STIM-Orai Channels

Supporting information

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.

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Gene Species Gene Symbol Gene Accession No. Protein Accession No.
STIM1 Human STIM1 NM_003156 Q13586
Mouse Stim1 NM_009287 P70302
Rat Stim1 NM_001108496 P84903
STIM2 Human STIM2 NM_020860 Q9P246
Mouse Stim2 NM_001081103 P83093
Rat Stim2 NM_001105750 XP_223454
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