ANK3
Encyclopedia
Ankyrin-3 also known as ankyrin-G, is a protein
from ankyrin
family that in humans is encoded by the ANK3 gene
.
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 neuron
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
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.
, a type of cardiac arrhythmia.
Other mutations in the ANK3 gene may be involved in the bipolar disorder
.
family of proteins that link the integral membrane proteins to the underlying spectrin
-actin
cytoskeleton
. 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.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
from ankyrin
Ankyrin
Ankyrins are a family of adaptor proteins that mediate the attachment of integral membrane proteins to the spectrin-actin based membrane skeleton. Ankyrins have binding sites for the beta subunit of spectrin and at least 12 families of integral membrane proteins...
family that in humans is encoded by the ANK3 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Function
The proteinProtein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
encoded by this gene, ankyrin-3 is an immunologically distinct gene product from ankyrins ANK1
ANK1
Ankyrin 1, erythrocytic, also known as ANK1, is a protein which 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 erythrocytes, but since has also been found in brain and...
and ANK2
ANK2
Ankyrin 2, neuronal, also known as ANK2, is a protein which in humans is encoded by the ANK2 gene.-Function:The protein encoded by this gene is required for targeting and stability of Na+/Ca++ exchanger 1 in cardiomyocytes. Mutations in this gene cause long QT syndrome 4...
, and was originally found at the axonal initial segment and nodes of Ranvier
Nodes of Ranvier
Myelin sheath gaps or nodes of Ranvier are the gaps formed between the myelin sheaths generated by different cells. A myelin sheath is a many-layered coating, largely composed of a fatty substance called myelin, that wraps around the axon of a neuron and very efficiently insulates it...
of neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
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
Neuromuscular junction
A neuromuscular junction is the synapse or junction of the axon terminal of a motor neuron with the motor end plate, the highly-excitable region of muscle fiber plasma membrane responsible for initiation of action potentials across the muscle's surface, ultimately causing the muscle to contract...
and the Nodes of Ranvier
Nodes of Ranvier
Myelin sheath gaps or nodes of Ranvier are the gaps formed between the myelin sheaths generated by different cells. A myelin sheath is a many-layered coating, largely composed of a fatty substance called myelin, that wraps around the axon of a neuron and very efficiently insulates it...
. 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
Axon hillock
The axon hillock is a specialized part of the cell body of a neuron that connects to the axon. As a result, the axon hillock is the last site in the soma where membrane potentials propagated from synaptic inputs are summated before being transmitted to the axon. For many years it was believed...
and for action potential
Action potential
In physiology, an action potential is a short-lasting event in which the electrical membrane potential of a cell rapidly rises and falls, following a consistent trajectory. Action potentials occur in several types of animal cells, called excitable cells, which include neurons, muscle cells, and...
firing.
Disease linkage
The ANK3 protein associates with the cardiac sodium channel Nav1.5 . 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 syndromeBrugada syndrome
The Brugada syndrome is a genetic disease that is characterised by abnormal electrocardiogram findings and an increased risk of sudden cardiac death. It is named by the Spanish cardiologists Pedro Brugada and Josep Brugada...
, a type of cardiac arrhythmia.
Other mutations in the ANK3 gene may be involved in the bipolar disorder
Bipolar disorder
Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...
.
Ankyrin family
The protein encoded by the ANK3 gene is a member of the ankyrinAnkyrin
Ankyrins are a family of adaptor proteins that mediate the attachment of integral membrane proteins to the spectrin-actin based membrane skeleton. Ankyrins have binding sites for the beta subunit of spectrin and at least 12 families of integral membrane proteins...
family of proteins that link the integral membrane proteins to the underlying spectrin
Spectrin
Spectrin is a cytoskeletal protein that lines the intracellular side of the plasma membrane of many cell types in pentagonal or hexagonal arrangements, forming a scaffolding and playing an important role in maintenance of plasma membrane integrity and cytoskeletal structure...
-actin
Actin
Actin is a globular, roughly 42-kDa moonlighting protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans...
cytoskeleton
Cytoskeleton
The cytoskeleton is a cellular "scaffolding" or "skeleton" contained within a cell's cytoplasm and is made out of protein. The cytoskeleton is present in all cells; it was once thought to be unique to eukaryotes, but recent research has identified the prokaryotic cytoskeleton...
. 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.