Function
Ankyrins (ANK) are proteins which mediate the attachment of membrane proteins to the membrane skeleton. ANKRD2 belongs to the conserved muscle ankyrin repeat protein (MARP) family.Also known as Arpp or stretch responsive muscle ANKRD2 gene contains 9 exons and spans about 12 kb. The 5-prime flanking region contains a TATA box and binding motifs for the muscle-specific transcription factors MYOD and for NF-kappa-B.
Kemp et.al cloned mouse Ankrd2 and obtained a partial human ANKRD2 cDNA. Northern blot and PCR analyses detected expression of mouse Ankrd2 only in tissues containing striated muscle. In situ hybridization of mouse embryos showed that Ankrd2 expression was restricted to the myotome of somites at day 9.5. At later developmental stages, Ankrd2 expression was stronger in outer back muscles than intercostal muscles, and it was not expressed in heart. See also
In mammals ANK is encoded by 3 genes: ANK1, ANK2 and ANK3.
- ANK1 or ankyrin-R is found in erythrocytes, brain and muscle.
- ANK2 or ankyrin-B is found in brain and muscle.
- ANK3 or ankyrin-G is found in the nervous system and associates with Na channels.
Gankyrin (GANK) is an oncoprotein which is a component of the 19S cap of the proteasome. GANK contains ankyrin repeats.
Disease
Mutations in erythrocyte ANK1 are associated with spherocytosis. Mutations in ANK2 are associated with cardiac arrhythmia syndrome. Mutations in ANK3 are associated with bipolar disorder.
Relevance
GANK is overexpressed in hepatocellular carcinoma.
Structural highlights
Ankyrin contains four domains: the N terminal which contains 24 ankyrin repeats, a spectrin-binding domain, a death domain which binds to proteins involved in apoptosis and a C terminal regulatory domain. The full-length 328-amino acid mouse protein contains an ATP/GTP-binding domain in its N-terminal half and an ankyrin repeat region in its C-terminal half. It also has a nuclear localization signal, 2 protein-destabilizing PEST sequences, and 2 phosphorylation sites. The ankyrin repeat is a protein-protein interaction motif. It is a 33 residue segment consisting of a helix-loop-helix motif. The long ankyrin repeat in human ankyrin-R contains 12 ankyrin repeats (residues 402-827) and is called D34 region..
