ID RYR1_MOUSE Reviewed; 5035 AA. AC E9PZQ0; Q60834; Q61779; Q61780; Q62173; Q62196; Q62235; Q78EJ6; Q7TNG1; AC Q80UQ5; Q80X16; Q99JF9; DT 22-FEB-2012, integrated into UniProtKB/Swiss-Prot. DT 05-APR-2011, sequence version 1. DT 24-JAN-2024, entry version 100. DE RecName: Full=Ryanodine receptor 1 {ECO:0000305|PubMed:18003898}; DE Short=RYR-1; DE Short=RyR1; DE AltName: Full=Skeletal muscle calcium release channel; DE AltName: Full=Skeletal muscle ryanodine receptor; DE AltName: Full=Skeletal muscle-type ryanodine receptor; DE AltName: Full=Type 1 ryanodine receptor; GN Name=Ryr1 {ECO:0000312|MGI:MGI:99659}; 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, TISSUE RP SPECIFICITY, AND MUTAGENESIS OF ILE-4895. RC STRAIN=BALB/c X CD-1; RX PubMed=18003898; DOI=10.1073/pnas.0709312104; RA Zvaritch E., Depreux F., Kraeva N., Loy R.E., Goonasekera S.A., RA Boncompagni S., Kraev A., Gramolini A.O., Dirksen R.T., RA Franzini-Armstrong C., Seidman C.E., Seidman J.G., MacLennan D.H.; RT "An Ryr1I4895T mutation abolishes Ca2+ release channel function and delays RT development in homozygous offspring of a mutant mouse line."; RL Proc. Natl. Acad. Sci. U.S.A. 104:18537-18542(2007). RN [2] RP ERRATUM OF PUBMED:18003898. RA Zvaritch E., Depreux F., Kraeva N., Loy R.E., Goonasekera S.A., RA Boncompagni S., Kraev A., Gramolini A.O., Dirksen R.T., RA Franzini-Armstrong C., Seidman C.E., Seidman J.G., MacLennan D.H.; RL Proc. Natl. Acad. Sci. U.S.A. 105:825-825(2008). RN [3] 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 [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-57, NUCLEOTIDE SEQUENCE [MRNA] OF RP 1-27, FUNCTION, AND DISRUPTION PHENOTYPE. RC STRAIN=129/J, and BALB/cJ; TISSUE=Skeletal muscle; RX PubMed=7515481; DOI=10.1038/369556a0; RA Takeshima H., Iino M., Takekura H., Nishi M., Kuno J., Minowa O., RA Takano H., Noda T.; RT "Excitation-contraction uncoupling and muscular degeneration in mice RT lacking functional skeletal muscle ryanodine-receptor gene."; RL Nature 369:556-559(1994). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 483-861. RC STRAIN=129; RA Kathirvel P.; RT "Characterisation of the murine Ryr1 gene."; RL Thesis (2000), University of Edinburgh, United Kingdom. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 4500-5035. RC STRAIN=FVB/N-3; TISSUE=Eye, and Mammary tumor; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 4537-5035, 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 [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 4762-5013. RC TISSUE=Brain; RX PubMed=7635066; DOI=10.1242/dev.121.7.2233; RA Ayabe T., Kopf G.S., Schultz R.M.; RT "Regulation of mouse egg activation: presence of ryanodine receptors and RT effects of microinjected ryanodine and cyclic ADP ribose on uninseminated RT and inseminated eggs."; RL Development 121:2233-2244(1995). RN [9] RP NUCLEOTIDE SEQUENCE [MRNA] OF 4913-5035, FUNCTION, TRANSPORTER ACTIVITY, RP SUBCELLULAR LOCATION, DOMAIN, ACTIVITY REGULATION, AND TISSUE SPECIFICITY. RC STRAIN=C57BL/6J; TISSUE=Skeletal muscle; 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 [10] RP DOMAIN. RX PubMed=7724570; DOI=10.1073/pnas.92.8.3381; RA Takekura H., Nishi M., Noda T., Takeshima H., Franzini-Armstrong C.; RT "Abnormal junctions between surface membrane and sarcoplasmic reticulum in RT skeletal muscle with a mutation targeted to the ryanodine receptor."; RL Proc. Natl. Acad. Sci. U.S.A. 92:3381-3385(1995). RN [11] RP FUNCTION, TRANSPORTER ACTIVITY, PHOSPHORYLATION AT SER-2844, RP S-NITROSYLATION, AND IDENTIFICATION IN A COMPLEX WITH PDE4D; PKA; FKBP1A RP AND PROTEIN PHOSPHATASE 1. RX PubMed=18268335; DOI=10.1073/pnas.0711074105; RA Bellinger A.M., Reiken S., Dura M., Murphy P.W., Deng S.X., Landry D.W., RA Nieman D., Lehnart S.E., Samaru M., LaCampagne A., Marks A.R.; RT "Remodeling of ryanodine receptor complex causes 'leaky' channels: a RT molecular mechanism for decreased exercise capacity."; RL Proc. Natl. Acad. Sci. U.S.A. 105:2198-2202(2008). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2844, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, 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 [13] RP FUNCTION IN BRAIN, S-NITROSYLATION, ACTIVITY REGULATION, AND TISSUE RP SPECIFICITY. RX PubMed=22036948; DOI=10.1038/emboj.2011.386; RA Kakizawa S., Yamazawa T., Chen Y., Ito A., Murayama T., Oyamada H., RA Kurebayashi N., Sato O., Watanabe M., Mori N., Oguchi K., Sakurai T., RA Takeshima H., Saito N., Iino M.; RT "Nitric oxide-induced calcium release via ryanodine receptors regulates RT neuronal function."; RL EMBO J. 31:417-428(2012). RN [14] RP FUNCTION, TRANSPORTER ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION, RP TISSUE SPECIFICITY, MUTAGENESIS OF ARG-165, AND PHOSPHORYLATION AT RP SER-2844. RX PubMed=21156754; DOI=10.1124/mol.110.067959; RA Feng W., Barrientos G.C., Cherednichenko G., Yang T., Padilla I.T., RA Truong K., Allen P.D., Lopez J.R., Pessah I.N.; RT "Functional and biochemical properties of ryanodine receptor type 1 RT channels from heterozygous R163C malignant hyperthermia-susceptible mice."; RL Mol. Pharmacol. 79:420-431(2011). RN [15] 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). CC -!- FUNCTION: Cytosolic calcium-activated calcium channel that mediates the CC release of Ca(2+) from the sarcoplasmic reticulum into the cytosol and CC thereby plays a key role in triggering muscle contraction following CC depolarization of T-tubules (PubMed:18003898, PubMed:7515481, CC PubMed:7621815, PubMed:21156754). Repeated very high-level exercise CC increases the open probability of the channel and leads to Ca(2+) CC leaking into the cytoplasm (PubMed:18268335). Can also mediate the CC release of Ca(2+) from intracellular stores in neurons, and may thereby CC promote prolonged Ca(2+) signaling in the brain (PubMed:22036948). CC Required for normal embryonic development of muscle fibers and skeletal CC muscle (PubMed:7515481). Required for normal heart morphogenesis, skin CC development and ossification during embryogenesis (PubMed:18003898, CC PubMed:7515481). {ECO:0000269|PubMed:18003898, CC ECO:0000269|PubMed:18268335, ECO:0000269|PubMed:21156754, CC ECO:0000269|PubMed:22036948, ECO:0000269|PubMed:7515481, CC ECO:0000269|PubMed:7621815}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Ca(2+)(in) = Ca(2+)(out); Xref=Rhea:RHEA:29671, CC ChEBI:CHEBI:29108; Evidence={ECO:0000269|PubMed:18268335, CC ECO:0000269|PubMed:21156754, ECO:0000269|PubMed:7621815}; CC -!- ACTIVITY REGULATION: The calcium release is activated by increased CC cytosolic calcium levels, by nitric oxyde (NO), caffeine and ATP CC (PubMed:7621815, PubMed:22036948, PubMed:21156754). Channel activity is CC modulated by the alkaloid ryanodine that binds to the open Ca-release CC channel with high affinity. At low concentrations, ryanodine maintains CC the channel in an open conformation. High ryanodine concentrations CC inhibit channel activity (PubMed:7621815). Channel activity is CC regulated by calmodulin (CALM). Channel activity is inhibited by CC magnesium ions, possibly by competition for calcium binding sites. CC {ECO:0000269|PubMed:21156754, ECO:0000269|PubMed:22036948, CC ECO:0000269|PubMed:7621815}. CC -!- SUBUNIT: Homotetramer (PubMed:18003898). Can also form heterotetramers CC with RYR2 (By similarity). Identified in a complex composed of RYR1, CC PDE4D, PKA, FKBP1A and protein phosphatase 1 (PP1) (PubMed:18268335). CC Repeated very high-level exercise decreases interaction with PDE4D and CC protein phosphatase 1 (PP1) (PubMed:18268335). Interacts with CALM; CC CALM with bound calcium inhibits the RYR1 channel activity (By CC similarity). Interacts with S100A1 (By similarity). Interacts with CC FKBP1A; this stabilizes the closed conformation of the channel. CC Interacts with CACNA1S; interaction with CACNA1S is important for CC activation of the RYR1 channel. Interacts with CACNB1. Interacts with CC TRDN and ASPH; these interactions stimulate RYR1 channel activity. CC Interacts with SELENON (By similarity). Interacts with scorpion calcins CC (AC P0DPT1; AC P0DM30; AC A0A1L4BJ42; AC P59868; AC P60254; AC B8QG00; CC AC L0GBR1; AC P60252; AC P60253) (By similarity). CC {ECO:0000250|UniProtKB:P11716, ECO:0000250|UniProtKB:P21817, CC ECO:0000269|PubMed:18003898, ECO:0000269|PubMed:18268335}. CC -!- INTERACTION: CC E9PZQ0; O55108: Bsg; NbExp=3; IntAct=EBI-642079, EBI-643315; CC E9PZQ0; P49070: Camlg; NbExp=3; IntAct=EBI-642079, EBI-309114; CC E9PZQ0; P26883: Fkbp1a; NbExp=2; IntAct=EBI-642079, EBI-6379901; CC -!- SUBCELLULAR LOCATION: Sarcoplasmic reticulum membrane CC {ECO:0000269|PubMed:18003898, ECO:0000269|PubMed:7621815}; Multi-pass CC membrane protein {ECO:0000255}. Note=The number of predicted CC transmembrane domains varies between orthologs. Both N-terminus and C- CC terminus are cytoplasmic. {ECO:0000250|UniProtKB:P11716}. CC -!- TISSUE SPECIFICITY: Detected in muscle and myotubes (at protein level) CC (PubMed:18003898). Ubiquitous. Detected in diaphragm, skeletal muscle, CC esophagus, spleen, submaxillary gland, adrenal gland, cerebellum, brain CC and in testis germ cells. {ECO:0000269|PubMed:18003898, CC ECO:0000269|PubMed:21156754, ECO:0000269|PubMed:22036948, CC ECO:0000269|PubMed:7621815, 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 constitutes the 'foot' CC structure spanning the junctional gap between the sarcoplasmic CC reticulum (SR) and the T-tubule (PubMed:7621815, PubMed:7724570). Pore CC opening is mediated via the cytoplasmic calcium-binding domains that CC mediate a small rotation of the channel-forming transmembrane regions CC that then leads to channel opening (By similarity). CC {ECO:0000250|UniProtKB:P11716, ECO:0000269|PubMed:7621815, CC ECO:0000269|PubMed:7724570}. CC -!- PTM: Channel activity is modulated by phosphorylation. Phosphorylation CC at Ser-2844 may increase channel activity. Repeated very high-level CC exercise increases phosphorylation at Ser-2844. CC {ECO:0000269|PubMed:18268335, ECO:0000269|PubMed:21156754}. CC -!- PTM: Activated by reversible S-nitrosylation (PubMed:22036948). CC Repeated very high-level exercise increases S-nitrosylation. CC {ECO:0000250, ECO:0000269|PubMed:18268335, CC ECO:0000269|PubMed:22036948}. CC -!- DISRUPTION PHENOTYPE: Perinatal lethality, due to severe defects in CC skeletal muscle development. Neonates do not breathe and do not move. CC Mutant mice show defects in muscle fiber development. Their muscles do CC not show a contractile response to electrical stimulation. In addition, CC mice display abnormal curvature of the spine, thin limbs, and an CC abnormal rib cage. {ECO:0000269|PubMed:7515481}. CC -!- SIMILARITY: Belongs to the ryanodine receptor (TC 1.A.3.1) family. RYR1 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; AY268935; AAP29981.1; -; mRNA. DR EMBL; AC164564; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC165142; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; D21798; BAA21010.1; -; Genomic_DNA. DR EMBL; D21796; BAA04821.1; -; mRNA. DR EMBL; D21797; BAA04822.1; -; Genomic_DNA. DR EMBL; AJ308737; CAC34624.1; -; Genomic_DNA. DR EMBL; BC051248; AAH51248.1; -; mRNA. DR EMBL; BC055487; AAH55487.1; -; mRNA. DR EMBL; X83932; CAA58784.1; -; mRNA. DR EMBL; U23754; AAA64955.1; -; mRNA. DR EMBL; D38216; BAA07391.1; -; mRNA. DR CCDS; CCDS39866.1; -. DR PIR; I48741; I48741. DR PIR; I58087; I58087. DR PIR; I78376; I78376. DR PIR; I78377; I78377. DR PIR; S56105; S56105. DR RefSeq; NP_033135.2; NM_009109.2. DR SMR; E9PZQ0; -. DR BioGRID; 203045; 10. DR ComplexPortal; CPX-3092; Ryanodine 1 complex. DR DIP; DIP-29705N; -. DR IntAct; E9PZQ0; 29. DR MINT; E9PZQ0; -. DR STRING; 10090.ENSMUSP00000137123; -. DR BindingDB; E9PZQ0; -. DR ChEMBL; CHEMBL2133; -. DR GlyGen; E9PZQ0; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; E9PZQ0; -. DR PhosphoSitePlus; E9PZQ0; -. DR MaxQB; E9PZQ0; -. DR PaxDb; 10090-ENSMUSP00000137123; -. DR PeptideAtlas; E9PZQ0; -. DR ProteomicsDB; 256854; -. DR Antibodypedia; 44914; 192 antibodies from 25 providers. DR DNASU; 20190; -. DR Ensembl; ENSMUST00000179893.9; ENSMUSP00000137123.2; ENSMUSG00000030592.19. DR GeneID; 20190; -. DR KEGG; mmu:20190; -. DR UCSC; uc009gao.1; mouse. DR AGR; MGI:99659; -. DR CTD; 6261; -. DR MGI; MGI:99659; Ryr1. DR VEuPathDB; HostDB:ENSMUSG00000030592; -. DR eggNOG; KOG2243; Eukaryota. DR GeneTree; ENSGT00940000155288; -. DR InParanoid; E9PZQ0; -. DR OrthoDB; 3144451at2759; -. DR PhylomeDB; E9PZQ0; -. DR TreeFam; TF315244; -. DR Reactome; R-MMU-2672351; Stimuli-sensing channels. DR Reactome; R-MMU-5578775; Ion homeostasis. DR BioGRID-ORCS; 20190; 2 hits in 78 CRISPR screens. DR ChiTaRS; Ryr1; mouse. DR PRO; PR:E9PZQ0; -. DR Proteomes; UP000000589; Chromosome 7. DR RNAct; E9PZQ0; Protein. DR Bgee; ENSMUSG00000030592; Expressed in triceps brachii and 117 other cell types or tissues. DR ExpressionAtlas; E9PZQ0; baseline and differential. DR GO; GO:0034704; C:calcium channel complex; IBA:GO_Central. DR GO; GO:0005938; C:cell cortex; ISO:MGI. DR GO; GO:0005737; C:cytoplasm; ISO:MGI. DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; ISO:MGI. DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; ISO:MGI. DR GO; GO:0031674; C:I band; ISO:MGI. DR GO; GO:0030314; C:junctional membrane complex; IDA:MGI. DR GO; GO:0016020; C:membrane; IDA:MGI. DR GO; GO:0031090; C:organelle membrane; ISS:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI. DR GO; GO:0005886; C:plasma membrane; ISO:MGI. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:1990425; C:ryanodine receptor complex; ISS:UniProtKB. DR GO; GO:0042383; C:sarcolemma; ISO:MGI. DR GO; GO:0030017; C:sarcomere; ISO:MGI. DR GO; GO:0016529; C:sarcoplasmic reticulum; IDA:MGI. DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; IDA:UniProtKB. DR GO; GO:0005790; C:smooth endoplasmic reticulum; IDA:MGI. DR GO; GO:0030315; C:T-tubule; IDA:MGI. DR GO; GO:0014802; C:terminal cisterna; ISS:UniProtKB. DR GO; GO:0031982; C:vesicle; ISO:MGI. DR GO; GO:0030018; C:Z disc; IBA:GO_Central. DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB. DR GO; GO:0005262; F:calcium channel activity; IMP:UniProtKB. DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB. DR GO; GO:0048763; F:calcium-induced calcium release activity; ISO:MGI. DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW. DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL. DR GO; GO:0002020; F:protease binding; IPI:UniProtKB. DR GO; GO:0005219; F:ryanodine-sensitive calcium-release channel activity; IMP:UniProtKB. DR GO; GO:0005245; F:voltage-gated calcium channel activity; IDA:UniProtKB. DR GO; GO:0006816; P:calcium ion transport; IDA:MGI. DR GO; GO:0071318; P:cellular response to ATP; ISO:MGI. DR GO; GO:0071313; P:cellular response to caffeine; IMP:UniProtKB. DR GO; GO:0071277; P:cellular response to calcium ion; ISS:UniProtKB. DR GO; GO:0006936; P:muscle contraction; IDA:MGI. DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISO:MGI. DR GO; GO:0043931; P:ossification involved in bone maturation; IMP:UniProtKB. DR GO; GO:0003151; P:outflow tract morphogenesis; IMP:UniProtKB. DR GO; GO:0051289; P:protein homotetramerization; ISS:UniProtKB. DR GO; GO:0051480; P:regulation of cytosolic calcium ion concentration; ISO:MGI. DR GO; GO:0006937; P:regulation of muscle contraction; TAS:MGI. DR GO; GO:0047484; P:regulation of response to osmotic stress; ISO:MGI. DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; IMP:MGI. DR GO; GO:0014808; P:release of sequestered calcium ion into cytosol by sarcoplasmic reticulum; IMP:UniProtKB. DR GO; GO:0031000; P:response to caffeine; ISO:MGI. DR GO; GO:0001666; P:response to hypoxia; ISO:MGI. DR GO; GO:0070296; P:sarcoplasmic reticulum calcium ion transport; ISO:MGI. DR GO; GO:0048741; P:skeletal muscle fiber development; IMP:UniProtKB. DR GO; GO:0043588; P:skin development; IMP:UniProtKB. DR GO; GO:0006941; P:striated muscle contraction; IBA:GO_Central. DR CDD; cd12877; SPRY1_RyR; 1. DR CDD; cd12878; SPRY2_RyR; 1. DR CDD; cd12879; SPRY3_RyR; 1. DR Gene3D; 1.10.287.70; -; 1. DR Gene3D; 1.10.490.160; -; 2. DR Gene3D; 2.60.120.920; -; 3. DR Gene3D; 2.80.10.50; -; 2. DR Gene3D; 6.20.350.10; -; 1. DR Gene3D; 1.25.10.30; IP3 receptor type 1 binding core, RIH domain; 1. DR InterPro; IPR001870; B30.2/SPRY. DR InterPro; IPR043136; B30.2/SPRY_sf. DR InterPro; IPR013320; ConA-like_dom_sf. DR InterPro; IPR011992; EF-hand-dom_pair. DR InterPro; IPR014821; Ins145_P3_rcpt. DR InterPro; IPR005821; Ion_trans_dom. DR InterPro; IPR036300; MIR_dom_sf. DR InterPro; IPR016093; MIR_motif. DR InterPro; IPR013662; RIH_assoc-dom. DR InterPro; IPR000699; RIH_dom. DR InterPro; IPR013333; Ryan_recept. DR InterPro; IPR015925; Ryanodine_IP3_receptor. DR InterPro; IPR003032; Ryanodine_rcpt. DR InterPro; IPR009460; Ryanrecept_TM4-6. DR InterPro; IPR048581; RYDR_Jsol. DR InterPro; IPR035910; RyR/IP3R_RIH_dom_sf. DR InterPro; IPR035761; SPRY1_RyR. DR InterPro; IPR035764; SPRY2_RyR. DR InterPro; IPR035762; SPRY3_RyR. DR InterPro; IPR003877; SPRY_dom. DR PANTHER; PTHR46399; B30.2/SPRY DOMAIN-CONTAINING PROTEIN; 1. DR PANTHER; PTHR46399:SF10; RYANODINE RECEPTOR 1; 1. DR Pfam; PF08709; Ins145_P3_rec; 1. DR Pfam; PF00520; Ion_trans; 1. DR Pfam; PF02815; MIR; 1. DR Pfam; PF08454; RIH_assoc; 1. DR Pfam; PF06459; RR_TM4-6; 1. DR Pfam; PF01365; RYDR_ITPR; 2. DR Pfam; PF21119; RYDR_Jsol; 1. DR Pfam; PF02026; RyR; 4. DR Pfam; PF00622; SPRY; 3. DR PRINTS; PR00795; RYANODINER. DR SMART; SM00472; MIR; 4. DR SMART; SM00449; SPRY; 3. DR SUPFAM; SSF49899; Concanavalin A-like lectins/glucanases; 3. DR SUPFAM; SSF47473; EF-hand; 1. DR SUPFAM; SSF100909; IP3 receptor type 1 binding core, domain 2; 2. DR SUPFAM; SSF82109; MIR domain; 2. DR PROSITE; PS50188; B302_SPRY; 3. DR PROSITE; PS50919; MIR; 5. DR Genevisible; E9PZQ0; MM. PE 1: Evidence at protein level; KW ATP-binding; Calcium; Calcium channel; Calcium transport; KW Calmodulin-binding; Developmental protein; Ion channel; Ion transport; KW Ligand-gated ion channel; Membrane; Metal-binding; Nucleotide-binding; KW Phosphoprotein; Receptor; Reference proteome; Repeat; S-nitrosylation; KW Sarcoplasmic reticulum; Transmembrane; Transmembrane helix; Transport. FT CHAIN 1..5035 FT /note="Ryanodine receptor 1" FT /id="PRO_0000415566" FT TOPO_DOM 1..4556 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:P11716" FT TRANSMEM 4557..4577 FT /note="Helical; Name=1" FT /evidence="ECO:0000250|UniProtKB:P11716" FT TOPO_DOM 4578..4638 FT /note="Lumenal" FT /evidence="ECO:0000250|UniProtKB:P11716" FT TRANSMEM 4639..4659 FT /note="Helical; Name=2" FT /evidence="ECO:0000250|UniProtKB:P11716" FT TOPO_DOM 4660..4777 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:P11716" FT TRANSMEM 4778..4800 FT /note="Helical; Name=3" FT /evidence="ECO:0000250|UniProtKB:P11716" FT TOPO_DOM 4801 FT /note="Lumenal" FT /evidence="ECO:0000250|UniProtKB:P11716" FT TRANSMEM 4802..4818 FT /note="Helical; Name=4" FT /evidence="ECO:0000250|UniProtKB:P11716" FT TOPO_DOM 4819..4833 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:P11716" FT TRANSMEM 4834..4854 FT /note="Helical; Name=5" FT /evidence="ECO:0000250|UniProtKB:P11716" FT TOPO_DOM 4855..4877 FT /note="Lumenal" FT /evidence="ECO:0000250|UniProtKB:P11716" FT INTRAMEM 4878..4897 FT /note="Pore-forming" FT /evidence="ECO:0000250|UniProtKB:P11716" FT TOPO_DOM 4898..4917 FT /note="Lumenal" FT /evidence="ECO:0000250|UniProtKB:P11716" FT TRANSMEM 4918..4938 FT /note="Helical; Name=6" FT /evidence="ECO:0000250|UniProtKB:P11716" FT TOPO_DOM 4939..5035 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:P11716" FT DOMAIN 99..154 FT /note="MIR 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131" FT DOMAIN 161..206 FT /note="MIR 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131" FT DOMAIN 212..266 FT /note="MIR 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131" FT DOMAIN 272..329 FT /note="MIR 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131" FT DOMAIN 337..394 FT /note="MIR 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131" FT DOMAIN 583..799 FT /note="B30.2/SPRY 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548" FT REPEAT 843..956 FT /note="1" FT REPEAT 957..1070 FT /note="2" FT DOMAIN 1015..1210 FT /note="B30.2/SPRY 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548" FT REPEAT 1346..1361 FT /note="3; truncated" FT DOMAIN 1359..1572 FT /note="B30.2/SPRY 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548" FT REPEAT 1374..1389 FT /note="4; truncated" FT REPEAT 2727..2846 FT /note="5" FT REPEAT 2847..2960 FT /note="6" FT DOMAIN 4078..4106 FT /note="EF-hand" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT REGION 671..682 FT /note="Interaction with FKBP1A" FT /evidence="ECO:0000250|UniProtKB:P11716" FT REGION 843..2960 FT /note="6 X approximate repeats" FT REGION 1309..1387 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1873..1928 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2391..2414 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2828..2859 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 3479..3502 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 3615..3644 FT /note="Interaction with CALM" FT /evidence="ECO:0000250" FT REGION 4255..4283 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 4378..4531 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 4586..4618 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 4892..4898 FT /note="Selectivity filter" FT /evidence="ECO:0000250|UniProtKB:P11716" FT COMPBIAS 1372..1387 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1874..1923 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2828..2844 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 4257..4274 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 4402..4418 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 4482..4496 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 4497..4513 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 4514..4528 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 3896 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:P11716" FT BINDING 3970 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:P11716" FT BINDING 4214..4218 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P11716" FT BINDING 4714 FT /ligand="caffeine" FT /ligand_id="ChEBI:CHEBI:27732" FT /evidence="ECO:0000250|UniProtKB:P11716" FT BINDING 4952..4957 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P11716" FT BINDING 4977..4983 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P11716" FT BINDING 4999 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:P11716" FT MOD_RES 1339 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:F1LMY4" FT MOD_RES 2346 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:F1LMY4" FT MOD_RES 2844 FT /note="Phosphoserine; by PKA and PKG" FT /evidence="ECO:0000269|PubMed:18268335, FT ECO:0000269|PubMed:21156754, ECO:0007744|PubMed:21183079" FT MOD_RES 3636 FT /note="S-nitrosocysteine" FT /evidence="ECO:0000250|UniProtKB:P11716" FT MOD_RES 4464 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:F1LMY4" FT MOD_RES 4468 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:F1LMY4" FT MOD_RES 4861 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P21817" FT MOD_RES 4864 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P21817" FT MUTAGEN 165 FT /note="R->C: Increased channel activity, leading to FT permanently increased cytoplasmic Ca(2+) levels. Increased FT activation by calcium, and increased ryanodine binding." FT /evidence="ECO:0000269|PubMed:21156754" FT MUTAGEN 4895 FT /note="I->T: Causes paralysis and perinatal death in FT homozygous mice, apparently due to asphyxia. Mutant mice FT have greatly reduced and amorphous skeletal muscle." FT /evidence="ECO:0000269|PubMed:18003898" FT CONFLICT 616 FT /note="R -> C (in Ref. 5; CAC34624)" FT /evidence="ECO:0000305" FT CONFLICT 1380 FT /note="A -> S (in Ref. 1; AAP29981)" FT /evidence="ECO:0000305" FT CONFLICT 3484 FT /note="D -> V (in Ref. 1; AAP29981)" FT /evidence="ECO:0000305" FT CONFLICT 4766 FT /note="I -> L (in Ref. 8; AAA64955)" FT /evidence="ECO:0000305" FT CONFLICT 4821 FT /note="L -> V (in Ref. 7; CAA58784)" FT /evidence="ECO:0000305" FT CONFLICT 4888 FT /note="G -> A (in Ref. 7; CAA58784)" FT /evidence="ECO:0000305" SQ SEQUENCE 5035 AA; 565039 MW; D15D2E764B445573 CRC64; MGDGGGEGED EVQFLRTDDE VVLQCSATVL KEQLKLCLAA EGFGNRLCFL EPTSNAQNVP PDLAICCFIL EQSLSVRALQ EMLANTVEAG VESSQGGGHR TLLYGHAILL RHAHSRMYLS CLTTSRSMTD KLAFDVGLQE DATGEACWWT MHPASKQRSE GEKVRVGDDL ILVSVSSERY LHLSTASGEL QVDASFMQTL WNMNPICSGC EEGFVTGGHV LRLFHGHMDE CLTISPSDSD DQRRLVYYEG GPVCTHARSL WRLEPLRISW SGSHLRWGQP LRIRHVTTGR YLGLTEDQGL VVVDASKAHT KATSFCFRIS KEKLDVAPKR DVEGMGPPEI KYGESLCFVQ HVASGLWLTY AAPDPKALRL GVLKKKAMLH QEGHMDDALS LTRCQQEESQ AARMIYSTAG LYNQFIKGLD SFSGKPRGSG PPAGSALPIE GVILSLQDLI GYFEPPSEEL QHEEKQTKLR SLRNRQSLFQ EEGMLSLVLN CIDRLNVYTT AAHFAEFAGE EAAESWKEIV NLLYELLASL IRGNRTNCAL FSTNLDWLVS KLDRLEASSG ILEVLYCVLI ESPEVLNIIQ ENHIKSIISL LDKHGRNHKV LDVLCSLCVC NGVAVRSNQD LITENLLPGR ELLLQTNLIN YVTSIRPNIF VGRAEGSTQY GKWYFEVMVD EVAPFLTAQA THLRVGWALS EGYSPYPGGG EGWGGNGVGD DLYSYGFDGL HLWTGHVARP VTSPGQHLLA PEDVVSCCLD LSVPSISFRI NGCPVQGVFE SFNLDGLFFP VVSFSAGIKV RFLLGGRHGE FKFLPPPGYA PCHEAVLPRE RLHLQPIKEY RREGPRGPHL VGPSRCLSHL DFVPCPVDTI QIVLPPHLER IREKLAENIH ELWALTRIEQ GWTYGPVRDD NKRLHPCLVN FHSLPEPERN YNLQMSGETL KTLLALGCHV GMADEKAEDN LKKTKLPKTY MMSNGYKPAP LDLSHVRLTP AQTTLVDRLA ENGHNVWARD RVAQGWSYSA VQDIPARRNP RLVPYRLLDE ATKRSNRDSL CQAVRTLLGY GYNIEPPDQE PSQVDSQSRG DRARIFRAEK SYAVQSGRWY FEFEAVTTGE MRVGWARPEL RPDVELGADD LAYVFNGHRG QRWHLGSEPF GRPWQSGDVV GCMIDLTENT IIFTLNGEVL MSDSGSETAF RDIEIGDGFL PVCSLGPGQV GHLNLGQDVS SLRFFAICGL QEGFEPFAIN MQRPVTTWFS KSLPQFEPVP LEHPHYEVAR MDGTVDTPPC LRLTHRTWGS QNSLVEMLFL RLSLPVQFHQ HFRCTAGATP LASPGLQPPA EDEARAAEPD TDYENLRRSA GGWGEAEGGK DGTAKEGTPG GTAQAGVEAQ PARAENEKDA TTEKNKKRGF LFKAKKVAMM TQPPSTPALP RLPRDVVPAD NRDDPEIILN TTTYYYSVRV FAGQEPSCVW VGWVTPDYHQ HDMSFDLSKV RAVTVTMGDE QGNVHSSLKC SNCYMVWGGD FVSPGQQGRI SHTDLVIGCL VDLATGLMTF TANGKESNTF FQVEPNTKLF PAVFVLPTHQ NVVQFELGKQ KNIMPLSAAM FLSERKNPAP QCPPRLEVQM LMPVSWSRMP NHFLQVDTRR AGERLGWAVQ CQEPLMMMAL HIPEENRCMD ILELSERLDL QRFHSHTLSL YRSVCALGNN RVAHALCSHV DQAQLLHALE DARLPGPLRA GYYDLLISIH LESACRSRRS MLSEYIVPLT PETRAITLFP PGRSAEDGPR RHGLPGVGVT TSLRPPHHFS PPCFVVALPA AGATEAPARL SPAIPLEALR DKALRMLGEA VRDGGQHARD PVGGSVEFQF VPVLKLVSTL LVMGVFSDED VKQILKMIEP EVFREEEEVE EEGEEEEEDE EEKEEDEEEE AHEKEDEEKE EAEDAAEEEK EELEEGLLQM KLPESVKLQM CHLLEYFCDQ ELQHRVESLA AFAECYVDKM QGNQRGRYGL LMKAFTMSAA ETARRTREFR SPPQEQINML LHFKNGADEE ECPLPEEIRQ ELVNFHQDLL AHCGIQLEGE EEEPEEESTL GSRLMSLLEK VKLVKKTEEK PEEEPAPEEH KPQSLQELVS HTVVRWAQED FVQSPELVRA MFSLLHRQYD GLGELLRALP RAYTISVSSV EDTMSLLECL GQIRSLLIVQ MGPQEENLMI QSIGNIMNNK VFYQHPNLMR ALGMHETVME VMVNVLGGGE SKEIRFPKMV TSCCRFLCYF CRISRQNQRS MFDHLSYLLE NSGIGLGMQG STPLDVAAAS VIDNNELALA LQEQDLEKVV SYLAGCGLQS CPMLLAKGYP DIGWNPCGGE RYLDFLRFAV FVNGESVEEN ANVVVRLLIR KPECFGPALR GEGGSGLLAA IEEAIRISED PARDGPGVRR DRRREHFGEE PPEENRVHLG HAIMSFYAAL IDLLGRCAPE THLIQAGKGE ALRIRAILRS LVPLDDLVGI ISLPLQIPTL GKDGALVQPK MSASFVPDHK ASMVLFLDRV YGIENQDFLL HVLDVGFLPD MRAAASLDTA TFSTTEMALA LNRYLCLAVL PLITKCAPLF AGTEHRAIMV DSMLHTVYRL SRGRSLTKAQ RDVIEDCLMA LCRYIRPSML QHLLRRLVFD VPILNEFAKM PLKLLTNHYE RCWKYYCLPT GWANFGVTSE EELHLTRKLF WGIFDSLAHK KYDQELYRIA MPCLCAIAGA LPPDYVDASY SSKTEKKATV DAEGNFDPRP VETLNVIIPE KLDSFINKFA EYTHEKWAFD KIQNNWSYGE NIDEELKTHP MLRPYKTFSE KDKEIYRWPI KESLKAMIAW EWTVEKAREG EEEKTEKKKT RKISQTAQTY DPREGYNPQP PDLSVVTLSR ELQAMAEQLA ENYHNTWGRK KKQELEAKGG GSHPLLVPYD TLTAKEKARD REKAQELLKF LQMNGYAVTR GLKDMELDTS SIEKRFAFGF LQQLLRWMDI SQEFIAHLEA VVSSGRVEKS PHEQEIKFFA KILLPLINQY FTNHCLYFLS TPAKVLGSGG HASNKEKEMI TSLFCKLAAL VRHRVSLFGT DAPAVVNCLH ILARSLDART VMKSGPEIVK AGLRSFFESA SEDIEKMVEN LRLGKVSQAR TQVKGVGQNL TYTTVALLPV LTTLFQHIAQ HQFGDDVILD DVQVSCYRTL CSIYSLGTTR NPYVEKLRPA LGECLARLAA AMPVAFLEPE LNEYNACSVY TTKSPRERAI LGLPNSVEEM CPDIPVLERL MAEIGGLAES GARYTEMPHV IEITLPMLCS YLPRWWERGP EAPPPALPAG APPPCTAVTS DHLNSLLGNI LRIIVNNLGI DEASWMKRLA VFAQPIVSRA RPELLRSHFI PTIGRLRKRA GKVVAEEEQL RLEAKAEAEE GELLVRDEFS VLCRDLYALY PLLIRYVDNN RAHWLTEPNP NAEELFRMVG EIFIYWSKSH NFKREEQNFV VQNEINNMSF LTADNKSKMA KAGDVQSGGS DQERTKKKRR GDRYSVQTSL IVATLKKMLP IGLNMCAPTD QDLIVLAKAR YALKDTDEEV REFLQNNLNL QGKVEGSPSL RWQMALYRGV PGREEDADDP EKIVRRVQEV SAVLYHLDQT EHPYKSKKAV WHKLLSKQRR RAVVACFRMT PLYNLPTHRA CNMFLESYKA SWILTEDHSF EDRMIDDLSK AGEQEEEEEE VEEKKPDPLH QLVLHFSRTA LTEKSKLDED YLYMAYADIM AKSCHLEEGG ENGEEGGEEE EVEVSFEEKE MEKQRLLYQQ SRLHNRGAAE MVLQMISACK GETGAMVSST LKLGISILNG GNAEVQQKML DYLKDKKEVG FFQSIQALMQ TCSVLDLNAF ERQNKAEGLG MVNEDGTVIN RQNGEKVMAD DEFTQDLFRF LQLLCEGHNN DFQNYLRTQT GNTTTINIII CTVDYLLRLQ ESISDFYWYY SGKDVIEEQG KRNFSKAMSV AKQVFNSLTE YIQGPCTGNQ QSLAHSRLWD AVVGFLHVFA HMMMKLAQDS SQIELLKELL DLQKDMVVML LSLLEGNVVN GMIARQMVDM LVESSSNVEM ILKFFDMFLK LKDIVGSEAF QDYVTDPRGL ISKKDFQKAM DSQKQFTGPE IQFLLSCSEA DENEMINCEE FANRFQEPAR DIGFNVAVLL TNLSEHVPHD PRLRNFLELA ESILEYFRPY LGRIEIMGAS RRIERIYFEI SETNRAQWEM PQVKESKRQF IFDVVNEGGE SEKMEMFVSF CEDTIFEMQI AAQISEPEGE PEEDEDEGAE EAEEGAAGSD GSGSAAAAGV WVWLAATAGR TLRGLSYRSL RRRVRRLRRL TAREAATAVA ALLWALVTRA GGAGAGAAAG ALRLLWGSLF GGGLVDSAKK VTVTELLAGM PDPTGDEVHG QQPSGAGSDA EGEGEGEGEG DAADGAGDEE AAADQAGTGG ADGAVAVADG SPFRPEGAGG LGDMGDTTPV EPPTPEGSPI LKRKLGVDGE EEEPPPEPEP EPEPEPEKAD TENGEKEVPE PPPEPPKKTP PPPPPKKEEA GGAGLEEFWG ELEVQRVKFL NYLSRNFYTL RFLALFLAFA INFILLFYKV SDSPPGEDDI EGSGAGDMSG AGSGDGSGWG SRAGEEVEGD EDENMVYYFL EESTGYMEPA LRCLSLLHTL VAFLCIIGYN CLKVPLVIFK REKELARKLE FDGLYITEQP EDDDVKGQWD RLVLNTPSFP SNYWDKFVKR KVLDKHGDIF GRERIAELLG MDLASLEITA HNERKPDPPP GLLTWIMSID VKYQIWKFGV IFTDNSFLYL GWYMVMSLLG HYNNFFFAAH LLDIAMGVKT LRTILSSVTH NGKQLVMTVG LLAVVVYLYT VVAFNFFRKF YNKSEDEDEP DMKCDDMMTC YLFHMYVGVR AGGGIGDEIE DPAGDEYELY RVVFDITFFF FVIVILLAII QGLIIDAFGE LRDQQEQVKE DMETKCFICG IGSDYFDTTP HGFETHTLEE HNLANYMFFL MYLINKDETE HTGQESYVWK MYQERCWDFF PAGDCFRKQY EDQLS //