We have isolated a novel cDNA encoding a peptide with 86% sequence homology to hSNF2L protein, a previously isolated human homologue of Drosophila ISWI. This gene, designated SMARCA5, contained an open reading frame of 3,156 nucleotides encoding a 1,052 amino-acid peptide (hSNF2H). As this product also revealed a significant (73%) identity in amino acid sequence to ISWI, a key component of chromatin-remodeling factors in Drosophila, hSNF2H may be another human homologue of this protein and, as such, could be involved in chromatin remodeling in humans. An ATPase domain characteristic of the SWI2/SNF2 family of proteins was highly conserved in ISWI, hSNF2L, and hSNF2H. Northern-blot analysis demonstrated ubiquitous expression of 5.1-kb and 4.1-kb transcripts of the hSNF2H gene. This gene was mapped by FISH to chromosome bands 4q31.1-->q31.2.