Annexins are calcium-dependent phospholipid-binding proteins. 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 first annexin to be identified was annexin VII (synexin) from the bovine adrenal medulla by creutz and team in 19781.
Annexins are grouped under 5 major classes (A-E), the 12 annexins which are commonly found in vertebrates are classified under annexin A family and named as annexins A1-A13 (or ANXA1-ANXA13), leaving A12 not assigned in the official nomenclature. Annexins outside vertebrates are classified under family B (in invertebrates), C (in fungi and under groups of unicellular eukaryotes), D (in plants), and E (in protists).
Each annexin is composed of two principal domains: the divergent NH2-terminal “head” and the conserved COOH-terminal protein core. The COOH-terminal protein core harbors the Ca2+ and membrane binding sites and is responsible for mediating the canonical membrane binding properties. An annexin core comprises four (in annexin A6 eight) segments of internal and inter annexin homology that are easily identified in a linear sequence alignment. It forms a highly alpha helical and tightly packed disk with a slight curvature and two principle sides. The more convex side contains Ca2+ binding sites, the so-called type II and type III sites, and faces the membrane when an annexin is associated peripherally with phospholipids2. Many annexins undergo posttranslational modifications viz., phosphorylation and myristoylation1.
Mode of action
The process of membrane aggregation requires the self association of annexin molecules where Ca2+ plays an important role. In case of synexin (annexin VII) at lower concentration of Ca2+ level it is soluble, if the concentration of Ca2+ increase it results in binding of annexins to membrane further increase in Ca2+ levels results in membrane aggregation and fusion.
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 channels1.
1. Moss SE, Morgan RO (2004). The Annexins. Genome Biol., 5(4): 219.
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