Annexins are traditionally thought of as calcium-dependent phospholipid-binding proteins, but recent work suggests a more complex set of functions. More than a thousand proteins of the annexin superfamily have been identified in major eukaryotic phyla, but annexins are absent from yeasts and prokaryotes. The unique annexin core domain is made up of four similar repeats | Protein family review The annexins Stephen E Moss and Reg O Morgan Addresses Division of Cell Biology Institute of Ophthalmology 11-43 Bath Street London EC1V 9EL UK. Department of Biochemistry and Molecular Biology Edificio Santiago Gascon Faculty of Medicine University of Oviedo E-33006 Oviedo Spain. Correspondence Stephen E Moss. E-mail Published 31 March 2004 Genome Biology 2004 5 219 The electronic version of this article is the complete one and can be found online at http 2004 5 4 219 2004 BioMed Central Ltd Summary Annexins are traditionally thought of as calcium-dependent phospholipid-binding proteins but recent work suggests a more complex set of functions. More than a thousand proteins of the annexin superfamily have been identified in major eukaryotic phyla but annexins are absent from yeasts and prokaryotes. The unique annexin core domain is made up of four similar repeats approximately 70 amino acids long each of which usually contains a characteristic type 2 motif for binding calcium ions. Animal and fungal annexins also have non-homologous amino-terminal domains of varying length and sequence which are responsible for the distinct localizations and specialized functions of the proteins through post-translational modification and binding to other proteins. Annexins interact with various cell-membrane components that are involved in the structural organization of the cell intracellular signaling by enzyme modulation and ion fluxes growth control and they can act as atypical calcium channels. Analysis of site-specific conservation in the core domain suggests a role for certain buried residues in the calcium-channel activity of vertebrate annexins and in the structural stability of their core domains. Evolutionarily significant differences between subfamilies are preferentially localized to accessible sites on the protein surface that determine membrane binding and interactions with cytosolic proteins. Gene organization
