RYR2
Developmental stage
Expressed in myometrium during pregnancy.
Domain
The calcium release channel activity resides in the C-terminal region while the remaining part of the protein resides in the cytoplasm.
Function
Cytosolic calcium-activated calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytosol and thereby plays a key role in triggering cardiac muscle contraction. Aberrant channel activation can lead to cardiac arrhythmia. In cardiac myocytes, calcium release is triggered by increased Ca(2+) cytosolic levels due to activation of the L-type calcium channel CACNA1C. The calcium channel activity is modulated by formation of heterotetramers with RYR3. Required for cellular calcium ion homeostasis. Required for embryonic heart development.
Involvement in disease
Ventricular tachycardia, catecholaminergic polymorphic, 1, with or without atrial dysfunction and/or dilated cardiomyopathy
CPVT1
An arrhythmogenic disorder characterized by stress-induced, bidirectional ventricular tachycardia that may degenerate into cardiac arrest and cause sudden death. Patients present with recurrent syncope, seizures, or sudden death after physical activity or emotional stress. CPVT1 inheritance is autosomal dominant.
None
The disease is caused by variants affecting the gene represented in this entry.
Ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome
VACRDS
An autosomal dominant arrhythmogenic disorder characterized by syncope, cardiac arrest and/or sudden unexpected death, often in association with physical exertion or acute emotional stress. Patients who survive manifest polymorphic ventricular tachycardia and ventricular fibrillation. Unlike typical catecholaminergic ventricular tachycardia, arrhythmias are not reproducible on exercise stress testing or adrenaline challenge.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Channel activity is modulated by phosphorylation. Phosphorylation at Ser-2808 and Ser-2814 increases the open probability of the calcium channel. Phosphorylation is increased in failing heart, leading to calcium leaks and increased cytoplasmic Ca(2+) levels.
Phosphorylation at Ser-2031 by PKA enhances the response to lumenal calcium.
Sequence Similarities
Belongs to the ryanodine receptor (TC 1.A.3.1) family. RYR2 subfamily.
Tissue Specificity
Detected in heart muscle (at protein level). Heart muscle, brain (cerebellum and hippocampus) and placenta.
Cellular localization
- Sarcoplasmic reticulum membrane
- Multi-pass membrane protein
Alternative names
Ryanodine receptor 2, RYR-2, RyR2, hRYR-2, Cardiac muscle ryanodine receptor, Cardiac muscle ryanodine receptor-calcium release channel, Type 2 ryanodine receptor, RYR2