RYR1_RAT
ID RYR1_RAT Reviewed; 5035 AA.
AC F1LMY4; O35208; Q9R1G1; Q9R272;
DT 22-FEB-2012, integrated into UniProtKB/Swiss-Prot.
DT 03-MAY-2011, sequence version 1.
DT 03-AUG-2022, entry version 83.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 523-677, AND TISSUE SPECIFICITY.
RC TISSUE=Skeletal muscle;
RX PubMed=10444400; DOI=10.1152/ajpcell.1999.277.2.c243;
RA Martin C., Hyvelin J.-M., Chapman K.E., Marthan R., Ashley R.H.,
RA Savineau J.P.;
RT "Pregnant rat myometrial cells show heterogeneous ryanodine- and caffeine-
RT sensitive calcium stores.";
RL Am. J. Physiol. 227:C243-C252(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4712-4960.
RC STRAIN=Wistar;
RA Brickley K., Mathie A., Lai F.A., Pearce B.;
RT "Changes in ryanodine and inositol trisphosphate receptor expression in
RT cultured rat cortical glia.";
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4863-4951.
RC STRAIN=Wistar;
RA Scott L.M., Demmer J., Hubbard M.J.;
RT "Expression of ryanodine receptors in rat enamel epithelium.";
RL Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=11316255; DOI=10.1007/s004240000484;
RA Jona I., Szegedi C., Sarkoezi S., Szentesi P., Csernoch L., Kovacs L.;
RT "Altered inhibition of the rat skeletal ryanodine receptor/calcium release
RT channel by magnesium in the presence of ATP.";
RL Pflugers Arch. 441:729-738(2001).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2344, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=16641100; DOI=10.1073/pnas.0600895103;
RA Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.;
RT "Quantitative phosphoproteomics of vasopressin-sensitive renal cells:
RT regulation of aquaporin-2 phosphorylation at two sites.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1338; SER-2840; THR-4464 AND
RP SER-4468, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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:11316255). Repeated very high-level exercise increases the open
CC probability of the channel and leads to Ca(2+) leaking into the
CC cytoplasm (By similarity). Can also mediate the release of Ca(2+) from
CC intracellular stores in neurons, and may thereby promote prolonged
CC Ca(2+) signaling in the brain. Required for normal embryonic
CC development of muscle fibers and skeletal muscle. Required for normal
CC heart morphogenesis, skin development and ossification during
CC embryogenesis (By similarity). {ECO:0000250|UniProtKB:E9PZQ0,
CC ECO:0000250|UniProtKB:P11716, ECO:0000305|PubMed:11316255}.
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) (By similarity). The
CC calcium release is activated by increased cytoplasmic calcium levels,
CC by nitric oxyde (NO), caffeine and ATP (PubMed:11316255). Channel
CC activity is inhibited by magnesium ions, possibly by competition for
CC calcium binding sites (PubMed:11316255). {ECO:0000250|UniProtKB:P11716,
CC ECO:0000269|PubMed:11316255}.
CC -!- SUBUNIT: Homotetramer. Can also form heterotetramers with RYR2 (By
CC similarity). Identified in a complex composed of RYR1, PDE4D, PKA,
CC FKBP1A and protein phosphatase 1 (PP1). Repeated very high-level
CC exercise decreases interaction with PDE4D and protein phosphatase 1
CC (PP1) (By similarity). Interacts with CALM; CALM with bound calcium
CC inhibits the RYR1 channel activity (By similarity). Interacts with
CC S100A1 (By similarity). Interacts with FKBP1A; this stabilizes the
CC closed conformation of the channel. Interacts with CACNA1S; interaction
CC with CACNA1S is important for activation of the RYR1 channel. Interacts
CC with CACNB1. Interacts with TRDN and ASPH; these interactions stimulate
CC RYR1 channel activity. Interacts with SELENON (By similarity).
CC Interacts with scorpion calcins (AC P0DPT1; AC P0DM30; AC A0A1L4BJ42;
CC AC P59868; AC P60254; AC B8QG00; AC L0GBR1; AC P60252; AC P60253) (By
CC similarity). {ECO:0000250|UniProtKB:E9PZQ0,
CC ECO:0000250|UniProtKB:P11716, ECO:0000250|UniProtKB:P21817}.
CC -!- SUBCELLULAR LOCATION: Sarcoplasmic reticulum membrane
CC {ECO:0000269|PubMed:11316255}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P11716}. Sarcoplasmic reticulum
CC {ECO:0000250|UniProtKB:P11716}. Membrane
CC {ECO:0000250|UniProtKB:P11716}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P11716}. Note=The number of predicted
CC transmembrane domains varies between orthologs, but the 3D-structures
CC show the presence of six transmembrane regions. Both N-terminus and C-
CC terminus are cytoplasmic. {ECO:0000250|UniProtKB:P11716}.
CC -!- TISSUE SPECIFICITY: Detected in skeletal muscle (at protein level)
CC (PubMed:11316255). Detected in myometrium smooth muscle
CC (PubMed:10444400). {ECO:0000269|PubMed:10444400,
CC ECO:0000269|PubMed:11316255}.
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. Pore opening is mediated via the
CC cytoplasmic calcium-binding domains that mediate a small rotation of
CC the channel-forming transmembrane regions that then leads to channel
CC opening. {ECO:0000250|UniProtKB:P11716}.
CC -!- PTM: Channel activity is modulated by phosphorylation. Phosphorylation
CC at Ser-2840 may increase channel activity. Repeated very high-level
CC exercise increases phosphorylation at Ser-2840.
CC {ECO:0000250|UniProtKB:P21817}.
CC -!- PTM: Activated by reversible S-nitrosylation (By similarity). Repeated
CC very high-level exercise increases S-nitrosylation (By similarity).
CC {ECO:0000250|UniProtKB:P11716, ECO:0000250|UniProtKB:P21817}.
CC -!- SIMILARITY: Belongs to the ryanodine receptor (TC 1.A.3.1) family.
CC {ECO:0000305}.
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DR EMBL; AF112256; AAD48899.1; -; mRNA.
DR EMBL; AF130879; AAD31270.1; -; mRNA.
DR EMBL; AF011788; AAB65756.1; -; mRNA.
DR SMR; F1LMY4; -.
DR CORUM; F1LMY4; -.
DR IntAct; F1LMY4; 3.
DR MINT; F1LMY4; -.
DR STRING; 10116.ENSRNOP00000027893; -.
DR CarbonylDB; F1LMY4; -.
DR iPTMnet; F1LMY4; -.
DR PhosphoSitePlus; F1LMY4; -.
DR PaxDb; F1LMY4; -.
DR PRIDE; F1LMY4; -.
DR UCSC; RGD:620313; rat.
DR RGD; 1586637; Ryr1.
DR eggNOG; KOG2243; Eukaryota.
DR InParanoid; F1LMY4; -.
DR TreeFam; TF315244; -.
DR Reactome; R-RNO-2672351; Stimuli-sensing channels.
DR Reactome; R-RNO-5578775; Ion homeostasis.
DR PRO; PR:F1LMY4; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005938; C:cell cortex; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IBA:GO_Central.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IDA:RGD.
DR GO; GO:0031674; C:I band; ISO:RGD.
DR GO; GO:0031301; C:integral component of organelle membrane; ISS:UniProtKB.
DR GO; GO:0030314; C:junctional membrane complex; ISO:RGD.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR GO; GO:1990425; C:ryanodine receptor complex; ISS:UniProtKB.
DR GO; GO:0042383; C:sarcolemma; IDA:RGD.
DR GO; GO:0016529; C:sarcoplasmic reticulum; IDA:RGD.
DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0005790; C:smooth endoplasmic reticulum; ISO:RGD.
DR GO; GO:0030315; C:T-tubule; ISO:RGD.
DR GO; GO:0014802; C:terminal cisterna; IDA:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0048763; F:calcium-induced calcium release activity; ISO:RGD.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0002020; F:protease binding; ISO:RGD.
DR GO; GO:0005219; F:ryanodine-sensitive calcium-release channel activity; IDA:UniProtKB.
DR GO; GO:0005245; F:voltage-gated calcium channel activity; ISS:UniProtKB.
DR GO; GO:0006816; P:calcium ion transport; IDA:BHF-UCL.
DR GO; GO:0071318; P:cellular response to ATP; IDA:UniProtKB.
DR GO; GO:0071313; P:cellular response to caffeine; ISS:UniProtKB.
DR GO; GO:0071277; P:cellular response to calcium ion; ISS: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; ISS:UniProtKB.
DR GO; GO:0051480; P:regulation of cytosolic calcium ion concentration; IDA:BHF-UCL.
DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; IDA:BHF-UCL.
DR GO; GO:0014808; P:release of sequestered calcium ion into cytosol by sarcoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0031000; P:response to caffeine; IDA:BHF-UCL.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR GO; GO:0001666; P:response to hypoxia; ISO:RGD.
DR GO; GO:0070296; P:sarcoplasmic reticulum calcium ion transport; IDA:RGD.
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; 2.
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 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_0000415567"
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..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 2723..2842
FT /note="5"
FT REPEAT 2843..2956
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..2956
FT /note="6 X approximate repeats"
FT REGION 1308..1386
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1666..1685
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1870..1923
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2389..2411
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2824..2855
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3613..3642
FT /note="Interaction with CALM"
FT /evidence="ECO:0000250"
FT REGION 4255..4284
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 1371..1386
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1871..1921
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2824..2840
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 4404..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 1338
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 2344
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT MOD_RES 2840
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 3634
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT MOD_RES 4464
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 4468
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
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 CONFLICT 673
FT /note="A -> V (in Ref. 2; AAD48899)"
FT /evidence="ECO:0000305"
FT CONFLICT 4728
FT /note="D -> H (in Ref. 3; AAD31270)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 5035 AA; 565483 MW; 51705805EDCAF5CB CRC64;
MGDGGGEGED EVQFLRTDDE VVLQCSATVL KEQLKLCLAA EGFGNRLCFL EPTSNAQNVP
PDLAICCFIL EQSLSVRALQ EMLANTVEAG VESSQGGGHR TLLYGHAILL RHAHSRMYLS
CLTTSRSMTD KLAFDVGLQE DATGEACWWT MHPASKQRSE GEKVRVGDDL ILVSVSSERY
LHLSTASGEL QVDASFMQTL WNMNPICSCC EEGFVTGGHV LRLFHGHMDE CLTISPSDSD
DQRRLVYYEG GPVCTHARSL WRLEPLRISW SGSHLRWGQP LRIRHVTTGR YLALTEDQGL
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 VTSPGQHLLG PEDVVSCCLD LSVPSISFRI NGCPVQGVFE SFNLDGLFFP
VVSFSAGIKV RFLLGGRHGE FKFLPPPGYA PCHEAVLPRE RLHLQPIKEY RREGPRGPHL
VGPSRCLSHL DFVPCPVDTI QIVLPPHLER IREKLAENIH ELWALTRIEQ GWTYGPVRDD
NKRLHPCLVD FHSLPEPERN YNLQMSGETL KTLLALGCHV GMADEKAEDN LKKTKLPKTY
MMNNGYKPAP LDLSHVRLTP AQTTLVDRLA ENGHNVWARD RVAQGWSYSA VQDIPARRNP
RLVPYRLLDE ATKRSNRDSL CQAVRTLLGY GYNIEPPDQE PSQVDSQSRG DRARIFRAEK
SYAVQSGRWY FEFEAVTTGR ELGWARPELR PDVELGADDL AYVFNGHRGQ RWHLGSEPFG
RPWQSGDVVG CMIDLTENTI IFTLNGEVLM SDSGSETAFR EIEIGDGFLP VCSLGPGQVG
HLNLGQDVSS LRFFAICGLQ EGFEPFAINM QRPVTTWFSK SLPQFEPVPL EHPHYEVARM
DGTVDTPPCL RLTHRTWGSQ NSLVEMLFLR LSLPVQFHQH FRCTAGATPL ASPGLQPPAE
DEARAAEPDT DYENLRRSAG GWGEAEAGKD GTAKEGTPGG AAQPGVEAQP ARAENEKDAT
TEKNKKRGFL FKAKKVAMMT QPPSTPALPR LPRDVVPADN RDDPEIILNT TTYYYSVRVF
AGQEPSCVWV GWVTPDYHQH DMSFDLSKVR AVTVTMGDEQ GNVHSSLKCS NCYMVWGGDF
VSPGQQGRIS HTDLVIGCLV DLATGLMTFT ANGKESNTFF QVEPNTKLFP AVFVLPTHQN
VVQFDLRPGA NIMPLSAAMF LSERKNPAPQ CPPRLEVQML MPVSWSRMPN HFLHVDTRRA
GERLGWAVQC QEPLMMMALH IPEENSEPYI HLKRAQLDPR DLRDYRDTKF DSESSDSDQT
PQPGCYHVDQ AQLLHALEDA HLPGPLRAGY YDLLISIHLE SACRSRRSML SEYIVPLTEE
TRAITLFPPG RSAEDGPRRH GLPGVGVTTS LRPPHHFSPP CFVVALPAAG AAEAPARLSP
AIPLEALRDK ALRMLGEAVR DGGQHARDPV GGSVEFQFVP VLKLVSTLLV MGVFSDEDVK
QILKMIEPEV FTEEEEVEEE EEEEEEDEEE KEEDEEEEAH EKEDEEKEEA EEAAEEEKEE
LEEGLLQMKL PESVKLQMCH LLEYFCDQEL QHRVESLAAF AERYVDKLQS NQRGRYGLLM
KAFTMSAAET ARRTREFRSP PQEQINMLLQ FKNGADEEDC PLPEEIREDL VNFHQDLLAH
CGIQLEGEEE EPEEESTLGS RLMSLLEKVR LVKKKEEKPE EEPAAEEHKP QSLQELVSHT
VVRWAQEDFV QSPELVRAMF SLLHRQYDGL GELLRALPRA YTISLSSVED TMSLLECLGQ
IRSLLIVQMG PQEENLMIQS IGNIMNNKVF YQHPNLMRAL GMHETVMEVM VNVLGGGESK
EIRFPKMVTS CCRFLCYFCR ISRQNQRSMF DHLSYLLENS GIGLGMQGST PLDVAAASVI
DNNELALALQ EQDLEKVVSY LAGCGLQSCP MLLAKGYPDI GWNPCGGERY LDFLRFAVFV
NGESVEENAN VVVRLLIRKP ECFGPALRGE GGSGLLAAIE EAIRISEDPA RDGPGVRRDR
RREHFGEEPP EENRVHLGHA IMSFYAALID LLGRCAPEMH LIQAGKGEAL RIRAILRSLV
PLDDLVGIIS LPLQIPTLGK DGALVQPKMS ASFVPDHKAS MVLFLDRVYG IENQDFLLHV
LDVGFLPDMR AAASLDTATF SRRWALALTR YLCAVLPLIT KCAPLLRGTE HRAIMVDSML
HTVYRLSRGR SLTKAQRDVI EDCLMALCRY IRPSMLQHLL RRLVFDVPIL NEFAKMPLKL
LTNHYERCWK YYCLPTGWAN FGVTSEEELH LTRKLFWGIF DSLAHKKYDQ ELYRIAMPCL
CAIAGALPPD YVDASYSSKT EKKATVDAEG NFDPRPVETL NVIIPEKLDS FINKFAEYAH
EKWAFDKIQN NWSYGENIDE ELKTHPMLRP YKTFSEKDKE IYRWPIKESL KAMIAWEWTV
EKAREGEEEK TEKKKTRKIS QTAQTYDPRE GYNPQPPDLS VVTLSRELQA MAEQLAENYH
NTWGRKKKQE LEAKGGGSHP LLVPYDTLTA KEKARDREKA QELLKFLQMN GYAVTRHGKD
MELDTSSIEK RFAFGFLQQL LRWMDISQEF IAHLEAVVSS GRVEKSPHEQ EIKFFAKILL
PLINQYFTNH CLYFLSTPAK VLGSGGHASN KEKEMITSLF CKLAALVRHR VSLFGTDAPA
VVNCLHILAR SLDARTVMKS GPEIVKAGLR SFFESASEDI EKMVENLRLG KVSQARTQVK
GVGQNLTYTT VALLPVLTTL FQHIAQHQFG DDVILDDVQV SCYRTLCSIY SLGTTRNPYV
EKLRPALGEC LARLAAAMPV AFLEPELNEY NACSVYTTKS PRERAILGLP NSVEEMCPDI
PVLERLMAEI GGLAESGARY TEMPHVIEIT LPMLCSYLPR WWERGPEAPP PALPAGAPPP
CTAVTSDHLN SLLGNILRII VNNLGIDEAS WMKRLAVFAQ PIVSRARPEL LRSHFIPTIG
RLRKRAGKVV AEEEQLRLEA KAEAEEGELL VRDEFSVLCR DLYALYPLLI RYVDNNRSAW
PRLPPSPSSS FSLPSPSELG RWLMKDHGHQ LYEESFTVPL ILDNAAFPLA RNQSRAIGCA
GVVRSGGSDQ ERTKKKRRGD RYSVQTSLIV ATLKKMLPIG LNMCAPTDQD LIVLAKARYA
LKDTDEEVRE FLQNNLNLQG KVEGSPSLRW QMALYRGVPG REEDADDPEK IVRRVQEVSA
VLYHLDQTEH PYKSKKAVWH KLLSKQRRRA VVACFRMTPL YNLPTHRACN MFLESYKASW
ILTEDHSFED RMIDDLSKAG EQEEEEEEVE EKKPDPLHQL VLHFSRTALT EKSKLDEDYL
YMAYADIMAK SCHLEEGGEN VEEGGEEEEV EVSFEEKEME KQRLLYQQSR LHNRGAAEMV
LQMISACKGE TGAMVSSTLK LGISILNGGN AEVQQKMLDY LKDKKEVGFF QSIQALMQTC
RWPHKTLSQR EGQEERVMKV QTSGTLVIIN 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 ESILDYFRPY LGRIEIMGAS RRIERIYFEI
SETNRAQWEM PQVKESKRQF IFDVVNEGGE SEKMELFVSF CEDTIFEMQI AAQISEPEGE
PEEDDDEGAE EAEEGAAGPD GSGSAAAAGV WTWLATAAGR TLRGLSYRSL RRRVRRLRRL
TAREAATAVA VLLWAMVARA GGAGAGAAAG VLRLLWGSLF GGGLVDSAKK VTVTELLAGM
PDPTGDEVHG QQPSGAGSDA EGEGQGEGEG DAAEGVGDEE VAADQAGTGG ADRTVAVADG
SPFRPEGAGG LGDMGDTTPV EPPTPEGSPI LKRKLGVDGE EEEPQPEPEP EPEPEPEKAD
TENGEKEVPE PPPEPPKKAP PPPPPKKEEA GGAGLEEFWG ELEVQRVKFL NYLSRNFYTL
RFLALFLAFA INFILLFYKV SDSPPGEDDI EGSGAGDMSG AGSGDGSGWG SRASEEVEGD
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 EDQLG
