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Database: UniProt
Entry: RYR2_HUMAN
LinkDB: RYR2_HUMAN
Original site: 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   13-FEB-2019, entry version 207.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; 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.,
RA   Walsh M.B., 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;
RP   PRO-433; 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
RT   type 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.,
RA   Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA   Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA   McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA   Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA   Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA   Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA   Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA   Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA   Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA   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.,
RA   Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA   Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA   Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA   Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA   Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA   Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA   Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA   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.,
RA   Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA   Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA   Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA   Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA   Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA   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,
RP   AND 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
RT   receptor/calcium-release channel genes in human tissues including the
RT   hippocampus and cerebellum.";
RL   Neuroscience 85:205-216(1998).
RN   [6]
RP   FUNCTION, IDENTIFICATION IN A COMPLEX WITH FKBP1B; PP1; PP2A AKAP6 AND
RP   PKA, INTERACTION WITH FKBP1B; PKA; PP1 AND PP2A, SUBCELLULAR LOCATION,
RP   TISSUE SPECIFICITY, MUTAGENESIS OF SER-2808, AND PHOSPHORYLATION AT
RP   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
RT   channel (ryanodine receptor): defective regulation in failing
RT   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+
RT   levels in right atrial myocardium of patients with atrial
RT   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
RT   the 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:0000244|PDB:4JKQ}
RP   X-RAY CRYSTALLOGRAPHY (2.39 ANGSTROMS) OF 1-606, AND CHARACTERIZATION
RP   OF 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.,
RA   Brahmbhatt B., Donarum E.A., Marino M., Tiso N., Viitasalo M.,
RA   Toivonen L., Stephan D.A., 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;
RP   SER-3946; LYS-4104; CYS-4497; ILE-4771; GLY-4860; MET-4867; ASP-4895
RP   AND LYS-4950.
RX   PubMed=12093772; DOI=10.1161/01.CIR.0000020013.73106.D8;
RA   Priori S.G., Napolitano C., Memmi M., Colombi B., Drago F.,
RA   Gasparini M., DeSimone L., Coltorti F., Bloise R., Keegan R.,
RA   Cruz Filho F.E.S., Vignati G., Benatar A., DeLogu A.;
RT   "Clinical and molecular characterization of patients with
RT   catecholaminergic 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
RP   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
RT   effort-induced polymorphic ventricular arrhythmias and sudden death:
RT   early 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;
RP   THR-4510; 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.,
RA   Ackerman M.J.;
RT   "Spectrum and frequency of cardiac channel defects in swimming-
RT   triggered 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
RT   medical 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)
RT   mutations in a cohort of unrelated patients referred explicitly for
RT   long QT syndrome 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.,
RA   Patry L., Massicotte C., Ambalavanan A., Spiegelman D., Diallo O.,
RA   Henrion E., Dionne-Laporte A., Fougerat A., Pshezhetsky A.V.,
RA   Venkateswaran S., 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 CPVT1 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
RT   is 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.,
RA   Xu L., Steinberg J.S., Markowitz S.M., Iwai S., Lacampagne A.,
RA   Lerman B.B., Marks A.R.;
RT   "Short-coupled polymorphic ventricular tachycardia at rest linked to a
RT   novel ryanodine receptor (RyR2) mutation: leaky RyR2 channels under
RT   non-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.,
RA   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
RP   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
RT   central domain cardiac ryanodine receptor mutations linked to
RT   arrhythmias.";
RL   J. Biol. Chem. 291:24528-24537(2016).
CC   -!- FUNCTION: Calcium channel that mediates the release of Ca(2+) from
CC       the sarcoplasmic reticulum into the cytoplasm and thereby plays a
CC       key role in triggering cardiac muscle contraction. Aberrant
CC       channel activation can lead to cardiac arrhythmia. In cardiac
CC       myocytes, calcium release is triggered by increased Ca(2+) levels
CC       due to activation of the L-type calcium channel CACNA1C. The
CC       calcium channel activity is modulated by formation of
CC       heterotetramers with RYR3. Required for cellular calcium ion
CC       homeostasis. Required for embryonic heart development.
CC       {ECO:0000269|PubMed:10830164, ECO:0000269|PubMed:20056922,
CC       ECO:0000269|PubMed:27733687}.
CC   -!- ACTIVITY REGULATION: Channel activity is modulated by the alkaloid
CC       ryanodine that binds to the open Ca-release channel with high
CC       affinity. At low concentrations, ryanodine maintains the channel
CC       in an open conformation. High ryanodine concentrations inhibit
CC       channel activity. Channel activity is regulated by calmodulin
CC       (CALM). The calcium release is activated by increased cytoplasmic
CC       calcium levels, by nitric oxyde (NO), caffeine and ATP. Channel
CC       activity is inhibited by magnesium ions, possibly by competition
CC       for calcium binding sites. {ECO:0000250|UniProtKB:P11716}.
CC   -!- SUBUNIT: Homotetramer. Can also form heterotetramers with RYR1 and
CC       RYR3 (By similarity). Interacts with FKBP1A and FKBP1B; these
CC       interactions may stabilize the channel in its closed state and
CC       prevent Ca(2+) leaks. Interacts with CALM and S100A1; these
CC       interactions regulate channel activity. Identified in a complex
CC       composed of RYR2, FKBP1B, PKA catalytic subunit, PRKAR2A, AKAP6,
CC       and the protein phosphatases PP2A and PP1. Interacts directly with
CC       FKBP1B, PKA, PP1 and PP2A. Interacts with SELENON (By similarity).
CC       In cardiac muscles, identified in a complex, composed of FSD2,
CC       CMYA5 and RYR2 (By similarity). {ECO:0000250|UniProtKB:E9Q401,
CC       ECO:0000250|UniProtKB:P30957, ECO:0000269|PubMed:10830164,
CC       ECO:0000269|PubMed:18650434}.
CC   -!- INTERACTION:
CC       P62942:FKBP1A; NbExp=2; IntAct=EBI-1170425, EBI-1027571;
CC       P68106:FKBP1B; NbExp=5; IntAct=EBI-1170425, EBI-6693977;
CC       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
CC       {ECO:0000305|PubMed:10830164}; Multi-pass membrane protein
CC       {ECO:0000305|PubMed:10830164}. Sarcoplasmic reticulum
CC       {ECO:0000250|UniProtKB:P30957}. Note=The number of predicted
CC       transmembrane domains varies between orthologs, but both N-
CC       terminus and 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).
CC       Heart 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-
CC       terminal region while the remaining part of the protein resides in
CC       the cytoplasm. {ECO:0000305}.
CC   -!- PTM: Channel activity is modulated by phosphorylation.
CC       Phosphorylation at Ser-2808 and Ser-2814 increases the open
CC       probability of the calcium channel. Phosphorylation is increased
CC       in failing heart, leading to calcium leaks and increased
CC       cytoplasmic Ca(2+) levels. {ECO:0000269|PubMed:10830164,
CC       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
CC       ventricle and loss of myocardial cells, resulting in ventricular
CC       and supraventricular arrhythmias. {ECO:0000269|PubMed:11159936}.
CC       Note=The disease is caused by mutations affecting the gene
CC       represented in this entry.
CC   -!- DISEASE: Ventricular tachycardia, catecholaminergic polymorphic,
CC       1, with or without atrial dysfunction and/or dilated
CC       cardiomyopathy (CPVT1) [MIM:604772]: An arrhythmogenic disorder
CC       characterized by stress-induced, bidirectional ventricular
CC       tachycardia that may degenerate into cardiac arrest and cause
CC       sudden death. Patients present with recurrent syncope, seizures,
CC       or sudden death after physical activity or emotional stress. CPVT1
CC       inheritance is autosomal dominant. {ECO:0000269|PubMed:11157710,
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:17984046,
CC       ECO:0000269|PubMed:24793461, ECO:0000269|PubMed:25372681,
CC       ECO:0000269|PubMed:27733687}. Note=The disease is caused by
CC       mutations affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the ryanodine receptor (TC 1.A.3.1) family.
CC       RYR2 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";
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   UniGene; Hs.109514; -.
DR   UniGene; Hs.738571; -.
DR   PDB; 4JKQ; X-ray; 2.39 A; A=1-606.
DR   PDBsum; 4JKQ; -.
DR   ProteinModelPortal; Q92736; -.
DR   SMR; Q92736; -.
DR   BioGrid; 112174; 27.
DR   ComplexPortal; CPX-3156; Ryanodine 2 complex.
DR   DIP; DIP-38325N; -.
DR   IntAct; Q92736; 13.
DR   MINT; Q92736; -.
DR   STRING; 9606.ENSP00000355533; -.
DR   ChEMBL; CHEMBL4403; -.
DR   DrugBank; DB09085; Tetracaine.
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   iPTMnet; Q92736; -.
DR   PhosphoSitePlus; Q92736; -.
DR   BioMuta; RYR2; -.
DR   DMDM; 308153558; -.
DR   EPD; Q92736; -.
DR   jPOST; Q92736; -.
DR   MaxQB; Q92736; -.
DR   PaxDb; Q92736; -.
DR   PeptideAtlas; Q92736; -.
DR   PRIDE; Q92736; -.
DR   ProteomicsDB; 75431; -.
DR   ProteomicsDB; 75432; -. [Q92736-2]
DR   Ensembl; ENST00000366574; ENSP00000355533; ENSG00000198626. [Q92736-1]
DR   GeneID; 6262; -.
DR   KEGG; hsa:6262; -.
DR   UCSC; uc001hyl.2; human. [Q92736-1]
DR   CTD; 6262; -.
DR   DisGeNET; 6262; -.
DR   EuPathDB; HostDB:ENSG00000198626.15; -.
DR   GeneCards; RYR2; -.
DR   GeneReviews; RYR2; -.
DR   HGNC; HGNC:10484; RYR2.
DR   HPA; HPA020028; -.
DR   MalaCards; RYR2; -.
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   eggNOG; KOG2243; Eukaryota.
DR   eggNOG; ENOG410YCNW; LUCA.
DR   GeneTree; ENSGT00940000154906; -.
DR   HOGENOM; HOG000231428; -.
DR   HOVERGEN; HBG006699; -.
DR   InParanoid; Q92736; -.
DR   KO; K04962; -.
DR   OMA; RFSMKDT; -.
DR   OrthoDB; 5161at2759; -.
DR   PhylomeDB; Q92736; -.
DR   TreeFam; TF315244; -.
DR   Reactome; R-HSA-2672351; Stimuli-sensing channels.
DR   Reactome; R-HSA-5578775; Ion homeostasis.
DR   SIGNOR; Q92736; -.
DR   ChiTaRS; RYR2; human.
DR   GeneWiki; Ryanodine_receptor_2; -.
DR   GenomeRNAi; 6262; -.
DR   PRO; PR:Q92736; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   Bgee; ENSG00000198626; Expressed in 151 organ(s), highest expression level in heart right ventricle.
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:0044325; F:ion channel binding; ISS: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:0030509; P:BMP signaling pathway; IEA:Ensembl.
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:0060070; P:canonical Wnt signaling pathway; IEA:Ensembl.
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:0072599; P:establishment of protein localization to endoplasmic reticulum; IDA:BHF-UCL.
DR   GO; GO:0034220; P:ion transmembrane transport; TAS:Reactome.
DR   GO; GO:0003220; P:left ventricular cardiac muscle tissue morphogenesis; ISS:BHF-UCL.
DR   GO; GO:1901896; P:positive regulation of calcium-transporting ATPase 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:1903779; P:regulation of cardiac conduction; TAS:Reactome.
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   InterPro; IPR001870; B30.2/SPRY.
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; IPR015925; Ryanodine_recept-rel.
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   PANTHER; PTHR13715; PTHR13715; 1.
DR   Pfam; PF13833; EF-hand_8; 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; 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   Complete proteome; Developmental protein; Disease mutation;
KW   Ion channel; Ion transport; Ligand-gated ion channel; Membrane;
KW   Phosphoprotein; Polymorphism; Receptor; Reference proteome; Repeat;
KW   Sarcoplasmic reticulum; Transmembrane; Transmembrane helix; Transport.
FT   CHAIN         1   4967       Ryanodine receptor 2.
FT                                /FTId=PRO_0000219361.
FT   TOPO_DOM      1   4281       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM   4282   4302       Helical. {ECO:0000255}.
FT   TRANSMEM   4504   4524       Helical. {ECO:0000255}.
FT   TRANSMEM   4580   4600       Helical. {ECO:0000255}.
FT   TRANSMEM   4730   4750       Helical. {ECO:0000255}.
FT   TRANSMEM   4769   4789       Helical. {ECO:0000255}.
FT   INTRAMEM   4820   4829       Pore-forming. {ECO:0000250}.
FT   TRANSMEM   4850   4870       Helical. {ECO:0000255}.
FT   TOPO_DOM   4871   4967       Cytoplasmic. {ECO:0000255}.
FT   DOMAIN      110    165       MIR 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00131}.
FT   DOMAIN      172    217       MIR 2. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00131}.
FT   DOMAIN      225    280       MIR 3. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00131}.
FT   DOMAIN      286    343       MIR 4. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00131}.
FT   DOMAIN      351    408       MIR 5. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00131}.
FT   DOMAIN      599    809       B30.2/SPRY 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00548}.
FT   REPEAT      853    966       1.
FT   REPEAT      967   1080       2.
FT   DOMAIN     1025   1222       B30.2/SPRY 2. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00548}.
FT   DOMAIN     1337   1562       B30.2/SPRY 3. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00548}.
FT   REPEAT     2692   2810       3.
FT   REPEAT     2812   2925       4.
FT   REGION      853   2925       4 X approximate repeats.
FT   REGION     3581   3610       Interaction with CALM.
FT                                {ECO:0000269|PubMed:18650434}.
FT   COILED     4412   4445       {ECO:0000255}.
FT   COMPBIAS   4414   4455       Glu-rich (acidic).
FT   MOD_RES    1341   1341       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:E9Q401}.
FT   MOD_RES    1869   1869       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:B0LPN4}.
FT   MOD_RES    2031   2031       Phosphoserine; by PKA.
FT                                {ECO:0000250|UniProtKB:E9Q401}.
FT   MOD_RES    2369   2369       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:E9Q401}.
FT   MOD_RES    2697   2697       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:B0LPN4}.
FT   MOD_RES    2797   2797       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:E9Q401}.
FT   MOD_RES    2808   2808       Phosphoserine; by CaMK2D and PKA.
FT                                {ECO:0000269|PubMed:10830164,
FT                                ECO:0000269|PubMed:20056922}.
FT   MOD_RES    2811   2811       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:E9Q401}.
FT   MOD_RES    2814   2814       Phosphoserine; by CaMK2D.
FT                                {ECO:0000269|PubMed:20056922}.
FT   MOD_RES    2947   2947       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:E9Q401}.
FT   VAR_SEQ    3715   3715       E -> EVTGSQRSK (in isoform 2).
FT                                {ECO:0000305}.
FT                                /FTId=VSP_005953.
FT   VARIANT      29     29       H -> D (found in a patient with short-
FT                                coupled polymorphic ventricular
FT                                tachycardia at rest; unknown pathological
FT                                significance; no effect on cytosolic
FT                                Ca(2+) activation).
FT                                {ECO:0000269|PubMed:25463374,
FT                                ECO:0000269|PubMed:26405799}.
FT                                /FTId=VAR_075283.
FT   VARIANT     164    164       P -> S (in CPVT1; dbSNP:rs764772142).
FT                                {ECO:0000269|PubMed:15466642}.
FT                                /FTId=VAR_044086.
FT   VARIANT     176    176       R -> Q (in ARVD2 and CPVT1;
FT                                dbSNP:rs794728708).
FT                                {ECO:0000269|PubMed:11159936,
FT                                ECO:0000269|PubMed:12106942,
FT                                ECO:0000269|PubMed:16188589}.
FT                                /FTId=VAR_044087.
FT   VARIANT     414    414       R -> L (in CPVT1; dbSNP:rs371121679).
FT                                {ECO:0000269|PubMed:15466642,
FT                                ECO:0000269|PubMed:16188589}.
FT                                /FTId=VAR_044088.
FT   VARIANT     419    419       I -> F (in CPVT1; decreases protein
FT                                stability; dbSNP:rs1349176732).
FT                                {ECO:0000269|PubMed:15466642,
FT                                ECO:0000269|PubMed:16188589,
FT                                ECO:0000269|PubMed:25372681}.
FT                                /FTId=VAR_044089.
FT   VARIANT     420    420       R -> W (in CPVT1; dbSNP:rs190140598).
FT                                {ECO:0000269|PubMed:12106942,
FT                                ECO:0000269|PubMed:15544015}.
FT                                /FTId=VAR_044090.
FT   VARIANT     433    433       L -> P (in ARVD2 and CPVT1;
FT                                dbSNP:rs121918602).
FT                                {ECO:0000269|PubMed:11159936,
FT                                ECO:0000269|PubMed:12106942}.
FT                                /FTId=VAR_011395.
FT   VARIANT     466    466       P -> A (in CPVT1; unknown pathological
FT                                significance; dbSNP:rs376612295).
FT                                {ECO:0000269|PubMed:16188589}.
FT                                /FTId=VAR_079513.
FT   VARIANT     507    507       V -> I (in dbSNP:rs16835270).
FT                                /FTId=VAR_044091.
FT   VARIANT    1886   1886       G -> S (in dbSNP:rs3766871).
FT                                /FTId=VAR_022078.
FT   VARIANT    2246   2246       S -> L (in CPVT1; dbSNP:rs121918597).
FT                                {ECO:0000269|PubMed:11208676,
FT                                ECO:0000269|PubMed:12093772,
FT                                ECO:0000269|PubMed:15544015}.
FT                                /FTId=VAR_011396.
FT   VARIANT    2306   2306       V -> I (in CPVT1; dbSNP:rs794728746).
FT                                {ECO:0000269|PubMed:14571276}.
FT                                /FTId=VAR_023694.
FT   VARIANT    2311   2311       E -> D (in CPVT1; dbSNP:rs794728747).
FT                                {ECO:0000269|PubMed:12093772}.
FT                                /FTId=VAR_044092.
FT   VARIANT    2328   2328       P -> S (in CPVT1; dbSNP:rs121918603).
FT                                {ECO:0000269|PubMed:11157710}.
FT                                /FTId=VAR_011397.
FT   VARIANT    2386   2386       N -> I (in ARVD2 and CPVT1;
FT                                dbSNP:rs121918601).
FT                                {ECO:0000269|PubMed:11159936,
FT                                ECO:0000269|PubMed:12106942}.
FT                                /FTId=VAR_011398.
FT   VARIANT    2387   2387       A -> P (in CPVT1; dbSNP:rs794728753).
FT                                {ECO:0000269|PubMed:15046073}.
FT                                /FTId=VAR_044093.
FT   VARIANT    2392   2392       Y -> C (in CPVT1; dbSNP:rs772220753).
FT                                {ECO:0000269|PubMed:12106942}.
FT                                /FTId=VAR_044094.
FT   VARIANT    2403   2403       A -> T (in CPVT1; dbSNP:rs1456929288).
FT                                {ECO:0000269|PubMed:15466642,
FT                                ECO:0000269|PubMed:16188589}.
FT                                /FTId=VAR_044095.
FT   VARIANT    2474   2474       R -> S (in CPVT1; dbSNP:rs121918598).
FT                                {ECO:0000269|PubMed:11208676,
FT                                ECO:0000269|PubMed:12093772}.
FT                                /FTId=VAR_011399.
FT   VARIANT    2504   2504       T -> M (in ARVD2 and CPVT1;
FT                                dbSNP:rs769219555).
FT                                {ECO:0000269|PubMed:11159936,
FT                                ECO:0000269|PubMed:12106942}.
FT                                /FTId=VAR_044096.
FT   VARIANT    2958   2958       Q -> R (in dbSNP:rs34967813).
FT                                {ECO:0000269|PubMed:11157710}.
FT                                /FTId=VAR_011590.
FT   VARIANT    3778   3778       L -> F (in CPVT1; dbSNP:rs1472508624).
FT                                {ECO:0000269|PubMed:12093772}.
FT                                /FTId=VAR_044097.
FT   VARIANT    3800   3800       C -> F (in CPVT1; dbSNP:rs1239093704).
FT                                {ECO:0000269|PubMed:16188589}.
FT                                /FTId=VAR_079514.
FT   VARIANT    3946   3946       G -> S (in CPVT1; changed ryanodine-
FT                                sensitive calcium-release channel
FT                                activity; increased sensitivity to
FT                                cytosolic calcium activation;
FT                                dbSNP:rs794728777).
FT                                {ECO:0000269|PubMed:12093772,
FT                                ECO:0000269|PubMed:27733687}.
FT                                /FTId=VAR_044098.
FT   VARIANT    4097   4097       N -> S (in CPVT1; dbSNP:rs794728784).
FT                                {ECO:0000269|PubMed:15544015}.
FT                                /FTId=VAR_044099.
FT   VARIANT    4104   4104       N -> K (in CPVT1; dbSNP:rs121918599).
FT                                {ECO:0000269|PubMed:11208676,
FT                                ECO:0000269|PubMed:12093772}.
FT                                /FTId=VAR_011400.
FT   VARIANT    4124   4124       S -> T (in CPVT1; changed ryanodine-
FT                                sensitive calcium-release channel
FT                                activity; increased sensitivity to
FT                                cytosolic calcium activation;
FT                                dbSNP:rs1385881911).
FT                                {ECO:0000269|PubMed:16188589,
FT                                ECO:0000269|PubMed:27733687}.
FT                                /FTId=VAR_079515.
FT   VARIANT    4146   4146       E -> K (in CPVT1; dbSNP:rs1349585791).
FT                                {ECO:0000269|PubMed:15544015}.
FT                                /FTId=VAR_044100.
FT   VARIANT    4158   4158       T -> P (in CPVT1; changed ryanodine-
FT                                sensitive calcium-release channel
FT                                activity; increased sensitivity to
FT                                cytosolic calcium activation;
FT                                dbSNP:rs1202962809).
FT                                {ECO:0000269|PubMed:15544015,
FT                                ECO:0000269|PubMed:27733687}.
FT                                /FTId=VAR_044101.
FT   VARIANT    4159   4159       Q -> P (in CPVT1; changed ryanodine-
FT                                sensitive calcium-release channel
FT                                activity; increased sensitivity to
FT                                cytosolic calcium activation;
FT                                dbSNP:rs1234963411).
FT                                {ECO:0000269|PubMed:24793461,
FT                                ECO:0000269|PubMed:27733687}.
FT                                /FTId=VAR_079516.
FT   VARIANT    4201   4201       Q -> R (in CPVT1; dbSNP:rs121918605).
FT                                {ECO:0000269|PubMed:11157710}.
FT                                /FTId=VAR_011401.
FT   VARIANT    4497   4497       R -> C (in CPVT1; dbSNP:rs121918600).
FT                                {ECO:0000269|PubMed:11208676,
FT                                ECO:0000269|PubMed:12093772,
FT                                ECO:0000269|PubMed:15544015}.
FT                                /FTId=VAR_011402.
FT   VARIANT    4499   4499       F -> C (in CPVT1; dbSNP:rs1457271141).
FT                                {ECO:0000269|PubMed:15466642,
FT                                ECO:0000269|PubMed:16188589}.
FT                                /FTId=VAR_044102.
FT   VARIANT    4504   4504       M -> I (in CPVT1; dbSNP:rs1323621379).
FT                                {ECO:0000269|PubMed:15046072}.
FT                                /FTId=VAR_044103.
FT   VARIANT    4510   4510       A -> T (in CPVT1; dbSNP:rs397516510).
FT                                {ECO:0000269|PubMed:15466642,
FT                                ECO:0000269|PubMed:16188589}.
FT                                /FTId=VAR_044104.
FT   VARIANT    4556   4556       A -> T (in CPVT1; dbSNP:rs189345192).
FT                                {ECO:0000269|PubMed:16188589}.
FT                                /FTId=VAR_079517.
FT   VARIANT    4607   4607       A -> P (in CPVT1; dbSNP:rs1359163728).
FT                                {ECO:0000269|PubMed:15046073}.
FT                                /FTId=VAR_044105.
FT   VARIANT    4653   4653       V -> F (in CPVT1; dbSNP:rs121918604).
FT                                {ECO:0000269|PubMed:11157710}.
FT                                /FTId=VAR_011403.
FT   VARIANT    4671   4671       G -> R (in CPVT1; dbSNP:rs1188352725).
FT                                {ECO:0000269|PubMed:15466642}.
FT                                /FTId=VAR_044106.
FT   VARIANT    4771   4771       V -> I (in CPVT1; dbSNP:rs794728804).
FT                                {ECO:0000269|PubMed:12093772}.
FT                                /FTId=VAR_044107.
FT   VARIANT    4848   4848       I -> V (in CPVT1; dbSNP:rs1363298408).
FT                                {ECO:0000269|PubMed:15466642,
FT                                ECO:0000269|PubMed:16188589}.
FT                                /FTId=VAR_044108.
FT   VARIANT    4860   4860       A -> G (in CPVT1; diminishes the response
FT                                to activation by luminal Ca(2+) but has
FT                                little effect on the sensitivity of the
FT                                channel to activation by cytosolic
FT                                Ca(2+); shows caffeine-induced Ca(2+)
FT                                release but exhibits no store-overload-
FT                                induced Ca(2+) release (SOICR); HL1
FT                                cardiac cells transfected with the G-4860
FT                                mutant displayed attenuated SOICR
FT                                activity compared to cells transfected
FT                                with wild-type RYR2; dbSNP:rs121918606).
FT                                {ECO:0000269|PubMed:12093772,
FT                                ECO:0000269|PubMed:17984046}.
FT                                /FTId=VAR_044109.
FT   VARIANT    4867   4867       I -> M (in CPVT1; dbSNP:rs1218096653).
FT                                {ECO:0000269|PubMed:12093772}.
FT                                /FTId=VAR_044110.
FT   VARIANT    4880   4880       V -> A (in CPVT1; dbSNP:rs1242723821).
FT                                {ECO:0000269|PubMed:15046072}.
FT                                /FTId=VAR_044111.
FT   VARIANT    4895   4895       N -> D (in CPVT1; dbSNP:rs1185619003).
FT                                {ECO:0000269|PubMed:12093772}.
FT                                /FTId=VAR_044112.
FT   VARIANT    4902   4902       P -> L (in CPVT1; dbSNP:rs1475453069).
FT                                {ECO:0000269|PubMed:14571276}.
FT                                /FTId=VAR_023695.
FT   VARIANT    4950   4950       E -> K (in CPVT1; dbSNP:rs886039172).
FT                                {ECO:0000269|PubMed:12093772}.
FT                                /FTId=VAR_044113.
FT   VARIANT    4955   4955       G -> E (probable disease-associated
FT                                mutation found in a patient with
FT                                intellectual disability, seizures, short
FT                                stature and severe atrial arrhythmias).
FT                                {ECO:0000269|PubMed:25356899}.
FT                                /FTId=VAR_078648.
FT   VARIANT    4959   4959       R -> Q (in CPVT1; dbSNP:rs794728811).
FT                                {ECO:0000269|PubMed:14571276,
FT                                ECO:0000269|PubMed:16188589}.
FT                                /FTId=VAR_023696.
FT   MUTAGEN    2808   2808       S->A: Abolishes phosphorylation by PKA.
FT                                {ECO:0000269|PubMed:10830164}.
FT   MUTAGEN    3946   3946       G->A: Changed ryanodine-sensitive
FT                                calcium-release channel activity
FT                                characterized by increased sensitivity to
FT                                cytosolic calcium activation.
FT                                {ECO:0000269|PubMed:27733687}.
FT   MUTAGEN    3978   3978       M->I: Changed ryanodine-sensitive
FT                                calcium-release channel activity
FT                                characterized by increased sensitivity to
FT                                cytosolic calcium activation.
FT                                {ECO:0000269|PubMed:27733687}.
FT   MUTAGEN    4108   4108       H->N: Changed ryanodine-sensitive
FT                                calcium-release channel activity
FT                                characterized by increased sensitivity to
FT                                cytosolic calcium activation.
FT                                {ECO:0000269|PubMed:27733687}.
FT   MUTAGEN    4108   4108       H->Q: Changed ryanodine-sensitive
FT                                calcium-release channel activity
FT                                characterized by increased sensitivity to
FT                                cytosolic calcium activation.
FT                                {ECO:0000269|PubMed:27733687}.
FT   CONFLICT   1037   1037       L -> P (in Ref. 1; CAA66975 and 2;
FT                                CAC18855). {ECO:0000305}.
FT   CONFLICT   2785   2789       WGWRI -> RTMRT (in Ref. 1; CAA66975 and
FT                                2; CAC18855). {ECO:0000305}.
FT   STRAND       19     28       {ECO:0000244|PDB:4JKQ}.
FT   STRAND       31     38       {ECO:0000244|PDB:4JKQ}.
FT   STRAND       48     51       {ECO:0000244|PDB:4JKQ}.
FT   TURN         53     57       {ECO:0000244|PDB:4JKQ}.
FT   HELIX        63     65       {ECO:0000244|PDB:4JKQ}.
FT   STRAND       67     73       {ECO:0000244|PDB:4JKQ}.
FT   TURN        108    110       {ECO:0000244|PDB:4JKQ}.
FT   STRAND      118    127       {ECO:0000244|PDB:4JKQ}.
FT   STRAND      129    132       {ECO:0000244|PDB:4JKQ}.
FT   TURN        139    141       {ECO:0000244|PDB:4JKQ}.
FT   STRAND      145    151       {ECO:0000244|PDB:4JKQ}.
FT   STRAND      159    166       {ECO:0000244|PDB:4JKQ}.
FT   STRAND      180    185       {ECO:0000244|PDB:4JKQ}.
FT   TURN        186    188       {ECO:0000244|PDB:4JKQ}.
FT   STRAND      191    196       {ECO:0000244|PDB:4JKQ}.
FT   STRAND      198    208       {ECO:0000244|PDB:4JKQ}.
FT   STRAND      212    218       {ECO:0000244|PDB:4JKQ}.
FT   STRAND      233    238       {ECO:0000244|PDB:4JKQ}.
FT   TURN        239    242       {ECO:0000244|PDB:4JKQ}.
FT   STRAND      243    246       {ECO:0000244|PDB:4JKQ}.
FT   STRAND      250    252       {ECO:0000244|PDB:4JKQ}.
FT   HELIX       256    258       {ECO:0000244|PDB:4JKQ}.
FT   STRAND      261    263       {ECO:0000244|PDB:4JKQ}.
FT   HELIX       265    269       {ECO:0000244|PDB:4JKQ}.
FT   HELIX       271    273       {ECO:0000244|PDB:4JKQ}.
FT   STRAND      275    280       {ECO:0000244|PDB:4JKQ}.
FT   TURN        283    286       {ECO:0000244|PDB:4JKQ}.
FT   STRAND      295    299       {ECO:0000244|PDB:4JKQ}.
FT   TURN        300    302       {ECO:0000244|PDB:4JKQ}.
FT   STRAND      305    308       {ECO:0000244|PDB:4JKQ}.
FT   STRAND      310    312       {ECO:0000244|PDB:4JKQ}.
FT   STRAND      314    317       {ECO:0000244|PDB:4JKQ}.
FT   HELIX       319    321       {ECO:0000244|PDB:4JKQ}.
FT   HELIX       324    327       {ECO:0000244|PDB:4JKQ}.
FT   STRAND      329    336       {ECO:0000244|PDB:4JKQ}.
FT   STRAND      340    342       {ECO:0000244|PDB:4JKQ}.
FT   TURN        356    358       {ECO:0000244|PDB:4JKQ}.
FT   STRAND      360    365       {ECO:0000244|PDB:4JKQ}.
FT   TURN        366    368       {ECO:0000244|PDB:4JKQ}.
FT   STRAND      371    375       {ECO:0000244|PDB:4JKQ}.
FT   STRAND      388    396       {ECO:0000244|PDB:4JKQ}.
FT   STRAND      403    407       {ECO:0000244|PDB:4JKQ}.
FT   HELIX       410    437       {ECO:0000244|PDB:4JKQ}.
FT   HELIX       442    444       {ECO:0000244|PDB:4JKQ}.
FT   HELIX       449    462       {ECO:0000244|PDB:4JKQ}.
FT   HELIX       472    491       {ECO:0000244|PDB:4JKQ}.
FT   HELIX       494    506       {ECO:0000244|PDB:4JKQ}.
FT   STRAND      508    510       {ECO:0000244|PDB:4JKQ}.
FT   HELIX       511    518       {ECO:0000244|PDB:4JKQ}.
FT   HELIX       520    541       {ECO:0000244|PDB:4JKQ}.
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
//
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