Annexin V is a phospholipase A2 and protein kinase C inhibitory protein with calcium channel activity and an undefined role in cellular signal transduction, inflammation, growth and differentiation. Three genomic clones for human annexin V (ANX5) were characterized by restriction analysis, Southern blotting and sequencing. ANX5 spans at least 29 kb of the human genome and contains 13 exons ranging in length from 44 to 513 bp and 12 introns from 232 bp to 8 kb. The absence of a typical TATA box and the presence of high G+C content and Sp1-binding sites in its promoter characterize it as a 'housekeeping' gene and account for its broad pattern of expression. Potential binding sites for cis-regulatory elements identified in the 5'-upstream region of annexin V are consistent with its known regulation by oncogenic and growth-related stimuli. ANX5, like its chick homologue, differs from the genes encoding annexins I, II and III in features of its promoter and in the size of its exons 1, 2 and 3 in ways that may impart individuality to its regulation and function.