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Target intelligence / Profile preview
Calcium Release-Activated Calcium Channel (CRAC)
- Target
- CRAC
- Molecular classification
- Ion channel, Calcium channel, Orai protein, STIM protein, Plasma membrane protein
01
Overview
Calcium release-activated calcium (CRAC) channels are highly selective plasma membrane ion channels that mediate the influx of Ca(^{2+}) into cells in response to depletion of intracellular calcium stores. They are composed of Orai proteins (Orai1 being the primary pore-forming subunit) and STIM proteins (STIM1 acting as an ER-resident Ca(^{2+}) sensor). Upon store depletion, STIM1 interacts with Orai proteins to open the channel. CRAC channels play a crucial role in immune cell activation, neuronal signaling, and other cellular processes. Dysfunction or mutations in CRAC components can lead to immunodeficiency and other disorders, making them a therapeutic target for immune-related diseases, chronic pain, and possibly cancer.
- Other names
- Store-operated calcium entrySOCECalcium release–activated calcium currentORAI1STIM1
02
Mechanism of action
Modulation of calcium influx through CRAC channels
03
Biological functions
Calcium signalingImmune response regulationT cell activationMast cell degranulationGene expression regulationNeuronal signaling
04
Disease associations
Severe combined immunodeficiency (SCID)Musculoskeletal disordersAutoimmune diseasesChronic painCancer
05
Safety considerations
Potential for immunosuppressionOff-target effects on other calcium channelsConstitutive channel opening leading to cellular toxicity
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