InterPro domain: IPR037104

The annexins (or lipocortins) are a family of proteins that bind to phospholipids in a calcium-dependent manner [ 1 ]. The 12 annexins common to vertebrates are classified in the annexin A family and named as annexins A1-A13 (or ANXA1-ANXA13), leaving A12 unassigned in the official nomenclature. Annexins outside vertebrates are classified into families B (in invertebrates), C (in fungi and some groups of unicellular eukaryotes), D (in plants), and E (in protists) [ 2 ]. Annexins are absent from yeasts and prokaryotes [ 3 ].

Most eukaryotic species have 1-20 annexin (ANX) genes. All annexins share a core domain made up of four similar repeats, each approximately 70 amino acids long [ 3 ]. Each individual annexin repeat (sometimes referred to as endonexin folds) is folded into five alpha-helices, and in turn are wound into a right-handed super-helix; they usually contain a characteristic 'type 2' motif for binding calcium ions with the sequence 'GxGT-[38 residues]-D/E'. Animal and fungal annexins also have variable amino-terminal domains. The core domains of most vertebrate annexins have been analysed by X-ray crystallography, revealing conservation of their secondary and tertiary structures despite only 45-55% amino-acid identity among individual members. The four repeats pack into a structure that resembles a flattened disc, with a slightly convex surface on which the Ca2+ -binding loops are located and a concave surface at which the amino and carboxyl termini come into close apposition.

Annexins are traditionally thought of as calcium-dependent phospholipid-binding proteins, but recent work suggests a more complex set of functions. The family has been linked with inhibition of phospholipase activity, exocytosis and endocytosis, signal transduction, organisation of the extracellular matrix, resistance to reactive oxygen species and DNA replication [ 3 ].

1. Amino acid sequence analysis of the annexin super-gene family of proteins. Eur. J. Biochem. 198, 749-60
2. The annexins. Genome Biol. 5, 219
3. Identification of the first fungal annexin: analysis of annexin gene duplications and implications for eukaryotic evolution. J. Mol. Evol. 47, 531-43