STIM-Orai Channels

STIM-Orai channels have recently been identified as the underlying molecular mechanism of store-operated calcium entry (SOCE). SOCE allows rapid Ca²⁺ efflux from the endoplasmic reticulum (ER), following the emptying of intracellular Ca²⁺ stores.

STIM (stromal interaction molecule) proteins, STIM1 and STIM2, serve as ER Ca²⁺ sensors. They contain N'-terminal Ca²⁺-sensing EF-hand domains and are localized to the tubular ER. Following Ca²⁺ store depletion, STIMs rapidly cluster and relocalize to the plasma membrane-adjacent ER regions, where they oligomerize and form 'puncta'.

Orai proteins, Orai1, Orai2 and Orai3, are STIM binding partners that form the pore of the channel. Orai proteins are uniformly distributed in the plasma membrane and exist as dimers in the resting state. STIM activation induces tetramerization of Orai proteins and subsequent STIM-Orai colocalization, which forms the active store-operated calcium channel.

STIM-Orai Channel Gene Data