Ankyrin

Ankyrins are a family of adaptor proteins that mediate the attachment of integral membrane proteins to the spectrin-actin based membrane skeleton. Ankyrins have binding sites for the beta subunit of spectrin and at least 12 families of integral membrane proteins. This linkage is required to maintain the integrity of the plasma membranes and to anchor specific ion channels, ion exchangers and ion transporters in the plasma membrane.

Structure
Ankyrins contain four functional domains: an N-terminal domain that contains 24 tandem ankyrin repeats, a central domain that binds to spectrin, a death domain that binds to proteins involved in apoptosis, and a C-terminal regulatory domain that is highly variable between different ankyrin proteins.

Subtypes
Ankyrins are encoded by three genes (ANK1, ANK2 and ANK3) in mammals. Each gene in turn produces multiple proteins through alternative splicing.

ANK1
The ANK1 gene encodes the AnkyrinR proteins. AnkyrinR was first characterized in human erythrocytes, where this ankyrin was referred to as erythrocyte ankyrin or band2.1. AnkyrinR enables erythrocytes to resist shear forces experienced in the circulation. Individuals with reduced or defective ankyrinR have a form of hemolytic anemia termed hereditary spherocytosis. In erythrocytes, AnkyrinR links the membrane skeleton to the Cl-/HCO3- anion exchanger.

Ankyrin 1 links membrane receptor CD44 to the inositol triphosphate receptor and the cytoskeleton.

ANK2
Subsequently, ankyrinB proteins (products of the ANK2 gene ) were identified in brain and muscle. AnkyrinB and AnkyrinG proteins are required for the polarized distribution of many membrane proteins including the Na+/K+ ATPase, the voltage gated Na+ channel and the Na+/Ca2+ exchanger.

ANK3
AnkyrinG proteins (products of the ANK3 gene ) were identified in epithelial cells and neurons. A large-scale genetic analysis conducted in 2008 shows the possibility that ANK3 is involved in the bipolar disorder.