Ankyrin
Encyclopedia
Ankyrins are a family of adaptor proteins that mediate the attachment of integral membrane protein
s 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. This linkage is required to maintain the integrity of the plasma membranes and to anchor specific ion channel
s, ion exchangers and ion transporters in the plasma membrane.
s, a central domain that binds to spectrin
, a death domain that binds to proteins involved in apoptosis
, and a C-terminal regulatory domain that is highly variable between different ankyrin proteins.
, ANK2
and ANK3
) in mammals. Each gene in turn produces multiple proteins through alternative splicing
.
gene encodes the AnkyrinR proteins. AnkyrinR was first characterized in human erythrocytes, where this ankyrin was referred to as erythrocyte ankyrin or band2.1. AnkyrinR enables erythrocytes to resist shear forces experienced in the circulation. Individuals with reduced or defective ankyrinR have a form of hemolytic anemia
termed hereditary spherocytosis
. In erythrocytes, AnkyrinR links the membrane skeleton to the Cl-/HCO3- anion exchanger
.
Ankyrin 1 links membrane receptor CD44
to the inositol triphosphate receptor
and the cytoskeleton
.
gene) were identified in brain and muscle. AnkyrinB and AnkyrinG proteins are required for the polarized distribution of many membrane proteins including the Na+/K+ ATPase, the voltage gated Na+ channel and the Na+/Ca2+ exchanger.
gene) were identified in epithelial cells and neurons. A large-scale genetic analysis conducted in 2008 shows the possibility that ANK3
is involved in the bipolar disorder
.
Integral membrane protein
An integral membrane protein is a protein molecule that is permanently attached to the biological membrane. Proteins that cross the membrane are surrounded by "annular" lipids, which are defined as lipids that are in direct contact with a membrane protein...
s to the 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...
based membrane skeleton. Ankyrins have binding sites for the beta subunit of spectrin and at least 12 families of integral membrane proteins. This linkage is required to maintain the integrity of the plasma membranes and to anchor specific ion channel
Ion channel
Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...
s, ion exchangers and ion transporters in the plasma membrane.
Structure
Ankyrins contain four functional domains: an N-terminal domain that contains 24 tandem ankyrin repeatAnkyrin repeat
The ankyrin repeat is a 33-residue motif in proteins consisting of two alpha helices separated by loops, first discovered in signaling proteins in yeast Cdc10 and Drosophila Notch. Ankyrin repeats mediate protein–protein interactions and are among the most common structural motifs in known proteins...
s, a central domain that binds to 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...
, a death domain that binds to proteins involved in apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
, and a C-terminal regulatory domain that is highly variable between different ankyrin proteins.
Subtypes
Ankyrins are encoded by three genes (ANK1ANK1
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...
, 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 ANK3
ANK3
Ankyrin-3 , also known as ankyrin-G, is a protein from ankyrin family that in humans is encoded by the ANK3 gene.- Function :...
) in mammals. Each gene in turn produces multiple proteins through alternative splicing
Alternative splicing
Alternative splicing is a process by which the exons of the RNA produced by transcription of a gene are reconnected in multiple ways during RNA splicing...
.
ANK1
The ANK1ANK1
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...
gene encodes the AnkyrinR proteins. AnkyrinR was first characterized in human erythrocytes, where this ankyrin was referred to as erythrocyte ankyrin or band2.1. AnkyrinR enables erythrocytes to resist shear forces experienced in the circulation. Individuals with reduced or defective ankyrinR have a form of hemolytic anemia
Hemolytic anemia
Hemolytic anemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells , either in the blood vessels or elsewhere in the human body . It has numerous possible causes, ranging from relatively harmless to life-threatening...
termed hereditary spherocytosis
Hereditary spherocytosis
Hereditary spherocytosis is a genetically-transmitted form of spherocytosis, an auto-hemolytic anemia characterized by the production of red blood cells that are sphere-shaped rather than bi-concave disk shaped , and therefore more prone to hemolysis.-Symptoms:As in non-hereditary spherocytosis,...
. In erythrocytes, AnkyrinR links the membrane skeleton to the Cl-/HCO3- anion exchanger
Band 3
Anion Exchanger 1 or Band 3 is a phylogenetically preserved transport protein responsible for mediating the exchange of chloride for bicarbonate across a plasma membrane. Functionally similar members of the AE clade are AE2 and AE3.It is ubiquitous throughout the vertebrates...
.
Ankyrin 1 links membrane receptor CD44
CD44
The CD44 antigen is a cell-surface glycoprotein involved in cell–cell interactions, cell adhesion and migration. In humans, the CD44 antigen is encoded by the CD44 gene.- Tissue distribution and isoforms :...
to the inositol triphosphate receptor
Inositol triphosphate receptor
Inositol trisphosphate receptor is a membrane glycoprotein complex acting as Ca2+ channel activated by inositol trisphosphate . InsP3R is very diverse among organisms, and is necessary for the control of cellular and physiological processes including cell division, cell proliferation, apoptosis,...
and the 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...
.
ANK2
Subsequently, ankyrinB proteins (products of the ANK2ANK2
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...
gene) were identified in brain and muscle. AnkyrinB and AnkyrinG proteins are required for the polarized distribution of many membrane proteins including the Na+/K+ ATPase, the voltage gated Na+ channel and the Na+/Ca2+ exchanger.
ANK3
AnkyrinG proteins (products of the ANK3ANK3
Ankyrin-3 , also known as ankyrin-G, is a protein from ankyrin family that in humans is encoded by the ANK3 gene.- Function :...
gene) were identified in epithelial cells and neurons. A large-scale genetic analysis conducted in 2008 shows the possibility that ANK3
ANK3
Ankyrin-3 , also known as ankyrin-G, is a protein from ankyrin family that in humans is encoded by the ANK3 gene.- Function :...
is 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...
.
See also
- DARPinDARPinDARPins are genetically engineered antibody mimetic proteins typically exhibiting highly specific and high-affinity target protein binding. They are derived from natural ankyrin proteins and consist of at least three, usually four or five repeat motifs of these proteins...
(designed ankyrin repeat protein), an engineered antibody mimetic based on the structure of ankyrin repeats