Ankyrin

ANK1, erythrocytic
Ribbon diagram of a fragment of the membrane-binding domain of ankyrin R.
Identifiers
Symbol	ANK1
Alt. symbols	AnkyrinR, Band2.1
Entrez	286
HUGO	492
OMIM	182900
PDB	1N11
RefSeq	NM_000037
UniProt	P16157
Other data
Locus	Chr. 8 p21.1-11.2

Ankyrin repeat
Identifiers
Symbol	Ank
Pfam	PF00023
InterPro	IPR002110
SMART	SM00248
PROSITE	PDOC50088
SCOP	1awc
SUPERFAMILY	1awc
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

ANK2, neuronal
Identifiers
Symbol	ANK2
Alt. symbols	AnkyrinB
Entrez	287
HUGO	493
OMIM	106410
RefSeq	NM_001148
UniProt	Q01484
Other data
Locus	Chr. 4 q25-q27

ANK3, node of Ranvier
Identifiers
Symbol	ANK3
Alt. symbols	AnkyrinG
Entrez	288
HUGO	494
OMIM	600465
RefSeq	NM_020987
UniProt	Q12955
Other data
Locus	Chr. 10 q21

Ankyrins are a family of adaptor 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 membrane proteins. This linkage is required to maintain the integrity of the plasma membranes and to anchor specific ion channels, ion exchangers and ion transporters in the plasma membrane. The name is derived from the Greek word for "fused".

Structure

Ankyrins contain four functional domains: an N-terminal domain that contains 24 tandem ankyrin repeats, 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.

Subtypes

Ankyrins are encoded by three genes (ANK1, ANK2 and ANK3) in mammals. Each gene in turn produces multiple proteins through alternative splicing.

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 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.

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

ANK2

Subsequently, ankyrinB proteins (products of the ANK2 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.

See also

• DARPin (designed ankyrin repeat protein), an engineered antibody mimetic based on the structure of ankyrin repeats

External links

• Ankyrins at the US National Library of Medicine Medical Subject Headings (MeSH)
• Proteopedia 1n11 Ankyrin-R