MGP Database

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MGP002739

UniProt Annotations

Entry Information
Gene Nameryanodine receptor 2 (cardiac)
Protein EntryRYR2_HUMAN
UniProt IDQ92736
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=1; IsoId=Q92736-1; Sequence=Displayed; Name=2; IsoId=Q92736-2; Sequence=VSP_005953;
Developmental StageExpressed in myometrium during pregnancy. {ECO:0000269|PubMed:9148749}.
DiseaseArrhythmogenic right ventricular dysplasia, familial, 2 (ARVD2) [MIM:600996]: A congenital heart disease characterized by infiltration of adipose and fibrous tissue into the right ventricle and loss of myocardial cells, resulting in ventricular and supraventricular arrhythmias. {ECO:0000269|PubMed:11159936}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseVentricular tachycardia, catecholaminergic polymorphic, 1, with or without atrial dysfunction and/or dilated cardiomyopathy (CPVT1) [MIM:604772]: 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. {ECO:0000269|PubMed:11157710, ECO:0000269|PubMed:12093772, ECO:0000269|PubMed:12106942, ECO:0000269|PubMed:15046072, ECO:0000269|PubMed:15046073, ECO:0000269|PubMed:15466642, ECO:0000269|PubMed:15544015}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DomainThe calcium release channel activity resides in the C- terminal region while the remaining part of the protein resides in the cytoplasm. {ECO:0000305}.
FunctionCalcium 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. {ECO:0000269|PubMed:10830164, ECO:0000269|PubMed:20056922}.
InductionBy TGFB1. {ECO:0000269|PubMed:9148749}.
InteractionP68106:FKBP1B; NbExp=2; IntAct=EBI-1170425, EBI-6693977; Q00987:MDM2; NbExp=2; IntAct=EBI-1170425, EBI-389668;
MiscellaneousChannel 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). {ECO:0000250}.
PtmChannel 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. {ECO:0000269|PubMed:10830164, ECO:0000269|PubMed:20056922}.
PtmPhosphorylation at Ser-2031 by PKA enhances the response to lumenal calcium. {ECO:0000250}.
Sequence CautionSequence=CAH71369.1; Type=Miscellaneous discrepancy; Note=Erroneous gene model prediction.; Evidence={ECO:0000305}; Sequence=CAH71393.1; Type=Miscellaneous discrepancy; Note=Erroneous gene model prediction.; Evidence={ECO:0000305}; Sequence=CAH73918.1; Type=Miscellaneous discrepancy; Note=Erroneous gene model prediction.; Evidence={ECO:0000305}; Sequence=CAI14440.1; Type=Miscellaneous discrepancy; Note=Erroneous gene model prediction.; Evidence={ECO:0000305}; Sequence=CAI15350.1; Type=Miscellaneous discrepancy; Note=Erroneous gene model prediction.; Evidence={ECO:0000305}; Sequence=CAI15936.1; Type=Miscellaneous discrepancy; Note=Erroneous gene model prediction.; Evidence={ECO:0000305}; Sequence=CAI22065.1; Type=Miscellaneous discrepancy; Note=Erroneous gene model prediction.; Evidence={ECO:0000305};
SimilarityBelongs to the ryanodine receptor (TC 1.A.3.1) family. RYR2 subfamily. {ECO:0000305}.
SimilarityContains 3 B30.2/SPRY domains. {ECO:0000255|PROSITE- ProRule:PRU00548}.
SimilarityContains 5 MIR domains. {ECO:0000255|PROSITE- ProRule:PRU00131}.
Subcellular LocationSarcoplasmic reticulum membrane {ECO:0000269|PubMed:10830164}; Multi-pass membrane protein {ECO:0000269|PubMed:10830164}. Membrane {ECO:0000305|PubMed:10830164}; Multi-pass membrane protein {ECO:0000305|PubMed:10830164}. Note=The number of predicted transmembrane domains varies between orthologs, but both N- terminus and C-terminus seem to be cytoplasmic. {ECO:0000250}.
SubunitHomotetramer. 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. {ECO:0000250, ECO:0000269|PubMed:10830164, ECO:0000269|PubMed:18650434}.
Tissue SpecificityDetected in heart muscle (at protein level). Heart muscle, brain (cerebellum and hippocampus) and placenta. {ECO:0000269|PubMed:10830164, ECO:0000269|PubMed:9607712}.
Web ResourceName=Wikipedia; Note=Ryanodine receptor entry; URL="http://en.wikipedia.org/wiki/Ryanodine_receptor";
Web ResourceName=Wikipedia; Note=RYR2 entry; URL="http://en.wikipedia.org/wiki/RYR2";
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