ANK1

Ankyrins are a family of proteins that link the integral membrane proteins to the underlying spectrin-actin cytoskeleton and play key roles in activities such as cell motility, activation, proliferation, contact and the maintenance of specialized membrane domains. Multiple isoforms of ankyrin with different affinities for various target proteins are expressed in a tissue-specific, developmentally regulated manner. Most ankyrins are typically composed of three structural domains: an amino-terminal domain containing multiple ankyrin repeats; a central region with a highly conserved spectrin binding domain; and a carboxy-terminal regulatory domain which is the least conserved and subject to variation. Ankyrin 1, the prototype of this family, was first discovered in the erythrocytes, but since has also been found in brain and muscles. Mutations in erythrocytic ankyrin 1 have been associated in approximately half of all patients with hereditary spherocytosis. Complex patterns of alternative splicing in the regulatory domain, giving rise to different isoforms of ankyrin 1 have been described. Truncated muscle-specific isoforms of ankyrin 1 resulting from usage of an alternate promoter have also been identified. [provided by RefSeq, Dec 2008]

Ankyrin 1

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.

Cytoskeleton organization Source: UniProtKB
Endoplasmic reticulum to Golgi vesicle-mediated transport Source: BHF-UCL
Exocytosis Source: UniProtKB
Maintenance of epithelial cell apical/basal polarity Source: UniProtKB
Positive regulation of organelle organization Source: Ensembl
Protein localization to plasma membrane Source: BHF-UCL
Signal transduction Source: InterPro

Isoform Er1: Cytoskeleton. Probably the other erythrocyte (Er) isoforms, are located near the surface of erythrocytic plasma membrane.
Isoform Mu17: Membrane; 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

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.

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.