Gene structures, protein domains and signature logos of vertebrate annexins. (a) The organization of the regions of family-A annexin genes encoding the core carboxy-terminal region. Exon numbers are shown above each gene; introns are indicated by vertical lines and homologous intron positions by dotted lines. The structures of the nine human annexin genes not shown are the same as that of ANXA11. ANXA13 is thought to have the gene structure closest to the ancestral vertebrate annexin gene; ANXA7 is intermediate between ANXA13 and the others, and most closely resembles ANXA11 in its amino-terminal half and ANXA13 in its carboxy-terminal half. (b) Annexin proteins generally consist of a unique amino-terminal region (of 0-191 amino acids in vertebrates, for example) and a carboxy-terminal 'core region' of four homologous repeats, each 68-69 amino acids long and containing five α helices and a type-2 calcium binding site with the sequence GxGT-[38 residues]-D/E. The indicated residues Glu89 and Arg265 are considered key components of the putative calcium channel function. (c) Sequence logo for the core domain of vertebrate annexins, derived from a hidden Markov model  generated from an alignment of 311 amino acids from 200 sequences representing the 12 subfamilies in 50 vertebrate species. The full height of each residue stack reflects the conservation level at that position; the height of symbols within the stack indicates the relative frequency of each amino acid . The two parts of the calcium-binding motif (GxGT and D/E) are indicated by asterisks. The four repeats are aligned to the right on their calcium-binding motifs.