ID RYR2_HUMAN Reviewed; 4967 AA. AC Q92736; Q15411; Q546N8; Q5T3P2; DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot. DT 05-OCT-2010, sequence version 3. DT 27-MAR-2024, entry version 236. DE RecName: Full=Ryanodine receptor 2 {ECO:0000305}; DE Short=RYR-2; DE Short=RyR2; DE Short=hRYR-2; DE AltName: Full=Cardiac muscle ryanodine receptor; DE AltName: Full=Cardiac muscle ryanodine receptor-calcium release channel; DE AltName: Full=Type 2 ryanodine receptor; GN Name=RYR2 {ECO:0000312|HGNC:HGNC:10484}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND ALTERNATIVE SPLICING. RC TISSUE=Heart muscle; RX PubMed=8809036; DOI=10.1042/bj3180477; RA Tunwell R.E.A., Wickenden C., Bertrand B.M.A., Shevchenko V.I., Walsh M.B., RA Allen P.D., Lai F.A.; RT "The human cardiac muscle ryanodine receptor-calcium release channel: RT identification, primary structure and topological analysis."; RL Biochem. J. 318:477-487(1996). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS CPVT1 GLN-176; PRO-433; RP ILE-2386 AND MET-2504. RX PubMed=11159936; DOI=10.1093/hmg/10.3.189; RA Tiso N., Stephan D.A., Nava A., Bagattin A., Devaney J.M., Stanchi F., RA Larderet G., Brahmbhatt B., Brown K., Bauce B., Muriago M., Basso C., RA Thiene G., Danieli G.A., Rampazzo A.; RT "Identification of mutations in the cardiac ryanodine receptor gene in RT families affected with arrhythmogenic right ventricular cardiomyopathy type RT 2 (ARVD2)."; RL Hum. Mol. Genet. 10:189-194(2001). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 9-87 AND 533-681, DEVELOPMENTAL STAGE, AND RP INDUCTION BY TGFB1. RC TISSUE=Heart muscle, and Myometrium; RX PubMed=9148749; DOI=10.1042/bj3220777; RA Awad S.S., Lamb H.K., Morgan J.M., Dunlop W., Gillespie J.I.; RT "Differential expression of ryanodine receptor RyR2 mRNA in the non- RT pregnant and pregnant human myometrium."; RL Biochem. J. 322:777-783(1997). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 4292-4479, AND TISSUE SPECIFICITY. RC TISSUE=Cerebellum, and Hippocampus; RX PubMed=9607712; DOI=10.1016/s0306-4522(97)00612-x; RA Martin C., Chapman K.E., Seckl J.R., Ashley R.H.; RT "Partial cloning and differential expression of ryanodine receptor/calcium- RT release channel genes in human tissues including the hippocampus and RT cerebellum."; RL Neuroscience 85:205-216(1998). RN [6] RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH FKBP1B; PP1; PP2A AKAP6 AND PKA, RP INTERACTION WITH FKBP1B; PKA; PP1 AND PP2A, SUBCELLULAR LOCATION, TISSUE RP SPECIFICITY, MUTAGENESIS OF SER-2808, AND PHOSPHORYLATION AT SER-2808. RX PubMed=10830164; DOI=10.1016/s0092-8674(00)80847-8; RA Marx S.O., Reiken S., Hisamatsu Y., Jayaraman T., Burkhoff D., RA Rosemblit N., Marks A.R.; RT "PKA phosphorylation dissociates FKBP12.6 from the calcium release channel RT (ryanodine receptor): defective regulation in failing hearts."; RL Cell 101:365-376(2000). RN [7] RP INTERACTION WITH CALM AND S100A1. RX PubMed=18650434; DOI=10.1074/jbc.m804432200; RA Wright N.T., Prosser B.L., Varney K.M., Zimmer D.B., Schneider M.F., RA Weber D.J.; RT "S100A1 and calmodulin compete for the same binding site on ryanodine RT receptor."; RL J. Biol. Chem. 283:26676-26683(2008). RN [8] RP FUNCTION, AND PHOSPHORYLATION AT SER-2808 AND SER-2814. RX PubMed=20056922; DOI=10.1161/circresaha.109.203836; RA Neef S., Dybkova N., Sossalla S., Ort K.R., Fluschnik N., Neumann K., RA Seipelt R., Schondube F.A., Hasenfuss G., Maier L.S.; RT "CaMKII-dependent diastolic SR Ca2+ leak and elevated diastolic Ca2+ levels RT in right atrial myocardium of patients with atrial fibrillation."; RL Circ. Res. 106:1134-1144(2010). RN [9] RP REVIEW. RX PubMed=11805843; DOI=10.1038/415198a; RA Bers D.M.; RT "Cardiac excitation-contraction coupling."; RL Nature 415:198-205(2002). RN [10] RP REVIEW. RX PubMed=19482609; DOI=10.2741/3591; RA Currie S.; RT "Cardiac ryanodine receptor phosphorylation by CaM Kinase II: keeping the RT balance right."; RL Front. Biosci. 14:5134-5156(2009). RN [11] RP REVIEW. RX PubMed=21472222; DOI=10.3892/mmr_00000240; RA Ozawa T.; RT "Modulation of ryanodine receptor Ca2+ channels."; RL Mol. Med. Report. 3:199-204(2010). RN [12] RP REVIEW. RX PubMed=20961976; DOI=10.1101/cshperspect.a003996; RA Lanner J.T., Georgiou D.K., Joshi A.D., Hamilton S.L.; RT "Ryanodine receptors: structure, expression, molecular details, and RT function in calcium release."; RL Cold Spring Harb. Perspect. Biol. 2:E3996-E3996(2010). RN [13] {ECO:0007744|PDB:4JKQ} RP X-RAY CRYSTALLOGRAPHY (2.39 ANGSTROMS) OF 1-606, AND CHARACTERIZATION OF RP VARIANT CPVT1 PHE-419. RX PubMed=25372681; DOI=10.1107/s1399004714020343; RA Borko L., Bauerova-Hlinkova V., Hostinova E., Gasperik J., Beck K., RA Lai F.A., Zahradnikova A., Sevcik J.; RT "Structural insights into the human RyR2 N-terminal region involved in RT cardiac arrhythmias."; RL Acta Crystallogr. D 70:2897-2912(2014). RN [14] RP VARIANTS CPVT1 LEU-2246; SER-2474; LYS-4104 AND CYS-4497. RX PubMed=11208676; DOI=10.1161/01.cir.103.2.196; RA Priori S.G., Napolitano C., Tiso N., Memmi M., Vignati G., Bloise R., RA Sorrentino V.V., Danieli G.A.; RT "Mutations in the cardiac ryanodine receptor gene (hRyR2) underlie RT catecholaminergic polymorphic ventricular tachycardia."; RL Circulation 103:196-200(2001). RN [15] RP VARIANTS CPVT1 SER-2328; ARG-4201 AND PHE-4653, AND VARIANT ARG-2958. RX PubMed=11157710; DOI=10.1161/01.cir.103.4.485; RA Laitinen P.J., Brown K.M., Piippo K., Swan H., Devaney J.M., Brahmbhatt B., RA Donarum E.A., Marino M., Tiso N., Viitasalo M., Toivonen L., Stephan D.A., RA Kontula K.; RT "Mutations of the cardiac ryanodine receptor (RyR2) gene in familial RT polymorphic ventricular tachycardia."; RL Circulation 103:485-490(2001). RN [16] RP VARIANTS CPVT1 LEU-2246; ASP-2311; SER-2474; PHE-3778; SER-3946; SER-3946; RP LYS-4104; CYS-4497; ILE-4771; MET-4867; ASP-4895 AND LYS-4950, AND VARIANT RP VACRDS GLY-4860. RX PubMed=12093772; DOI=10.1161/01.cir.0000020013.73106.d8; RA Priori S.G., Napolitano C., Memmi M., Colombi B., Drago F., Gasparini M., RA DeSimone L., Coltorti F., Bloise R., Keegan R., Cruz Filho F.E.S., RA Vignati G., Benatar A., DeLogu A.; RT "Clinical and molecular characterization of patients with catecholaminergic RT polymorphic ventricular tachycardia."; RL Circulation 106:69-74(2002). RN [17] RP VARIANTS CPVT1 GLN-176; TRP-420; PRO-433; ILE-2386; CYS-2392 AND MET-2504. RX PubMed=12106942; DOI=10.1016/s0735-1097(02)01946-0; RA Bauce B., Rampazzo A., Basso C., Bagattin A., Daliento L., Tiso N., RA Turrini P., Thiene G., Danieli G.A., Nava A.; RT "Screening for ryanodine receptor type 2 mutations in families with effort- RT induced polymorphic ventricular arrhythmias and sudden death: early RT diagnosis of asymptomatic carriers."; RL J. Am. Coll. Cardiol. 40:341-349(2002). RN [18] RP VARIANTS CPVT1 ILE-2306; LEU-4902 AND GLN-4959. RX PubMed=14571276; DOI=10.1038/sj.ejhg.5201061; RA Laitinen P.J., Swan H., Kontula K.; RT "Molecular genetics of exercise-induced polymorphic ventricular RT tachycardia: identification of three novel cardiac ryanodine receptor RT mutations and two common calsequestrin 2 amino-acid polymorphisms."; RL Eur. J. Hum. Genet. 11:888-891(2003). RN [19] RP VARIANTS CPVT1 SER-164; LEU-414; PHE-419; THR-2403; CYS-4499; THR-4510; RP ARG-4671 AND VAL-4848. RX PubMed=15466642; DOI=10.1161/01.cir.0000144471.98080.ca; RA Choi G., Kopplin L.J., Tester D.J., Will M.L., Haglund C.M., Ackerman M.J.; RT "Spectrum and frequency of cardiac channel defects in swimming-triggered RT arrhythmia syndromes."; RL Circulation 110:2119-2124(2004). RN [20] RP VARIANTS CPVT1 ILE-4504 AND ALA-4880. RX PubMed=15046072; RA Bagattin A., Veronese C., Rampazzo A., Danieli G.A.; RT "Gene symbol: RYR2. Disease: effort-induced polymorphic ventricular RT arrhythmias."; RL Hum. Genet. 114:404-404(2004). RN [21] RP VARIANTS CPVT1 PRO-2387 AND PRO-4607. RX PubMed=15046073; RA Bagattin A., Veronese C., Rampazzo A., Danieli G.A.; RT "Gene symbol: RYR2. Disease: effort-induced polymorphic ventricular RT arrhythmias."; RL Hum. Genet. 114:405-405(2004). RN [22] RP VARIANTS CPVT1 TRP-420; LEU-2246; SER-4097; LYS-4146; PRO-4158 AND RP CYS-4497. RX PubMed=15544015; DOI=10.4065/79.11.1380; RA Tester D.J., Spoon D.B., Valdivia H.H., Makielski J.C., Ackerman M.J.; RT "Targeted mutational analysis of the RyR2-encoded cardiac ryanodine RT receptor in sudden unexplained death: a molecular autopsy of 49 medical RT examiner/coroner's cases."; RL Mayo Clin. Proc. 79:1380-1384(2004). RN [23] RP VARIANTS CPVT1 GLN-176; LEU-414; PHE-419; ALA-466; THR-2403; PHE-3800; RP THR-4124; CYS-4499; THR-4510; THR-4556; VAL-4848 AND GLN-4959. RX PubMed=16188589; DOI=10.1016/j.hrthm.2005.07.012; RA Tester D.J., Kopplin L.J., Will M.L., Ackerman M.J.; RT "Spectrum and prevalence of cardiac ryanodine receptor (RyR2) mutations in RT a cohort of unrelated patients referred explicitly for long QT syndrome RT genetic testing."; RL Heart Rhythm 2:1099-1105(2005). RN [24] RP VARIANT GLU-4955. RX PubMed=25356899; DOI=10.1371/journal.pgen.1004772; RA Hamdan F.F., Srour M., Capo-Chichi J.M., Daoud H., Nassif C., Patry L., RA Massicotte C., Ambalavanan A., Spiegelman D., Diallo O., Henrion E., RA Dionne-Laporte A., Fougerat A., Pshezhetsky A.V., Venkateswaran S., RA Rouleau G.A., Michaud J.L.; RT "De novo mutations in moderate or severe intellectual disability."; RL PLoS Genet. 10:E1004772-E1004772(2014). RN [25] RP CHARACTERIZATION OF VARIANT VACRDS GLY-4860, FUNCTION, AND TRANSPORTER RP ACTIVITY. RX PubMed=17984046; DOI=10.1073/pnas.0706573104; RA Jiang D., Chen W., Wang R., Zhang L., Chen S.R.W.; RT "Loss of luminal Ca(2+) activation in the cardiac ryanodine receptor is RT associated with ventricular fibrillation and sudden death."; RL Proc. Natl. Acad. Sci. U.S.A. 104:18309-18314(2007). RN [26] RP VARIANT CPVT1 PRO-4159. RX PubMed=24793461; DOI=10.1016/j.hrthm.2014.04.037; RA Di Pino A., Caruso E., Costanzo L., Guccione P.; RT "A novel RyR2 mutation in a 2-year-old baby presenting with atrial RT fibrillation, atrial flutter, and atrial ectopic tachycardia."; RL Heart Rhythm 11:1480-1483(2014). RN [27] RP VARIANT ASP-29. RX PubMed=25463374; DOI=10.1016/j.ijcard.2014.11.119; RA Cheung J.W., Meli A.C., Xie W., Mittal S., Reiken S., Wronska A., Xu L., RA Steinberg J.S., Markowitz S.M., Iwai S., Lacampagne A., Lerman B.B., RA Marks A.R.; RT "Short-coupled polymorphic ventricular tachycardia at rest linked to a RT novel ryanodine receptor (RyR2) mutation: leaky RyR2 channels under non- RT stress conditions."; RL Int. J. Cardiol. 180:228-236(2015). RN [28] RP CHARACTERIZATION OF VARIANT ASP-29. RX PubMed=26405799; DOI=10.1371/journal.pone.0139058; RA Xiao Z., Guo W., Yuen S.M., Wang R., Zhang L., Van Petegem F., Chen S.R.; RT "The H29D nutation does not enhance cytosolic Ca2+ activation of the RT cardiac ryanodine receptor."; RL PLoS ONE 10:E0139058-E0139058(2015). RN [29] RP CHARACTERIZATION OF VARIANTS CVPT1 SER-3946; THR-4124; PRO-4158 AND RP PRO-4159, MUTAGENESIS OF GLY-3946; MET-3978 AND HIS-4108, FUNCTION, AND RP TRANSPORTER ACTIVITY. RX PubMed=27733687; DOI=10.1074/jbc.m116.756528; RA Xiao Z., Guo W., Sun B., Hunt D.J., Wei J., Liu Y., Wang Y., Wang R., RA Jones P.P., Back T.G., Chen S.R.; RT "Enhanced cytosolic Ca2+ activation underlies a common defect of central RT domain cardiac ryanodine receptor mutations linked to arrhythmias."; RL J. Biol. Chem. 291:24528-24537(2016). RN [30] RP VARIANTS VACRDS LEU-3774; ILE-4196; ALA-4646; GLY-4860 AND PHE-4938, RP INVOLVEMENT IN VACRDS, CHARACTERIZATION OF VARIANTS VACRDS LEU-3774; RP ILE-4196; ALA-4646; GLY-4860 AND PHE-4938, MUTAGENESIS OF ILE-3995; RP ASP-4112; ILE-4855 AND GLN-4879, FUNCTION, AND TRANSPORTER ACTIVITY. RX PubMed=33536282; DOI=10.1126/scitranslmed.aba7287; RA Sun B., Yao J., Ni M., Wei J., Zhong X., Guo W., Zhang L., Wang R., RA Belke D., Chen Y.X., Lieve K.V.V., Broendberg A.K., Roston T.M., RA Blankoff I., Kammeraad J.A., von Alvensleben J.C., Lazarte J., RA Vallmitjana A., Bohne L.J., Rose R.A., Benitez R., Hove-Madsen L., RA Napolitano C., Hegele R.A., Fill M., Sanatani S., Wilde A.A.M., RA Roberts J.D., Priori S.G., Jensen H.K., Chen S.R.W.; RT "Cardiac ryanodine receptor calcium release deficiency syndrome."; RL Sci. Transl. Med. 13:0-0(2021). CC -!- FUNCTION: Cytosolic calcium-activated calcium channel that mediates the CC release of Ca(2+) from the sarcoplasmic reticulum into the cytosol and CC thereby plays a key role in triggering cardiac muscle contraction. CC Aberrant channel activation can lead to cardiac arrhythmia. In cardiac CC myocytes, calcium release is triggered by increased Ca(2+) cytosolic CC levels due to activation of the L-type calcium channel CACNA1C. The CC calcium channel activity is modulated by formation of heterotetramers CC with RYR3. Required for cellular calcium ion homeostasis. Required for CC embryonic heart development. {ECO:0000269|PubMed:10830164, CC ECO:0000269|PubMed:17984046, ECO:0000269|PubMed:20056922, CC ECO:0000269|PubMed:27733687, ECO:0000269|PubMed:33536282}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Ca(2+)(in) = Ca(2+)(out); Xref=Rhea:RHEA:29671, CC ChEBI:CHEBI:29108; Evidence={ECO:0000269|PubMed:17984046, CC ECO:0000269|PubMed:27733687, ECO:0000269|PubMed:33536282}; CC -!- ACTIVITY REGULATION: The calcium release is activated by increased CC cytosolic calcium levels, by nitric oxyde (NO), caffeine and ATP. CC Channel activity is modulated by the alkaloid ryanodine that binds to CC the open Ca-release channel with high affinity. At low concentrations, CC ryanodine maintains the channel in an open conformation. High ryanodine CC concentrations inhibit channel activity. Channel activity is regulated CC by calmodulin (CALM). Channel activity is inhibited by magnesium ions, CC possibly by competition for calcium binding sites. CC {ECO:0000250|UniProtKB:P11716}. CC -!- SUBUNIT: Homotetramer. Can also form heterotetramers with RYR1 and RYR3 CC (By similarity). Interacts with FKBP1A and FKBP1B; these interactions CC may stabilize the channel in its closed state and prevent Ca(2+) leaks. CC Interacts with CALM and S100A1; these interactions regulate channel CC activity. Identified in a complex composed of RYR2, FKBP1B, PKA CC catalytic subunit, PRKAR2A, AKAP6, and the protein phosphatases PP2A CC and PP1. Interacts directly with FKBP1B, PKA, PP1 and PP2A. Interacts CC with SELENON (By similarity). In cardiac muscles, identified in a CC complex, composed of FSD2, CMYA5 and RYR2 (By similarity). CC {ECO:0000250|UniProtKB:E9Q401, ECO:0000250|UniProtKB:P30957, CC ECO:0000269|PubMed:10830164, ECO:0000269|PubMed:18650434}. CC -!- INTERACTION: CC Q92736; P62942: FKBP1A; NbExp=2; IntAct=EBI-1170425, EBI-1027571; CC Q92736; P68106: FKBP1B; NbExp=5; IntAct=EBI-1170425, EBI-6693977; CC Q92736; Q00987: MDM2; NbExp=2; IntAct=EBI-1170425, EBI-389668; CC -!- SUBCELLULAR LOCATION: Sarcoplasmic reticulum membrane CC {ECO:0000269|PubMed:10830164}; Multi-pass membrane protein CC {ECO:0000269|PubMed:10830164}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q92736-1; Sequence=Displayed; CC Name=2; CC IsoId=Q92736-2; Sequence=VSP_005953; CC -!- TISSUE SPECIFICITY: Detected in heart muscle (at protein level). Heart CC muscle, brain (cerebellum and hippocampus) and placenta. CC {ECO:0000269|PubMed:10830164, ECO:0000269|PubMed:9607712}. CC -!- DEVELOPMENTAL STAGE: Expressed in myometrium during pregnancy. CC {ECO:0000269|PubMed:9148749}. CC -!- INDUCTION: By TGFB1. {ECO:0000269|PubMed:9148749}. CC -!- DOMAIN: The calcium release channel activity resides in the C-terminal CC region while the remaining part of the protein resides in the CC cytoplasm. {ECO:0000250|UniProtKB:P11716}. CC -!- PTM: Channel activity is modulated by phosphorylation. Phosphorylation CC at Ser-2808 and Ser-2814 increases the open probability of the calcium CC channel. Phosphorylation is increased in failing heart, leading to CC calcium leaks and increased cytoplasmic Ca(2+) levels. CC {ECO:0000269|PubMed:10830164, ECO:0000269|PubMed:20056922}. CC -!- PTM: Phosphorylation at Ser-2031 by PKA enhances the response to CC lumenal calcium. {ECO:0000250}. CC -!- DISEASE: Ventricular tachycardia, catecholaminergic polymorphic, 1, CC with or without atrial dysfunction and/or dilated cardiomyopathy CC (CPVT1) [MIM:604772]: An arrhythmogenic disorder characterized by CC stress-induced, bidirectional ventricular tachycardia that may CC degenerate into cardiac arrest and cause sudden death. Patients present CC with recurrent syncope, seizures, or sudden death after physical CC activity or emotional stress. CPVT1 inheritance is autosomal dominant. CC {ECO:0000269|PubMed:11157710, ECO:0000269|PubMed:11159936, CC ECO:0000269|PubMed:11208676, ECO:0000269|PubMed:12093772, CC ECO:0000269|PubMed:12106942, ECO:0000269|PubMed:14571276, CC ECO:0000269|PubMed:15046072, ECO:0000269|PubMed:15046073, CC ECO:0000269|PubMed:15466642, ECO:0000269|PubMed:15544015, CC ECO:0000269|PubMed:16188589, ECO:0000269|PubMed:24793461, CC ECO:0000269|PubMed:25372681, ECO:0000269|PubMed:27733687}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Ventricular arrhythmias due to cardiac ryanodine receptor CC calcium release deficiency syndrome (VACRDS) [MIM:115000]: An autosomal CC dominant arrhythmogenic disorder characterized by syncope, cardiac CC arrest and/or sudden unexpected death, often in association with CC physical exertion or acute emotional stress. Patients who survive CC manifest polymorphic ventricular tachycardia and ventricular CC fibrillation. Unlike typical catecholaminergic ventricular tachycardia, CC arrhythmias are not reproducible on exercise stress testing or CC adrenaline challenge. {ECO:0000269|PubMed:12093772, CC ECO:0000269|PubMed:17984046, ECO:0000269|PubMed:33536282}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the ryanodine receptor (TC 1.A.3.1) family. RYR2 CC subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=CAH71369.1; Type=Miscellaneous discrepancy; Note=Erroneous gene model prediction.; Evidence={ECO:0000305}; CC Sequence=CAH71393.1; Type=Miscellaneous discrepancy; Note=Erroneous gene model prediction.; Evidence={ECO:0000305}; CC Sequence=CAH73918.1; Type=Miscellaneous discrepancy; Note=Erroneous gene model prediction.; Evidence={ECO:0000305}; CC Sequence=CAI14440.1; Type=Miscellaneous discrepancy; Note=Erroneous gene model prediction.; Evidence={ECO:0000305}; CC Sequence=CAI15350.1; Type=Miscellaneous discrepancy; Note=Erroneous gene model prediction.; Evidence={ECO:0000305}; CC Sequence=CAI15936.1; Type=Miscellaneous discrepancy; Note=Erroneous gene model prediction.; Evidence={ECO:0000305}; CC Sequence=CAI22065.1; Type=Miscellaneous discrepancy; Note=Erroneous gene model prediction.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Ryanodine receptor entry; CC URL="https://en.wikipedia.org/wiki/Ryanodine_receptor"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=RYR2 entry; CC URL="https://en.wikipedia.org/wiki/RYR2"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X98330; CAA66975.1; -; mRNA. DR EMBL; AJ300340; CAC18855.1; -; Genomic_DNA. DR EMBL; AJ300341; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300342; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300343; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300347; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300349; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300351; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300353; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300355; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300364; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300363; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300362; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300361; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300360; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300359; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300358; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300357; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300356; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300373; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300372; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300371; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300370; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300369; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300368; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300367; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300366; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300365; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300382; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300381; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300380; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300379; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300378; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300377; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300376; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300375; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300374; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300399; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300398; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300397; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300396; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300395; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300394; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300393; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300392; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300391; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300416; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300415; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300414; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300413; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300412; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300411; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300410; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300409; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300408; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300433; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300432; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300431; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300430; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300429; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300428; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300427; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300426; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300425; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300444; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300443; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300442; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300441; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300440; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300439; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300438; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300437; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300436; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300435; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300434; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300424; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300423; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300422; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300421; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300420; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300419; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300418; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300417; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300407; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300406; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300405; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300404; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300403; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300402; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300401; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300400; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300390; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300389; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300388; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300387; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300386; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300385; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300384; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300383; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300354; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300352; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300350; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300348; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300346; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300345; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AJ300344; CAC18855.1; JOINED; Genomic_DNA. DR EMBL; AL365332; CAH71369.1; ALT_SEQ; Genomic_DNA. DR EMBL; AL356773; CAH71369.1; JOINED; Genomic_DNA. DR EMBL; AL359924; CAH71369.1; JOINED; Genomic_DNA. DR EMBL; AL391809; CAH71369.1; JOINED; Genomic_DNA. DR EMBL; AL442065; CAH71369.1; JOINED; Genomic_DNA. DR EMBL; AL445473; CAH71369.1; JOINED; Genomic_DNA. DR EMBL; AL513130; CAH71369.1; JOINED; Genomic_DNA. DR EMBL; AL445473; CAH71393.1; ALT_SEQ; Genomic_DNA. DR EMBL; AL356773; CAH71393.1; JOINED; Genomic_DNA. DR EMBL; AL359924; CAH71393.1; JOINED; Genomic_DNA. DR EMBL; AL365332; CAH71393.1; JOINED; Genomic_DNA. DR EMBL; AL391809; CAH71393.1; JOINED; Genomic_DNA. DR EMBL; AL442065; CAH71393.1; JOINED; Genomic_DNA. DR EMBL; AL513130; CAH71393.1; JOINED; Genomic_DNA. DR EMBL; AL356773; CAH73918.1; ALT_SEQ; Genomic_DNA. DR EMBL; AL359924; CAH73918.1; JOINED; Genomic_DNA. DR EMBL; AL365332; CAH73918.1; JOINED; Genomic_DNA. DR EMBL; AL391809; CAH73918.1; JOINED; Genomic_DNA. DR EMBL; AL442065; CAH73918.1; JOINED; Genomic_DNA. DR EMBL; AL445473; CAH73918.1; JOINED; Genomic_DNA. DR EMBL; AL513130; CAH73918.1; JOINED; Genomic_DNA. DR EMBL; AL391809; CAI14440.1; ALT_SEQ; Genomic_DNA. DR EMBL; AL356773; CAI14440.1; JOINED; Genomic_DNA. DR EMBL; AL359924; CAI14440.1; JOINED; Genomic_DNA. DR EMBL; AL365332; CAI14440.1; JOINED; Genomic_DNA. DR EMBL; AL442065; CAI14440.1; JOINED; Genomic_DNA. DR EMBL; AL445473; CAI14440.1; JOINED; Genomic_DNA. DR EMBL; AL513130; CAI14440.1; JOINED; Genomic_DNA. DR EMBL; AL442065; CAI15350.1; ALT_SEQ; Genomic_DNA. DR EMBL; AL356773; CAI15350.1; JOINED; Genomic_DNA. DR EMBL; AL359924; CAI15350.1; JOINED; Genomic_DNA. DR EMBL; AL365332; CAI15350.1; JOINED; Genomic_DNA. DR EMBL; AL391809; CAI15350.1; JOINED; Genomic_DNA. DR EMBL; AL445473; CAI15350.1; JOINED; Genomic_DNA. DR EMBL; AL513130; CAI15350.1; JOINED; Genomic_DNA. DR EMBL; AL513130; CAI15936.1; ALT_SEQ; Genomic_DNA. DR EMBL; AL356773; CAI15936.1; JOINED; Genomic_DNA. DR EMBL; AL359924; CAI15936.1; JOINED; Genomic_DNA. DR EMBL; AL365332; CAI15936.1; JOINED; Genomic_DNA. DR EMBL; AL391809; CAI15936.1; JOINED; Genomic_DNA. DR EMBL; AL442065; CAI15936.1; JOINED; Genomic_DNA. DR EMBL; AL445473; CAI15936.1; JOINED; Genomic_DNA. DR EMBL; AL359924; CAI22065.1; ALT_SEQ; Genomic_DNA. DR EMBL; AL356773; CAI22065.1; JOINED; Genomic_DNA. DR EMBL; AL365332; CAI22065.1; JOINED; Genomic_DNA. DR EMBL; AL391809; CAI22065.1; JOINED; Genomic_DNA. DR EMBL; AL442065; CAI22065.1; JOINED; Genomic_DNA. DR EMBL; AL445473; CAI22065.1; JOINED; Genomic_DNA. DR EMBL; AL513130; CAI22065.1; JOINED; Genomic_DNA. DR EMBL; Y08218; CAA69395.1; -; mRNA. DR EMBL; X91869; CAA62975.1; -; mRNA. DR EMBL; AJ002511; CAA05502.1; -; mRNA. DR CCDS; CCDS55691.1; -. [Q92736-1] DR PIR; S72269; S72269. DR RefSeq; NP_001026.2; NM_001035.2. [Q92736-1] DR RefSeq; XP_006711868.1; XM_006711805.3. [Q92736-2] DR PDB; 4JKQ; X-ray; 2.39 A; A=1-606. DR PDB; 6Y4O; X-ray; 1.84 A; B=3581-3607. DR PDB; 6Y4P; X-ray; 2.13 A; B=3581-3607. DR PDB; 7KL5; X-ray; 1.65 A; B=4246-4275. DR PDB; 7U9Q; EM; 3.11 A; A/B/C/D=1-4967. DR PDB; 7U9R; EM; 3.69 A; A/B/C/D=1-4967. DR PDB; 7U9T; EM; 2.68 A; A/B/C/D=1-4967. DR PDB; 7U9X; EM; 2.58 A; A/B/C/D=1-4967. DR PDB; 7U9Z; EM; 3.29 A; A/B/C/D=1-4967. DR PDB; 7UA1; EM; 2.99 A; A/B/C/D=1-4967. DR PDB; 7UA3; EM; 2.97 A; A/B/C/D=1-4967. DR PDB; 7UA4; EM; 2.93 A; A/B/C/D=1-4967. DR PDB; 7UA5; EM; 2.83 A; A/B/C/D=1-4967. DR PDB; 7UA9; EM; 3.59 A; A/B/C/D=1-4967. DR PDB; 8UQ2; EM; 2.98 A; A/B/C/D=1-4967. DR PDB; 8UQ3; EM; 3.18 A; A/B/C/D=1-4967. DR PDB; 8UQ4; EM; 3.64 A; A/B/C/D=1-4967. DR PDB; 8UQ5; EM; 3.96 A; A/B/C/D=1-4967. DR PDB; 8UXC; EM; 2.86 A; A/B/C/D=1-4967. DR PDB; 8UXE; EM; 3.53 A; A/B/C/D=1-4967. DR PDB; 8UXF; EM; 3.13 A; A/B/C/D=1-4967. DR PDB; 8UXG; EM; 3.08 A; A/B/C/D=1-4967. DR PDB; 8UXH; EM; 3.52 A; A/B/C/D=1-4967. DR PDB; 8UXI; EM; 3.29 A; A/B/C/D=1-4967. DR PDB; 8UXL; EM; 3.12 A; A/B/C/D=1-4967. DR PDB; 8UXM; EM; 3.56 A; A/B/C/D=1-4967. DR PDBsum; 4JKQ; -. DR PDBsum; 6Y4O; -. DR PDBsum; 6Y4P; -. DR PDBsum; 7KL5; -. DR PDBsum; 7U9Q; -. DR PDBsum; 7U9R; -. DR PDBsum; 7U9T; -. DR PDBsum; 7U9X; -. DR PDBsum; 7U9Z; -. DR PDBsum; 7UA1; -. DR PDBsum; 7UA3; -. DR PDBsum; 7UA4; -. DR PDBsum; 7UA5; -. DR PDBsum; 7UA9; -. DR PDBsum; 8UQ2; -. DR PDBsum; 8UQ3; -. DR PDBsum; 8UQ4; -. DR PDBsum; 8UQ5; -. DR PDBsum; 8UXC; -. DR PDBsum; 8UXE; -. DR PDBsum; 8UXF; -. DR PDBsum; 8UXG; -. DR PDBsum; 8UXH; -. DR PDBsum; 8UXI; -. DR PDBsum; 8UXL; -. DR PDBsum; 8UXM; -. DR BMRB; Q92736; -. DR EMDB; EMD-26139; -. DR EMDB; EMD-26405; -. DR EMDB; EMD-26407; -. DR EMDB; EMD-26408; -. DR EMDB; EMD-26409; -. DR EMDB; EMD-26410; -. DR EMDB; EMD-26412; -. DR EMDB; EMD-26413; -. DR EMDB; EMD-26414; -. DR EMDB; EMD-26415; -. DR EMDB; EMD-26416; -. DR EMDB; EMD-42458; -. DR EMDB; EMD-42459; -. DR EMDB; EMD-42460; -. DR EMDB; EMD-42461; -. DR EMDB; EMD-42759; -. DR EMDB; EMD-42761; -. DR EMDB; EMD-42762; -. DR EMDB; EMD-42763; -. DR EMDB; EMD-42764; -. DR EMDB; EMD-42765; -. DR EMDB; EMD-42768; -. DR EMDB; EMD-42769; -. DR SMR; Q92736; -. DR BioGRID; 112174; 41. DR ComplexPortal; CPX-3156; Ryanodine 2 complex. DR DIP; DIP-38325N; -. DR IntAct; Q92736; 15. DR MINT; Q92736; -. DR STRING; 9606.ENSP00000355533; -. DR ChEMBL; CHEMBL4403; -. DR DrugBank; DB11093; Calcium citrate. DR DrugBank; DB11348; Calcium Phosphate. DR DrugBank; DB14481; Calcium phosphate dihydrate. DR DrugBank; DB01195; Flecainide. DR DrugBank; DB09085; Tetracaine. DR DrugCentral; Q92736; -. DR GuidetoPHARMACOLOGY; 748; -. DR TCDB; 1.A.3.1.1; the ryanodine-inositol 1,4,5-triphosphate receptor ca(2+) channel (rir-cac) family. DR CarbonylDB; Q92736; -. DR GlyCosmos; Q92736; 1 site, 1 glycan. DR GlyGen; Q92736; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q92736; -. DR PhosphoSitePlus; Q92736; -. DR SwissPalm; Q92736; -. DR BioMuta; RYR2; -. DR DMDM; 308153558; -. DR EPD; Q92736; -. DR jPOST; Q92736; -. DR MassIVE; Q92736; -. DR MaxQB; Q92736; -. DR PaxDb; 9606-ENSP00000355533; -. DR PeptideAtlas; Q92736; -. DR ProteomicsDB; 75431; -. [Q92736-1] DR ProteomicsDB; 75432; -. [Q92736-2] DR Pumba; Q92736; -. DR Antibodypedia; 3476; 278 antibodies from 31 providers. DR DNASU; 6262; -. DR Ensembl; ENST00000366574.7; ENSP00000355533.2; ENSG00000198626.18. [Q92736-1] DR GeneID; 6262; -. DR KEGG; hsa:6262; -. DR MANE-Select; ENST00000366574.7; ENSP00000355533.2; NM_001035.3; NP_001026.2. DR UCSC; uc001hyl.2; human. [Q92736-1] DR AGR; HGNC:10484; -. DR CTD; 6262; -. DR DisGeNET; 6262; -. DR GeneCards; RYR2; -. DR GeneReviews; RYR2; -. DR HGNC; HGNC:10484; RYR2. DR HPA; ENSG00000198626; Tissue enriched (heart). DR MalaCards; RYR2; -. DR MIM; 115000; phenotype. DR MIM; 180902; gene. DR MIM; 604772; phenotype. DR neXtProt; NX_Q92736; -. DR OpenTargets; ENSG00000198626; -. DR Orphanet; 3286; Catecholaminergic polymorphic ventricular tachycardia. DR Orphanet; 293888; Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant. DR Orphanet; 293910; Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant. DR Orphanet; 293899; Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant. DR VEuPathDB; HostDB:ENSG00000198626; -. DR eggNOG; KOG2243; Eukaryota. DR GeneTree; ENSGT00940000154906; -. DR HOGENOM; CLU_000040_2_0_1; -. DR InParanoid; Q92736; -. DR OMA; HYEDTSD; -. DR OrthoDB; 3144451at2759; -. DR PhylomeDB; Q92736; -. DR TreeFam; TF315244; -. DR PathwayCommons; Q92736; -. DR Reactome; R-HSA-2672351; Stimuli-sensing channels. DR Reactome; R-HSA-5578775; Ion homeostasis. DR SignaLink; Q92736; -. DR SIGNOR; Q92736; -. DR BioGRID-ORCS; 6262; 7 hits in 1152 CRISPR screens. DR ChiTaRS; RYR2; human. DR GeneWiki; Ryanodine_receptor_2; -. DR GenomeRNAi; 6262; -. DR Pharos; Q92736; Tclin. DR PRO; PR:Q92736; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q92736; Protein. DR Bgee; ENSG00000198626; Expressed in heart right ventricle and 139 other cell types or tissues. DR ExpressionAtlas; Q92736; baseline and differential. DR GO; GO:0034704; C:calcium channel complex; IDA:BHF-UCL. DR GO; GO:0014701; C:junctional sarcoplasmic reticulum membrane; TAS:BHF-UCL. DR GO; GO:0016020; C:membrane; IDA:BHF-UCL. DR GO; GO:0005886; C:plasma membrane; ISS:BHF-UCL. DR GO; GO:0032991; C:protein-containing complex; IDA:MGI. DR GO; GO:0042383; C:sarcolemma; IBA:GO_Central. DR GO; GO:0016529; C:sarcoplasmic reticulum; IDA:BHF-UCL. DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; ISS:UniProtKB. DR GO; GO:0005790; C:smooth endoplasmic reticulum; IBA:GO_Central. DR GO; GO:0030018; C:Z disc; IDA:BHF-UCL. DR GO; GO:0005262; F:calcium channel activity; ISS:UniProtKB. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0048763; F:calcium-induced calcium release activity; IDA:BHF-UCL. DR GO; GO:0015278; F:calcium-release channel activity; IDA:BHF-UCL. DR GO; GO:0005516; F:calmodulin binding; IDA:UniProtKB. DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL. DR GO; GO:0042802; F:identical protein binding; IPI:BHF-UCL. DR GO; GO:0034236; F:protein kinase A catalytic subunit binding; IDA:BHF-UCL. DR GO; GO:0034237; F:protein kinase A regulatory subunit binding; IDA:BHF-UCL. DR GO; GO:0043621; F:protein self-association; IEA:Ensembl. DR GO; GO:0005219; F:ryanodine-sensitive calcium-release channel activity; IDA:UniProtKB. DR GO; GO:0043924; F:suramin binding; IMP:BHF-UCL. DR GO; GO:0044325; F:transmembrane transporter binding; ISS:BHF-UCL. DR GO; GO:0006816; P:calcium ion transport; IDA:BHF-UCL. DR GO; GO:0060402; P:calcium ion transport into cytosol; IDA:BHF-UCL. DR GO; GO:0019722; P:calcium-mediated signaling; ISS:UniProtKB. DR GO; GO:0035584; P:calcium-mediated signaling using intracellular calcium source; IDA:BHF-UCL. DR GO; GO:0060048; P:cardiac muscle contraction; IMP:BHF-UCL. DR GO; GO:0003300; P:cardiac muscle hypertrophy; ISS:BHF-UCL. DR GO; GO:0086064; P:cell communication by electrical coupling involved in cardiac conduction; IC:BHF-UCL. DR GO; GO:0071313; P:cellular response to caffeine; IDA:BHF-UCL. DR GO; GO:0071872; P:cellular response to epinephrine stimulus; ISS:BHF-UCL. DR GO; GO:0005513; P:detection of calcium ion; IDA:BHF-UCL. DR GO; GO:0003143; P:embryonic heart tube morphogenesis; ISS:UniProtKB. DR GO; GO:0051649; P:establishment of localization in cell; IEA:Ensembl. DR GO; GO:0072599; P:establishment of protein localization to endoplasmic reticulum; IDA:BHF-UCL. DR GO; GO:0006874; P:intracellular calcium ion homeostasis; ISS:UniProtKB. DR GO; GO:0003220; P:left ventricular cardiac muscle tissue morphogenesis; ISS:BHF-UCL. DR GO; GO:1901896; P:positive regulation of ATPase-coupled calcium transmembrane transporter activity; IDA:BHF-UCL. DR GO; GO:0010460; P:positive regulation of heart rate; ISS:BHF-UCL. DR GO; GO:0051284; P:positive regulation of sequestering of calcium ion; IDA:BHF-UCL. DR GO; GO:0098735; P:positive regulation of the force of heart contraction; IMP:BHF-UCL. DR GO; GO:0086029; P:Purkinje myocyte to ventricular cardiac muscle cell signaling; ISS:BHF-UCL. DR GO; GO:0098910; P:regulation of atrial cardiac muscle cell action potential; IMP:BHF-UCL. DR GO; GO:0098904; P:regulation of AV node cell action potential; IMP:BHF-UCL. DR GO; GO:0055117; P:regulation of cardiac muscle contraction; IMP:BHF-UCL. DR GO; GO:0010882; P:regulation of cardiac muscle contraction by calcium ion signaling; IMP:BHF-UCL. DR GO; GO:0010881; P:regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion; ISS:BHF-UCL. DR GO; GO:0051480; P:regulation of cytosolic calcium ion concentration; ISS:BHF-UCL. DR GO; GO:0002027; P:regulation of heart rate; IMP:BHF-UCL. DR GO; GO:0098907; P:regulation of SA node cell action potential; IMP:BHF-UCL. DR GO; GO:0098911; P:regulation of ventricular cardiac muscle cell action potential; IMP:BHF-UCL. DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; IDA:BHF-UCL. DR GO; GO:0014808; P:release of sequestered calcium ion into cytosol by sarcoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0031000; P:response to caffeine; IDA:BHF-UCL. DR GO; GO:0001666; P:response to hypoxia; ISS:BHF-UCL. DR GO; GO:0014850; P:response to muscle activity; IMP:BHF-UCL. DR GO; GO:0035994; P:response to muscle stretch; IMP:BHF-UCL. DR GO; GO:0051775; P:response to redox state; IDA:BHF-UCL. DR GO; GO:0070296; P:sarcoplasmic reticulum calcium ion transport; TAS:BHF-UCL. DR GO; GO:0006941; P:striated muscle contraction; IBA:GO_Central. DR GO; GO:0097050; P:type B pancreatic cell apoptotic process; IMP:BHF-UCL. DR GO; GO:0086005; P:ventricular cardiac muscle cell action potential; ISS:BHF-UCL. DR CDD; cd12877; SPRY1_RyR; 1. DR CDD; cd12878; SPRY2_RyR; 1. DR CDD; cd12879; SPRY3_RyR; 1. DR Gene3D; 1.10.287.70; -; 1. DR Gene3D; 1.10.490.160; -; 3. DR Gene3D; 2.60.120.920; -; 3. DR Gene3D; 2.80.10.50; -; 2. DR Gene3D; 1.10.238.10; EF-hand; 1. DR Gene3D; 1.25.10.30; IP3 receptor type 1 binding core, RIH domain; 1. DR InterPro; IPR001870; B30.2/SPRY. DR InterPro; IPR043136; B30.2/SPRY_sf. DR InterPro; IPR013320; ConA-like_dom_sf. DR InterPro; IPR011992; EF-hand-dom_pair. DR InterPro; IPR002048; EF_hand_dom. DR InterPro; IPR014821; Ins145_P3_rcpt. DR InterPro; IPR005821; Ion_trans_dom. DR InterPro; IPR036300; MIR_dom_sf. DR InterPro; IPR016093; MIR_motif. DR InterPro; IPR013662; RIH_assoc-dom. DR InterPro; IPR000699; RIH_dom. DR InterPro; IPR013333; Ryan_recept. DR InterPro; IPR015925; Ryanodine_IP3_receptor. DR InterPro; IPR003032; Ryanodine_rcpt. DR InterPro; IPR009460; Ryanrecept_TM4-6. DR InterPro; IPR048581; RYDR_Jsol. DR InterPro; IPR035910; RyR/IP3R_RIH_dom_sf. DR InterPro; IPR035761; SPRY1_RyR. DR InterPro; IPR035764; SPRY2_RyR. DR InterPro; IPR035762; SPRY3_RyR. DR InterPro; IPR003877; SPRY_dom. DR PANTHER; PTHR46399; B30.2/SPRY DOMAIN-CONTAINING PROTEIN; 1. DR PANTHER; PTHR46399:SF7; RYANODINE RECEPTOR 2; 1. DR Pfam; PF13499; EF-hand_7; 1. DR Pfam; PF08709; Ins145_P3_rec; 1. DR Pfam; PF00520; Ion_trans; 1. DR Pfam; PF02815; MIR; 1. DR Pfam; PF08454; RIH_assoc; 1. DR Pfam; PF06459; RR_TM4-6; 1. DR Pfam; PF01365; RYDR_ITPR; 2. DR Pfam; PF21119; RYDR_Jsol; 1. DR Pfam; PF02026; RyR; 4. DR Pfam; PF00622; SPRY; 3. DR PRINTS; PR00795; RYANODINER. DR SMART; SM00472; MIR; 4. DR SMART; SM00449; SPRY; 3. DR SUPFAM; SSF49899; Concanavalin A-like lectins/glucanases; 2. DR SUPFAM; SSF47473; EF-hand; 1. DR SUPFAM; SSF100909; IP3 receptor type 1 binding core, domain 2; 2. DR SUPFAM; SSF82109; MIR domain; 2. DR PROSITE; PS50188; B302_SPRY; 3. DR PROSITE; PS50919; MIR; 5. DR Genevisible; Q92736; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Calcium; Calcium channel; KW Calcium transport; Calmodulin-binding; Cardiomyopathy; Coiled coil; KW Developmental protein; Disease variant; Ion channel; Ion transport; KW Ligand-gated ion channel; Membrane; Phosphoprotein; Receptor; KW Reference proteome; Repeat; Sarcoplasmic reticulum; Transmembrane; KW Transmembrane helix; Transport. FT CHAIN 1..4967 FT /note="Ryanodine receptor 2" FT /id="PRO_0000219361" FT TOPO_DOM 1..4281 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 4282..4302 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 4504..4524 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 4580..4600 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 4730..4750 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 4769..4789 FT /note="Helical" FT /evidence="ECO:0000255" FT INTRAMEM 4820..4829 FT /note="Pore-forming" FT /evidence="ECO:0000250" FT TRANSMEM 4850..4870 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 4871..4967 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 110..165 FT /note="MIR 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131" FT DOMAIN 172..217 FT /note="MIR 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131" FT DOMAIN 225..280 FT /note="MIR 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131" FT DOMAIN 286..343 FT /note="MIR 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131" FT DOMAIN 351..408 FT /note="MIR 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131" FT DOMAIN 599..809 FT /note="B30.2/SPRY 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548" FT REPEAT 853..966 FT /note="1" FT REPEAT 967..1080 FT /note="2" FT DOMAIN 1025..1222 FT /note="B30.2/SPRY 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548" FT DOMAIN 1337..1562 FT /note="B30.2/SPRY 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548" FT REPEAT 2692..2810 FT /note="3" FT REPEAT 2812..2925 FT /note="4" FT REGION 853..2925 FT /note="4 X approximate repeats" FT REGION 1856..1891 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2354..2379 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 3581..3610 FT /note="Interaction with CALM" FT /evidence="ECO:0000269|PubMed:18650434" FT REGION 4210..4229 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 4415..4467 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 4412..4445 FT /evidence="ECO:0000255" FT COMPBIAS 4212..4229 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 4418..4467 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 1341 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:E9Q401" FT MOD_RES 1869 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:B0LPN4" FT MOD_RES 2031 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000250|UniProtKB:E9Q401" FT MOD_RES 2369 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:E9Q401" FT MOD_RES 2697 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:B0LPN4" FT MOD_RES 2797 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:E9Q401" FT MOD_RES 2808 FT /note="Phosphoserine; by CaMK2D and PKA" FT /evidence="ECO:0000269|PubMed:10830164, FT ECO:0000269|PubMed:20056922" FT MOD_RES 2811 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:E9Q401" FT MOD_RES 2814 FT /note="Phosphoserine; by CaMK2D" FT /evidence="ECO:0000269|PubMed:20056922" FT MOD_RES 2947 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:E9Q401" FT VAR_SEQ 3715 FT /note="E -> EVTGSQRSK (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_005953" FT VARIANT 29 FT /note="H -> D (found in a patient with short-coupled FT polymorphic ventricular tachycardia at rest; uncertain FT significance; no effect on cytosolic Ca(2+) activation)" FT /evidence="ECO:0000269|PubMed:25463374, FT ECO:0000269|PubMed:26405799" FT /id="VAR_075283" FT VARIANT 164 FT /note="P -> S (in CPVT1; dbSNP:rs764772142)" FT /evidence="ECO:0000269|PubMed:15466642" FT /id="VAR_044086" FT VARIANT 176 FT /note="R -> Q (in CPVT1; dbSNP:rs794728708)" FT /evidence="ECO:0000269|PubMed:11159936, FT ECO:0000269|PubMed:12106942, ECO:0000269|PubMed:16188589" FT /id="VAR_044087" FT VARIANT 414 FT /note="R -> L (in CPVT1; dbSNP:rs371121679)" FT /evidence="ECO:0000269|PubMed:15466642, FT ECO:0000269|PubMed:16188589" FT /id="VAR_044088" FT VARIANT 419 FT /note="I -> F (in CPVT1; decreases protein stability; FT dbSNP:rs1349176732)" FT /evidence="ECO:0000269|PubMed:15466642, FT ECO:0000269|PubMed:16188589, ECO:0000269|PubMed:25372681" FT /id="VAR_044089" FT VARIANT 420 FT /note="R -> W (in CPVT1; dbSNP:rs190140598)" FT /evidence="ECO:0000269|PubMed:12106942, FT ECO:0000269|PubMed:15544015" FT /id="VAR_044090" FT VARIANT 433 FT /note="L -> P (in CPVT1; dbSNP:rs121918602)" FT /evidence="ECO:0000269|PubMed:11159936, FT ECO:0000269|PubMed:12106942" FT /id="VAR_011395" FT VARIANT 466 FT /note="P -> A (in CPVT1; uncertain significance; FT dbSNP:rs376612295)" FT /evidence="ECO:0000269|PubMed:16188589" FT /id="VAR_079513" FT VARIANT 507 FT /note="V -> I (in dbSNP:rs16835270)" FT /id="VAR_044091" FT VARIANT 1886 FT /note="G -> S (in dbSNP:rs3766871)" FT /id="VAR_022078" FT VARIANT 2246 FT /note="S -> L (in CPVT1; dbSNP:rs121918597)" FT /evidence="ECO:0000269|PubMed:11208676, FT ECO:0000269|PubMed:12093772, ECO:0000269|PubMed:15544015" FT /id="VAR_011396" FT VARIANT 2306 FT /note="V -> I (in CPVT1; dbSNP:rs794728746)" FT /evidence="ECO:0000269|PubMed:14571276" FT /id="VAR_023694" FT VARIANT 2311 FT /note="E -> D (in CPVT1; dbSNP:rs794728747)" FT /evidence="ECO:0000269|PubMed:12093772" FT /id="VAR_044092" FT VARIANT 2328 FT /note="P -> S (in CPVT1; dbSNP:rs121918603)" FT /evidence="ECO:0000269|PubMed:11157710" FT /id="VAR_011397" FT VARIANT 2386 FT /note="N -> I (in CPVT1; dbSNP:rs121918601)" FT /evidence="ECO:0000269|PubMed:11159936, FT ECO:0000269|PubMed:12106942" FT /id="VAR_011398" FT VARIANT 2387 FT /note="A -> P (in CPVT1; dbSNP:rs794728753)" FT /evidence="ECO:0000269|PubMed:15046073" FT /id="VAR_044093" FT VARIANT 2392 FT /note="Y -> C (in CPVT1; dbSNP:rs772220753)" FT /evidence="ECO:0000269|PubMed:12106942" FT /id="VAR_044094" FT VARIANT 2403 FT /note="A -> T (in CPVT1; dbSNP:rs1456929288)" FT /evidence="ECO:0000269|PubMed:15466642, FT ECO:0000269|PubMed:16188589" FT /id="VAR_044095" FT VARIANT 2474 FT /note="R -> S (in CPVT1; dbSNP:rs121918598)" FT /evidence="ECO:0000269|PubMed:11208676, FT ECO:0000269|PubMed:12093772" FT /id="VAR_011399" FT VARIANT 2504 FT /note="T -> M (in CPVT1; dbSNP:rs769219555)" FT /evidence="ECO:0000269|PubMed:11159936, FT ECO:0000269|PubMed:12106942" FT /id="VAR_044096" FT VARIANT 2958 FT /note="Q -> R (in dbSNP:rs34967813)" FT /evidence="ECO:0000269|PubMed:11157710" FT /id="VAR_011590" FT VARIANT 3774 FT /note="Q -> L (in VACRDS; decreased function in release of FT sequestered calcium ion into cytosol by sarcoplasmic FT reticulum; changed ryanodine-sensitive calcium-release FT channel activity; mutant channels are less responsive to FT activation by caffeine and store calcium overload; affects FT channel sensitivity to cytosolic and luminal calcium FT activation)" FT /evidence="ECO:0000269|PubMed:33536282" FT /id="VAR_085649" FT VARIANT 3778 FT /note="L -> F (in CPVT1; dbSNP:rs1472508624)" FT /evidence="ECO:0000269|PubMed:12093772" FT /id="VAR_044097" FT VARIANT 3800 FT /note="C -> F (in CPVT1; dbSNP:rs1239093704)" FT /evidence="ECO:0000269|PubMed:16188589" FT /id="VAR_079514" FT VARIANT 3946 FT /note="G -> S (in CPVT1; changed ryanodine-sensitive FT calcium-release channel activity; increased sensitivity to FT cytosolic calcium activation; dbSNP:rs794728777)" FT /evidence="ECO:0000269|PubMed:12093772, FT ECO:0000269|PubMed:27733687" FT /id="VAR_044098" FT VARIANT 4097 FT /note="N -> S (in CPVT1; dbSNP:rs794728784)" FT /evidence="ECO:0000269|PubMed:15544015" FT /id="VAR_044099" FT VARIANT 4104 FT /note="N -> K (in CPVT1; dbSNP:rs121918599)" FT /evidence="ECO:0000269|PubMed:11208676, FT ECO:0000269|PubMed:12093772" FT /id="VAR_011400" FT VARIANT 4124 FT /note="S -> T (in CPVT1; changed ryanodine-sensitive FT calcium-release channel activity; increased sensitivity to FT cytosolic calcium activation; dbSNP:rs1385881911)" FT /evidence="ECO:0000269|PubMed:16188589, FT ECO:0000269|PubMed:27733687" FT /id="VAR_079515" FT VARIANT 4146 FT /note="E -> K (in CPVT1; dbSNP:rs1349585791)" FT /evidence="ECO:0000269|PubMed:15544015" FT /id="VAR_044100" FT VARIANT 4158 FT /note="T -> P (in CPVT1; changed ryanodine-sensitive FT calcium-release channel activity; increased sensitivity to FT cytosolic calcium activation; dbSNP:rs1202962809)" FT /evidence="ECO:0000269|PubMed:15544015, FT ECO:0000269|PubMed:27733687" FT /id="VAR_044101" FT VARIANT 4159 FT /note="Q -> P (in CPVT1; changed ryanodine-sensitive FT calcium-release channel activity; increased sensitivity to FT cytosolic calcium activation; dbSNP:rs1234963411)" FT /evidence="ECO:0000269|PubMed:24793461, FT ECO:0000269|PubMed:27733687" FT /id="VAR_079516" FT VARIANT 4196 FT /note="T -> I (in VACRDS; decreased function in release of FT sequestered calcium ion into cytosol by sarcoplasmic FT reticulum; changed ryanodine-sensitive calcium-release FT channel activity; mutant channels are less respositive to FT activation by caffeine and store calcium overload; affects FT channel sensitivity to cytosolic and luminal calcium FT activation)" FT /evidence="ECO:0000269|PubMed:33536282" FT /id="VAR_085650" FT VARIANT 4201 FT /note="Q -> R (in CPVT1; dbSNP:rs121918605)" FT /evidence="ECO:0000269|PubMed:11157710" FT /id="VAR_011401" FT VARIANT 4497 FT /note="R -> C (in CPVT1; dbSNP:rs121918600)" FT /evidence="ECO:0000269|PubMed:11208676, FT ECO:0000269|PubMed:12093772, ECO:0000269|PubMed:15544015" FT /id="VAR_011402" FT VARIANT 4499 FT /note="F -> C (in CPVT1; dbSNP:rs1457271141)" FT /evidence="ECO:0000269|PubMed:15466642, FT ECO:0000269|PubMed:16188589" FT /id="VAR_044102" FT VARIANT 4504 FT /note="M -> I (in CPVT1; dbSNP:rs1323621379)" FT /evidence="ECO:0000269|PubMed:15046072" FT /id="VAR_044103" FT VARIANT 4510 FT /note="A -> T (in CPVT1; dbSNP:rs397516510)" FT /evidence="ECO:0000269|PubMed:15466642, FT ECO:0000269|PubMed:16188589" FT /id="VAR_044104" FT VARIANT 4556 FT /note="A -> T (in CPVT1; dbSNP:rs189345192)" FT /evidence="ECO:0000269|PubMed:16188589" FT /id="VAR_079517" FT VARIANT 4607 FT /note="A -> P (in CPVT1; dbSNP:rs1359163728)" FT /evidence="ECO:0000269|PubMed:15046073" FT /id="VAR_044105" FT VARIANT 4646 FT /note="D -> A (in VACRDS; decreased function in release of FT sequestered calcium ion into cytosol by sarcoplasmic FT reticulum; changed ryanodine-sensitive calcium-release FT channel activity; mutant channels are less resposive to FT activation by caffeine and store calcium overload; affects FT channel sensitivity to cytosolic and luminal calcium FT activation; dbSNP:rs1658967336)" FT /evidence="ECO:0000269|PubMed:33536282" FT /id="VAR_085651" FT VARIANT 4653 FT /note="V -> F (in CPVT1; dbSNP:rs121918604)" FT /evidence="ECO:0000269|PubMed:11157710" FT /id="VAR_011403" FT VARIANT 4671 FT /note="G -> R (in CPVT1; dbSNP:rs1188352725)" FT /evidence="ECO:0000269|PubMed:15466642" FT /id="VAR_044106" FT VARIANT 4771 FT /note="V -> I (in CPVT1; dbSNP:rs794728804)" FT /evidence="ECO:0000269|PubMed:12093772" FT /id="VAR_044107" FT VARIANT 4848 FT /note="I -> V (in CPVT1; dbSNP:rs1363298408)" FT /evidence="ECO:0000269|PubMed:15466642, FT ECO:0000269|PubMed:16188589" FT /id="VAR_044108" FT VARIANT 4860 FT /note="A -> G (in VACRDS; decreased function in release of FT sequestered calcium ion into cytosol by sarcoplasmic FT reticulum; changed ryanodine-sensitive calcium-release FT channel activity; diminishes the response to activation by FT luminal Ca(2+) but has little effect on the sensitivity of FT the channel to activation by cytosolic Ca(2+); shows FT caffeine-induced Ca(2+) release but exhibits no FT store-overload-induced Ca(2+) release (SOICR); HL1 cardiac FT cells transfected with the G-4860 mutant displayed FT attenuated SOICR activity compared to cells transfected FT with wild-type RYR2; dbSNP:rs121918606)" FT /evidence="ECO:0000269|PubMed:12093772, FT ECO:0000269|PubMed:17984046, ECO:0000269|PubMed:33536282" FT /id="VAR_044109" FT VARIANT 4867 FT /note="I -> M (in CPVT1; dbSNP:rs1218096653)" FT /evidence="ECO:0000269|PubMed:12093772" FT /id="VAR_044110" FT VARIANT 4880 FT /note="V -> A (in CPVT1; dbSNP:rs1242723821)" FT /evidence="ECO:0000269|PubMed:15046072" FT /id="VAR_044111" FT VARIANT 4895 FT /note="N -> D (in CPVT1; dbSNP:rs1185619003)" FT /evidence="ECO:0000269|PubMed:12093772" FT /id="VAR_044112" FT VARIANT 4902 FT /note="P -> L (in CPVT1; dbSNP:rs1475453069)" FT /evidence="ECO:0000269|PubMed:14571276" FT /id="VAR_023695" FT VARIANT 4938 FT /note="S -> F (in VACRDS; decreased function in release of FT sequestered calcium ion into cytosol by sarcoplasmic FT reticulum; changed ryanodine-sensitive calcium-release FT channel activity; mutant channels are less respositive to FT activation by caffeine and store calcium overload; affects FT channel sensitivity to cytosolic and luminal calcium FT activation)" FT /evidence="ECO:0000269|PubMed:33536282" FT /id="VAR_085652" FT VARIANT 4950 FT /note="E -> K (in CPVT1; dbSNP:rs886039172)" FT /evidence="ECO:0000269|PubMed:12093772" FT /id="VAR_044113" FT VARIANT 4955 FT /note="G -> E (found in a patient with intellectual FT disability, seizures, short stature and severe atrial FT arrhythmias; likely pathogenic; dbSNP:rs1553343100)" FT /evidence="ECO:0000269|PubMed:25356899" FT /id="VAR_078648" FT VARIANT 4959 FT /note="R -> Q (in CPVT1; dbSNP:rs794728811)" FT /evidence="ECO:0000269|PubMed:14571276, FT ECO:0000269|PubMed:16188589" FT /id="VAR_023696" FT MUTAGEN 2808 FT /note="S->A: Abolishes phosphorylation by PKA." FT /evidence="ECO:0000269|PubMed:10830164" FT MUTAGEN 3946 FT /note="G->A: Changed ryanodine-sensitive calcium-release FT channel activity characterized by increased sensitivity to FT cytosolic calcium activation." FT /evidence="ECO:0000269|PubMed:27733687" FT MUTAGEN 3978 FT /note="M->I: Changed ryanodine-sensitive calcium-release FT channel activity characterized by increased sensitivity to FT cytosolic calcium activation." FT /evidence="ECO:0000269|PubMed:27733687" FT MUTAGEN 3995 FT /note="I->V: Decreased function in release of sequestered FT calcium ion into cytosol by sarcoplasmic reticulum. Changed FT ryanodine-sensitive calcium-release channel activity. FT Mutant channels are less respositive to activation by FT caffeine and store calcium overload. Affects channel FT sensitivity to cytosolic and luminal calcium activation." FT /evidence="ECO:0000269|PubMed:33536282" FT MUTAGEN 4108 FT /note="H->N: Changed ryanodine-sensitive calcium-release FT channel activity characterized by increased sensitivity to FT cytosolic calcium activation." FT /evidence="ECO:0000269|PubMed:27733687" FT MUTAGEN 4108 FT /note="H->Q: Changed ryanodine-sensitive calcium-release FT channel activity characterized by increased sensitivity to FT cytosolic calcium activation." FT /evidence="ECO:0000269|PubMed:27733687" FT MUTAGEN 4112 FT /note="D->N: Decreased function in release of sequestered FT calcium ion into cytosol by sarcoplasmic reticulum. Changed FT ryanodine-sensitive calcium-release channel activity. FT Mutant channels are less respositive to activation by FT caffeine and store calcium overload. Affects channel FT sensitivity to cytosolic and luminal calcium activation." FT /evidence="ECO:0000269|PubMed:33536282" FT MUTAGEN 4855 FT /note="I->M: Decreased function in release of sequestered FT calcium ion into cytosol by sarcoplasmic reticulum. Changed FT ryanodine-sensitive calcium-release channel activity. FT Mutant channels are less respositive to activation by FT caffeine and store calcium overload. Affects channel FT sensitivity to cytosolic and luminal calcium activation." FT /evidence="ECO:0000269|PubMed:33536282" FT MUTAGEN 4879 FT /note="Q->H: Decreased function in release of sequestered FT calcium ion into cytosol by sarcoplasmic reticulum. Changed FT ryanodine-sensitive calcium-release channel activity. FT Mutant channels are less respositive to activation by FT caffeine and store calcium overload. Affects channel FT sensitivity to cytosolic and luminal calcium activation." FT /evidence="ECO:0000269|PubMed:33536282" FT CONFLICT 1037 FT /note="L -> P (in Ref. 1; CAA66975 and 2; CAC18855)" FT /evidence="ECO:0000305" FT CONFLICT 2785..2789 FT /note="WGWRI -> RTMRT (in Ref. 1; CAA66975 and 2; FT CAC18855)" FT /evidence="ECO:0000305" FT STRAND 19..28 FT /evidence="ECO:0007829|PDB:4JKQ" FT STRAND 31..38 FT /evidence="ECO:0007829|PDB:4JKQ" FT STRAND 48..51 FT /evidence="ECO:0007829|PDB:4JKQ" FT TURN 53..57 FT /evidence="ECO:0007829|PDB:4JKQ" FT HELIX 63..65 FT /evidence="ECO:0007829|PDB:4JKQ" FT STRAND 67..73 FT /evidence="ECO:0007829|PDB:4JKQ" FT TURN 108..110 FT /evidence="ECO:0007829|PDB:4JKQ" FT STRAND 118..127 FT /evidence="ECO:0007829|PDB:4JKQ" FT STRAND 129..132 FT /evidence="ECO:0007829|PDB:4JKQ" FT TURN 139..141 FT /evidence="ECO:0007829|PDB:4JKQ" FT STRAND 145..151 FT /evidence="ECO:0007829|PDB:4JKQ" FT STRAND 159..166 FT /evidence="ECO:0007829|PDB:4JKQ" FT STRAND 180..185 FT /evidence="ECO:0007829|PDB:4JKQ" FT TURN 186..188 FT /evidence="ECO:0007829|PDB:4JKQ" FT STRAND 191..196 FT /evidence="ECO:0007829|PDB:4JKQ" FT STRAND 198..208 FT /evidence="ECO:0007829|PDB:4JKQ" FT STRAND 212..218 FT /evidence="ECO:0007829|PDB:4JKQ" FT STRAND 233..238 FT /evidence="ECO:0007829|PDB:4JKQ" FT TURN 239..242 FT /evidence="ECO:0007829|PDB:4JKQ" FT STRAND 243..246 FT /evidence="ECO:0007829|PDB:4JKQ" FT STRAND 250..252 FT /evidence="ECO:0007829|PDB:4JKQ" FT HELIX 256..258 FT /evidence="ECO:0007829|PDB:4JKQ" FT STRAND 261..263 FT /evidence="ECO:0007829|PDB:4JKQ" FT HELIX 265..269 FT /evidence="ECO:0007829|PDB:4JKQ" FT HELIX 271..273 FT /evidence="ECO:0007829|PDB:4JKQ" FT STRAND 275..280 FT /evidence="ECO:0007829|PDB:4JKQ" FT TURN 283..286 FT /evidence="ECO:0007829|PDB:4JKQ" FT STRAND 295..299 FT /evidence="ECO:0007829|PDB:4JKQ" FT TURN 300..302 FT /evidence="ECO:0007829|PDB:4JKQ" FT STRAND 305..308 FT /evidence="ECO:0007829|PDB:4JKQ" FT STRAND 310..312 FT /evidence="ECO:0007829|PDB:4JKQ" FT STRAND 314..317 FT /evidence="ECO:0007829|PDB:4JKQ" FT HELIX 319..321 FT /evidence="ECO:0007829|PDB:4JKQ" FT HELIX 324..327 FT /evidence="ECO:0007829|PDB:4JKQ" FT STRAND 329..336 FT /evidence="ECO:0007829|PDB:4JKQ" FT STRAND 340..342 FT /evidence="ECO:0007829|PDB:4JKQ" FT TURN 356..358 FT /evidence="ECO:0007829|PDB:4JKQ" FT STRAND 360..365 FT /evidence="ECO:0007829|PDB:4JKQ" FT TURN 366..368 FT /evidence="ECO:0007829|PDB:4JKQ" FT STRAND 371..375 FT /evidence="ECO:0007829|PDB:4JKQ" FT STRAND 388..396 FT /evidence="ECO:0007829|PDB:4JKQ" FT STRAND 403..407 FT /evidence="ECO:0007829|PDB:4JKQ" FT HELIX 410..437 FT /evidence="ECO:0007829|PDB:4JKQ" FT HELIX 442..444 FT /evidence="ECO:0007829|PDB:4JKQ" FT HELIX 449..462 FT /evidence="ECO:0007829|PDB:4JKQ" FT HELIX 472..491 FT /evidence="ECO:0007829|PDB:4JKQ" FT HELIX 494..506 FT /evidence="ECO:0007829|PDB:4JKQ" FT STRAND 508..510 FT /evidence="ECO:0007829|PDB:4JKQ" FT HELIX 511..518 FT /evidence="ECO:0007829|PDB:4JKQ" FT HELIX 520..541 FT /evidence="ECO:0007829|PDB:4JKQ" FT HELIX 3584..3604 FT /evidence="ECO:0007829|PDB:6Y4O" FT HELIX 4247..4272 FT /evidence="ECO:0007829|PDB:7KL5" SQ SEQUENCE 4967 AA; 564567 MW; 44984485F8677B42 CRC64; MADGGEGEDE IQFLRTDDEV VLQCTATIHK EQQKLCLAAE GFGNRLCFLE STSNSKNVPP DLSICTFVLE QSLSVRALQE MLANTVEKSE GQVDVEKWKF MMKTAQGGGH RTLLYGHAIL LRHSYSGMYL CCLSTSRSST DKLAFDVGLQ EDTTGEACWW TIHPASKQRS EGEKVRVGDD LILVSVSSER YLHLSYGNGS LHVDAAFQQT LWSVAPISSG SEAAQGYLIG GDVLRLLHGH MDECLTVPSG EHGEEQRRTV HYEGGAVSVH ARSLWRLETL RVAWSGSHIR WGQPFRLRHV TTGKYLSLME DKNLLLMDKE KADVKSTAFT FRSSKEKLDV GVRKEVDGMG TSEIKYGDSV CYIQHVDTGL WLTYQSVDVK SVRMGSIQRK AIMHHEGHMD DGISLSRSQH EESRTARVIR STVFLFNRFI RGLDALSKKA KASTVDLPIE SVSLSLQDLI GYFHPPDEHL EHEDKQNRLR ALKNRQNLFQ EEGMINLVLE CIDRLHVYSS AAHFADVAGR EAGESWKSIL NSLYELLAAL IRGNRKNCAQ FSGSLDWLIS RLERLEASSG ILEVLHCVLV ESPEALNIIK EGHIKSIISL LDKHGRNHKV LDVLCSLCVC HGVAVRSNQH LICDNLLPGR DLLLQTRLVN HVSSMRPNIF LGVSEGSAQY KKWYYELMVD HTEPFVTAEA THLRVGWAST EGYSPYPGGG EEWGGNGVGD DLFSYGFDGL HLWSGCIART VSSPNQHLLR TDDVISCCLD LSAPSISFRI NGQPVQGMFE NFNIDGLFFP VVSFSAGIKV RFLLGGRHGE FKFLPPPGYA PCYEAVLPKE KLKVEHSREY KQERTYTRDL LGPTVSLTQA AFTPIPVDTS QIVLPPHLER IREKLAENIH ELWVMNKIEL GWQYGPVRDD NKRQHPCLVE FSKLPEQERN YNLQMSLETL KTLLALGCHV GISDEHAEDK VKKMKLPKNY QLTSGYKPAP MDLSFIKLTP SQEAMVDKLA ENAHNVWARD RIRQGWTYGI QQDVKNRRNP RLVPYTLLDD RTKKSNKDSL REAVRTLLGY GYNLEAPDQD HAARAEVCSG TGERFRIFRA EKTYAVKAGR WYFEFETVTA GDMRVGWSRP GCQPDQELGS DERAFAFDGF KAQRWHQGNE HYGRSWQAGD VVGCMVDMNE HTMMFTLNGE ILLDDSGSEL AFKDFDVGDG FIPVCSLGVA QVGRMNFGKD VSTLKYFTIC GLQEGYEPFA VNTNRDITMW LSKRLPQFLQ VPSNHEHIEV TRIDGTIDSS PCLKVTQKSF GSQNSNTDIM FYRLSMPIEC AEVFSKTVAG GLPGAGLFGP KNDLEDYDAD SDFEVLMKTA HGHLVPDRVD KDKEATKPEF NNHKDYAQEK PSRLKQRFLL RRTKPDYSTS HSARLTEDVL ADDRDDYDFL MQTSTYYYSV RIFPGQEPAN VWVGWITSDF HQYDTGFDLD RVRTVTVTLG DEKGKVHESI KRSNCYMVCA GESMSPGQGR NNNGLEIGCV VDAASGLLTF IANGKELSTY YQVEPSTKLF PAVFAQATSP NVFQFELGRI KNVMPLSAGL FKSEHKNPVP QCPPRLHVQF LSHVLWSRMP NQFLKVDVSR ISERQGWLVQ CLDPLQFMSL HIPEENRSVD ILELTEQEEL LKFHYHTLRL YSAVCALGNH RVAHALCSHV DEPQLLYAIE NKYMPGLLRA GYYDLLIDIH LSSYATARLM MNNEYIVPMT EETKSITLFP DENKKHGLPG IGLSTSLRPR MQFSSPSFVS ISNECYQYSP EFPLDILKSK TIQMLTEAVK EGSLHARDPV GGTTEFLFVP LIKLFYTLLI MGIFHNEDLK HILQLIEPSV FKEAATPEEE SDTLEKELSV DDAKLQGAGE EEAKGGKRPK EGLLQMKLPE PVKLQMCLLL QYLCDCQVRH RIEAIVAFSD DFVAKLQDNQ RFRYNEVMQA LNMSAALTAR KTKEFRSPPQ EQINMLLNFK DDKSECPCPE EIRDQLLDFH EDLMTHCGIE LDEDGSLDGN SDLTIRGRLL SLVEKVTYLK KKQAEKPVES DSKKSSTLQQ LISETMVRWA QESVIEDPEL VRAMFVLLHR QYDGIGGLVR ALPKTYTING VSVEDTINLL ASLGQIRSLL SVRMGKEEEK LMIRGLGDIM NNKVFYQHPN LMRALGMHET VMEVMVNVLG GGESKEITFP KMVANCCRFL CYFCRISRQN QKAMFDHLSY LLENSSVGLA SPAMRGSTPL DVAAASVMDN NELALALREP DLEKVVRYLA GCGLQSCQML VSKGYPDIGW NPVEGERYLD FLRFAVFCNG ESVEENANVV VRLLIRRPEC FGPALRGEGG NGLLAAMEEA IKIAEDPSRD GPSPNSGSSK TLDTEEEEDD TIHMGNAIMT FYSALIDLLG RCAPEMHLIH AGKGEAIRIR SILRSLIPLG DLVGVISIAF QMPTIAKDGN VVEPDMSAGF CPDHKAAMVL FLDRVYGIEV QDFLLHLLEV GFLPDLRAAA SLDTAALSAT DMALALNRYL CTAVLPLLTR CAPLFAGTEH HASLIDSLLH TVYRLSKGCS LTKAQRDSIE VCLLSICGQL RPSMMQHLLR RLVFDVPLLN EHAKMPLKLL TNHYERCWKY YCLPGGWGNF GAASEEELHL SRKLFWGIFD ALSQKKYEQE LFKLALPCLS AVAGALPPDY MESNYVSMME KQSSMDSEGN FNPQPVDTSN ITIPEKLEYF INKYAEHSHD KWSMDKLANG WIYGEIYSDS SKVQPLMKPY KLLSEKEKEI YRWPIKESLK TMLAWGWRIE RTREGDSMAL YNRTRRISQT SQVSVDAAHG YSPRAIDMSN VTLSRDLHAM AEMMAENYHN IWAKKKKMEL ESKGGGNHPL LVPYDTLTAK EKAKDREKAQ DILKFLQING YAVSRGFKDL ELDTPSIEKR FAYSFLQQLI RYVDEAHQYI LEFDGGSRGK GEHFPYEQEI KFFAKVVLPL IDQYFKNHRL YFLSAASRPL CSGGHASNKE KEMVTSLFCK LGVLVRHRIS LFGNDATSIV NCLHILGQTL DARTVMKTGL ESVKSALRAF LDNAAEDLEK TMENLKQGQF THTRNQPKGV TQIINYTTVA LLPMLSSLFE HIGQHQFGED LILEDVQVSC YRILTSLYAL GTSKSIYVER QRSALGECLA AFAGAFPVAF LETHLDKHNI YSIYNTKSSR ERAALSLPTN VEDVCPNIPS LEKLMEEIVE LAESGIRYTQ MPHVMEVILP MLCSYMSRWW EHGPENNPER AEMCCTALNS EHMNTLLGNI LKIIYNNLGI DEGAWMKRLA VFSQPIINKV KPQLLKTHFL PLMEKLKKKA ATVVSEEDHL KAEARGDMSE AELLILDEFT TLARDLYAFY PLLIRFVDYN RAKWLKEPNP EAEELFRMVA EVFIYWSKSH NFKREEQNFV VQNEINNMSF LITDTKSKMS KAAVSDQERK KMKRKGDRYS MQTSLIVAAL KRLLPIGLNI CAPGDQELIA LAKNRFSLKD TEDEVRDIIR SNIHLQGKLE DPAIRWQMAL YKDLPNRTDD TSDPEKTVER VLDIANVLFH LEQKSKRVGR RHYCLVEHPQ RSKKAVWHKL LSKQRKRAVV ACFRMAPLYN LPRHRAVNLF LQGYEKSWIE TEEHYFEDKL IEDLAKPGAE PPEEDEGTKR VDPLHQLILL FSRTALTEKC KLEEDFLYMA YADIMAKSCH DEEDDDGEEE VKSFEEKEME KQKLLYQQAR LHDRGAAEMV LQTISASKGE TGPMVAATLK LGIAILNGGN STVQQKMLDY LKEKKDVGFF QSLAGLMQSC SVLDLNAFER QNKAEGLGMV TEEGSGEKVL QDDEFTCDLF RFLQLLCEGH NSDFQNYLRT QTGNNTTVNI IISTVDYLLR VQESISDFYW YYSGKDVIDE QGQRNFSKAI QVAKQVFNTL TEYIQGPCTG NQQSLAHSRL WDAVVGFLHV FAHMQMKLSQ DSSQIELLKE LMDLQKDMVV MLLSMLEGNV VNGTIGKQMV DMLVESSNNV EMILKFFDMF LKLKDLTSSD TFKEYDPDGK GVISKRDFHK AMESHKHYTQ SETEFLLSCA ETDENETLDY EEFVKRFHEP AKDIGFNVAV LLTNLSEHMP NDTRLQTFLE LAESVLNYFQ PFLGRIEIMG SAKRIERVYF EISESSRTQW EKPQVKESKR QFIFDVVNEG GEKEKMELFV NFCEDTIFEM QLAAQISESD LNERSANKEE SEKERPEEQG PRMAFFSILT VRSALFALRY NILTLMRMLS LKSLKKQMKK VKKMTVKDMV TAFFSSYWSI FMTLLHFVAS VFRGFFRIIC SLLLGGSLVE GAKKIKVAEL LANMPDPTQD EVRGDGEEGE RKPLEAALPS EDLTDLKELT EESDLLSDIF GLDLKREGGQ YKLIPHNPNA GLSDLMSNPV PMPEVQEKFQ EQKAKEEEKE EKEETKSEPE KAEGEDGEKE EKAKEDKGKQ KLRQLHTHRY GEPEVPESAF WKKIIAYQQK LLNYFARNFY NMRMLALFVA FAINFILLFY KVSTSSVVEG KELPTRSSSE NAKVTSLDSS SHRIIAVHYV LEESSGYMEP TLRILAILHT VISFFCIIGY YCLKVPLVIF KREKEVARKL EFDGLYITEQ PSEDDIKGQW DRLVINTQSF PNNYWDKFVK RKVMDKYGEF YGRDRISELL GMDKAALDFS DAREKKKPKK DSSLSAVLNS IDVKYQMWKL GVVFTDNSFL YLAWYMTMSV LGHYNNFFFA AHLLDIAMGF KTLRTILSSV THNGKQLVLT VGLLAVVVYL YTVVAFNFFR KFYNKSEDGD TPDMKCDDML TCYMFHMYVG VRAGGGIGDE IEDPAGDEYE IYRIIFDITF FFFVIVILLA IIQGLIIDAF GELRDQQEQV KEDMETKCFI CGIGNDYFDT VPHGFETHTL QEHNLANYLF FLMYLINKDE TEHTGQESYV WKMYQERCWE FFPAGDCFRK QYEDQLN //