ANK3
Description
The ANK3 (ankyrin 3) is a protein-coding gene located on chromosome 10.
Ankyrin-3 (ANK-3), also known as Ankyrin-G, is a protein from ankyrin family that in humans is encoded by the ANK3 gene.
The protein encoded by this gene, ankyrin-3 is an immunologically distinct gene product from ankyrins ANK1 and ANK2, and was originally found at the axonal initial segment and nodes of Ranvier of neurons in the central and peripheral nervous systems. Alternatively spliced variants may be expressed in other tissues. Although multiple transcript variants encoding several different isoforms have been found for this gene, the full-length nature of only two have been characterized. Within the nervous system, ankyrin-G is specifically localized to the neuromuscular junction, the axon initial segment and the Nodes of Ranvier. Within the nodes of Ranvier where action potentials are actively propagated, ankyrin-G has long been thought to be the intermediate binding partner to neurofascin and voltage-gated sodium channels. The genetic deletion of ankyrin-G from multiple neuron types has shown that ankyrin-G is required for the normal clustering of voltage-gated sodium channels at the axon hillock and for action potential firing.
The ANK3 protein associates with the cardiac sodium channel Nav1.5 (SCN5A). Both proteins are highly expressed at ventricular intercalated disc and T-tubule membranes in cardiomyocytes. A mutation in the Nav1.5 protein blocks interaction with ANK3 binding and therefore disrupts surface expression of Nav1.5 in cardiomyocytes resulting in Brugada syndrome, a type of cardiac arrhythmia.
Ankyrin-3 (ANK3) is a membrane-cytoskeleton linker protein that plays a role in the maintenance and targeting of ion channels and cell adhesion molecules at the nodes of Ranvier and axonal initial segments. In skeletal muscle, ANK3 is required for the costamere localization of dystrophin (DMD) and beta-dystroglycan (betaDAG1). ANK3 regulates the activity of the potassium channel KCNA1 in response to dietary magnesium levels, contributing to the regulation of renal magnesium reabsorption. ANK3 is essential for intracellular adhesion and junctional conductance in myocytes, potentially by stabilizing the abundance of the gap junction protein GJA1/CX43 and promoting the localization of PKP2, GJA1/CX43, and SCN5A/Nav1.5 to cell-cell junctions.
ANK3 is also known as ANKYRIN-G, MRT37.
Associated Diseases
- Intellectual developmental disorder, autosomal recessive 37
- ANK3-related intellectual disability-sleep disturbance syndrome
