ANKs
Definition: Ankyrins are peripheral membrane proteins thought to interconnect integral proteins with the spectrin-based membrane skeleton.
Members
| ANK1 | ANK2 | ANK3 |
Erythrocytic ankyrin, also known as ankyrin-1 coded by ANK1 (MIM.182900) and brain ankyrin, also known as ankyrin-2 (ANK2) (MIM.106410) are distinct forms.
Ankyrin has been shown to associate with the voltage-dependent sodium channel in vitro and to colocalize with this molecule at nodes of Ranvier, axonal initial segments, and the neuromuscular junction.
Ankyrin and spectrin were first discovered as binding partners in the membrane skeleton of human erythrocytes.
Mutations in genes encoding these proteins cause hereditary spherocytosis.
Recent advances reveal that ankyrin and spectrin are required for organization of a surprisingly diverse set of proteins, including ion channels and cell adhesion molecules that are localized in specialized membrane domains in many cell types.
New insights into the cell biology of ankyrin and spectrin reveal that these proteins actively participate in assembly of specialized membrane domains in addition to their conventional maintenance role as scaffolding proteins.
Recently described inherited human diseases due to defects in spectrin or ankyrin include spinocerebellar ataxia type 5 and a cardiac arrhythmia, termed sick sinus syndrome with bradycardia or ankyrin-B syndrome.
Pathology
ANK1 mutations in hereditary spherocytosis (MIM.182900) (8p11.2)
ANK2 mutations in autosomal dominant type 4 long QT syndrome (MIM.600919)
ANK2 mutations in sick sinus syndrome with bradycardia (MIM.600919)
References
Bennett V, Healy J. Organizing the fluid membrane bilayer: diseases linked to spectrin and ankyrin. Trends Mol Med. 2007 Dec 13; PMID: #18083066#