Sipa1, previously called Spa1, is transcriptionally induced in the murine lymphoid cells following mitogenic stimulation and encodes a protein with a domain related to Rap1 GTPase activating protein (Rap1GAP) at the N-terminus and to PEST sequences followed by a leucine zipper motif at the C-terminus. Herein mouse genomic Si,pal, which consisted of 16 exons, was cloned. Gene linkage analysis using (BXD) recombinant inbred strains indicated that Sipa1 was mapped to the most centromeric region of chromosome 19 syntenic with the long arm of human chromosome II. Human SIPA1 cDNA exhibited a striking homology to that of mouse throughout the entire region, with the overall identity being 90% at the amino acid level. Human genomic clones, which hybridized with both mouse and human SIPA1 cDNA but not with RAP1GAP cDNA, were then isolated. Fluorescence in situ hybridization (FISH) analysis using the human genomic clones indicated that SIPA1 was indeed mapped to chromosome 11q13, most Likely to the 11q13.3 subregion. It was further indicated by double-color FISH that SIPA1 was located in the centromeric neighborhood of CCND1/PRAD1, a presumed BCL1 oncogene. (C) 1997 Academic Press