InterPro domain: IPR014752

This superfamily represents the C-terminal domain of arrestin, and Vacuolar protein sorting protein 26 (VPS26), consisting of an immunoglobulin-like beta-sandwich structure.

Arrestins comprise a family of closely-related proteins. In addition to the inactivation of G protein-coupled receptors, arrestins have been implicated in the endocytosis of receptors and cross talk with other signalling pathways. S-Arrestin (retinal S-antigen) is a major protein of the retinal rod outer segments. It interacts with photo-activated phosphorylated rhodopsin, inhibiting or 'arresting' its ability to interact with transducin [ 1 ]. Beta-arrestin-1 and -2, which regulate the function of beta-adrenergic receptors by binding to their phosphorylated forms, impairing their capacity to activate G(S) proteins; Cone photoreceptors C-arrestin (arrestin-X) [ 2 ], which could bind to phosphorylated red/green opsins; and Drosophila phosrestins I and II, which undergo light-induced phosphorylation, and probably play a role in photoreceptor transduction [ 3 , 4 , 5 ]. The crystal structure of bovine retinal arrestin comprises two domains of antiparallel beta-sheets connected through a hinge region and one short alpha-helix on the back of the amino-terminal fold [ 6 ].

VPS26 assembles into a multimeric complex with other vacuolar protein sorting proteins (VPSs) and plays a role in vesicular protein sorting [ 7 ].

1. Arresting G-protein coupled receptor activity. Curr. Biol. 3, 683-6
2. The arrestin superfamily: cone arrestins are a fourth family. FEBS Lett. 362, 247-55
3. Arrestin-subtypes in insect antennae. Cell. Signal. 5, 69-80
4. Beta-arrestin2, a novel member of the arrestin/beta-arrestin gene family. J. Biol. Chem. 267, 17882-90
5. A 49-kilodalton phosphoprotein in the Drosophila photoreceptor is an arrestin homolog. Science 248, 483-6
6. X-ray crystal structure of arrestin from bovine rod outer segments. Nature 391, 918-21
7. Human orthologs of yeast vacuolar protein sorting proteins Vps26, 29, and 35: assembly into multimeric complexes. Mol. Biol. Cell 11, 4105-16