ANK2 : ankyrin 2

Description

The ANK2 (ankyrin 2) is a protein-coding gene located on chromosome 4.

The ANK2 gene provides instructions for making a protein called ankyrin-B. Ankyrin-B is part of a family of ankyrin proteins, which interact with many other types of proteins in cells throughout the body. Ankyrins help organize the cell‘s structural framework (the cytoskeleton) and link certain proteins that span the cell membrane to this framework. Additionally, ankyrins play key roles in important functions including cell movement (migration) and cell growth and division (proliferation).The ankyrin-B protein is active in many cell types, particularly in the brain and in heart (cardiac) muscle. This protein mainly interacts with ion channels and ion transporters, which are complexes of proteins that move charged atoms (ions) across cell membranes. In the heart, the flow of ions (such as sodium, potassium, and calcium) through ion channels and ion transporters generates the electrical signals that control the heartbeat and maintain a normal heart rhythm. Ankyrin-B ensures these channels and transporters are in their proper locations in the cell membrane so they can regulate the flow of ions into and out of cardiac muscle cells. In addition, ankyrin-B helps ensure that signaling molecules that regulate the activity of ion channels and ion transporters are in the proper location.

ANK2 plays a critical role in the proper localization and stabilization of ion channels and transporters within cell membranes, particularly in cardiomyocytes and striated muscle cells. In skeletal muscle, it ensures the correct placement of DMD and DCTN4 proteins, and is essential for the formation and/or stability of specific microtubules associated with costameres and neuromuscular junctions. Within cardiomyocytes, ANK2 coordinates the assembly of the Na/Ca exchanger (SLC8A1/NCX1), the Na/K ATPases (ATP1A1 and ATP1A2), and inositol 1,4,5-trisphosphate (InsP3) receptors at the sarcoplasmic reticulum/sarcolemma interface. Furthermore, ANK2 is required for the expression and proper targeting of SPTBN1 in neonatal cardiomyocytes, directly influencing the contraction rate of these cells. In the inner segments of rod photoreceptors, ANK2 is crucial for the coordinated expression of the Na/K ATPase, Na/Ca exchanger, and beta-2-spectrin (SPTBN1). Additionally, ANK2 is involved in endocytosis and intracellular protein transport. It interacts with phosphatidylinositol 3-phosphate (PI3P)-positive organelles and binds dynactin, promoting long-range cell motility. ANK2 recruits RABGAP1L to PI3P-positive early endosomes, where RABGAP1L inactivates RAB22A, facilitating polarized trafficking to the leading edge of migrating cells. The ANK2/RABGAP1L complex is essential for the polarized recycling of fibronectin receptor ITGA5 ITGB1 to the plasma membrane, enabling continuous directional cell migration.

ANK2 is also known as ANK-2, CFAP87, FAP87, LQT4, brank-2.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing