InterPro domain: IPR033480

Cache is an extracellular domain that is predicted to have a role in small-molecule recognition in a wide range of proteins, including the animal dihydropyridine-sensitive voltage-gated Ca2 channel alpha-2delta subunit, and various bacterial chemotaxis receptors. The name Cache comes from CAlcium channels and CHEmotaxis receptors.

The Cache domain, also known as the extracellular PAS domain, consists of an N-terminal part with three predicted strands and an alpha-helix, and a C-terminal part with a strand dyad followed by a relatively unstructured region. The N-terminal portion of the Cache domain containing the three predicted strands could form a sheet analogous to that present in the core of the PAS domain structure. Cache domains are particularly widespread in bacteria, such as Vibrio cholerae. The animal calcium channel alpha-2delta subunits might have acquired a part of their extracellular domains from a bacterial source [ 1 ]. The Cache domain appears to have arisen from the GAF-PAS fold, despite their divergent functions [ 2 , 3 ].

This entry represents the single Cache domain 2 (sCache_2), which contains the long N-terminal helix domain [ 4 ].

1. Cache - a signaling domain common to animal Ca(2+)-channel subunits and a class of prokaryotic chemotaxis receptors. Trends Biochem. Sci. 25, 535-7
2. Regulatory potential, phyletic distribution and evolution of ancient, intracellular small-molecule-binding domains. J. Mol. Biol. 307, 1271-92
3. Cache Domains That are Homologous to, but Different from PAS Domains Comprise the Largest Superfamily of Extracellular Sensors in Prokaryotes. PLoS Comput. Biol. 12, e1004862