A region of the C-terminus of adenovirus type 2/5 E1A protein has been associated with negative modulation of tumorigenicity, as well as the extent of oncogenic transformation. In contrast with the N-terminus of the E1A protein, which has been extensively characterized and shown to associate with a number of cellular proteins, the function of the C-terminus is poorly understood. To date, a single 48-kDa protein, CTBP1, has been shown to associate with this region. Here we report the identification and sequence of a novel gene in human (CTBP2) and mouse (Ctbp2), both highly related to CTBP1 and thus also likely to bind to the E1A protein. We found that CTBP2 is expressed in all tissues tested, with a higher level of expression in the heart, skeletal muscle, and pancreas. We mapped CTBP1 and CTBP2 to human chromosomes 4p16 and 21q21.3, respectively.