ANK1
Domain
The 55 kDa regulatory domain is involved in regulating binding of SPTB/spectrin (beta chain) and SLC4A1/erythrocyte membrane protein band 3.
The ANK repeat region forms a spiral around a large central cavity and is involved in binding of ion transporters. Adopts a T-shaped arrangement, in the ankyrin-1 complex, in which ANK 1-5 repeats are orthogonal to ANK 6-24 repeats, with the peptide binding groove of ANK 1-5 repeats oriented toward the membrane (PubMed:35835865). The rearrangement of the ANK 1-5 repeats orients the canonical protein binding groove to directly face the membrane, to interact the membrane-embedded targets RHCE and AQP1 (PubMed:35835865).
The tandem configuration of the two ZU5 and the UPA domains forms a structural supramodule termed ZZU. ZU5-1 mediates interaction with beta-spectrin, and the ZU5-1/UPA interface is required for ankyrin's function other than binding to spectrin (By similarity).
Function
Component of the ankyrin-1 complex, a multiprotein complex involved in the stability and shape of the erythrocyte membrane (PubMed:35835865). Attaches integral membrane proteins to cytoskeletal elements; binds to the erythrocyte membrane protein band 4.2, to Na-K ATPase, to the lymphocyte membrane protein GP85, and to the cytoskeletal proteins fodrin, tubulin, vimentin and desmin. Erythrocyte ankyrins also link spectrin (beta chain) to the cytoplasmic domain of the erythrocytes anion exchange protein; they retain most or all of these binding functions.
Isoform Mu17
Together with obscurin in skeletal muscle may provide a molecular link between the sarcoplasmic reticulum and myofibrils.
Involvement in disease
Spherocytosis 1
SPH1
A form of spherocytosis, a hematologic disorder leading to chronic hemolytic anemia and characterized by numerous abnormally shaped erythrocytes which are generally spheroidal. SPH1 is characterized by severe hemolytic anemia. Inheritance can be autosomal dominant or autosomal recessive. Patients with homozygous mutations have a more severe disorder.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Regulated by phosphorylation.
Palmitoylated.
Hydroxylated by HIF1AN at several asparagine and 1 aspartate residue within ANK repeat region. Hydroxylation seems to increase the conformational stability of this region and may also modulate protein-protein interactions mediated by the ANK repeat region.
(Microbial infection) Probably cleaved by P.falciparum SERA6; the cleavage probably causes the disruption of the actin cytoskeleton and the rupture of the erythrocyte cell membrane releasing the merozoites.
Tissue Specificity
Isoform Mu17, isoform Mu18, isoform Mu19 and isoform Mu20 are expressed in skeletal muscle. Isoform Br21 is expressed in brain.
Cellular localization
- Isoform Er1
- Cytoplasm
- Cytoskeleton
- Probably the other erythrocyte (Er) isoforms, are located near the surface of erythrocytic plasma membrane.
- Isoform Mu17
- Membrane
- Cytoplasm
- Myofibril
- Sarcomere
- M line
- Colocalizes with OBSCN isoform 3/obscurin at the M line in differentiated skeletal muscle cells.
- Isoform Mu18
- Sarcoplasmic reticulum
- Isoform Mu19
- Sarcoplasmic reticulum
- Isoform Mu20
- Sarcoplasmic reticulum
Alternative names
ANK, ANK1, Ankyrin-1, ANK-1, Ankyrin-R, Erythrocyte ankyrin