcome the cohesive forces that hold sister chromatids together. This regulatory function of PTTG suggests that defective regulation of cohesion may contribute to cancer by promoting chromosome instability. Although vertebrate PTTG shares cell-cycle functions with its yeast securin counterparts Pds1p and Cut2, none share sequence homology.