Ankyrin

Protein family

Ankyrins are a family of proteins that mediate the attachment of integral membrane proteins to the spectrin actin based membrane cytoskeleton. 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. The name is derived from the Greek word ἄγκυρα (ankyra) for "anchor".

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. 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. It has been suggested that Ankyrin 1 interacts with KAHRP (shown via selective pull downs, SPR and ELISA).

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.

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 bipolar disorder.