Ankyrin-1

Tissue distribution

The protein encoded by this gene, Ankyrin 1, is the prototype of the ankyrin family, was first discovered in erythrocytes, but since has also been found in brain and muscles.

Genetics

Complex patterns of alternative splicing in the regulatory domain, giving rise to different isoforms of ankyrin 1 have been described, however, the precise functions of the various isoforms are not known. Alternative polyadenylation accounting for the different sized erythrocytic ankyrin 1 mRNAs, has also been reported. Truncated muscle-specific isoforms of ankyrin 1 resulting from usage of an alternate promoter have also been identified.

Disease linkage

Mutations in erythrocytic ankyrin 1 have been associated in approximately half of all patients with hereditary spherocytosis.

ANK1 shows altered methylation and expression in Alzheimer's disease. A gene expression study of postmortem brains has suggested ANK1 interacts with interferon-γ signalling.

Function

The ANK1 protein belongs to the ankyrin family that are believed to 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 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.

The small ANK1 (sAnk1) protein splice variants makes contacts with obscurin, a giant protein surrounding the contractile apparatus in striated muscle.

Interactions

ANK1 has been shown to interact with T-cell lymphoma invasion and metastasis-inducing protein 1, Titin, RHAG and OBSCN.

References

References

1. (March 1990). "cDNA sequence for human erythrocyte ankyrin". Proceedings of the National Academy of Sciences of the United States of America.
2. "Entrez Gene: ANK1 ankyrin 1, erythrocytic".
3. (September 2014). "Alzheimer's disease: early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci". Nature Neuroscience.
4. (September 2014). "Methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer's disease". Nature Neuroscience.
5. (2014). "Differential Co-Expression between α-Synuclein and IFN-γ Signaling Genes across Development and in Parkinson's Disease". PLOS ONE.
6. (November 2007). "Mapping the binding site on small ankyrin 1 for obscurin". The Journal of Biological Chemistry.
7. (July 2000). "Ankyrin-Tiam1 interaction promotes Rac1 signaling and metastatic breast tumor cell invasion and migration". The Journal of Cell Biology.
8. (February 2003). "The hydrophilic domain of small ankyrin-1 interacts with the two N-terminal immunoglobulin domains of titin". The Journal of Biological Chemistry.
9. (July 2003). "Rh-RhAG/ankyrin-R, a new interaction site between the membrane bilayer and the red cell skeleton, is impaired by Rh(null)-associated mutation". The Journal of Biological Chemistry.
10. (March 2003). "Obscurin is a ligand for small ankyrin 1 in skeletal muscle". Molecular Biology of the Cell.