Ankyrin-3 (ANK-3), also known as ankyrin-G, is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

from

ankyrin 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 mem ...

family that in humans is encoded by the ''ANK3''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

Function

The

encoded by this gene, ankyrin-3 is an immunologically distinct gene product from ankyrins

ANK1 Ankyrin 1, also known as ANK-1, and erythrocyte ankyrin, is a protein that in humans is encoded by the ''ANK1'' gene. Tissue distribution The protein encoded by this gene, Ankyrin 1, is the prototype of the ankyrin family, was first discovered in ...

and

ANK2 Ankyrin-2, also known as Ankyrin-B, and Brain ankyrin, is a protein which in humans is encoded by the ''ANK2'' gene. Ankyrin-2 is ubiquitously expressed, but shows high expression in cardiac muscle. Ankyrin-2 plays an essential role in the localiz ...

, and was originally found at the

axonal initial segment An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action p ...

and

nodes of Ranvier In neuroscience and anatomy, nodes of Ranvier ( ), also known as myelin-sheath gaps, occur along a myelinated axon where the axolemma is exposed to the extracellular space. Nodes of Ranvier are uninsulated and highly enriched in ion channels, al ...

neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...

s 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 A neuromuscular junction (or myoneural junction) is a chemical synapse between a motor neuron and a muscle fiber. It allows the motor neuron to transmit a signal to the muscle fiber, causing muscle contraction. Muscles require innervation to ...

, the axon initial segment and the

Nodes of Ranvier In neuroscience and anatomy, nodes of Ranvier ( ), also known as myelin-sheath gaps, occur along a myelinated axon where the axolemma is exposed to the extracellular space. Nodes of Ranvier are uninsulated and highly enriched in ion channels, al ...

. Within the nodes of Ranvier where

action potentials An action potential occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, c ...

are actively propagated, ankyrin-G has long been thought to be the intermediate binding partner to

neurofascin Neurofascin is a protein that in humans is encoded by the ''NFASC'' gene. Function Neurofascin is an L1 family immunoglobulin cell adhesion molecule (see L1CAM) involved in axon subcellular targeting and synapse formation during neural develop ...

and voltage-gated

sodium channels Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's membrane. They belong to the superfamily of cation channels and can be classified according to the trigger that opens the chann ...

. The genetic deletion of ankyrin-G from multiple neuron types has shown that ankyrin-G is required for the normal clustering of voltage-gated

at the

axon hillock The axon hillock is a specialized part of the cell body (or soma) of a neuron that connects to the axon. It can be identified using light microscopy from its appearance and location in a neuron and from its sparse distribution of Nissl substance. ...

and for

action potential An action potential occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, ...

firing.

Disease linkage

The ANK3 protein associates with the cardiac sodium channel Na_v1.5 (). Both proteins are highly expressed at ventricular intercalated disc and T-tubule membranes in

cardiomyocyte Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle th ...

s. A mutation in the Na_v1.5 protein blocks interaction with ANK3 binding and therefore disrupts surface expression of Na_v1.5 in cardiomyocytes resulting in

Brugada syndrome Brugada syndrome (BrS) is a genetic disorder in which the electrical activity of the heart is abnormal due to channelopathy. It increases the risk of abnormal heart rhythms and sudden cardiac death. Those affected may have episodes of syncope ...

, a type of cardiac

arrhythmia Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adults ...

. Other mutations in the ANK3 gene may be involved in the

bipolar disorder Bipolar disorder, previously known as manic depression, is a mental disorder characterized by periods of depression and periods of abnormally elevated mood that last from days to weeks each. If the elevated mood is severe or associated with ...

and

intellectual disability Intellectual disability (ID), also known as general learning disability in the United Kingdom and formerly mental retardation,Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010). is a generalized neurodevelopmental disorder characterized by signifi ...

Ankyrin family

The protein encoded by the ANK3 gene is a member of the

family of proteins that link the integral membrane proteins to the underlying

spectrin Spectrin is a cytoskeletal protein that lines the intracellular side of the plasma membrane in eukaryotic cells. Spectrin forms pentagonal or hexagonal arrangements, forming a scaffold and playing an important role in maintenance of plasma membr ...

actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of over ...

cytoskeleton The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...

. Ankyrins play key roles in activities such as cell motility, activation, proliferation, contact and the maintenance of specialized membrane domains. 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.

References

External links

* * {{Cytoskeletal proteins Biology of bipolar disorder

Function

Disease linkage

Ankyrin family

References

Further reading

External links