Anchorin CII (annexin V) was first characterized as a collagen-binding protein and later identified as the chick homologue of human endonexin II, a member of the annexin gene family. Its gene (anx5) structure and sequence have been investigated to provide insight into the evolution and regulation of this important protein, and to elucidate its putative role in signal transduction and cellular differentiation. Four chick genomic clones encoding anchorin CII were isolated and characterized by restriction analysis, Southern blotting and sequencing. The anchorin CII-encoding gene spans about 24 kb and consists of 13 exons ranging in length from 50 to 561 bp, interrupted by 12 introns of 94 bp to 7 kb. Its promoter sequence contained no TATA box, but did display a high G+C content and multiple Sp1-binding sites typical of 'housekeeping' genes. Potential binding sites for transcription factors in the 5'-upstream region are consistent with regulation of anx5 expression by mitogens, oncoproteins, steroids and possibly metals. Genomic Southern blotting confirmed that chick anx5 is present as a single-copy gene.