ANK1, erythrocytic
Ribbon diagram of a fragment of the membrane-binding domain of ankyrin R.[1]
Identifiers
Symbol	ANK1
Alt. symbols	AnkyrinR, Band2.1
NCBI gene	286
HGNC	492
OMIM	182900
PDB	1N11
RefSeq	NM_000037
UniProt	P16157
Other data
Locus	Chr. 8p21.1-11.2
Search for Structures Swiss-model Domains InterPro

Ankyrins are a family of proteins that mediate the attachment ofintegral membrane proteins to thespectrin-actin based membrane cytoskeleton.^[2] 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 theplasma membranes and to anchor specificion channels,ion exchangers andion transporters in the plasma membrane. The name is derived from theGreek wordἄγκυρα (ankyra) for "anchor".

Ankyrins contain four functionaldomains: anN-terminal domain that contains 24 tandemankyrin repeats, a central domain that binds tospectrin, a death domain that binds to proteins involved inapoptosis, and aC-terminal regulatory domain that is highly variable between different ankyrin proteins.^[2]

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 theamino acids. 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.

Ankyrins are encoded by three genes (ANK1,ANK2 andANK3) in mammals. Each gene in turn produces multiple proteins throughalternative splicing.

TheANK1 gene encodes the AnkyrinR proteins. AnkyrinR was first characterized in human erythrocytes, where this ankyrin was referred to as erythrocyte ankyrin or band2.1.^[3] AnkyrinR enables erythrocytes to resist shear forces experienced in the circulation. Individuals with reduced or defective ankyrinR have a form ofhemolytic anemia termedhereditary spherocytosis.^[4] In erythrocytes, AnkyrinR links the membrane skeleton to theCl⁻/HCO₃⁻ anion exchanger.^[5]

Ankyrin 1 links membrane receptorCD44 to theinositol triphosphate receptor and thecytoskeleton.^[6]

It has been suggested that Ankyrin 1 interacts withKAHRP (shown via selective pull-downs,SPR andELISA).^[7]

Subsequently, ankyrinB proteins (products of theANK2 gene^[8]) 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.

AnkyrinG proteins (products of theANK3 gene^[9]) were identified in epithelial cells and neurons. A large-scale genetic analysis conducted in 2008 shows the possibility thatANK3 is involved inbipolar disorder.^[10][11]

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

• Ankyrins at the U.S. National Library of MedicineMedical Subject Headings (MeSH)
• Proteopedia1n11 Ankyrin-R

• Genes on human chromosome 8
• Genes on human chromosome 4
• Genes on human chromosome 10
• Peripheral membrane proteins
• Biology of bipolar disorder

• Articles with short description
• Short description matches Wikidata
• Protein pages needing a picture