8.A.28 The Ankyrin (Ankyrin) Family
Ankyrin-B (Ank2, ankyrin-2; 3924 aas) interacts directly with and is required for targeting and stability of the Na+/Ca2+ exchanger 1 in cardiomyocytes (Cunha et al., 2007). It is also required for assembly of the Na+,K+ ATPase and various membrane receptors and transporters (Liu et al., 2008). Exon organization and alternative splicing give rise to at least 30 ANK2 mRNA transcripts. The ANK2 gene consists of 53 exons spanning ~560 kbps (Cunha et al., 2008).
Ankyrins are a family of adaptor proteins which associate with a group of structurally diverse ion channels and transporters including the Na/Ca exchanger (Li et al., 1993; Mohler et al., 2003; Mohler et al., 2005), the Na/K ATPase, voltage-gated Na+ channels, and the anion exchanger. Multiple lines of evidence predict a role for ankyrin polypeptides in the proper localization and stability of the Na/Ca exchanger at the cardiomyocyte plasma membrane. Ankyrin polypeptides directly bind to the cardiac Na/Ca exchanger with high affinity (Li et al., 1993; Mohler et al., 2005).
Ankyrins have N-terminal Ank repeat units that are homologous to those of channel proteins in families 1.A.4 and 1.A.1. These repeats of about 100 residues, comprise of ankyrin B. They generally attach integral membrane proteins to cytoskeletal proteins. They are regulated by phosphorylation. Defects in Ank2 cause sick sinus syndrome with bradycardia (also called "human sinus node dysfunction (SND)) (Le Scouarnec et al., 2008).