ID:RYR2_HUMAN DESCRIPTION: RecName: Full=Ryanodine receptor 2; Short=RYR-2; Short=RyR2; Short=hRYR-2; AltName: Full=Cardiac muscle ryanodine receptor; AltName: Full=Cardiac muscle ryanodine receptor-calcium release channel; AltName: Full=Type 2 ryanodine receptor; FUNCTION: Calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytoplasm 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+) 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. SUBUNIT: Homotetramer. Can also form heterotetramers with RYR1 and RYR3 (By similarity). Interacts with FKBP1A and FKBP1B; these interactions may stabilize the channel in its closed state and prevent Ca(2+) leaks. Interacts with CALM and S100A1; these interactions regulate channel activity. Identified in a complex composed of RYR2, FKBP1B, PKA catalytic subunit, PRKAR2A, AKAP6, and the protein phosphatases PP2A and PP1. Interacts directly with FKBP1B, PKA, PP1 and PP2A. INTERACTION: Q00987:MDM2; NbExp=2; IntAct=EBI-1170425, EBI-389668; SUBCELLULAR LOCATION: Sarcoplasmic reticulum membrane; Multi-pass membrane protein. Membrane; Multi-pass membrane protein (Probable). Note=The number of predicted transmembrane domains varies between orthologs, but both N-terminus and C-terminus seem to be cytoplasmic (By similarity). TISSUE SPECIFICITY: Detected in heart muscle (at protein level). Heart muscle, brain (cerebellum and hippocampus) and placenta. DEVELOPMENTAL STAGE: Expressed in myometrium during pregnancy. INDUCTION: By TGFB1. DOMAIN: The calcium release channel activity resides in the C- terminal region while the remaining part of the protein resides in the cytoplasm (Probable). PTM: 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. DISEASE: Defects in RYR2 are the cause of familial arrhythmogenic right ventricular dysplasia type 2 (ARVD2) [MIM:600996]; also known as arrhythmogenic right ventricular cardiomyopathy 2 (ARVC2). ARVD is an autosomal dominant disease characterized by partial degeneration of the myocardium of the right ventricle, electrical instability, and sudden death. It is clinically defined by electrocardiographic and angiographic criteria; pathologic findings, replacement of ventricular myocardium with fatty and fibrous elements, preferentially involve the right ventricular free wall. DISEASE: Defects in RYR2 are the cause of catecholaminergic polymorphic ventricular tachycardia type 1 (CPVT1) [MIM:604772]; also known as stress-induced polymorphic ventricular tachycardia (VTSIP). CPVT1 is an autosomal dominant form of arrhythmogenic disorder characterized by stress-induced, bidirectional ventricular tachycardia that may degenerate into cardiac arrest and cause sudden death. MISCELLANEOUS: Channel activity is modulated by the alkaloid ryanodine that binds to the open Ca-release channel with high affinity. At low concentrations, ryanodine maintains the channel in an open conformation. High ryanodine concentrations inhibit channel activity. Channel activity is regulated by calmodulin (CALM). The calcium release is activated by increased cytoplasmic calcium levels, by nitric oxyde (NO), caffeine and ATP. Channel activity is inhibited by magnesium ions, possibly by competition for calcium binding sites (By similarity). SIMILARITY: Belongs to the ryanodine receptor (TC 1.A.3.1) family. RYR2 subfamily. SIMILARITY: Contains 3 B30.2/SPRY domains. SIMILARITY: Contains 5 MIR domains. SEQUENCE CAUTION: Sequence=CAH71369.1; Type=Miscellaneous discrepancy; Note=Erroneous gene model prediction; Sequence=CAH71393.1; Type=Miscellaneous discrepancy; Note=Erroneous gene model prediction; Sequence=CAH73918.1; Type=Miscellaneous discrepancy; Note=Erroneous gene model prediction; Sequence=CAI14440.1; Type=Miscellaneous discrepancy; Note=Erroneous gene model prediction; Sequence=CAI15350.1; Type=Miscellaneous discrepancy; Note=Erroneous gene model prediction; Sequence=CAI15936.1; Type=Miscellaneous discrepancy; Note=Erroneous gene model prediction; Sequence=CAI22065.1; Type=Miscellaneous discrepancy; Note=Erroneous gene model prediction; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/RYR2"; WEB RESOURCE: Name=Wikipedia; Note=Ryanodine receptor entry; URL="http://en.wikipedia.org/wiki/Ryanodine_receptor"; WEB RESOURCE: Name=Wikipedia; Note=RYR2 entry; URL="http://en.wikipedia.org/wiki/RYR2";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Pfam Domains: PF00520 - Ion transport protein PF00622 - SPRY domain PF01365 - RIH domain PF02026 - RyR domain PF02815 - MIR domain PF06459 - Ryanodine Receptor TM 4-6 PF08454 - RyR and IP3R Homology associated PF08709 - Inositol 1,4,5-trisphosphate/ryanodine receptor
SCOP Domains: 48371 - ARM repeat 100909 - IP3 receptor type 1 binding core, domain 2 47473 - EF-hand 49899 - Concanavalin A-like lectins/glucanases 82109 - MIR domain
ModBase Predicted Comparative 3D Structure on Q92736
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0001666 response to hypoxia GO:0002027 regulation of heart rate GO:0003143 embryonic heart tube morphogenesis GO:0003220 left ventricular cardiac muscle tissue morphogenesis GO:0003300 cardiac muscle hypertrophy GO:0005513 detection of calcium ion GO:0006811 ion transport GO:0006816 calcium ion transport GO:0006874 cellular calcium ion homeostasis GO:0007275 multicellular organism development GO:0010460 positive regulation of heart rate GO:0010881 regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion GO:0010882 regulation of cardiac muscle contraction by calcium ion signaling GO:0014808 release of sequestered calcium ion into cytosol by sarcoplasmic reticulum GO:0014850 response to muscle activity GO:0019722 calcium-mediated signaling GO:0030509 BMP signaling pathway GO:0031000 response to caffeine GO:0034220 ion transmembrane transport GO:0035584 calcium-mediated signaling using intracellular calcium source GO:0035994 response to muscle stretch GO:0051209 release of sequestered calcium ion into cytosol GO:0051284 positive regulation of sequestering of calcium ion GO:0051480 regulation of cytosolic calcium ion concentration GO:0051775 response to redox state GO:0055085 transmembrane transport GO:0055117 regulation of cardiac muscle contraction GO:0060048 cardiac muscle contraction GO:0060070 canonical Wnt signaling pathway GO:0060401 cytosolic calcium ion transport GO:0060402 calcium ion transport into cytosol GO:0070296 sarcoplasmic reticulum calcium ion transport GO:0070588 calcium ion transmembrane transport GO:0071313 cellular response to caffeine GO:0071872 cellular response to epinephrine stimulus GO:0072599 establishment of protein localization to endoplasmic reticulum GO:0086005 ventricular cardiac muscle cell action potential GO:0086029 Purkinje myocyte to ventricular cardiac muscle cell signaling GO:0086064 cell communication by electrical coupling involved in cardiac conduction GO:0097050 type B pancreatic cell apoptotic process GO:0098735 positive regulation of the force of heart contraction GO:0098904 regulation of AV node cell action potential GO:0098907 regulation of SA node cell action potential GO:0098910 regulation of atrial cardiac muscle cell action potential GO:0098911 regulation of ventricular cardiac muscle cell action potential GO:1901896 positive regulation of calcium-transporting ATPase activity GO:1903779 regulation of cardiac conduction
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
