RYR2_MOUSE
ID RYR2_MOUSE Reviewed; 4966 AA.
AC E9Q401; O70181; Q62174; Q62197; Q9ERN6;
DT 22-FEB-2012, integrated into UniProtKB/Swiss-Prot.
DT 05-APR-2011, sequence version 1.
DT 03-AUG-2022, entry version 97.
DE RecName: Full=Ryanodine receptor 2;
DE Short=RYR-2;
DE Short=RyR2;
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, AND
RP MUTAGENESIS OF GLY-4819; ARG-4821; GLY-4823; GLY-4824; GLY-4825; GLY-4827
RP AND ASP-4828.
RX PubMed=10473538; DOI=10.1074/jbc.274.37.25971;
RA Zhao M., Li P., Li X., Zhang L., Winkfein R.J., Chen S.R.;
RT "Molecular identification of the ryanodine receptor pore-forming segment.";
RL J. Biol. Chem. 274:25971-25974(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-16, FUNCTION, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=9628868; DOI=10.1093/emboj/17.12.3309;
RA Takeshima H., Komazaki S., Hirose K., Nishi M., Noda T., Iino M.;
RT "Embryonic lethality and abnormal cardiac myocytes in mice lacking
RT ryanodine receptor type 2.";
RL EMBO J. 17:3309-3316(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4145-4966, AND TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ; TISSUE=Brain;
RX PubMed=7876312; DOI=10.1083/jcb.128.5.893;
RA Giannini G., Conti A., Mammarella S., Scrobogna M., Sorrentino V.;
RT "The ryanodine receptor/calcium channel genes are widely and differentially
RT expressed in murine brain and peripheral tissues.";
RL J. Cell Biol. 128:893-904(1995).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4863-4966, AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J; TISSUE=Heart;
RX PubMed=7621815; DOI=10.1002/j.1460-2075.1995.tb07302.x;
RA Takeshima H., Yamazawa T., Ikemoto T., Takekura H., Nishi M., Noda T.,
RA Iino M.;
RT "Ca(2+)-induced Ca2+ release in myocytes from dyspedic mice lacking the
RT type-1 ryanodine receptor.";
RL EMBO J. 14:2999-3006(1995).
RN [6]
RP PHOSPHORYLATION AT SER-2030.
RX PubMed=17693412; DOI=10.1074/jbc.m703510200;
RA Xiao B., Tian X., Xie W., Jones P.P., Cai S., Wang X., Jiang D., Kong H.,
RA Zhang L., Chen K., Walsh M.P., Cheng H., Chen S.R.W.;
RT "Functional consequence of protein kinase A-dependent phosphorylation of
RT the cardiac ryanodine receptor: sensitization of store overload-induced
RT Ca2+ release.";
RL J. Biol. Chem. 282:30256-30264(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1341; SER-2368; SER-2796;
RP SER-2807; SER-2810; SER-2813 AND SER-2946, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, and Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP FUNCTION, PHOSPHORYLATION AT SER-2807 AND SER-2813, INTERACTION WITH
RP FKBP1B, AND MUTAGENESIS OF SER-2813.
RX PubMed=21098440; DOI=10.1161/circulationaha.110.982298;
RA van Oort R.J., McCauley M.D., Dixit S.S., Pereira L., Yang Y.,
RA Respress J.L., Wang Q., De Almeida A.C., Skapura D.G., Anderson M.E.,
RA Bers D.M., Wehrens X.H.;
RT "Ryanodine receptor phosphorylation by calcium/calmodulin-dependent protein
RT kinase II promotes life-threatening ventricular arrhythmias in mice with
RT heart failure.";
RL Circulation 122:2669-2679(2010).
RN [9]
RP FUNCTION, INTERACTION WITH FKBP1A AND FKBP1B, AND PHOSPHORYLATION AT
RP SER-2807.
RX PubMed=20431056; DOI=10.1161/circresaha.110.219816;
RA Guo T., Cornea R.L., Huke S., Camors E., Yang Y., Picht E., Fruen B.R.,
RA Bers D.M.;
RT "Kinetics of FKBP12.6 binding to ryanodine receptors in permeabilized
RT cardiac myocytes and effects on Ca sparks.";
RL Circ. Res. 106:1743-1752(2010).
RN [10]
RP REVIEW.
RX PubMed=20214899; DOI=10.1016/j.febslet.2010.03.005;
RA Kushnir A., Betzenhauser M.J., Marks A.R.;
RT "Ryanodine receptor studies using genetically engineered mice.";
RL FEBS Lett. 584:1956-1965(2010).
RN [11]
RP SUBUNIT.
RX PubMed=28740084; DOI=10.1038/s41598-017-06395-6;
RA Benson M.A., Tinsley C.L., Waite A.J., Carlisle F.A., Sweet S.M.M.,
RA Ehler E., George C.H., Lai F.A., Martin-Rendon E., Blake D.J.;
RT "Ryanodine receptors are part of the myospryn complex in cardiac muscle.";
RL Sci. Rep. 7:6312-6312(2017).
RN [12]
RP MUTAGENESIS OF ASP-4645.
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).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 1-217, AND MUTAGENESIS OF ALA-77
RP AND VAL-186.
RX PubMed=19913485; DOI=10.1016/j.str.2009.08.016;
RA Lobo P.A., Van Petegem F.;
RT "Crystal structures of the N-terminal domains of cardiac and skeletal
RT muscle ryanodine receptors: insights into disease mutations.";
RL Structure 17:1505-1514(2009).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1-217.
RX PubMed=21645850; DOI=10.1016/j.str.2011.03.016;
RA Lobo P.A., Kimlicka L., Tung C.C., Van Petegem F.;
RT "The deletion of exon 3 in the cardiac ryanodine receptor is rescued by
RT beta strand switching.";
RL Structure 19:790-798(2011).
RN [15] {ECO:0007744|PDB:4ETV}
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 2699-2904.
RX PubMed=22705209; DOI=10.1016/j.str.2012.04.015;
RA Yuchi Z., Lau K., Van Petegem F.;
RT "Disease mutations in the ryanodine receptor central region: crystal
RT structures of a phosphorylation hot spot domain.";
RL Structure 20:1201-1211(2012).
RN [16] {ECO:0007744|PDB:2MC2, ECO:0007744|PDB:4KEI, ECO:0007744|PDB:4KEJ, ECO:0007744|PDB:4KEK}
RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 1-217, AND DISULFIDE BONDS.
RX PubMed=23978697; DOI=10.1016/j.jmb.2013.08.015;
RA Amador F.J., Kimlicka L., Stathopulos P.B., Gasmi-Seabrook G.M.,
RA Maclennan D.H., Van Petegem F., Ikura M.;
RT "Type 2 ryanodine receptor domain A contains a unique and dynamic alpha-
RT helix that transitions to a beta-strand in a mutant linked with a heritable
RT cardiomyopathy.";
RL J. Mol. Biol. 425:4034-4046(2013).
RN [17] {ECO:0007744|PDB:5C33}
RP X-RAY CRYSTALLOGRAPHY (1.21 ANGSTROMS) OF 650-844.
RX PubMed=26245150; DOI=10.1038/ncomms8947;
RA Yuchi Z., Yuen S.M., Lau K., Underhill A.Q., Cornea R.L., Fessenden J.D.,
RA Van Petegem F.;
RT "Crystal structures of ryanodine receptor SPRY1 and tandem-repeat domains
RT reveal a critical FKBP12 binding determinant.";
RL Nat. Commun. 6:7947-7947(2015).
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:10473538, ECO:0000269|PubMed:20431056,
CC ECO:0000269|PubMed:21098440, ECO:0000269|PubMed:9628868}.
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 (By
CC similarity). {ECO:0000250|UniProtKB:P11716}.
CC -!- SUBUNIT: Homotetramer. Can also form heterotetramers with RYR1 and
CC RYR3. Interacts with CALM and S100A1; these interactions regulate
CC channel 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 (By
CC similarity). Interacts with FKBP1A and FKBP1B; these interactions may
CC stabilize the channel in its closed state and prevent Ca(2+) leaks.
CC Interacts with SELENON (By similarity). Identified in a complex,
CC composed of FSD2, CMYA5 and RYR2 (PubMed:28740084).
CC {ECO:0000250|UniProtKB:P30957, ECO:0000250|UniProtKB:Q92736,
CC ECO:0000269|PubMed:10473538, ECO:0000269|PubMed:20431056,
CC ECO:0000269|PubMed:21098440, ECO:0000269|PubMed:28740084}.
CC -!- INTERACTION:
CC E9Q401; Q6PHZ2: Camk2d; NbExp=2; IntAct=EBI-643628, EBI-2308458;
CC E9Q401; Q9Z2I2: Fkbp1b; NbExp=3; IntAct=EBI-643628, EBI-6379859;
CC E9Q401; Q8K4S1: Plce1; NbExp=2; IntAct=EBI-643628, EBI-6902760;
CC E9Q401; E9Q401: Ryr2; NbExp=7; IntAct=EBI-643628, EBI-643628;
CC E9Q401; P23327: HRC; Xeno; NbExp=3; IntAct=EBI-643628, EBI-9639760;
CC -!- SUBCELLULAR LOCATION: Sarcoplasmic reticulum membrane
CC {ECO:0000305|PubMed:10473538}; Multi-pass membrane protein
CC {ECO:0000305|PubMed:10473538}. Membrane {ECO:0000305|PubMed:10473538};
CC Multi-pass membrane protein {ECO:0000305|PubMed:10473538}. 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 -!- TISSUE SPECIFICITY: Highly expressed in heart, lung, cerebellum and
CC brain. Detected at lower levels in adrenal gland, stomach, thymus,
CC esophagus and ovary. {ECO:0000269|PubMed:7621815,
CC ECO:0000269|PubMed:7876312}.
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-2807 and Ser-2813 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:17693412, ECO:0000269|PubMed:20431056,
CC ECO:0000269|PubMed:21098440}.
CC -!- PTM: Phosphorylation at Ser-2030 by PKA enhances the response to
CC lumenal calcium. {ECO:0000269|PubMed:17693412}.
CC -!- DISRUPTION PHENOTYPE: Embryonically lethal. Embryos die at about 10
CC dpc, due to defects in heart tube development. Cardiac myotubes display
CC enlarged rough endoplasmic reticulum and cytoplasmic vesicles that
CC contain high levels of Ca(2+). {ECO:0000269|PubMed:9628868}.
CC -!- SIMILARITY: Belongs to the ryanodine receptor (TC 1.A.3.1) family. RYR2
CC subfamily. {ECO:0000305}.
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; AF295105; AAG34081.1; -; mRNA.
DR EMBL; AC131329; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC159208; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CT010468; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CT572985; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AB012003; BAA25137.1; -; Genomic_DNA.
DR EMBL; X83933; CAA58785.1; -; mRNA.
DR EMBL; D38217; BAA07392.1; -; mRNA.
DR CCDS; CCDS49206.1; -.
DR PIR; I48742; I48742.
DR RefSeq; NP_076357.2; NM_023868.2.
DR PDB; 2MC2; NMR; -; A=10-224.
DR PDB; 3IM5; X-ray; 2.55 A; A/B=1-217.
DR PDB; 3IM6; X-ray; 1.70 A; A=1-217.
DR PDB; 3IM7; X-ray; 2.21 A; A=1-217.
DR PDB; 3QR5; X-ray; 2.30 A; A/B=1-217.
DR PDB; 4ETV; X-ray; 1.65 A; A/B=2699-2904.
DR PDB; 4KEI; X-ray; 2.41 A; A=1-217.
DR PDB; 4KEJ; X-ray; 2.55 A; A=1-217.
DR PDB; 4KEK; X-ray; 2.15 A; A=1-217.
DR PDB; 4L4H; X-ray; 2.00 A; A=1-547.
DR PDB; 4L4I; X-ray; 2.15 A; A=1-547.
DR PDB; 4P9I; X-ray; 1.34 A; A=1080-1253.
DR PDB; 4P9L; X-ray; 1.44 A; A=1080-1253.
DR PDB; 5C33; X-ray; 1.21 A; A/B=650-844.
DR PDB; 5VSN; X-ray; 1.44 A; A=1084-1252.
DR PDB; 6J6L; X-ray; 1.45 A; A/B=650-844.
DR PDB; 6MM5; X-ray; 1.95 A; C=2799-2810.
DR PDB; 6MM6; X-ray; 2.39 A; D/F=2699-2904.
DR PDB; 6MM7; X-ray; 1.85 A; C/E=2699-2904.
DR PDB; 6MM8; X-ray; 1.85 A; D=2699-2904.
DR PDB; 6WOU; EM; 3.27 A; A/B/C/D=1-4966.
DR PDB; 6WOV; EM; 5.10 A; A/B/C/D=1-4966.
DR PDBsum; 2MC2; -.
DR PDBsum; 3IM5; -.
DR PDBsum; 3IM6; -.
DR PDBsum; 3IM7; -.
DR PDBsum; 3QR5; -.
DR PDBsum; 4ETV; -.
DR PDBsum; 4KEI; -.
DR PDBsum; 4KEJ; -.
DR PDBsum; 4KEK; -.
DR PDBsum; 4L4H; -.
DR PDBsum; 4L4I; -.
DR PDBsum; 4P9I; -.
DR PDBsum; 4P9L; -.
DR PDBsum; 5C33; -.
DR PDBsum; 5VSN; -.
DR PDBsum; 6J6L; -.
DR PDBsum; 6MM5; -.
DR PDBsum; 6MM6; -.
DR PDBsum; 6MM7; -.
DR PDBsum; 6MM8; -.
DR PDBsum; 6WOU; -.
DR PDBsum; 6WOV; -.
DR BMRB; E9Q401; -.
DR SMR; E9Q401; -.
DR BioGRID; 203046; 22.
DR ComplexPortal; CPX-3137; Ryanodine 2 complex.
DR IntAct; E9Q401; 66.
DR MINT; E9Q401; -.
DR STRING; 10090.ENSMUSP00000021750; -.
DR MoonDB; E9Q401; Predicted.
DR iPTMnet; E9Q401; -.
DR PhosphoSitePlus; E9Q401; -.
DR SwissPalm; E9Q401; -.
DR jPOST; E9Q401; -.
DR MaxQB; E9Q401; -.
DR PaxDb; E9Q401; -.
DR PeptideAtlas; E9Q401; -.
DR PRIDE; E9Q401; -.
DR ProteomicsDB; 260963; -.
DR Antibodypedia; 3476; 245 antibodies from 31 providers.
DR DNASU; 20191; -.
DR Ensembl; ENSMUST00000021750; ENSMUSP00000021750; ENSMUSG00000021313.
DR GeneID; 20191; -.
DR KEGG; mmu:20191; -.
DR UCSC; uc007pld.1; mouse.
DR CTD; 6262; -.
DR MGI; MGI:99685; Ryr2.
DR VEuPathDB; HostDB:ENSMUSG00000021313; -.
DR eggNOG; KOG2243; Eukaryota.
DR GeneTree; ENSGT00940000154906; -.
DR HOGENOM; CLU_000040_2_0_1; -.
DR InParanoid; E9Q401; -.
DR OMA; HYEDTSD; -.
DR OrthoDB; 5161at2759; -.
DR PhylomeDB; E9Q401; -.
DR TreeFam; TF315244; -.
DR Reactome; R-MMU-2672351; Stimuli-sensing channels.
DR Reactome; R-MMU-5578775; Ion homeostasis.
DR BioGRID-ORCS; 20191; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Ryr2; mouse.
DR PRO; PR:E9Q401; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; E9Q401; protein.
DR Bgee; ENSMUSG00000021313; Expressed in myocardium of ventricle and 145 other tissues.
DR ExpressionAtlas; E9Q401; baseline and differential.
DR Genevisible; E9Q401; MM.
DR GO; GO:0031672; C:A band; ISO:MGI.
DR GO; GO:0034704; C:calcium channel complex; IDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IC:MGI.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0043005; C:neuron projection; ISO:MGI.
DR GO; GO:0005635; C:nuclear envelope; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0042383; C:sarcolemma; ISO:MGI.
DR GO; GO:0030017; C:sarcomere; IDA:BHF-UCL.
DR GO; GO:0016529; C:sarcoplasmic reticulum; IDA:BHF-UCL.
DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; IDA:MGI.
DR GO; GO:0005790; C:smooth endoplasmic reticulum; IDA:MGI.
DR GO; GO:0030018; C:Z disc; IDA:MGI.
DR GO; GO:0005262; F:calcium channel activity; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central.
DR GO; GO:0048763; F:calcium-induced calcium release activity; ISO:MGI.
DR GO; GO:0015278; F:calcium-release channel activity; IDA:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; IDA:MGI.
DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0097159; F:organic cyclic compound binding; IPI:MGI.
DR GO; GO:0034236; F:protein kinase A catalytic subunit binding; ISO:MGI.
DR GO; GO:0034237; F:protein kinase A regulatory subunit binding; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; IPI:BHF-UCL.
DR GO; GO:0043621; F:protein self-association; IMP:UniProtKB.
DR GO; GO:0005219; F:ryanodine-sensitive calcium-release channel activity; IDA:MGI.
DR GO; GO:0097110; F:scaffold protein binding; ISO:MGI.
DR GO; GO:0043924; F:suramin binding; ISO:MGI.
DR GO; GO:0097553; P:calcium ion transmembrane import into cytosol; IMP:MGI.
DR GO; GO:0070588; P:calcium ion transmembrane transport; IMP:MGI.
DR GO; GO:0006816; P:calcium ion transport; IDA:UniProtKB.
DR GO; GO:0060402; P:calcium ion transport into cytosol; ISO:MGI.
DR GO; GO:0019722; P:calcium-mediated signaling; IMP:UniProtKB.
DR GO; GO:0035584; P:calcium-mediated signaling using intracellular calcium source; ISO:MGI.
DR GO; GO:0060048; P:cardiac muscle contraction; ISO:MGI.
DR GO; GO:0003300; P:cardiac muscle hypertrophy; IMP:MGI.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IMP:UniProtKB.
DR GO; GO:0071313; P:cellular response to caffeine; IDA:UniProtKB.
DR GO; GO:0071872; P:cellular response to epinephrine stimulus; IMP:BHF-UCL.
DR GO; GO:0005513; P:detection of calcium ion; ISO:MGI.
DR GO; GO:0003143; P:embryonic heart tube morphogenesis; IMP:UniProtKB.
DR GO; GO:0051649; P:establishment of localization in cell; IMP:MGI.
DR GO; GO:0072599; P:establishment of protein localization to endoplasmic reticulum; ISO:MGI.
DR GO; GO:0034220; P:ion transmembrane transport; ISO:MGI.
DR GO; GO:0003220; P:left ventricular cardiac muscle tissue morphogenesis; IMP:MGI.
DR GO; GO:0071421; P:manganese ion transmembrane transport; ISO:MGI.
DR GO; GO:0051481; P:negative regulation of cytosolic calcium ion concentration; ISO:MGI.
DR GO; GO:1901896; P:positive regulation of ATPase-coupled calcium transmembrane transporter activity; ISO:MGI.
DR GO; GO:0010460; P:positive regulation of heart rate; IMP:MGI.
DR GO; GO:0051284; P:positive regulation of sequestering of calcium ion; ISO:MGI.
DR GO; GO:0098735; P:positive regulation of the force of heart contraction; ISO:MGI.
DR GO; GO:0086029; P:Purkinje myocyte to ventricular cardiac muscle cell signaling; IMP:BHF-UCL.
DR GO; GO:0098910; P:regulation of atrial cardiac muscle cell action potential; ISO:MGI.
DR GO; GO:0098904; P:regulation of AV node cell action potential; ISO:MGI.
DR GO; GO:0055117; P:regulation of cardiac muscle contraction; ISO:MGI.
DR GO; GO:0010882; P:regulation of cardiac muscle contraction by calcium ion signaling; ISO:MGI.
DR GO; GO:0010881; P:regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion; IGI:BHF-UCL.
DR GO; GO:0051480; P:regulation of cytosolic calcium ion concentration; ISO:MGI.
DR GO; GO:0002027; P:regulation of heart rate; IMP:BHF-UCL.
DR GO; GO:0098907; P:regulation of SA node cell action potential; ISO:MGI.
DR GO; GO:0098911; P:regulation of ventricular cardiac muscle cell action potential; ISO:MGI.
DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; ISO:MGI.
DR GO; GO:0014808; P:release of sequestered calcium ion into cytosol by sarcoplasmic reticulum; IDA:BHF-UCL.
DR GO; GO:0031000; P:response to caffeine; IDA:UniProtKB.
DR GO; GO:0051592; P:response to calcium ion; ISO:MGI.
DR GO; GO:0001666; P:response to hypoxia; IDA:BHF-UCL.
DR GO; GO:0032026; P:response to magnesium ion; ISO:MGI.
DR GO; GO:0014850; P:response to muscle activity; ISO:MGI.
DR GO; GO:0035994; P:response to muscle stretch; ISO:MGI.
DR GO; GO:0051775; P:response to redox state; ISO:MGI.
DR GO; GO:0070296; P:sarcoplasmic reticulum calcium ion transport; ISO:MGI.
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; IMP: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; Calcium; Calcium channel; Calcium transport;
KW Calmodulin-binding; Developmental protein; Ion channel; Ion transport;
KW Ligand-gated ion channel; Membrane; Phosphoprotein; Reference proteome;
KW Repeat; Sarcoplasmic reticulum; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..4966
FT /note="Ryanodine receptor 2"
FT /id="PRO_0000415582"
FT TOPO_DOM 1..4231
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 4232..4252
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 4278..4298
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 4502..4522
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 4579..4599
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 4729..4749
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 4768..4788
FT /note="Helical"
FT /evidence="ECO:0000255"
FT INTRAMEM 4819..4828
FT /note="Pore-forming"
FT /evidence="ECO:0000305"
FT TRANSMEM 4849..4869
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 4870..4966
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 1357..1563
FT /note="B30.2/SPRY 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT REPEAT 2691..2809
FT /note="3"
FT REPEAT 2811..2924
FT /note="4"
FT REGION 853..2924
FT /note="4 X approximate repeats"
FT REGION 1358..1377
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1857..1890
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2353..2372
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3580..3609
FT /note="Interaction with CALM"
FT /evidence="ECO:0000250"
FT REGION 4335..4363
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 4417..4466
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1859..1890
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 4343..4363
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1341
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1870
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:B0LPN4"
FT MOD_RES 2030
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:17693412"
FT MOD_RES 2368
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 2696
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:B0LPN4"
FT MOD_RES 2796
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 2807
FT /note="Phosphoserine; by CaMK2D and PKA"
FT /evidence="ECO:0000269|PubMed:20431056,
FT ECO:0000269|PubMed:21098440, ECO:0007744|PubMed:21183079"
FT MOD_RES 2810
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 2813
FT /note="Phosphoserine; by CaMK2D"
FT /evidence="ECO:0000269|PubMed:21098440,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 2946
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MUTAGEN 77
FT /note="A->V: No change to global protein fold or protein
FT stability. Alters local protein folding."
FT /evidence="ECO:0000269|PubMed:19913485"
FT MUTAGEN 186
FT /note="V->M: No change to global protein fold or protein
FT stability. Alters local protein folding."
FT /evidence="ECO:0000269|PubMed:19913485"
FT MUTAGEN 2813
FT /note="S->A: Protects against tachycardia and subsequent
FT death due to heart failure."
FT /evidence="ECO:0000269|PubMed:21098440"
FT MUTAGEN 2813
FT /note="S->D: Abolishes phosphorylation by CaMK2D. Tendency
FT to tachycardia and subsequent death due to heart failure."
FT /evidence="ECO:0000269|PubMed:21098440"
FT MUTAGEN 4645
FT /note="D->A: Mutant mice show systolic arrhythmogenic
FT abnormalities. Spontaneous Ca(2+) release from the
FT sarcoplasmic reticulum in the heart is diminished."
FT /evidence="ECO:0000269|PubMed:33536282"
FT MUTAGEN 4819
FT /note="G->A: Strongly reduced calcium channel activity.
FT Abolishes ryanodine binding."
FT /evidence="ECO:0000269|PubMed:10473538"
FT MUTAGEN 4821
FT /note="R->A: No effect on calcium channel activity.
FT Abolishes ryanodine binding."
FT /evidence="ECO:0000269|PubMed:10473538"
FT MUTAGEN 4823
FT /note="G->A: Reduced calcium channel activity. Reduces
FT single channel conductance by 97%. No effect on ryaodine
FT binding."
FT /evidence="ECO:0000269|PubMed:10473538"
FT MUTAGEN 4824
FT /note="G->A: No effect on calcium channel activity.
FT Abolishes ryanodine binding."
FT /evidence="ECO:0000269|PubMed:10473538"
FT MUTAGEN 4825
FT /note="G->A: Strongly reduced calcium channel activity.
FT Abolishes ryanodine binding."
FT /evidence="ECO:0000269|PubMed:10473538"
FT MUTAGEN 4827
FT /note="G->A: No effect on calcium channel activity.
FT Abolishes ryanodine binding."
FT /evidence="ECO:0000269|PubMed:10473538"
FT MUTAGEN 4828
FT /note="D->A: No effect on calcium channel activity.
FT Abolishes ryanodine binding."
FT /evidence="ECO:0000269|PubMed:10473538"
FT CONFLICT 1332
FT /note="N -> S (in Ref. 1; AAG34081)"
FT /evidence="ECO:0000305"
FT CONFLICT 1412
FT /note="D -> G (in Ref. 1; AAG34081)"
FT /evidence="ECO:0000305"
FT CONFLICT 1962
FT /note="R -> K (in Ref. 1; AAG34081)"
FT /evidence="ECO:0000305"
FT CONFLICT 2265
FT /note="V -> VA (in Ref. 1; AAG34081)"
FT /evidence="ECO:0000305"
FT CONFLICT 2532
FT /note="P -> R (in Ref. 1; AAG34081)"
FT /evidence="ECO:0000305"
FT CONFLICT 3192
FT /note="A -> T (in Ref. 1; AAG34081)"
FT /evidence="ECO:0000305"
FT CONFLICT 3533
FT /note="L -> F (in Ref. 1; AAG34081)"
FT /evidence="ECO:0000305"
FT CONFLICT 4324
FT /note="I -> T (in Ref. 4; CAA58785)"
FT /evidence="ECO:0000305"
FT CONFLICT 4853
FT /note="V -> E (in Ref. 4; CAA58785)"
FT /evidence="ECO:0000305"
FT STRAND 15..17
FT /evidence="ECO:0007829|PDB:4KEJ"
FT STRAND 19..28
FT /evidence="ECO:0007829|PDB:3IM6"
FT STRAND 31..38
FT /evidence="ECO:0007829|PDB:3IM6"
FT STRAND 41..43
FT /evidence="ECO:0007829|PDB:3IM6"
FT STRAND 48..51
FT /evidence="ECO:0007829|PDB:3IM6"
FT TURN 53..57
FT /evidence="ECO:0007829|PDB:4L4H"
FT HELIX 62..64
FT /evidence="ECO:0007829|PDB:3IM6"
FT STRAND 67..73
FT /evidence="ECO:0007829|PDB:3IM6"
FT HELIX 75..84
FT /evidence="ECO:0007829|PDB:3IM6"
FT STRAND 97..102
FT /evidence="ECO:0007829|PDB:3QR5"
FT STRAND 118..123
FT /evidence="ECO:0007829|PDB:3IM6"
FT TURN 124..126
FT /evidence="ECO:0007829|PDB:3IM6"
FT STRAND 129..132
FT /evidence="ECO:0007829|PDB:3IM6"
FT STRAND 145..151
FT /evidence="ECO:0007829|PDB:3IM6"
FT STRAND 154..156
FT /evidence="ECO:0007829|PDB:3IM6"
FT STRAND 159..167
FT /evidence="ECO:0007829|PDB:3IM6"
FT STRAND 180..185
FT /evidence="ECO:0007829|PDB:3IM6"
FT TURN 186..188
FT /evidence="ECO:0007829|PDB:3IM6"
FT STRAND 191..196
FT /evidence="ECO:0007829|PDB:3IM6"
FT STRAND 198..208
FT /evidence="ECO:0007829|PDB:3IM6"
FT STRAND 212..216
FT /evidence="ECO:0007829|PDB:3IM6"
FT HELIX 220..222
FT /evidence="ECO:0007829|PDB:4L4H"
FT STRAND 233..238
FT /evidence="ECO:0007829|PDB:4L4H"
FT TURN 239..242
FT /evidence="ECO:0007829|PDB:4L4H"
FT STRAND 243..246
FT /evidence="ECO:0007829|PDB:4L4H"
FT HELIX 256..258
FT /evidence="ECO:0007829|PDB:4L4H"
FT STRAND 261..264
FT /evidence="ECO:0007829|PDB:4L4H"
FT HELIX 265..269
FT /evidence="ECO:0007829|PDB:4L4H"
FT HELIX 271..273
FT /evidence="ECO:0007829|PDB:4L4H"
FT STRAND 275..280
FT /evidence="ECO:0007829|PDB:4L4H"
FT TURN 283..286
FT /evidence="ECO:0007829|PDB:4L4H"
FT STRAND 294..299
FT /evidence="ECO:0007829|PDB:4L4H"
FT TURN 300..302
FT /evidence="ECO:0007829|PDB:4L4H"
FT STRAND 305..308
FT /evidence="ECO:0007829|PDB:4L4H"
FT STRAND 314..317
FT /evidence="ECO:0007829|PDB:4L4H"
FT HELIX 319..321
FT /evidence="ECO:0007829|PDB:4L4H"
FT HELIX 324..327
FT /evidence="ECO:0007829|PDB:4L4H"
FT STRAND 329..333
FT /evidence="ECO:0007829|PDB:4L4H"
FT TURN 356..358
FT /evidence="ECO:0007829|PDB:4L4H"
FT STRAND 360..365
FT /evidence="ECO:0007829|PDB:4L4H"
FT TURN 366..368
FT /evidence="ECO:0007829|PDB:4L4H"
FT STRAND 371..374
FT /evidence="ECO:0007829|PDB:4L4H"
FT STRAND 389..396
FT /evidence="ECO:0007829|PDB:4L4H"
FT STRAND 403..407
FT /evidence="ECO:0007829|PDB:4L4H"
FT HELIX 410..436
FT /evidence="ECO:0007829|PDB:4L4H"
FT HELIX 449..462
FT /evidence="ECO:0007829|PDB:4L4H"
FT HELIX 472..491
FT /evidence="ECO:0007829|PDB:4L4H"
FT HELIX 494..505
FT /evidence="ECO:0007829|PDB:4L4H"
FT STRAND 508..510
FT /evidence="ECO:0007829|PDB:4L4H"
FT HELIX 511..518
FT /evidence="ECO:0007829|PDB:4L4H"
FT HELIX 520..541
FT /evidence="ECO:0007829|PDB:4L4H"
FT STRAND 653..658
FT /evidence="ECO:0007829|PDB:5C33"
FT STRAND 672..681
FT /evidence="ECO:0007829|PDB:5C33"
FT STRAND 693..699
FT /evidence="ECO:0007829|PDB:5C33"
FT HELIX 700..702
FT /evidence="ECO:0007829|PDB:5C33"
FT STRAND 704..706
FT /evidence="ECO:0007829|PDB:5C33"
FT HELIX 707..709
FT /evidence="ECO:0007829|PDB:5C33"
FT STRAND 710..712
FT /evidence="ECO:0007829|PDB:5C33"
FT STRAND 724..727
FT /evidence="ECO:0007829|PDB:5C33"
FT STRAND 729..734
FT /evidence="ECO:0007829|PDB:5C33"
FT STRAND 737..740
FT /evidence="ECO:0007829|PDB:5C33"
FT STRAND 754..760
FT /evidence="ECO:0007829|PDB:5C33"
FT TURN 761..764
FT /evidence="ECO:0007829|PDB:5C33"
FT STRAND 765..770
FT /evidence="ECO:0007829|PDB:5C33"
FT STRAND 788..794
FT /evidence="ECO:0007829|PDB:5C33"
FT STRAND 799..803
FT /evidence="ECO:0007829|PDB:5C33"
FT HELIX 822..825
FT /evidence="ECO:0007829|PDB:5C33"
FT STRAND 833..839
FT /evidence="ECO:0007829|PDB:5C33"
FT STRAND 1086..1089
FT /evidence="ECO:0007829|PDB:4P9I"
FT HELIX 1092..1094
FT /evidence="ECO:0007829|PDB:4P9I"
FT STRAND 1096..1109
FT /evidence="ECO:0007829|PDB:4P9I"
FT STRAND 1111..1118
FT /evidence="ECO:0007829|PDB:4P9I"
FT STRAND 1130..1138
FT /evidence="ECO:0007829|PDB:4P9I"
FT TURN 1139..1142
FT /evidence="ECO:0007829|PDB:4P9I"
FT STRAND 1143..1153
FT /evidence="ECO:0007829|PDB:4P9I"
FT STRAND 1161..1167
FT /evidence="ECO:0007829|PDB:4P9I"
FT TURN 1168..1171
FT /evidence="ECO:0007829|PDB:4P9I"
FT STRAND 1172..1177
FT /evidence="ECO:0007829|PDB:4P9I"
FT STRAND 1191..1194
FT /evidence="ECO:0007829|PDB:4P9I"
FT STRAND 1201..1207
FT /evidence="ECO:0007829|PDB:4P9I"
FT STRAND 1213..1216
FT /evidence="ECO:0007829|PDB:4P9I"
FT HELIX 1221..1223
FT /evidence="ECO:0007829|PDB:4P9I"
FT TURN 1227..1235
FT /evidence="ECO:0007829|PDB:4P9I"
FT HELIX 1239..1242
FT /evidence="ECO:0007829|PDB:4P9I"
FT HELIX 2714..2716
FT /evidence="ECO:0007829|PDB:4ETV"
FT HELIX 2717..2737
FT /evidence="ECO:0007829|PDB:4ETV"
FT TURN 2748..2751
FT /evidence="ECO:0007829|PDB:4ETV"
FT HELIX 2754..2756
FT /evidence="ECO:0007829|PDB:6MM6"
FT HELIX 2759..2761
FT /evidence="ECO:0007829|PDB:4ETV"
FT HELIX 2764..2783
FT /evidence="ECO:0007829|PDB:4ETV"
FT STRAND 2787..2790
FT /evidence="ECO:0007829|PDB:4ETV"
FT STRAND 2792..2795
FT /evidence="ECO:0007829|PDB:6MM8"
FT HELIX 2796..2799
FT /evidence="ECO:0007829|PDB:4ETV"
FT HELIX 2811..2816
FT /evidence="ECO:0007829|PDB:6MM7"
FT HELIX 2817..2819
FT /evidence="ECO:0007829|PDB:4ETV"
FT HELIX 2827..2829
FT /evidence="ECO:0007829|PDB:4ETV"
FT HELIX 2834..2861
FT /evidence="ECO:0007829|PDB:4ETV"
FT HELIX 2873..2875
FT /evidence="ECO:0007829|PDB:4ETV"
FT HELIX 2878..2897
FT /evidence="ECO:0007829|PDB:4ETV"
FT STRAND 2900..2903
FT /evidence="ECO:0007829|PDB:4ETV"
SQ SEQUENCE 4966 AA; 564819 MW; F43425091AF7114F CRC64;
MADAGEGEDE IQFLRTDDEV VLQCTATIHK EQQKLCLAAE GFGNRLCFLE STSNSKNVPP
DLSICTFVLE QSLSVRALQE MLANTVEKSE GQVDVEKWKF MMKTAQGGGH RTLLYGHAIL
LRHSYSGMYL CCLSTSRSST DKLAFDVGLQ EDTTGEACWW TIHPASKQRS EGEKVRVGDD
LILVSVSSER YLHLSYGNSS WHVDAAFQQT LWSVAPISSG SEAAQGYLIG GDVLRLLHGH
MDECLTVPSG EHGEEQRRTV HYEGGAVSVH ARSLWRLETL RVAWSGSHIR WGQPFRLRHV
TTGKYLSLME DKNLLLMDKE KADVKSTAFA FRSSKEKLDV GVRKEVDGMG TSEIKYGDSI
CYIQHVDTGL WLTYQAVDVK SARMGSIQRK AIMHHEGHMD DGLNLSRSQH EESRTARVIR
STVFLFNRFI RGLDALSKKV KLPTIDLPIE 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 ACYEAVLPKE KLKVEHSREY
KQERTYTRDL LGPTVSLTQA AFTPVPVDTS QIVLPPHLER IRERLAENIH ELWVMNKIEL
GWQYGPVRDD NKRQHPCLVE FCKLPEQERN YNLQMSLETL KTLLALGCHV GIADEHAEEK
VKKMKLPKNY QLTSGYKPAP MDLSFIKLTP SQEAMVDKLA ENAHNVWARD RIRQGWTYGI
QQDVKNRRNP RLVPYTLLDD RTKKSNKDSL REAVRTLLGY GYHLEAPDQD HASRAEVCSG
TGERFRIFRA EKTYAVKAGR WYFEFEAVTA GDMRVGWSRP GCQPDLELGS DDRAFAFDGF
KAQRWHQGNE HYGRSWQAGD VVGCMVDMNE HTMMFTLNGE ILLDDSGSEL AFKDFDVGDG
FIPVCSLGVA QVGRMNFGKD VSTLKYFTIC GLQEGYEPFA VNTNRDITMW LSKRLPQFLQ
VPSNHEHIEV TRIDGTIDSS PCLKVTQKSF GSQNNNTDIM FYRLSMPIEC AEVFSKSVAG
GLPGAGFYGP KNDLEDFDVD SDFEVLMKTA HGHLVPDRID KDKETPKPEF NNHKDYAQEK
PSRLKQRFLL RRTKPDYSTG HSARLTEDVL ADDRDDYEYL MQTSTYYYSV RIFPGQEPAN
VWVGWITSDF HQYDTGFDLD RVRTVTVTLG DEKGKVHESI KRSNCYMVCA GESMSPGQGR
NNSNGLEIGC VVDAASGLLT FIANGKELST YYQVEPSTKL FPAVFAQATS PNVFQFELGR
IKNVMPLSAG LFKSEHKNPV PQCPPRLHVQ FLSHVLWSRM PNQFLKVDVS RISERQGWLV
QCLDPLQFMS LHIPEENRSV DILELTEQEE LLQFHYHTLR LYSAVCALGN HRVAHALCSH
VDEPQLLYAI ENKYMPGLLR AGYYDLLIDI HLSSYATARL MMNNEFIVPM TEETKSITLF
PDENKKHGLP GIGLSTSLRP RMRFSSPSFV SISNDCYQYS PEFPLDILKA KTIQMLTEAV
KEGSLHARDP VGGTTEFLFV PLIKLFYTLL IMGIFHNEDL KHILQLIEPS VFKEAAVPEE
EGGTPEKEIS IEDAKLEGEE EAKGGKRPKE GLLQMKLPEP VKLQMCLLLQ YLCDCQVRHR
IEAIVAFSDD FVAKLQDNQR FRYNEVMQAL NMSAALTARK TREFRSPPQE QINMLLNFKD
DKSECPCPEE IRDQLLDFHE DLMTHCGIEL DEDGSLDGSN DLTIRGRLLS LVEKVTYLKK
KQAEKPVASD SRKCSSLQQL ISETMVRWAQ ESVIEDPELV RAMFVLLHRQ YDGIGGLVRA
LPKTYTINGV SVEDTINLLA SLGQIRSLLS VRMGKEEEKL MIRGLGDIMN NKVFYQHPNL
MRALGMHETV MEVMVNVLGG GESKEITFPK MVANCCRFLC YFCRISRQNQ KAMFDHLSYL
LENSSVGLAS PAMRGSTPLD VAAASVMDNN ELALALREPD LEKVVRYLAG CGLQSCQMLV
SKGYPDIGWN PVEGERYLDF LRFAVFCNGE SVEENANVVV RLLIRRPECF GPALRGEGGN
GLLAAMEEAI KIAEDPSRDG PSPTSGSSKT LDIEEEEDDT IHMGNAIMTF YAALIDLLGR
CAPEMHLIHA GKGEAIRIRS ILRSLIPLGD LVGVISIAFQ MPTIAKDGKV VEPDMSAGFC
PDHKAAMVLF LDRVYGIEVQ DFLLHLLEVG FLPDLRAAAS LDTAALSATD MALALNRYLC
TAVLPLLTRC APLFAGTEHH ASLIDSLLHT VYRLSKGCSL TKAQRDSIEV CLLSICGQLR
PSMMQHLLRR LVFDVPLLNE HAKMPLKLLT NHYERCWKYY CLPGGWGNFG AASEEELHLS
RKLFWGIFDA LSQKKYEQEL FKLALPCLSA VAGALPPDYM ESNYVSMMEK QSSMDSEGNF
NPQPVDTSNI TIPEKLEYFI NKYAEHSHDK WSMDKLANGW IYGEIYSDSS KIQPLMKPYK
LLSEKEKEIY RWPIKESLKT MLAWGWRIER TREGDSMALY NRTRRISQTS QVSIDAAHGY
SPRAIDMSNV TLSRDLHAMA EMMAENYHNI WAKKKKLELE SKGGGNHPLL VPYDTLTAKE
KAKDREKAQD IFKFLQISGY VVSRGFKDLD LDTPSIEKRF AYSFLQQLIR YVDEAHQYIL
EFDGGSRSKG EHFPYEQEIK FFAKVVLPLI DQYFKNHRLY FLSAASRPLC TGGHASNKEK
EMVTSLFCKL GVLVRHRISL FGNDATSIVN CLHILGQTLD ARTVMKTGLD SVKSALRAFL
DNAAEDLEKT MENLKQGQFT HTRSQPKGVT QIINYTTVAL LPMLSSLFEH IGQHQFGEDL
ILEDVQVSCY RILTSLYALG TSKSIYVERQ RSALGECLAA FAGAFPIAFL ETHLDKHNVY
SIYNTRSSRE RAALSLPANV EDVCPNIPSL EKLMTEIIEL AESGIRYTQM PYMMEVVLPM
LCSYMSRWWE HGPENHPERA EMCCTALNSE HMNTLLGNIL KIIYNNLGID EGAWMKRLAV
FSQPIINKVK PQLLKTHFLP LMEKLKKKAA MVVSEEDHLK AEARGDMSEA ELLILDEFTT
LARDLYAFYP LLIRFVDYNR AKWLKEPNPE AEELFRMVAE VFIYWSKSHN FKREEQNFVV
QNEINNMSFL ITDTKSKMSK AAISDQERKK MKRKGDRYSM QTSLIVAALK RLLPIGLNIC
APGDQELIAL AKNRFSLKDT EEEVRDIIRS NIHLQGKLED PAIRWQMALY KDLPNRTEDP
SDPERTVERV LGIANVLFHL EQKSKYTGRG YFSLVEHPQR SKKAVWHKLL SKQRKRAVVA
CFRMAPLYNL PRHRAVNLFL QGYEKSWIET EEHYFEDKLI EDLAKPGAEL PEEDEAMKRV
DPLHQLILLF SRTALTEKCK LEEDFLYMAY ADIMAKSCHD EEDDDGEEEV KSFEEKEMEK
QKLLYQQARL HDRGAAEMVL QTISASKGET GPMVAATLKL GIAILNGGNS TVQQKMLDYL
KEKKDVGFFQ SLAGLMQSCS VLDLNAFERQ NKAEGLGMVT EEGSGEKVLQ DDEFTCDLFR
FLQLLCEGHN SDFQNYLRTQ TGNNTTVNII ISTVDYLLRV QESISDFYWY YSGKDIIDEQ
GQRNFSKAIQ VAKQVFNTLT EYIQGPCTGN QQSLAHSRLW DAVVGFLHVF AHMQMKLSQD
SSQIELLKEL MDLQKDMVVM LLSMLEGNVV NGTIGKQMVD MLVESSNNVE MILKFFDMFL
KLKDLTSSDT FKEYDPDGKG VISKRDFHKA MESHKHYTQS ETEFLLSCAE TDENETLDYE
EFVKRFHEPA KDIGFNVAVL LTNLSEHMPN DTRLQTFLEL AESVLNYFQP FLGRIEIMGS
AKRIERVYFE ISESSRTQWE KPQVKESKRQ FIFDVVNEGG EKEKMELFVN FCEDTIFEMQ
LAAQISESDL NERLANKEES EKERPEEQAP RMGFFSLLTI QSALFALRYN VLTLVRMLSL
KSLKKQMKRM KKMTVKDMVL AFFSSYWSVF VTLLHFVASV CRGFFRIVSS LLLGGSLVEG
AKKIKVAELL ANMPDPTQDE VRGDEEEGER KPLESALPSE DLTDLKELTE ESDLLSDIFG
LDLKREGGQY KLIPHNPNAG LSDLMTNPVP VPEVQEKFQE QKAKEEKEEK EETKSEPEKA
EGEDGEKEEK AKDEKSKQKL RQLHTHRYGE PEVPESAFWK KIIAYQQKLL NYFARNFYNM
RMLALFVAFA INFILLFYKV STSSVVEGKE LPTRTSSDTA KVTNSLDSSP HRIIAVHYVL
EESSGYMEPT LRILAILHTI ISFFCIIGYY CLKVPLVIFK REKEVARKLE FDGLYITEQP
SEDDIKGQWD RLVINTQSFP NNYWDKFVKR KVMDKYGEFY GRDRISELLG MDKAALDFSD
AREKKKPKKD SSLSAVLNSI DVKYQMWKLG VVFTDNSFLY LAWYMTMSVL GHYNNFFFAA
HLLDIAMGFK TLRTILSSVT HNGKQLVLTV GLLAVVVYLY TVVAFNFFRK FYNKSEDGDT
PDMKCDDMLT CYMFHMYVGV RAGGGIGDEI EDPAGDEYEI YRIIFDITFF FFVIVILLAI
IQGLIIDAFG ELRDQQEQVK EDMETKCFIC GIGNDYFDTV PHGFETHTLQ EHNLANYLFF
LMYLINKDET EHTGQESYVW KMYQERCWEF FPAGDCFRKQ YEDQLN
