The SNF2 gene family consists of a large group of proteins involved in transcriptional regulation, maintenance of chromosome integrity, and various aspects of DNA repair. We cloned a novel SNF2 family human cDNA, with sequence identity to the Escherichia coli RNA polymerase-binding protein HepA and named the human hepA-related protein (HHARP/SMARCAL1). In addition, the mouse ortholog (Mharp/Smarcal1) was cloned, and the Caenorhabditis elegans ortholog (CEHARP) was identified in the GenBank database. Phylogenetic analysis indicates that the HARP proteins share a high level of sequence similarity to the seven motif helicase core region (SNF2 domain) with identifiable orthologs in other eukaryotic species, except for yeast. Purified His-tagged HARP/SMARCAL1 protein exhibits single-stranded DNA-dependent ATPase activity, consistent with it being a member of the SNF2 family of proteins. Both the human and the mouse genes consist of 17 exons and 16 introns. The human gene maps to chromosome 2q34–q36, and the mouse gene is localized to the syntenic region of chromosome 1 (between markers Gls and Acrg). HARP/SMARCAL1 transcripts are ubiquitously expressed in human and mouse tissues, with testis presenting the highest levels of mRNA expression in humans.