RYR2_HUMAN
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 03-AUG-2022, entry version 227.
DE RecName: Full=Ryanodine receptor 2;
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;
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 ARVD2 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.
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, AND FUNCTION.
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, AND FUNCTION.
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: Calcium channel that mediates the release of Ca(2+) from the
CC sarcoplasmic reticulum into the cytoplasm and thereby plays a key role
CC in triggering cardiac muscle contraction. Aberrant channel activation
CC can lead to cardiac arrhythmia. In cardiac myocytes, calcium release is
CC triggered by increased Ca(2+) levels due to activation of the L-type
CC calcium channel CACNA1C. The calcium channel activity is modulated by
CC formation of heterotetramers with RYR3. Required for cellular calcium
CC ion homeostasis. Required for embryonic heart development.
CC {ECO:0000269|PubMed:10830164, ECO:0000269|PubMed:20056922,
CC ECO:0000269|PubMed:27733687, ECO:0000269|PubMed:33536282}.
CC -!- ACTIVITY REGULATION: Channel activity is modulated by the alkaloid
CC ryanodine that binds to the open Ca-release channel with high affinity.
CC At low concentrations, ryanodine maintains the channel in an open
CC conformation. High ryanodine concentrations inhibit channel activity.
CC Channel activity is regulated by calmodulin (CALM). The calcium release
CC is activated by increased cytoplasmic calcium levels, by nitric oxyde
CC (NO), caffeine and ATP. Channel activity is inhibited by magnesium
CC ions, 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}. Membrane {ECO:0000305|PubMed:10830164};
CC Multi-pass membrane protein {ECO:0000305|PubMed:10830164}. Sarcoplasmic
CC reticulum {ECO:0000250|UniProtKB:P30957}. Note=The number of predicted
CC transmembrane domains varies between orthologs, but both N-terminus and
CC C-terminus seem to be cytoplasmic. {ECO:0000250}.
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:0000305}.
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: Arrhythmogenic right ventricular dysplasia, familial, 2
CC (ARVD2) [MIM:600996]: A congenital heart disease characterized by
CC infiltration of adipose and fibrous tissue into the right ventricle and
CC loss of myocardial cells, resulting in ventricular and supraventricular
CC arrhythmias. {ECO:0000269|PubMed:11159936}. Note=The disease is caused
CC by variants affecting the gene represented in this entry.
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:11208676,
CC ECO:0000269|PubMed:12093772, ECO:0000269|PubMed:12106942,
CC ECO:0000269|PubMed:14571276, ECO:0000269|PubMed:15046072,
CC ECO:0000269|PubMed:15046073, ECO:0000269|PubMed:15466642,
CC ECO:0000269|PubMed:15544015, ECO:0000269|PubMed:16188589,
CC ECO:0000269|PubMed:24793461, ECO:0000269|PubMed:25372681,
CC ECO:0000269|PubMed:27733687}. Note=The disease is caused by variants
CC affecting the gene represented in this 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 PDBsum; 4JKQ; -.
DR PDBsum; 6Y4O; -.
DR PDBsum; 6Y4P; -.
DR PDBsum; 7KL5; -.
DR BMRB; Q92736; -.
DR SMR; Q92736; -.
DR BioGRID; 112174; 34.
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 GlyGen; Q92736; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q92736; -.
DR PhosphoSitePlus; Q92736; -.
DR BioMuta; RYR2; -.
DR DMDM; 308153558; -.
DR EPD; Q92736; -.
DR jPOST; Q92736; -.
DR MassIVE; Q92736; -.
DR MaxQB; Q92736; -.
DR PaxDb; Q92736; -.
DR PeptideAtlas; Q92736; -.
DR PRIDE; Q92736; -.
DR ProteomicsDB; 75431; -. [Q92736-1]
DR ProteomicsDB; 75432; -. [Q92736-2]
DR Antibodypedia; 3476; 245 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 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; 600996; phenotype.
DR MIM; 604772; phenotype.
DR neXtProt; NX_Q92736; -.
DR OpenTargets; ENSG00000198626; -.
DR Orphanet; 3286; Catecholaminergic polymorphic ventricular tachycardia.
DR Orphanet; 293899; Familial isolated arrhythmogenic ventricular dysplasia, biventricular form.
DR Orphanet; 293888; Familial isolated arrhythmogenic ventricular dysplasia, left dominant form.
DR Orphanet; 293910; Familial isolated arrhythmogenic ventricular dysplasia, right dominant form.
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; 5161at2759; -.
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; 5 hits in 1068 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 137 other tissues.
DR ExpressionAtlas; Q92736; baseline and differential.
DR Genevisible; Q92736; HS.
DR GO; GO:0034704; C:calcium channel complex; IDA:BHF-UCL.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IBA:GO_Central.
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:BHF-UCL.
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; IBA:GO_Central.
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:BHF-UCL.
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:0006874; P:cellular calcium ion homeostasis; ISS:UniProtKB.
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: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; IMP:BHF-UCL.
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: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; 2.60.120.920; -; 3.
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; IPR003032; Ryanodine_rcpt.
DR InterPro; IPR009460; Ryanrecept_TM4-6.
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 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; PF02026; RyR; 4.
DR Pfam; PF00622; SPRY; 3.
DR PRINTS; PR00795; RYANODINER.
DR SMART; SM00472; MIR; 4.
DR SMART; SM00449; SPRY; 3.
DR SUPFAM; SSF100909; SSF100909; 2.
DR SUPFAM; SSF47473; SSF47473; 1.
DR SUPFAM; SSF49899; SSF49899; 2.
DR SUPFAM; SSF82109; SSF82109; 2.
DR PROSITE; PS50188; B302_SPRY; 3.
DR PROSITE; PS50919; MIR; 5.
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; unknown
FT pathological significance; no effect on cytosolic Ca(2+)
FT 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 ARVD2 and 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 ARVD2 and 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; unknown pathological 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 ARVD2 and 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 ARVD2 and 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 resposive 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 resposive 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)"
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 store-
FT overload-induced Ca(2+) release (SOICR); HL1 cardiac cells
FT transfected with the G-4860 mutant displayed attenuated
FT SOICR activity compared to cells transfected with wild-type
FT 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 resposive 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 (probable disease-associated variant found in
FT a patient with intellectual disability, seizures, short
FT stature and severe atrial arrhythmias; 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 resposive 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 resposive 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 resposive 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 resposive 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
