RYR1_RABIT
ID RYR1_RABIT Reviewed; 5037 AA.
AC P11716;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1989, sequence version 1.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Ryanodine receptor 1;
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;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, DOMAIN, TISSUE
RP SPECIFICITY, AND SUBCELLULAR LOCATION.
RC TISSUE=Skeletal muscle;
RX PubMed=2725677; DOI=10.1038/339439a0;
RA Takeshima H., Nishimura S., Matsumoto T., Ishido H., Kangawa K.,
RA Minamino N., Matsuo H., Ueda M., Hanaoka M., Hirose T., Numa S.;
RT "Primary structure and expression from complementary DNA of skeletal muscle
RT ryanodine receptor.";
RL Nature 339:439-445(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Skeletal muscle;
RX PubMed=2298749; DOI=10.1016/s0021-9258(19)39968-5;
RA Zorzato F., Fujii J., Otsu K., Phillips M.S., Green N.M., Lai F.A.,
RA Meissner G., Maclennan D.H.;
RT "Molecular cloning of cDNA encoding human and rabbit forms of the Ca2+
RT release channel (ryanodine receptor) of skeletal muscle sarcoplasmic
RT reticulum.";
RL J. Biol. Chem. 265:2244-2256(1990).
RN [3]
RP PROTEIN SEQUENCE OF 3631-3650, S-NITROSYLATION AT CYS-3635, AND INTERACTION
RP WITH CALM.
RX PubMed=10601232; DOI=10.1074/jbc.274.52.36831;
RA Porter Moore C., Zhang J.Z., Hamilton S.L.;
RT "A role for cysteine 3635 of RYR1 in redox modulation and calmodulin
RT binding.";
RL J. Biol. Chem. 274:36831-36834(1999).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=3722165; DOI=10.1016/s0021-9258(19)84428-9;
RA Pessah I.N., Francini A.O., Scales D.J., Waterhouse A.L., Casida J.E.;
RT "Calcium-ryanodine receptor complex. Solubilization and partial
RT characterization from skeletal muscle junctional sarcoplasmic reticulum
RT vesicles.";
RL J. Biol. Chem. 261:8643-8648(1986).
RN [5]
RP PHOSPHORYLATION AT SER-2843.
RX PubMed=8380342; DOI=10.1016/0167-4889(93)90023-i;
RA Suko J., Maurer-Fogy I., Plank B., Bertel O., Wyskovsky W., Hohenegger M.,
RA Hellmann G.;
RT "Phosphorylation of serine 2843 in ryanodine receptor-calcium release
RT channel of skeletal muscle by cAMP-, cGMP- and CaM-dependent protein
RT kinase.";
RL Biochim. Biophys. Acta 1175:193-206(1993).
RN [6]
RP INTERACTION WITH FKBP1A, AND TISSUE SPECIFICITY.
RX PubMed=7669046; DOI=10.1006/bbrc.1995.2283;
RA Xin H.B., Timerman A.P., Onoue H., Wiederrecht G.J., Fleischer S.;
RT "Affinity purification of the ryanodine receptor/calcium release channel
RT from fast twitch skeletal muscle based on its tight association with
RT FKBP12.";
RL Biochem. Biophys. Res. Commun. 214:263-270(1995).
RN [7]
RP INTERACTION WITH FKBP1A.
RX PubMed=10603943; DOI=10.1111/j.1749-6632.1998.tb08263.x;
RA Ondrias K., Marx S.O., Gaburjakova M., Marks A.R.;
RT "FKBP12 modulates gating of the ryanodine receptor/calcium release
RT channel.";
RL Ann. N. Y. Acad. Sci. 853:149-156(1998).
RN [8]
RP INTERACTION WITH TRDN.
RX PubMed=9737879; DOI=10.1021/bi972803d;
RA Ohkura M., Furukawa K., Fujimori H., Kuruma A., Kawano S., Hiraoka M.,
RA Kuniyasu A., Nakayama H., Ohizumi Y.;
RT "Dual regulation of the skeletal muscle ryanodine receptor by triadin and
RT calsequestrin.";
RL Biochemistry 37:12987-12993(1998).
RN [9]
RP INTERACTION WITH CACNA1S, AND FUNCTION.
RX PubMed=10388749; DOI=10.1016/s0006-3495(99)76881-5;
RA Dulhunty A.F., Laver D.R., Gallant E.M., Casarotto M.G., Pace S.M.,
RA Curtis S.;
RT "Activation and inhibition of skeletal RyR channels by a part of the
RT skeletal DHPR II-III loop: effects of DHPR Ser687 and FKBP12.";
RL Biophys. J. 77:189-203(1999).
RN [10]
RP FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, MUTAGENESIS OF
RP ILE-4897, AND SUBUNIT.
RX PubMed=10097181; DOI=10.1073/pnas.96.7.4164;
RA Lynch P.J., Tong J., Lehane M., Mallet A., Giblin L., Heffron J.J.A.,
RA Vaughan P., Zafra G., MacLennan D.H., McCarthy T.V.;
RT "A mutation in the transmembrane/luminal domain of the ryanodine receptor
RT is associated with abnormal Ca(2+) release channel function and severe
RT central core disease.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:4164-4169(1999).
RN [11]
RP S-NITROSYLATION AT CYS-3635, MUTAGENESIS OF CYS-3635, AND INTERACTION WITH
RP CALM.
RX PubMed=11562475; DOI=10.1073/pnas.201289098;
RA Sun J., Xin C., Eu J.P., Stamler J.S., Meissner G.;
RT "Cysteine-3635 is responsible for skeletal muscle ryanodine receptor
RT modulation by NO.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:11158-11162(2001).
RN [12]
RP INTERACTION WITH RYR2.
RX PubMed=12213830; DOI=10.1074/jbc.m208210200;
RA Xiao B., Masumiya H., Jiang D., Wang R., Sei Y., Zhang L., Murayama T.,
RA Ogawa Y., Lai F.A., Wagenknecht T., Chen S.R.;
RT "Isoform-dependent formation of heteromeric Ca2+ release channels
RT (ryanodine receptors).";
RL J. Biol. Chem. 277:41778-41785(2002).
RN [13]
RP SUBCELLULAR LOCATION, AND MEMBRANE TOPOLOGY.
RX PubMed=12486242; DOI=10.1073/pnas.012688999;
RA Du G.G., Sandhu B., Khanna V.K., Guo X.H., MacLennan D.H.;
RT "Topology of the Ca2+ release channel of skeletal muscle sarcoplasmic
RT reticulum (RyR1).";
RL Proc. Natl. Acad. Sci. U.S.A. 99:16725-16730(2002).
RN [14]
RP FUNCTION, SUBCELLULAR LOCATION, ACTIVITY REGULATION, AND MUTAGENESIS OF
RP ARG-164; GLY-342; ARG-615; ARG-2163; VAL-2168; ARG-2458 AND THR-4825.
RX PubMed=12732639; DOI=10.1074/jbc.m302165200;
RA Yang T., Ta T.A., Pessah I.N., Allen P.D.;
RT "Functional defects in six ryanodine receptor isoform-1 (RyR1) mutations
RT associated with malignant hyperthermia and their impact on skeletal
RT excitation-contraction coupling.";
RL J. Biol. Chem. 278:25722-25730(2003).
RN [15]
RP INTERACTION WITH SELENON.
RX PubMed=18713863; DOI=10.1073/pnas.0806015105;
RA Jurynec M.J., Xia R., Mackrill J.J., Gunther D., Crawford T.,
RA Flanigan K.M., Abramson J.J., Howard M.T., Grunwald D.J.;
RT "Selenoprotein N is required for ryanodine receptor calcium release channel
RT activity in human and zebrafish muscle.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:12485-12490(2008).
RN [16]
RP INTERACTION WITH TRDN AND ASPH.
RX PubMed=19398037; DOI=10.1016/j.biocel.2009.04.017;
RA Wei L., Gallant E.M., Dulhunty A.F., Beard N.A.;
RT "Junctin and triadin each activate skeletal ryanodine receptors but junctin
RT alone mediates functional interactions with calsequestrin.";
RL Int. J. Biochem. Cell Biol. 41:2214-2224(2009).
RN [17]
RP INTERACTION WITH CACNB1.
RX PubMed=21320436; DOI=10.1016/j.bpj.2011.01.022;
RA Rebbeck R.T., Karunasekara Y., Gallant E.M., Board P.G., Beard N.A.,
RA Casarotto M.G., Dulhunty A.F.;
RT "The beta(1a) subunit of the skeletal DHPR binds to skeletal RyR1 and
RT activates the channel via its 35-residue C-terminal tail.";
RL Biophys. J. 100:922-930(2011).
RN [18]
RP FUNCTION, ACTIVITY REGULATION, S-NITROSYLATION AT CYS-3635, AND MUTAGENESIS
RP OF CYS-3635.
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 [19]
RP INTERACTION WITH SCORPION CALCIN.
RX PubMed=27114612; DOI=10.1085/jgp.201511499;
RA Xiao L., Gurrola G.B., Zhang J., Valdivia C.R., SanMartin M., Zamudio F.Z.,
RA Zhang L., Possani L.D., Valdivia H.H.;
RT "Structure-function relationships of peptides forming the calcin family of
RT ryanodine receptor ligands.";
RL J. Gen. Physiol. 147:375-394(2016).
RN [20]
RP STRUCTURE BY ELECTRON MICROSCOPY (10 ANGSTROMS), SUBUNIT, TISSUE
RP SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=15908964; DOI=10.1038/nsmb938;
RA Samso M., Wagenknecht T., Allen P.D.;
RT "Internal structure and visualization of transmembrane domains of the RyR1
RT calcium release channel by cryo-EM.";
RL Nat. Struct. Mol. Biol. 12:539-544(2005).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 3614-3643 IN COMPLEX WITH CALM.
RX PubMed=17027503; DOI=10.1016/j.str.2006.08.011;
RA Maximciuc A.A., Putkey J.A., Shamoo Y., Mackenzie K.R.;
RT "Complex of calmodulin with a ryanodine receptor target reveals a novel,
RT flexible binding mode.";
RL Structure 14:1547-1556(2006).
RN [22]
RP STRUCTURE BY ELECTRON MICROSCOPY (9.6 ANGSTROMS), AND SUBUNIT.
RX PubMed=18621707; DOI=10.1073/pnas.0803189105;
RA Serysheva I.I., Ludtke S.J., Baker M.L., Cong Y., Topf M., Eramian D.,
RA Sali A., Hamilton S.L., Chiu W.;
RT "Subnanometer-resolution electron cryomicroscopy-based domain models for
RT the cytoplasmic region of skeletal muscle RyR channel.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:9610-9615(2008).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 1-210.
RX PubMed=19541610; DOI=10.1073/pnas.0905186106;
RA Amador F.J., Liu S., Ishiyama N., Plevin M.J., Wilson A., MacLennan D.H.,
RA Ikura M.;
RT "Crystal structure of type I ryanodine receptor amino-terminal beta-trefoil
RT domain reveals a disease-associated mutation 'hot spot' loop.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:11040-11044(2009).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 9-205.
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 [25]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 1-559.
RX PubMed=21048710; DOI=10.1038/nature09471;
RA Tung C.C., Lobo P.A., Kimlicka L., Van Petegem F.;
RT "The amino-terminal disease hotspot of ryanodine receptors forms a
RT cytoplasmic vestibule.";
RL Nature 468:585-588(2010).
RN [26] {ECO:0007744|PDB:3RQR}
RP X-RAY CRYSTALLOGRAPHY (2.16 ANGSTROMS) OF 2733-2940.
RX PubMed=22913516; DOI=10.1111/j.1742-4658.2012.08755.x;
RA Sharma P., Ishiyama N., Nair U., Li W., Dong A., Miyake T., Wilson A.,
RA Ryan T., MacLennan D.H., Kislinger T., Ikura M., Dhe-Paganon S.,
RA Gramolini A.O.;
RT "Structural determination of the phosphorylation domain of the ryanodine
RT receptor.";
RL FEBS J. 279:3952-3964(2012).
RN [27] {ECO:0007744|PDB:4ERT, ECO:0007744|PDB:4ESU, ECO:0007744|PDB:4ETU}
RP X-RAY CRYSTALLOGRAPHY (1.59 ANGSTROMS) OF 2734-2940, AND MUTAGENESIS OF
RP LEU-2867.
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 [28] {ECO:0007744|PDB:4I0Y, ECO:0007744|PDB:4I1E, ECO:0007744|PDB:4I2S, ECO:0007744|PDB:4I37, ECO:0007744|PDB:4I3N, ECO:0007744|PDB:4I6I, ECO:0007744|PDB:4I7I, ECO:0007744|PDB:4I8M, ECO:0007744|PDB:4I96}
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 1-536.
RX PubMed=23422674; DOI=10.1038/ncomms2501;
RA Kimlicka L., Lau K., Tung C.C., Van Petegem F.;
RT "Disease mutations in the ryanodine receptor N-terminal region couple to a
RT mobile intersubunit interface.";
RL Nat. Commun. 4:1506-1506(2013).
RN [29] {ECO:0007744|PDB:4P9J}
RP X-RAY CRYSTALLOGRAPHY (1.84 ANGSTROMS) OF 1070-1246, AND MUTAGENESIS OF
RP ARG-1076.
RX PubMed=25370123; DOI=10.1038/ncomms6397;
RA Lau K., Van Petegem F.;
RT "Crystal structures of wild type and disease mutant forms of the ryanodine
RT receptor SPRY2 domain.";
RL Nat. Commun. 5:5397-5397(2014).
RN [30] {ECO:0007744|PDB:5C30}
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 857-1054, INTERACTION WITH
RP FKBP1A, FUNCTION, ACTIVITY REGULATION, AND MUTAGENESIS OF 674-PHE-LEU-675;
RP ASN-760; ARG-1044; GLY-1050 AND VAL-2461.
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).
RN [31] {ECO:0007744|PDB:4UWA, ECO:0007744|PDB:4UWE}
RP STRUCTURE BY ELECTRON MICROSCOPY (6.10 ANGSTROMS), SUBCELLULAR LOCATION,
RP TOPOLOGY, AND TISSUE SPECIFICITY.
RX PubMed=25470059; DOI=10.1038/nature13916;
RA Efremov R.G., Leitner A., Aebersold R., Raunser S.;
RT "Architecture and conformational switch mechanism of the ryanodine
RT receptor.";
RL Nature 517:39-43(2015).
RN [32] {ECO:0007744|PDB:3J8H}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.80 ANGSTROMS) IN COMPLEX WITH FKBP1A,
RP SUBUNIT, SUBCELLULAR LOCATION, TOPOLOGY, TISSUE SPECIFICITY, AND DOMAIN.
RX PubMed=25517095; DOI=10.1038/nature14063;
RA Yan Z., Bai X.C., Yan C., Wu J., Li Z., Xie T., Peng W., Yin C.C., Li X.,
RA Scheres S.H., Shi Y., Yan N.;
RT "Structure of the rabbit ryanodine receptor RyR1 at near-atomic
RT resolution.";
RL Nature 517:50-55(2015).
RN [33] {ECO:0007744|PDB:5T15, ECO:0007744|PDB:5T9M, ECO:0007744|PDB:5T9V, ECO:0007744|PDB:5TA3, ECO:0007744|PDB:5TAL, ECO:0007744|PDB:5TAM, ECO:0007744|PDB:5TAN}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.60 ANGSTROMS) OF 12-1275; 1573-2479;
RP 2734-2939 AND 3639-5037 IN COMPLEXES WITH CALCIUM; ATP; RYANODINE AND
RP CAFFEINE, FUNCTION, ACTIVITY REGULATION, SUBUNIT, SUBCELLULAR LOCATION,
RP DOMAIN, AND TOPOLOGY.
RX PubMed=27662087; DOI=10.1016/j.cell.2016.08.075;
RA des Georges A., Clarke O.B., Zalk R., Yuan Q., Condon K.J., Grassucci R.A.,
RA Hendrickson W.A., Marks A.R., Frank J.;
RT "Structural basis for gating and activation of RyR1.";
RL Cell 167:145-157(2016).
RN [34] {ECO:0007744|PDB:5J8V}
RP STRUCTURE BY ELECTRON MICROSCOPY (4.90 ANGSTROMS), SUBUNIT, SUBCELLULAR
RP LOCATION, TOPOLOGY, AND TISSUE SPECIFICITY.
RX PubMed=27573175; DOI=10.1038/cr.2016.99;
RA Wei R., Wang X., Zhang Y., Mukherjee S., Zhang L., Chen Q., Huang X.,
RA Jing S., Liu C., Li S., Wang G., Xu Y., Zhu S., Williams A.J., Sun F.,
RA Yin C.C.;
RT "Structural insights into Ca(2+)-activated long-range allosteric channel
RT gating of RyR1.";
RL Cell Res. 26:977-994(2016).
RN [35] {ECO:0007744|PDB:5GKY, ECO:0007744|PDB:5GKZ, ECO:0007744|PDB:5GL0, ECO:0007744|PDB:5GL1}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.80 ANGSTROMS) IN COMPLEX WITH FKBP1A,
RP SUBUNIT, SUBCELLULAR LOCATION, TOPOLOGY, TISSUE SPECIFICITY, AND DOMAIN.
RX PubMed=27468892; DOI=10.1038/cr.2016.89;
RA Bai X.C., Yan Z., Wu J., Li Z., Yan N.;
RT "The central domain of RyR1 is the transducer for long-range allosteric
RT gating of channel opening.";
RL Cell Res. 26:995-1006(2016).
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 muscle contraction following depolarization of T-tubules
CC (PubMed:3722165, PubMed:10388749, PubMed:10097181, PubMed:12732639,
CC PubMed:22036948, PubMed:26245150, PubMed:27662087). Repeated very high-
CC level exercise increases the open probability of the channel and leads
CC to Ca(2+) leaking into the cytoplasm (By similarity). Can also mediate
CC the release of Ca(2+) from intracellular stores in neurons, and may
CC thereby promote prolonged Ca(2+) signaling in the brain. Required for
CC normal embryonic development of muscle fibers and skeletal muscle.
CC Required for normal heart morphogenesis, skin development and
CC ossification during embryogenesis (By similarity).
CC {ECO:0000250|UniProtKB:E9PZQ0, ECO:0000269|PubMed:10388749,
CC ECO:0000269|PubMed:12732639, ECO:0000269|PubMed:22036948,
CC ECO:0000269|PubMed:27662087, ECO:0000305|PubMed:10097181,
CC ECO:0000305|PubMed:26245150, ECO:0000305|PubMed:3722165}.
CC -!- ACTIVITY REGULATION: Channel activity is modulated by the alkaloid
CC ryanodine that binds to the open Ca-release channel with high affinity
CC (PubMed:27662087). At low concentrations, ryanodine maintains the
CC channel in an open conformation (PubMed:27662087). High ryanodine
CC concentrations inhibit channel activity (PubMed:27662087). Channel
CC activity is regulated by calmodulin (CALM). The calcium release is
CC activated by increased cytoplasmic calcium levels, by nitric oxyde
CC (NO), caffeine and ATP (PubMed:12732639, PubMed:22036948,
CC PubMed:26245150, PubMed:27662087). Channel activity is inhibited by
CC magnesium ions, possibly by competition for calcium binding sites
CC (PubMed:12732639). {ECO:0000269|PubMed:12732639,
CC ECO:0000269|PubMed:22036948, ECO:0000269|PubMed:26245150,
CC ECO:0000269|PubMed:27662087}.
CC -!- SUBUNIT: Homotetramer (PubMed:10097181, PubMed:15908964,
CC PubMed:17027503, PubMed:18621707, PubMed:25470059, PubMed:25517095,
CC PubMed:27662087, PubMed:27573175, PubMed:27468892). Can also form
CC heterotetramers with RYR2 (PubMed:12213830). Identified in a complex
CC composed of RYR1, PDE4D, PKA, FKBP1A and protein phosphatase 1 (PP1).
CC Repeated very high-level exercise decreases interaction with PDE4D and
CC protein phosphatase 1 (PP1) (By similarity). Interacts with CALM; CALM
CC with bound calcium inhibits the RYR1 channel activity (PubMed:10601232,
CC PubMed:11562475, PubMed:17027503). Interacts with S100A1 (By
CC similarity). Interacts with FKBP1A; this stabilizes the closed
CC conformation of the channel (PubMed:7669046, PubMed:10603943,
CC PubMed:26245150, PubMed:25517095, PubMed:27468892). Interacts with
CC CACNA1S; interaction with CACNA1S is important for activation of the
CC RYR1 channel (PubMed:10388749). Interacts with CACNB1
CC (PubMed:21320436). Interacts with TRDN and ASPH; these interactions
CC stimulate RYR1 channel activity (PubMed:9737879, PubMed:19398037).
CC Interacts with SELENON (PubMed:18713863). Interacts with scorpion
CC calcins (AC P0DPT1; AC P0DM30; AC A0A1L4BJ42; AC P59868; AC P60254; AC
CC B8QG00; AC L0GBR1; AC P60252; AC P60253) (PubMed:27114612).
CC {ECO:0000250|UniProtKB:E9PZQ0, ECO:0000250|UniProtKB:P21817,
CC ECO:0000269|PubMed:10097181, ECO:0000269|PubMed:10388749,
CC ECO:0000269|PubMed:10601232, ECO:0000269|PubMed:10603943,
CC ECO:0000269|PubMed:11562475, ECO:0000269|PubMed:12213830,
CC ECO:0000269|PubMed:15908964, ECO:0000269|PubMed:17027503,
CC ECO:0000269|PubMed:18621707, ECO:0000269|PubMed:18713863,
CC ECO:0000269|PubMed:19398037, ECO:0000269|PubMed:21320436,
CC ECO:0000269|PubMed:25470059, ECO:0000269|PubMed:25517095,
CC ECO:0000269|PubMed:26245150, ECO:0000269|PubMed:27468892,
CC ECO:0000269|PubMed:27573175, ECO:0000269|PubMed:27662087,
CC ECO:0000269|PubMed:7669046, ECO:0000269|PubMed:9737879}.
CC -!- INTERACTION:
CC P11716; P62943: FKBP1A; NbExp=2; IntAct=EBI-6477441, EBI-16134925;
CC P11716; P11716: RYR1; NbExp=7; IntAct=EBI-6477441, EBI-6477441;
CC P11716; P28652: Camk2b; Xeno; NbExp=4; IntAct=EBI-6477441, EBI-397029;
CC P11716; P62942: FKBP1A; Xeno; NbExp=2; IntAct=EBI-6477441, EBI-1027571;
CC P11716; P68106-1: FKBP1B; Xeno; NbExp=2; IntAct=EBI-6477441, EBI-15766566;
CC P11716; P02639: S100A1; Xeno; NbExp=3; IntAct=EBI-6477441, EBI-6477285;
CC -!- SUBCELLULAR LOCATION: Sarcoplasmic reticulum membrane
CC {ECO:0000269|PubMed:12486242, ECO:0000269|PubMed:25517095,
CC ECO:0000269|PubMed:2725677, ECO:0000269|PubMed:27468892,
CC ECO:0000269|PubMed:27573175, ECO:0000269|PubMed:27662087,
CC ECO:0000269|PubMed:3722165}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:25470059, ECO:0000269|PubMed:25517095,
CC ECO:0000269|PubMed:27468892, ECO:0000269|PubMed:27573175,
CC ECO:0000269|PubMed:27662087}. Sarcoplasmic reticulum
CC {ECO:0000269|PubMed:18713863}. Membrane {ECO:0000269|PubMed:12732639};
CC Multi-pass membrane protein {ECO:0000269|PubMed:25470059,
CC ECO:0000269|PubMed:25517095, ECO:0000269|PubMed:27468892,
CC ECO:0000269|PubMed:27573175, ECO:0000269|PubMed:27662087}. Note=The
CC number of predicted transmembrane domains varies between orthologs, but
CC the 3D-structures show the presence of six transmembrane regions. Both
CC N-terminus and C-terminus are cytoplasmic.
CC {ECO:0000269|PubMed:12486242, ECO:0000269|PubMed:25470059,
CC ECO:0000269|PubMed:27468892, ECO:0000269|PubMed:27573175,
CC ECO:0000269|PubMed:27662087}.
CC -!- TISSUE SPECIFICITY: Detected in skeletal muscle (at protein level)
CC (PubMed:2725677, PubMed:3722165, PubMed:25470059, PubMed:25517095,
CC PubMed:27573175, PubMed:27468892). Fast- or slow-twitch skeletal
CC muscle. {ECO:0000269|PubMed:15908964, ECO:0000269|PubMed:25470059,
CC ECO:0000269|PubMed:25517095, ECO:0000269|PubMed:2725677,
CC ECO:0000269|PubMed:27468892, ECO:0000269|PubMed:27573175,
CC ECO:0000269|PubMed:3722165, ECO:0000269|PubMed:7669046}.
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:2725677, PubMed:25517095,
CC PubMed:27662087, PubMed:27573175, PubMed:27468892). Pore opening is
CC mediated via the cytoplasmic calcium-binding domains that mediate a
CC small rotation of the channel-forming transmembrane regions that then
CC leads to channel opening (PubMed:27468892).
CC {ECO:0000269|PubMed:25517095, ECO:0000269|PubMed:2725677,
CC ECO:0000269|PubMed:27468892, ECO:0000269|PubMed:27573175,
CC ECO:0000269|PubMed:27662087}.
CC -!- PTM: The N-terminus is blocked.
CC -!- PTM: Channel activity is modulated by phosphorylation. Phosphorylation
CC at Ser-2843 may increase channel activity. Repeated very high-level
CC exercise increases phosphorylation at Ser-2843.
CC {ECO:0000250|UniProtKB:P21817}.
CC -!- PTM: Activated by reversible S-nitrosylation (PubMed:22036948).
CC Repeated very high-level exercise increases S-nitrosylation (By
CC similarity). {ECO:0000250|UniProtKB:P21817,
CC ECO:0000269|PubMed:22036948}.
CC -!- MISCELLANEOUS: Coexpression of normal and mutant Thr-4897 RYR1 in a 1:1
CC ratio produces RYR1 channels with normal halothane and caffeine
CC sensitivities, but maximal levels of Ca(2+) release are reduced by 67%.
CC Binding of [3H]ryanodine indicates that the heterozygous channel is
CC activated by Ca(2+) concentrations 4-fold lower than normal. Single-
CC cell analysis of cotransfected cells shows a significantly increased
CC resting cytoplasmic Ca(2+) level and a significantly reduced luminal
CC Ca(2+) level. These data indicated a leaky channel, possibly caused by
CC a reduction in the Ca(2+) concentration required for channel
CC activation. {ECO:0000269|PubMed:10097181}.
CC -!- SIMILARITY: Belongs to the ryanodine receptor (TC 1.A.3.1) family. RYR1
CC subfamily. {ECO:0000305}.
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DR EMBL; X15209; CAA33279.1; -; mRNA.
DR EMBL; X15750; CAA33762.1; -; mRNA.
DR PIR; S04654; B35041.
DR RefSeq; NP_001095188.1; NM_001101718.1.
DR PDB; 2BCX; X-ray; 2.00 A; B=3614-3643.
DR PDB; 2XOA; X-ray; 2.50 A; A=1-559.
DR PDB; 3HSM; X-ray; 2.50 A; A/B=1-210.
DR PDB; 3ILA; X-ray; 2.90 A; A/B/C/D/E/F/G/H/I=9-205.
DR PDB; 3J8H; EM; 3.80 A; A/C/E/G=1-5037.
DR PDB; 3RQR; X-ray; 2.16 A; A=2733-2940.
DR PDB; 4ERT; X-ray; 1.95 A; A=2734-2940.
DR PDB; 4ESU; X-ray; 1.59 A; A=2734-2940.
DR PDB; 4ETT; X-ray; 2.20 A; A=2734-2940.
DR PDB; 4ETU; X-ray; 2.19 A; A=2734-2938.
DR PDB; 4I0Y; X-ray; 2.80 A; A=1-536.
DR PDB; 4I1E; X-ray; 2.40 A; A=1-536.
DR PDB; 4I2S; X-ray; 2.50 A; A=1-536.
DR PDB; 4I37; X-ray; 2.95 A; A=1-536.
DR PDB; 4I3N; X-ray; 2.95 A; A=1-536.
DR PDB; 4I6I; X-ray; 2.50 A; A=1-559.
DR PDB; 4I7I; X-ray; 2.90 A; A=1-536.
DR PDB; 4I8M; X-ray; 2.80 A; A=1-536.
DR PDB; 4I96; X-ray; 2.73 A; A=217-536.
DR PDB; 4P9J; X-ray; 1.84 A; A/B/C=1070-1246.
DR PDB; 4UWA; EM; 6.10 A; A/B/C/D=1-5037.
DR PDB; 4UWE; EM; 8.50 A; A/B/C/D=1-5037.
DR PDB; 5C30; X-ray; 1.55 A; A=857-1054.
DR PDB; 5GKY; EM; 3.80 A; A/C/E/G=1-5037.
DR PDB; 5GKZ; EM; 4.00 A; A/C/E/G=1-5037.
DR PDB; 5GL0; EM; 4.20 A; A/C/E/G=1-5037.
DR PDB; 5GL1; EM; 5.70 A; A/C/E/G=1-5037.
DR PDB; 5J8V; EM; 4.90 A; A/B/C/D=1-5037.
DR PDB; 5T15; EM; 3.80 A; B/E/G/I=12-1275, B/E/G/I=1573-2479, B/E/G/I=2734-2939, B/E/G/I=3639-5037.
DR PDB; 5T9M; EM; 3.80 A; B/E/G/I=12-1275, B/E/G/I=1573-2479, B/E/G/I=2734-2939, B/E/G/I=3639-5037.
DR PDB; 5T9N; EM; 3.80 A; B/E/G/I=12-1275, B/E/G/I=1573-2479, B/E/G/I=2734-2939, B/E/G/I=3639-5037.
DR PDB; 5T9R; EM; 3.80 A; B/E/G/I=12-1275, B/E/G/I=1573-2479, B/E/G/I=2734-2939, B/E/G/I=3639-5037.
DR PDB; 5T9S; EM; 3.80 A; B/E/G/I=12-1275, B/E/G/I=1573-2479, B/E/G/I=2734-2939, B/E/G/I=3639-5037.
DR PDB; 5T9V; EM; 3.80 A; B/E/G/I=12-1275, B/E/G/I=1573-2479, B/E/G/I=2734-2939, B/E/G/I=3639-4253, B/E/G/I=4540-5037.
DR PDB; 5TA3; EM; 3.80 A; B/E/G/I=12-1275, B/E/G/I=1573-2479, B/E/G/I=2734-2939, B/E/G/I=3639-4253, B/E/G/I=4541-5037.
DR PDB; 5TAL; EM; 3.80 A; B/E/G/I=12-1275, B/E/G/I=1573-2479, B/E/G/I=2734-2939, B/E/G/I=3639-4253, B/E/G/I=4541-5037.
DR PDB; 5TAM; EM; 3.80 A; B/E/G/I=12-1275, B/E/G/I=1573-2479, B/E/G/I=2734-2939, B/E/G/I=3639-4253, B/E/G/I=4541-5037.
DR PDB; 5TAN; EM; 3.80 A; B/E/G/I=12-1275, B/E/G/I=1573-2479, B/E/G/I=2734-2939, B/E/G/I=3639-4253, B/E/G/I=4541-5037.
DR PDB; 5TAP; EM; 3.80 A; B/E/G/I=12-1275, B/E/G/I=1573-2479, B/E/G/I=2734-2939, B/E/G/I=3639-4253, B/E/G/I=4541-5037.
DR PDB; 5TAQ; EM; 3.80 A; B/E/G/I=12-1275, B/E/G/I=1573-2479, B/E/G/I=2734-2939, B/E/G/I=3639-4253, B/E/G/I=4541-5037.
DR PDB; 5TAS; EM; 3.80 A; B/E/G/I=12-1275, B/E/G/I=1573-2479, B/E/G/I=2734-2939, B/E/G/I=3639-4253, B/E/G/I=4541-5037.
DR PDB; 5TAT; EM; 3.80 A; B/E/G/I=12-1275, B/E/G/I=1573-2479, B/E/G/I=2734-2939, B/E/G/I=3639-4253, B/E/G/I=4541-5037.
DR PDB; 5TAU; EM; 3.80 A; B/E/G/I=12-1275, B/E/G/I=1573-2479, B/E/G/I=2734-2939, B/E/G/I=3639-4253, B/E/G/I=4541-5037.
DR PDB; 5TAV; EM; 3.80 A; B/E/G/I=12-1275, B/E/G/I=1573-2479, B/E/G/I=2734-2939, B/E/G/I=3639-4253, B/E/G/I=4541-5037.
DR PDB; 5TAW; EM; 3.80 A; B/E/G/I=12-1275, B/E/G/I=1573-2479, B/E/G/I=2734-2939, B/E/G/I=3639-4253, B/E/G/I=4541-5037.
DR PDB; 5TAX; EM; 3.80 A; B/E/G/I=12-1275, B/E/G/I=1573-2479, B/E/G/I=2734-2939, B/E/G/I=3639-4253, B/E/G/I=4541-5037.
DR PDB; 5TAY; EM; 3.80 A; B/E/G/I=12-1275, B/E/G/I=1573-2479, B/E/G/I=2734-2939, B/E/G/I=3639-4253, B/E/G/I=4541-5037.
DR PDB; 5TAZ; EM; 3.80 A; B/E/G/I=12-1275, B/E/G/I=1573-2479, B/E/G/I=2734-2939, B/E/G/I=3639-4253, B/E/G/I=4541-5037.
DR PDB; 5TB0; EM; 3.80 A; B/E/G/I=1-5037.
DR PDB; 5TB1; EM; 3.80 A; B/E/G/I=12-1275, B/E/G/I=1573-2479, B/E/G/I=2734-2939, B/E/G/I=3639-4253, B/E/G/I=4541-5037.
DR PDB; 5TB2; EM; 3.80 A; B/E/G/I=12-1275, B/E/G/I=1573-2479, B/E/G/I=2734-2939, B/E/G/I=3639-4253, B/E/G/I=4541-5037.
DR PDB; 5TB3; EM; 3.80 A; B/E/G/I=12-1275, B/E/G/I=1573-2479, B/E/G/I=2734-2939, B/E/G/I=3639-4253, B/E/G/I=4541-5037.
DR PDB; 5TB4; EM; 3.80 A; B/E/G/I=12-1275, B/E/G/I=1573-2479, B/E/G/I=2734-2939, B/E/G/I=3639-4253, B/E/G/I=4541-5037.
DR PDB; 6FG3; EM; 7.30 A; A/B/C/D=1-5037.
DR PDB; 6FOO; EM; 8.20 A; A/B/C/D=1-5037.
DR PDB; 6M2W; EM; 3.80 A; A/D/G/J=1-5037.
DR PDB; 6WOT; EM; 3.54 A; A/B/C/D=1-5037.
DR PDB; 7CF9; EM; 4.70 A; A/C/E/G=1-5037.
DR PDB; 7M6A; EM; 3.36 A; A/B/G/I=1-5037.
DR PDB; 7M6L; EM; 3.98 A; A/B/G/I=1-5037.
DR PDB; 7TDG; EM; 3.80 A; A/B/C/D=1-5037.
DR PDB; 7TDH; EM; 4.00 A; A/B/C/D=1-5037.
DR PDB; 7TDI; EM; 3.30 A; A/B/C/D=1-5037.
DR PDB; 7TDJ; EM; 3.70 A; A/B/C/D=1-5037.
DR PDB; 7TDK; EM; 3.80 A; A/B/C/D=1-5037.
DR PDBsum; 2BCX; -.
DR PDBsum; 2XOA; -.
DR PDBsum; 3HSM; -.
DR PDBsum; 3ILA; -.
DR PDBsum; 3J8H; -.
DR PDBsum; 3RQR; -.
DR PDBsum; 4ERT; -.
DR PDBsum; 4ESU; -.
DR PDBsum; 4ETT; -.
DR PDBsum; 4ETU; -.
DR PDBsum; 4I0Y; -.
DR PDBsum; 4I1E; -.
DR PDBsum; 4I2S; -.
DR PDBsum; 4I37; -.
DR PDBsum; 4I3N; -.
DR PDBsum; 4I6I; -.
DR PDBsum; 4I7I; -.
DR PDBsum; 4I8M; -.
DR PDBsum; 4I96; -.
DR PDBsum; 4P9J; -.
DR PDBsum; 4UWA; -.
DR PDBsum; 4UWE; -.
DR PDBsum; 5C30; -.
DR PDBsum; 5GKY; -.
DR PDBsum; 5GKZ; -.
DR PDBsum; 5GL0; -.
DR PDBsum; 5GL1; -.
DR PDBsum; 5J8V; -.
DR PDBsum; 5T15; -.
DR PDBsum; 5T9M; -.
DR PDBsum; 5T9N; -.
DR PDBsum; 5T9R; -.
DR PDBsum; 5T9S; -.
DR PDBsum; 5T9V; -.
DR PDBsum; 5TA3; -.
DR PDBsum; 5TAL; -.
DR PDBsum; 5TAM; -.
DR PDBsum; 5TAN; -.
DR PDBsum; 5TAP; -.
DR PDBsum; 5TAQ; -.
DR PDBsum; 5TAS; -.
DR PDBsum; 5TAT; -.
DR PDBsum; 5TAU; -.
DR PDBsum; 5TAV; -.
DR PDBsum; 5TAW; -.
DR PDBsum; 5TAX; -.
DR PDBsum; 5TAY; -.
DR PDBsum; 5TAZ; -.
DR PDBsum; 5TB0; -.
DR PDBsum; 5TB1; -.
DR PDBsum; 5TB2; -.
DR PDBsum; 5TB3; -.
DR PDBsum; 5TB4; -.
DR PDBsum; 6FG3; -.
DR PDBsum; 6FOO; -.
DR PDBsum; 6M2W; -.
DR PDBsum; 6WOT; -.
DR PDBsum; 7CF9; -.
DR PDBsum; 7M6A; -.
DR PDBsum; 7M6L; -.
DR PDBsum; 7TDG; -.
DR PDBsum; 7TDH; -.
DR PDBsum; 7TDI; -.
DR PDBsum; 7TDJ; -.
DR PDBsum; 7TDK; -.
DR SMR; P11716; -.
DR BioGRID; 1172559; 3.
DR ComplexPortal; CPX-3136; Ryanodine 1 complex.
DR DIP; DIP-41872N; -.
DR IntAct; P11716; 8.
DR MINT; P11716; -.
DR BindingDB; P11716; -.
DR ChEMBL; CHEMBL3288; -.
DR iPTMnet; P11716; -.
DR SwissPalm; P11716; -.
DR PRIDE; P11716; -.
DR GeneID; 100009540; -.
DR KEGG; ocu:100009540; -.
DR CTD; 6261; -.
DR InParanoid; P11716; -.
DR OrthoDB; 5161at2759; -.
DR EvolutionaryTrace; P11716; -.
DR PRO; PR:P11716; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0031301; C:integral component of organelle membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:AgBase.
DR GO; GO:1990425; C:ryanodine receptor complex; IDA:UniProtKB.
DR GO; GO:0016529; C:sarcoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0014802; C:terminal cisterna; IDA:BHF-UCL.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0035381; F:ATP-gated ion channel activity; IDA:CAFA.
DR GO; GO:0005262; F:calcium channel activity; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0015278; F:calcium-release channel activity; IMP:AgBase.
DR GO; GO:0005516; F:calmodulin binding; IDA:BHF-UCL.
DR GO; GO:0097718; F:disordered domain specific binding; IPI:CAFA.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0005219; F:ryanodine-sensitive calcium-release channel activity; IDA:UniProtKB.
DR GO; GO:0015643; F:toxic substance binding; IDA:AgBase.
DR GO; GO:0044325; F:transmembrane transporter binding; IPI:BHF-UCL.
DR GO; GO:0005245; F:voltage-gated calcium channel activity; ISS:UniProtKB.
DR GO; GO:0070588; P:calcium ion transmembrane transport; IDA:UniProtKB.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IEA:InterPro.
DR GO; GO:0071313; P:cellular response to caffeine; IDA:UniProtKB.
DR GO; GO:0071277; P:cellular response to calcium ion; IDA:UniProtKB.
DR GO; GO:0006936; P:muscle contraction; ISS:UniProtKB.
DR GO; GO:0043931; P:ossification involved in bone maturation; ISS:UniProtKB.
DR GO; GO:0003151; P:outflow tract morphogenesis; ISS:UniProtKB.
DR GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB.
DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; IDA:CAFA.
DR GO; GO:0014808; P:release of sequestered calcium ion into cytosol by sarcoplasmic reticulum; IMP:UniProtKB.
DR GO; GO:0048741; P:skeletal muscle fiber development; ISS:UniProtKB.
DR GO; GO:0043588; P:skin development; ISS:UniProtKB.
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; 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; IPR033215; RyR1.
DR InterPro; IPR035761; SPRY1_RyR.
DR InterPro; IPR035764; SPRY2_RyR.
DR InterPro; IPR035762; SPRY3_RyR.
DR InterPro; IPR003877; SPRY_dom.
DR PANTHER; PTHR13715:SF15; PTHR13715:SF15; 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; 1.
DR SUPFAM; SSF47473; SSF47473; 1.
DR SUPFAM; SSF49899; SSF49899; 3.
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; ATP-binding; Calcium; Calcium channel; Calcium transport;
KW Calmodulin-binding; Developmental protein; Direct protein sequencing;
KW Ion channel; Ion transport; Ligand-gated ion channel; Membrane;
KW Metal-binding; Nucleotide-binding; Phosphoprotein; Receptor;
KW Reference proteome; Repeat; S-nitrosylation; Sarcoplasmic reticulum;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..5037
FT /note="Ryanodine receptor 1"
FT /id="PRO_0000219360"
FT TOPO_DOM 1..4558
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:25470059,
FT ECO:0000269|PubMed:25517095, ECO:0000269|PubMed:27468892,
FT ECO:0000269|PubMed:27573175"
FT TRANSMEM 4559..4579
FT /note="Helical; Name=1"
FT /evidence="ECO:0000269|PubMed:25470059,
FT ECO:0000269|PubMed:25517095, ECO:0000269|PubMed:27468892,
FT ECO:0000269|PubMed:27573175"
FT TOPO_DOM 4580..4640
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:25470059,
FT ECO:0000269|PubMed:25517095, ECO:0000269|PubMed:27468892,
FT ECO:0000269|PubMed:27573175"
FT TRANSMEM 4641..4661
FT /note="Helical; Name=2"
FT /evidence="ECO:0000269|PubMed:25470059,
FT ECO:0000269|PubMed:25517095, ECO:0000269|PubMed:27468892,
FT ECO:0000269|PubMed:27573175"
FT TOPO_DOM 4662..4779
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:25470059,
FT ECO:0000269|PubMed:25517095, ECO:0000269|PubMed:27468892,
FT ECO:0000269|PubMed:27573175"
FT TRANSMEM 4780..4802
FT /note="Helical; Name=3"
FT /evidence="ECO:0000269|PubMed:25470059,
FT ECO:0000269|PubMed:25517095, ECO:0000269|PubMed:27468892,
FT ECO:0000269|PubMed:27573175"
FT TOPO_DOM 4803
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:25470059,
FT ECO:0000269|PubMed:25517095, ECO:0000269|PubMed:27468892,
FT ECO:0000269|PubMed:27573175"
FT TRANSMEM 4804..4820
FT /note="Helical; Name=4"
FT /evidence="ECO:0000269|PubMed:25470059,
FT ECO:0000269|PubMed:25517095, ECO:0000269|PubMed:27468892,
FT ECO:0000269|PubMed:27573175"
FT TOPO_DOM 4821..4835
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:25470059,
FT ECO:0000269|PubMed:25517095, ECO:0000269|PubMed:27468892,
FT ECO:0000269|PubMed:27573175"
FT TRANSMEM 4836..4856
FT /note="Helical; Name=5"
FT /evidence="ECO:0000269|PubMed:25470059,
FT ECO:0000269|PubMed:25517095, ECO:0000269|PubMed:27468892,
FT ECO:0000269|PubMed:27573175"
FT TOPO_DOM 4857..4879
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:25470059,
FT ECO:0000269|PubMed:25517095, ECO:0000269|PubMed:27468892,
FT ECO:0000269|PubMed:27573175"
FT INTRAMEM 4880..4899
FT /note="Pore-forming"
FT /evidence="ECO:0000269|PubMed:25470059,
FT ECO:0000269|PubMed:25517095, ECO:0000269|PubMed:27468892,
FT ECO:0000269|PubMed:27573175"
FT TOPO_DOM 4900..4919
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:25470059,
FT ECO:0000269|PubMed:25517095, ECO:0000269|PubMed:27468892,
FT ECO:0000269|PubMed:27573175"
FT TRANSMEM 4920..4940
FT /note="Helical; Name=6"
FT /evidence="ECO:0000269|PubMed:25470059,
FT ECO:0000269|PubMed:25517095, ECO:0000269|PubMed:27468892,
FT ECO:0000269|PubMed:27573175"
FT TOPO_DOM 4941..5037
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:25470059,
FT ECO:0000269|PubMed:25517095, ECO:0000269|PubMed:27468892,
FT ECO:0000269|PubMed:27573175"
FT DOMAIN 98..153
FT /note="MIR 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT DOMAIN 160..205
FT /note="MIR 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT DOMAIN 211..265
FT /note="MIR 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT DOMAIN 271..334
FT /note="MIR 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT DOMAIN 336..394
FT /note="MIR 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT DOMAIN 582..798
FT /note="B30.2/SPRY 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT REPEAT 842..955
FT /note="1"
FT REPEAT 956..1069
FT /note="2"
FT DOMAIN 1014..1209
FT /note="B30.2/SPRY 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT REPEAT 1345..1360
FT /note="3; truncated"
FT DOMAIN 1358..1571
FT /note="B30.2/SPRY 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT REPEAT 1373..1388
FT /note="4; truncated"
FT REPEAT 2726..2845
FT /note="5"
FT REPEAT 2846..2959
FT /note="6"
FT DOMAIN 4075..4103
FT /note="EF-hand"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:27573175"
FT REGION 670..681
FT /note="Interaction with FKBP1A"
FT /evidence="ECO:0000269|PubMed:26245150"
FT REGION 842..2959
FT /note="6 X approximate repeats"
FT REGION 1308..1383
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1867..1922
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2390..2412
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2828..2858
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3478..3501
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3614..3643
FT /note="Interaction with CALM"
FT REGION 4252..4282
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 4381..4534
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 4588..4620
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 4894..4900
FT /note="Selectivity filter"
FT /evidence="ECO:0000305|PubMed:25517095,
FT ECO:0000305|PubMed:27573175, ECO:0000305|PubMed:27662087"
FT COMPBIAS 1870..1920
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2828..2843
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 4255..4270
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 4484..4504
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 3893
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000305|PubMed:27662087,
FT ECO:0007744|PDB:5TA3, ECO:0007744|PDB:5TAL,
FT ECO:0007744|PDB:5TAM, ECO:0007744|PDB:5TAN"
FT BINDING 3967
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000305|PubMed:27662087,
FT ECO:0007744|PDB:5TA3, ECO:0007744|PDB:5TAL,
FT ECO:0007744|PDB:5TAM, ECO:0007744|PDB:5TAN"
FT BINDING 4211..4215
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305|PubMed:27662087,
FT ECO:0007744|PDB:5T9V, ECO:0007744|PDB:5TA3,
FT ECO:0007744|PDB:5TAL, ECO:0007744|PDB:5TAM,
FT ECO:0007744|PDB:5TAN, ECO:0007744|PDB:5TAS,
FT ECO:0007744|PDB:5TAT, ECO:0007744|PDB:5TAU"
FT BINDING 4716
FT /ligand="caffeine"
FT /ligand_id="ChEBI:CHEBI:27732"
FT /evidence="ECO:0000305|PubMed:27662087,
FT ECO:0007744|PDB:5TAN"
FT BINDING 4954..4959
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305|PubMed:27662087,
FT ECO:0007744|PDB:5T9V, ECO:0007744|PDB:5TA3,
FT ECO:0007744|PDB:5TAL, ECO:0007744|PDB:5TAM,
FT ECO:0007744|PDB:5TAN, ECO:0007744|PDB:5TAS,
FT ECO:0007744|PDB:5TAT, ECO:0007744|PDB:5TAU"
FT BINDING 4979..4985
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305|PubMed:27662087,
FT ECO:0007744|PDB:5T9V, ECO:0007744|PDB:5TA3,
FT ECO:0007744|PDB:5TAL, ECO:0007744|PDB:5TAM,
FT ECO:0007744|PDB:5TAN, ECO:0007744|PDB:5TAS,
FT ECO:0007744|PDB:5TAT, ECO:0007744|PDB:5TAU"
FT BINDING 5001
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000305|PubMed:27662087,
FT ECO:0007744|PDB:5TA3, ECO:0007744|PDB:5TAL,
FT ECO:0007744|PDB:5TAM, ECO:0007744|PDB:5TAN"
FT MOD_RES 1338
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:F1LMY4"
FT MOD_RES 2345
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:F1LMY4"
FT MOD_RES 2843
FT /note="Phosphoserine; by PKA and PKG"
FT /evidence="ECO:0000269|PubMed:8380342"
FT MOD_RES 3635
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000269|PubMed:10601232,
FT ECO:0000269|PubMed:11562475, ECO:0000269|PubMed:22036948"
FT MOD_RES 4466
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:F1LMY4"
FT MOD_RES 4470
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:F1LMY4"
FT MOD_RES 4863
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P21817"
FT MOD_RES 4866
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P21817"
FT MUTAGEN 164
FT /note="R->C: Decreases threshold for channel activation by
FT K(+), caffeine and 4-chloro-m-cresol. Decreases inhibition
FT by Mg(2+)."
FT /evidence="ECO:0000269|PubMed:12732639"
FT MUTAGEN 342
FT /note="G->R: Decreases threshold for channel activation by
FT K(+), caffeine and 4-chloro-m-cresol. Decreases inhibition
FT by Mg(2+)."
FT /evidence="ECO:0000269|PubMed:12732639"
FT MUTAGEN 615
FT /note="R->C: Decreases threshold for channel activation by
FT K(+), caffeine and 4-chloro-m-cresol. Decreases inhibition
FT by Mg(2+)."
FT /evidence="ECO:0000269|PubMed:12732639"
FT MUTAGEN 674..675
FT /note="FL->AA: Loss of interaction with FKBP1A."
FT /evidence="ECO:0000269|PubMed:26245150"
FT MUTAGEN 760
FT /note="N->D: Impairs interaction with FKBP1A."
FT /evidence="ECO:0000269|PubMed:26245150"
FT MUTAGEN 1044
FT /note="R->C: Decreases protein stability."
FT /evidence="ECO:0000269|PubMed:26245150"
FT MUTAGEN 1050
FT /note="G->S: Decreases protein stability."
FT /evidence="ECO:0000269|PubMed:26245150"
FT MUTAGEN 1076
FT /note="R->W: Decreases protein stability."
FT /evidence="ECO:0000269|PubMed:25370123"
FT MUTAGEN 2163
FT /note="R->C: Decreases threshold for channel activation by
FT K(+), caffeine and 4-chloro-m-cresol. Decreases inhibition
FT by Mg(2+)."
FT /evidence="ECO:0000269|PubMed:12732639"
FT MUTAGEN 2168
FT /note="V->M: Decreases threshold for channel activation by
FT K(+), caffeine and 4-chloro-m-cresol. Decreases inhibition
FT by Mg(2+)."
FT /evidence="ECO:0000269|PubMed:12732639"
FT MUTAGEN 2458
FT /note="R->H: Decreases threshold for channel activation by
FT K(+), caffeine and 4-chloro-m-cresol. Decreases inhibition
FT by Mg(2+)."
FT /evidence="ECO:0000269|PubMed:12732639"
FT MUTAGEN 2461
FT /note="V->G: Impairs interaction with FKBP1A."
FT /evidence="ECO:0000269|PubMed:26245150"
FT MUTAGEN 2867
FT /note="L->G: Decreases protein stability."
FT /evidence="ECO:0000269|PubMed:22705209"
FT MUTAGEN 3635
FT /note="C->A: Abolishes S-nitrosocysteine formation."
FT /evidence="ECO:0000269|PubMed:11562475,
FT ECO:0000269|PubMed:22036948"
FT MUTAGEN 4825
FT /note="T->I: Decreases threshold for channel activation by
FT K(+), caffeine and 4-chloro-m-cresol. Decreases inhibition
FT by Mg(2+)."
FT /evidence="ECO:0000269|PubMed:12732639"
FT MUTAGEN 4897
FT /note="I->T: Loss of channel activation by halothane and
FT caffeine due to Ca(2+) store depletion, probably due to
FT constant Ca(2+) leakage through the mutant channel."
FT /evidence="ECO:0000269|PubMed:10097181"
FT CONFLICT 2015
FT /note="E -> D (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 3481..3485
FT /note="Missing (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT STRAND 19..28
FT /evidence="ECO:0007829|PDB:4I1E"
FT STRAND 31..38
FT /evidence="ECO:0007829|PDB:4I1E"
FT STRAND 42..44
FT /evidence="ECO:0007829|PDB:3HSM"
FT STRAND 48..51
FT /evidence="ECO:0007829|PDB:4I1E"
FT TURN 53..57
FT /evidence="ECO:0007829|PDB:4I1E"
FT TURN 63..65
FT /evidence="ECO:0007829|PDB:4I1E"
FT STRAND 67..73
FT /evidence="ECO:0007829|PDB:4I1E"
FT HELIX 75..83
FT /evidence="ECO:0007829|PDB:4I1E"
FT STRAND 106..111
FT /evidence="ECO:0007829|PDB:4I1E"
FT TURN 112..114
FT /evidence="ECO:0007829|PDB:4I1E"
FT STRAND 117..120
FT /evidence="ECO:0007829|PDB:4I1E"
FT STRAND 133..140
FT /evidence="ECO:0007829|PDB:4I1E"
FT HELIX 144..146
FT /evidence="ECO:0007829|PDB:4I6I"
FT STRAND 147..154
FT /evidence="ECO:0007829|PDB:4I1E"
FT STRAND 164..166
FT /evidence="ECO:0007829|PDB:3ILA"
FT STRAND 168..173
FT /evidence="ECO:0007829|PDB:4I1E"
FT TURN 174..176
FT /evidence="ECO:0007829|PDB:4I1E"
FT STRAND 179..183
FT /evidence="ECO:0007829|PDB:4I1E"
FT STRAND 186..188
FT /evidence="ECO:0007829|PDB:4I8M"
FT STRAND 190..196
FT /evidence="ECO:0007829|PDB:4I1E"
FT STRAND 200..206
FT /evidence="ECO:0007829|PDB:4I1E"
FT STRAND 219..223
FT /evidence="ECO:0007829|PDB:4I1E"
FT STRAND 225..233
FT /evidence="ECO:0007829|PDB:4I1E"
FT TURN 239..242
FT /evidence="ECO:0007829|PDB:4I1E"
FT STRAND 245..250
FT /evidence="ECO:0007829|PDB:4I1E"
FT HELIX 251..254
FT /evidence="ECO:0007829|PDB:4I1E"
FT HELIX 256..258
FT /evidence="ECO:0007829|PDB:4I1E"
FT STRAND 260..265
FT /evidence="ECO:0007829|PDB:4I1E"
FT TURN 268..271
FT /evidence="ECO:0007829|PDB:4I1E"
FT STRAND 280..284
FT /evidence="ECO:0007829|PDB:4I1E"
FT TURN 285..287
FT /evidence="ECO:0007829|PDB:4I1E"
FT STRAND 290..294
FT /evidence="ECO:0007829|PDB:4I1E"
FT TURN 295..297
FT /evidence="ECO:0007829|PDB:4I1E"
FT STRAND 298..302
FT /evidence="ECO:0007829|PDB:4I1E"
FT HELIX 304..306
FT /evidence="ECO:0007829|PDB:4I1E"
FT HELIX 309..312
FT /evidence="ECO:0007829|PDB:4I1E"
FT STRAND 314..319
FT /evidence="ECO:0007829|PDB:4I1E"
FT STRAND 332..334
FT /evidence="ECO:0007829|PDB:2XOA"
FT TURN 341..343
FT /evidence="ECO:0007829|PDB:4I1E"
FT STRAND 346..350
FT /evidence="ECO:0007829|PDB:4I1E"
FT TURN 351..353
FT /evidence="ECO:0007829|PDB:4I1E"
FT STRAND 356..359
FT /evidence="ECO:0007829|PDB:4I1E"
FT STRAND 373..381
FT /evidence="ECO:0007829|PDB:4I1E"
FT STRAND 388..392
FT /evidence="ECO:0007829|PDB:4I1E"
FT HELIX 395..420
FT /evidence="ECO:0007829|PDB:4I1E"
FT TURN 421..423
FT /evidence="ECO:0007829|PDB:4I1E"
FT HELIX 438..451
FT /evidence="ECO:0007829|PDB:4I1E"
FT HELIX 461..480
FT /evidence="ECO:0007829|PDB:4I1E"
FT HELIX 483..494
FT /evidence="ECO:0007829|PDB:4I1E"
FT STRAND 497..499
FT /evidence="ECO:0007829|PDB:4I1E"
FT HELIX 500..504
FT /evidence="ECO:0007829|PDB:4I1E"
FT HELIX 509..512
FT /evidence="ECO:0007829|PDB:4I1E"
FT HELIX 515..530
FT /evidence="ECO:0007829|PDB:4I1E"
FT HELIX 865..867
FT /evidence="ECO:0007829|PDB:5C30"
FT HELIX 868..888
FT /evidence="ECO:0007829|PDB:5C30"
FT TURN 899..902
FT /evidence="ECO:0007829|PDB:5C30"
FT HELIX 910..912
FT /evidence="ECO:0007829|PDB:5C30"
FT HELIX 915..934
FT /evidence="ECO:0007829|PDB:5C30"
FT STRAND 939..941
FT /evidence="ECO:0007829|PDB:5C30"
FT HELIX 946..949
FT /evidence="ECO:0007829|PDB:5C30"
FT HELIX 957..959
FT /evidence="ECO:0007829|PDB:5C30"
FT HELIX 979..990
FT /evidence="ECO:0007829|PDB:5C30"
FT STRAND 994..997
FT /evidence="ECO:0007829|PDB:5C30"
FT TURN 998..1001
FT /evidence="ECO:0007829|PDB:5C30"
FT STRAND 1002..1005
FT /evidence="ECO:0007829|PDB:5C30"
FT STRAND 1021..1023
FT /evidence="ECO:0007829|PDB:5C30"
FT HELIX 1024..1026
FT /evidence="ECO:0007829|PDB:5C30"
FT HELIX 1029..1048
FT /evidence="ECO:0007829|PDB:5C30"
FT STRAND 1051..1053
FT /evidence="ECO:0007829|PDB:5C30"
FT STRAND 1073..1075
FT /evidence="ECO:0007829|PDB:4P9J"
FT HELIX 1079..1081
FT /evidence="ECO:0007829|PDB:4P9J"
FT STRAND 1083..1096
FT /evidence="ECO:0007829|PDB:4P9J"
FT STRAND 1098..1105
FT /evidence="ECO:0007829|PDB:4P9J"
FT STRAND 1121..1125
FT /evidence="ECO:0007829|PDB:4P9J"
FT TURN 1126..1129
FT /evidence="ECO:0007829|PDB:4P9J"
FT STRAND 1130..1140
FT /evidence="ECO:0007829|PDB:4P9J"
FT STRAND 1148..1154
FT /evidence="ECO:0007829|PDB:4P9J"
FT TURN 1155..1158
FT /evidence="ECO:0007829|PDB:4P9J"
FT STRAND 1159..1164
FT /evidence="ECO:0007829|PDB:4P9J"
FT STRAND 1178..1181
FT /evidence="ECO:0007829|PDB:4P9J"
FT STRAND 1188..1194
FT /evidence="ECO:0007829|PDB:4P9J"
FT STRAND 1200..1203
FT /evidence="ECO:0007829|PDB:4P9J"
FT HELIX 1208..1210
FT /evidence="ECO:0007829|PDB:4P9J"
FT TURN 1214..1222
FT /evidence="ECO:0007829|PDB:4P9J"
FT HELIX 1226..1229
FT /evidence="ECO:0007829|PDB:4P9J"
FT HELIX 1242..1244
FT /evidence="ECO:0007829|PDB:4P9J"
FT HELIX 2749..2751
FT /evidence="ECO:0007829|PDB:4ESU"
FT HELIX 2752..2772
FT /evidence="ECO:0007829|PDB:4ESU"
FT TURN 2783..2786
FT /evidence="ECO:0007829|PDB:4ESU"
FT HELIX 2794..2796
FT /evidence="ECO:0007829|PDB:4ESU"
FT HELIX 2799..2818
FT /evidence="ECO:0007829|PDB:4ESU"
FT STRAND 2822..2825
FT /evidence="ECO:0007829|PDB:4ESU"
FT HELIX 2862..2864
FT /evidence="ECO:0007829|PDB:4ETT"
FT HELIX 2869..2897
FT /evidence="ECO:0007829|PDB:4ESU"
FT HELIX 2908..2910
FT /evidence="ECO:0007829|PDB:4ESU"
FT HELIX 2913..2932
FT /evidence="ECO:0007829|PDB:4ESU"
FT STRAND 2935..2938
FT /evidence="ECO:0007829|PDB:4ESU"
FT HELIX 3617..3638
FT /evidence="ECO:0007829|PDB:2BCX"
SQ SEQUENCE 5037 AA; 565253 MW; 4ABD87AA26697070 CRC64;
MGDGGEGEDE VQFLRTDDEV VLQCSATVLK EQLKLCLAAE GFGNRLCFLE PTSNAQNVPP
DLAICCFTLE QSLSVRALQE MLANTVEAGV ESSQGGGHRT LLYGHAILLR HAHSRMYLSC
LTTSRSMTDK LAFDVGLQED ATGEACWWTM HPASKQRSEG EKVRVGDDLI LVSVSSERYL
HLSTASGELQ VDASFMQTLW NMNPICSCCE EGYVTGGHVL RLFHGHMDEC LTISAADSDD
QRRLVYYEGG AVCTHARSLW RLEPLRISWS GSHLRWGQPL RIRHVTTGRY LALTEDQGLV
VVDACKAHTK ATSFCFRVSK EKLDTAPKRD VEGMGPPEIK YGESLCFVQH VASGLWLTYA
APDPKALRLG VLKKKAILHQ EGHMDDALFL TRCQQEESQA ARMIHSTAGL YNQFIKGLDS
FSGKPRGSGP PAGPALPIEA VILSLQDLIG YFEPPSEELQ HEEKQSKLRS LRNRQSLFQE
EGMLSLVLNC IDRLNVYTTA AHFAEYAGEE AAESWKEIVN LLYELLASLI RGNRANCALF
STNLDWVVSK LDRLEASSGI LEVLYCVLIE SPEVLNIIQE NHIKSIISLL DKHGRNHKVL
DVLCSLCVCN GVAVRSNQDL ITENLLPGRE LLLQTNLINY VTSIRPNIFV GRAEGSTQYG
KWYFEVMVDE VVPFLTAQAT HLRVGWALTE GYSPYPGGGE GWGGNGVGDD LYSYGFDGLH
LWTGHVARPV TSPGQHLLAP EDVVSCCLDL SVPSISFRIN GCPVQGVFEA FNLDGLFFPV
VSFSAGVKVR FLLGGRHGEF KFLPPPGYAP CHEAVLPRER LRLEPIKEYR REGPRGPHLV
GPSRCLSHTD FVPCPVDTVQ IVLPPHLERI REKLAENIHE LWALTRIEQG WTYGPVRDDN
KRLHPCLVNF HSLPEPERNY NLQMSGETLK TLLALGCHVG MADEKAEDNL KKTKLPKTYM
MSNGYKPAPL DLSHVRLTPA QTTLVDRLAE NGHNVWARDR VAQGWSYSAV QDIPARRNPR
LVPYRLLDEA TKRSNRDSLC QAVRTLLGYG YNIEPPDQEP SQVENQSRWD RVRIFRAEKS
YTVQSGRWYF EFEAVTTGEM RVGWARPELR PDVELGADEL AYVFNGHRGQ RWHLGSEPFG
RPWQSGDVVG CMIDLTENTI IFTLNGEVLM SDSGSETAFR EIEIGDGFLP VCSLGPGQVG
HLNLGQDVSS LRFFAICGLQ EGFEPFAINM QRPVTTWFSK SLPQFEPVPP EHPHYEVARM
DGTVDTPPCL RLAHRTWGSQ NSLVEMLFLR LSLPVQFHQH FRCTAGATPL APPGLQPPAE
DEARAAEPDP DYENLRRSAG GWGEAEGGKE GTAKEGTPGG TPQPGVEAQP VRAENEKDAT
TEKNKKRGFL FKAKKAAMMT QPPATPALPR LPHDVVPADN RDDPEIILNT TTYYYSVRVF
AGQEPSCVWV GWVTPDYHQH DMNFDLSKVR AVTVTMGDEQ GNVHSSLKCS NCYMVWGGDF
VSPGQQGRIS HTDLVIGCLV DLATGLMTFT ANGKESNTFF QVEPNTKLFP AVFVLPTHQN
VIQFELGKQK NIMPLSAAMF LSERKNPAPQ CPPRLEVQML MPVSWSRMPN HFLQVETRRA
GERLGWAVQC QDPLTMMALH IPEENRCMDI LELSERLDLQ RFHSHTLRLY RAVCALGNNR
VAHALCSHVD QAQLLHALED AHLPGPLRAG YYDLLISIHL ESACRSRRSM LSEYIVPLTP
ETRAITLFPP GRKGGNARRH GLPGVGVTTS LRPPHHFSPP CFVAALPAAG VAEAPARLSP
AIPLEALRDK ALRMLGEAVR DGGQHARDPV GGSVEFQFVP VLKLVSTLLV MGIFGDEDVK
QILKMIEPEV FTEEEEEEEE EEEEEEEEEE DEEEKEEDEE EEEKEDAEKE EEEAPEGEKE
DLEEGLLQMK LPESVKLQMC NLLEYFCDQE LQHRVESLAA FAERYVDKLQ ANQRSRYALL
MRAFTMSAAE TARRTREFRS PPQEQINMLL HFKDEADEED CPLPEDIRQD LQDFHQDLLA
HCGIQLEGEE EEPEEETSLS SRLRSLLETV RLVKKKEEKP EEELPAEEKK PQSLQELVSH
MVVRWAQEDY VQSPELVRAM FSLLHRQYDG LGELLRALPR AYTISPSSVE DTMSLLECLG
QIRSLLIVQM GPQEENLMIQ SIGNIMNNKV FYQHPNLMRA LGMHETVMEV MVNVLGGGET
KEIRFPKMVT SCCRFLCYFC RISRQNQRSM FDHLSYLLEN SGIGLGMQGS TPLDVAAASV
IDNNELALAL QEQDLEKVVS YLAGCGLQSC PMLLAKGYPD IGWNPCGGER YLDFLRFAVF
VNGESVEENA NVVVRLLIRK PECFGPALRG EGGSGLLAAI EEAIRISEDP ARDGPGVRRD
RRREHFGEEP PEENRVHLGH AIMSFYAALI DLLGRCAPEM HLIQAGKGEA LRIRAILRSL
VPLDDLVGII SLPLQIPTLG KDGALVQPKM SASFVPDHKA SMVLFLDRVY GIENQDFLLH
VLDVGFLPDM RAAASLDTAT FSTTEMALAL NRYLCLAVLP LITKCAPLFA GTEHRAIMVD
SMLHTVYRLS RGRSLTKAQR DVIEDCLMAL CRYIRPSMLQ HLLRRLVFDV PILNEFAKMP
LKLLTNHYER CWKYYCLPTG WANFGVTSEE ELHLTRKLFW GIFDSLAHKK YDQELYRMAM
PCLCAIAGAL PPDYVDASYS SKAEKKATVD AEGNFDPRPV ETLNVIIPEK LDSFINKFAE
YTHEKWAFDK IQNNWSYGEN VDEELKTHPM LRPYKTFSEK DKEIYRWPIK ESLKAMIAWE
WTIEKAREGE EERTEKKKTR KISQTAQTYD PREGYNPQPP DLSGVTLSRE LQAMAEQLAE
NYHNTWGRKK KQELEAKGGG THPLLVPYDT LTAKEKARDR EKAQELLKFL QMNGYAVTRG
LKDMELDTSS IEKRFAFGFL QQLLRWMDIS QEFIAHLEAV VSSGRVEKSP HEQEIKFFAK
ILLPLINQYF TNHCLYFLST PAKVLGSGGH ASNKEKEMIT SLFCKLAALV RHRVSLFGTD
APAVVNCLHI LARSLDARTV MKSGPEIVKA GLRSFFESAS EDIEKMVENL RLGKVSQART
QVKGVGQNLT YTTVALLPVL TTLFQHIAQH QFGDDVILDD VQVSCYRTLC SIYSLGTTKN
TYVEKLRPAL GECLARLAAA MPVAFLEPQL NEYNACSVYT TKSPRERAIL GLPNSVEEMC
PDIPVLDRLM ADIGGLAESG ARYTEMPHVI EITLPMLCSY LPRWWERGPE APPPALPAGA
PPPCTAVTSD HLNSLLGNIL RIIVNNLGID EATWMKRLAV FAQPIVSRAR PELLHSHFIP
TIGRLRKRAG KVVAEEEQLR LEAKAEAEEG ELLVRDEFSV LCRDLYALYP LLIRYVDNNR
AHWLTEPNAN AEELFRMVGE IFIYWSKSHN FKREEQNFVV QNEINNMSFL TADSKSKMAK
AGDAQSGGSD QERTKKKRRG DRYSVQTSLI VATLKKMLPI GLNMCAPTDQ DLIMLAKTRY
ALKDTDEEVR EFLQNNLHLQ GKVEGSPSLR WQMALYRGLP GREEDADDPE KIVRRVQEVS
AVLYHLEQTE HPYKSKKAVW HKLLSKQRRR AVVACFRMTP LYNLPTHRAC NMFLESYKAA
WILTEDHSFE DRMIDDLSKA GEQEEEEEEV EEKKPDPLHQ LVLHFSRTAL TEKSKLDEDY
LYMAYADIMA KSCHLEEGGE NGEAEEEEVE VSFEEKEMEK QRLLYQQSRL HTRGAAEMVL
QMISACKGET GAMVSSTLKL GISILNGGNA EVQQKMLDYL KDKKEVGFFQ SIQALMQTCS
VLDLNAFERQ NKAEGLGMVN EDGTVINRQN GEKVMADDEF TQDLFRFLQL LCEGHNNDFQ
NYLRTQTGNT TTINIIICTV DYLLRLQESI SDFYWYYSGK DVIEEQGKRN FSKAMSVAKQ
VFNSLTEYIQ GPCTGNQQSL AHSRLWDAVV GFLHVFAHMM MKLAQDSSQI ELLKELLDLQ
KDMVVMLLSL LEGNVVNGMI ARQMVDMLVE SSSNVEMILK FFDMFLKLKD IVGSEAFQDY
VTDPRGLISK KDFQKAMDSQ KQFTGPEIQF LLSCSEADEN EMINFEEFAN RFQEPARDIG
FNVAVLLTNL SEHVPHDPRL RNFLELAESI LEYFRPYLGR IEIMGASRRI ERIYFEISET
NRAQWEMPQV KESKRQFIFD VVNEGGEAEK MELFVSFCED TIFEMQIAAQ ISEPEGEPEA
DEDEGMGEAA AEGAEEGAAG AEGAAGTVAA GATARLAAAA ARALRGLSYR SLRRRVRRLR
RLTAREAATA LAALLWAVVA RAGAAGAGAA AGALRLLWGS LFGGGLVEGA KKVTVTELLA
GMPDPTSDEV HGEQPAGPGG DADGAGEGEG EGDAAEGDGD EEVAGHEAGP GGAEGVVAVA
DGGPFRPEGA GGLGDMGDTT PAEPPTPEGS PILKRKLGVD GEEEELVPEP EPEPEPEPEK
ADEENGEKEE VPEAPPEPPK KAPPSPPAKK EEAGGAGMEF WGELEVQRVK FLNYLSRNFY
TLRFLALFLA FAINFILLFY KVSDSPPGED DMEGSAAGDL AGAGSGGGSG WGSGAGEEAE
GDEDENMVYY FLEESTGYME PALWCLSLLH TLVAFLCIIG YNCLKVPLVI FKREKELARK
LEFDGLYITE QPGDDDVKGQ WDRLVLNTPS FPSNYWDKFV KRKVLDKHGD IFGRERIAEL
LGMDLASLEI TAHNERKPDP PPGLLTWLMS IDVKYQIWKF GVIFTDNSFL YLGWYMVMSL
LGHYNNFFFA AHLLDIAMGV KTLRTILSSV THNGKQLVMT VGLLAVVVYL YTVVAFNFFR
KFYNKSEDED EPDMKCDDMM TCYLFHMYVG VRAGGGIGDE IEDPAGDEYE LYRVVFDITF
FFFVIVILLA IIQGLIIDAF GELRDQQEQV KEDMETKCFI CGIGSDYFDT TPHGFETHTL
EEHNLANYMF FLMYLINKDE TEHTGQESYV WKMYQERCWD FFPAGDCFRK QYEDQLS
