Ankyrins are a family of proteins that mediate the attachment of

integral membrane protein An integral, or intrinsic, membrane protein (IMP) is a type of membrane protein that is permanently attached to the biological membrane. All transmembrane proteins can be classified as IMPs, but not all IMPs are transmembrane proteins. IMPs comp ...

s to the

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 mem ...

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 ...

based membrane cytoskeleton. 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 membrane The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...

s and to anchor specific

ion channel Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by Gating (electrophysiol ...

s, ion exchangers and

ion transporter In biology, an ion transporter is a transmembrane protein that moves ions (or other small molecules) across a biological membrane to accomplish many different biological functions, including cellular communication, maintaining homeostasis, energy ...

s in the plasma membrane. The name is derived from the

Greek Greek may refer to: Anything of, from, or related to Greece, a country in Southern Europe: *Greeks, an ethnic group *Greek language, a branch of the Indo-European language family **Proto-Greek language, the assumed last common ancestor of all kno ...

word ἄγκυρα (''ankyra'') for "anchor".

Structure

Ankyrins contain four functional domains: an

N-terminal The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...

domain that contains 24 tandem ankyrin repeats, a central domain that binds to

, a death domain that binds to proteins involved in

apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...

, and a

C-terminal The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When t ...

regulatory domain that is highly variable between different ankyrin proteins.

Membrane protein recognition

The 24 tandem ankyrin repeats are responsible for the recognition of a wide range of membrane proteins. These 24 repeats contain 3 structurally distinct binding sites ranging from repeat 1-14. These binding sites are quasi-independent of each other and can be used in combination. The interactions the sites use to bind to membrane proteins are non-specific and consist of: hydrogen bonding, hydrophobic interactions and electrostatic interactions. These non-specific interactions give ankyrin the property to recognise a large range of proteins as the sequence doesn't have to be conserved, just the properties of the

amino acids Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the Proteinogenic amino acid, 22 α-amino acids incorporated into p ...

. The quasi-independence means that if a binding site is not used, it won't have a large effect on the overall binding. These two properties in combination give rise to large repertoire of proteins ankyrin can recognise.

Subtypes

Ankyrins are encoded by three genes ( ANK1,

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 locali ...

and ANK3) in mammals. Each gene in turn produces multiple proteins through

alternative splicing Alternative splicing, alternative RNA splicing, or differential splicing, is an alternative RNA splicing, splicing process during gene expression that allows a single gene to produce different splice variants. For example, some exons of a gene ma ...

ANK1

The ANK1 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 or haemolytic anaemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells (RBCs), either in the blood vessels (intravascular hemolysis) or elsewhere in the human body (extravascular). This most commonl ...

termed

hereditary spherocytosis Hereditary spherocytosis (HS) is a congenital hemolytic disorder wherein a genetic genetic mutation, mutation coding for a structural membrane protein phenotype causes the red blood cells to be sphere-shaped (spherocytosis), rather than the norma ...

. In erythrocytes, AnkyrinR links the membrane skeleton to the Cl⁻/HCO₃⁻ anion exchanger. Ankyrin 1 links membrane receptor

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 on chromosome 11. CD44 has been referred to as HCAM (homing cell adhes ...

to the

inositol triphosphate receptor Inositol trisphosphate receptor (InsP3R) is a membrane glycoprotein complex acting as a calcium channel, Ca2+ channel activated by inositol trisphosphate (InsP3). InsP3R is very diverse among organisms, and is necessary for the control of cell ...

and the

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 ...

. It has been suggested that Ankyrin 1 interacts with KAHRP (shown via selective pull-downs, SPR and

ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay is a solid-phase type of enzyme immunoassay (EIA) to detect the presence of ...

ANK2

Subsequently, ankyrinB proteins (products of the

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 ANK3 gene) were identified in epithelial cells and neurons. A large-scale genetic analysis conducted in 2008 shows the possibility that ANK3 is involved in

bipolar disorder Bipolar disorder (BD), previously known as manic depression, is a mental disorder characterized by periods of Depression (mood), depression and periods of abnormally elevated Mood (psychology), mood that each last from days to weeks, and in ...

References

External links

* * Ankyrin-R {{Cytoskeletal proteins Peripheral membrane proteins Biology of bipolar disorder it:Anchirina