Calcium release activated channel
| Calcium release-activated calcium channel protein 1 (olf186-F) | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | Orai | ||||||||
| Pfam | PF07856 | ||||||||
| InterPro | IPR012446 | ||||||||
| TCDB | 1.A.52 | ||||||||
| OPM superfamily | 467 | ||||||||
| OPM protein | 4hkr | ||||||||
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| Available protein structures: | |
|---|---|
| Pfam | structures |
| PDB | RCSB PDB; PDBe; PDBj |
| PDBsum | structure summary |
Calcium release-activated channels (CRAC) are specialized plasma membrane Ca2+ ion channels. When calcium ions (Ca2+) are depleted from the endoplasmic reticulum (a major store of Ca2+) of mammalian cells, the CRAC channel is activated to slowly replenish the level of calcium in the endoplasmic reticulum. The Ca2+ Release-activated Ca2+ (CRAC) Channel (CRAC-C) Family (TC# 1.A.52) is a member of the Cation Diffusion Facilitator (CDF) Superfamily. These proteins typically have between 4 and 6 transmembrane α-helical spanners (TMSs). The 4 TMS CRAC channels arose by loss of 2TMSs from 6TMS CDF carriers, an example of 'reverse' evolution'.
There are several proteins that belong to the CRAC-C family. A list of the currently classified members of the CRAC-C family can be found in the Transporter Classification Database. This classification is based on sequence similarity which also happens to coincide with functional and structural similarities between homologues.
Almost all CRAC homologues are about 250 residues long, but some are up to 100 residues longer (e.g., the Drosophila melanogaster Olf186-F, TC# 1.A.52.1.5).
The plasma membrane protein "Orai" (ORAI1 and ORAI2 in humans) forms the pore of the CRAC channel. The protein ORAI1 is a structural component of the CRAC calcium channel. ORAI1 interacts with the STIM1 protein. STIM1 is a transmembrane protein of the endoplasmic reticulum (ER). STIM1 can sense the concentration of Ca2+ inside the ER. When the concentration of Ca2+ inside the ER becomes low, STIM1 proteins aggregate and interact with ORAI1 located in the cell surface membrane. When the concentration of Ca2+ inside the ER approaches an upper set point, another protein, SARAF (TMEM66) associates with STIM1 to inactivate the store-operated calcium channel (SOCE).
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