ANK3

Ankyrins are a family of proteins that are believed to link the integral membrane proteins to the underlying spectrin-actin cytoskeleton and play key roles in activities such as cell motility, activation, proliferation, contact, and the maintenance of specialized membrane domains. Multiple isoforms of ankyrin with different affinities for various target proteins are expressed in a tissue-specific, developmentally regulated manner. Most ankyrins are typically composed of three structural domains: an amino-terminal domain containing multiple ankyrin repeats; a central region with a highly conserved spectrin binding domain; and a carboxy-terminal regulatory domain which is the least conserved and subject to variation. Ankyrin 3 is an immunologically distinct gene product from ankyrins 1 and 2, and was originally found at the axonal initial segment and nodes of Ranvier of neurons in the central and peripheral nervous systems. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Feb 2011]

Ankyrin 3

In skeletal muscle, required for costamere localization of DMD and betaDAG1 (By similarity). Membrane-cytoskeleton linker. May participate in the maintenance/targeting of ion channels and cell adhesion molecules at the nodes of Ranvier and axonal initial segments. Regulates KCNA1 channel activity in function of dietary Mg2+ levels, and thereby contributes to the regulation of renal Mg2+ reabsorption (PubMed:23903368).
Isoform 5: May be part of a Golgi-specific membrane cytoskeleton in association with beta-spectrin.

Axonogenesis Source: BHF-UCL
Cellular response to magnesium ion Source: UniProtKB
Endoplasmic reticulum to Golgi vesicle-mediated transport Source: Reactome
Establishment of protein localization Source: UniProtKB
Golgi to plasma membrane protein transport Source: BHF-UCL
Magnesium ion homeostasis Source: UniProtKB
Maintenance of protein location in plasma membrane Source: BHF-UCL
Membrane assembly Source: BHF-UCL
Mitotic cytokinesis Source: BHF-UCL
Negative regulation of delayed rectifier potassium channel activity Source: UniProtKB
Neuromuscular junction development Source: BHF-UCL
Neuronal action potential Source: BHF-UCL
Plasma membrane organization Source: BHF-UCL
Positive regulation of cation channel activity Source: BHF-UCL
Positive regulation of cell communication by electrical coupling Source: BHF-UCL
Positive regulation of gene expression Source: BHF-UCL
Positive regulation of homotypic cell-cell adhesion Source: BHF-UCL
Positive regulation of membrane depolarization during cardiac muscle cell action potential Source: BHF-UCL
Positive regulation of membrane potential Source: BHF-UCL
Positive regulation of protein targeting to membrane Source: BHF-UCL
Positive regulation of sodium ion transmembrane transporter activity Source: BHF-UCL
Positive regulation of sodium ion transport Source: BHF-UCL
Protein localization to axon Source: UniProtKB
Protein localization to plasma membrane Source: BHF-UCL
Regulation of potassium ion transport Source: BHF-UCL
Signal transduction Source: InterPro

Sarcolemma; Postsynaptic cell membrane; T-tubule; Cytoskeleton; Lysosome; Axon. In skeletal muscle, localized at costameres and neuromuscular junctions. In macrophages, associated with lysosomes.
Isoform 5: Golgi apparatus; Cytoskeleton

Mental retardation, autosomal recessive 37 (MRT37): The disease is caused by variants affecting the gene represented in this entry. A homozygous deletion in ANK3 predicted to result in frameshift and premature truncation, has been shown to be the cause of moderate intellectual disability, an ADHD-like phenotype and behavioral problems in a consanguineous family (PubMed:23390136).A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT37 patients manifest delayed global development with speech delay, hypotonia, spasticity, and a sleep disorder. Severe behavioral abnormalities include aggression, hyperactivity, and grinding of the teeth.