SRCAP increased transcription of a reporter plasmid when it was cotransfected with the transcription activation domain of CBP. Endogenous SRCAP immunoprecipitated from nuclear extracts of a human lung epithelial cell line had ATPase activity, and the C-terminal half of SRCAP enhanced the ability of CBP to activate transcription. Adenovirus protein E1A blocked the ability of CBP to function as a coactivator for a number of transcription factors. The deduced 2,971-amino acid protein has a calculated molecular mass of 315 kD. It has a highly charged N-terminal domain, a central CBP-binding domain, a second charged domain, and a putative C-terminal DNA-binding domain. A complete ATPase domain, consisting of 7 highly conserved regions, are dispersed over the length of the protein.