RYR2_RAT
ID RYR2_RAT Reviewed; 4953 AA.
AC B0LPN4; D7UNT3;
DT 22-FEB-2012, integrated into UniProtKB/Swiss-Prot.
DT 22-FEB-2012, sequence version 2.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Ryanodine receptor 2;
DE Short=RYR-2;
DE Short=RyR2;
DE AltName: Full=Cardiac muscle ryanodine receptor;
DE AltName: Full=Cardiac muscle ryanodine receptor-calcium release channel;
DE AltName: Full=Type 2 ryanodine receptor;
GN Name=Ryr2;
OS 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 [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Cerebral artery;
RX PubMed=20445169; DOI=10.1152/ajpcell.00318.2009;
RA Vaithianathan T., Narayanan D., Asuncion-Chin M.T., Jeyakumar L.H., Liu J.,
RA Fleischer S., Jaggar J.H., Dopico A.M.;
RT "Subtype identification and functional characterization of ryanodine
RT receptors in rat cerebral artery myocytes.";
RL Am. J. Physiol. 299:C264-C278(2010).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Pancreatic islet;
RX PubMed=20471962; DOI=10.1016/j.bbrc.2010.05.051;
RA Takasawa S., Kuroki M., Nata K., Noguchi N., Ikeda T., Yamauchi A., Ota H.,
RA Itaya-Hironaka A., Sakuramoto-Tsuchida S., Takahashi I., Yoshikawa T.,
RA Shimosegawa T., Okamoto H.;
RT "A novel ryanodine receptor expressed in pancreatic islets by alternative
RT splicing from type 2 ryanodine receptor gene.";
RL Biochem. Biophys. Res. Commun. 397:140-145(2010).
RN [3]
RP PHOSPHORYLATION AT SER-2798 AND SER-2804, AND TISSUE SPECIFICITY.
RX PubMed=18755143; DOI=10.1016/j.bbrc.2008.08.084;
RA Huke S., Bers D.M.;
RT "Ryanodine receptor phosphorylation at serine 2030, 2808 and 2814 in rat
RT cardiomyocytes.";
RL Biochem. Biophys. Res. Commun. 376:80-85(2008).
RN [4]
RP FUNCTION, INTERACTION WITH FKBP1A AND FKBP1B, AND TISSUE SPECIFICITY.
RX PubMed=20431056; DOI=10.1161/circresaha.110.219816;
RA Guo T., Cornea R.L., Huke S., Camors E., Yang Y., Picht E., Fruen B.R.,
RA Bers D.M.;
RT "Kinetics of FKBP12.6 binding to ryanodine receptors in permeabilized
RT cardiac myocytes and effects on Ca sparks.";
RL Circ. Res. 106:1743-1752(2010).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1334; SER-1863; SER-2021;
RP SER-2687; SER-2798; SER-2801 AND SER-2804, AND IDENTIFICATION BY MASS
RP 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).
RN [6]
RP STRUCTURE BY NMR OF 3561-3572 IN COMPLEX WITH S100A1, AND INTERACTION WITH
RP CALM AND S100A1.
RX PubMed=18650434; DOI=10.1074/jbc.m804432200;
RA Wright N.T., Prosser B.L., Varney K.M., Zimmer D.B., Schneider M.F.,
RA Weber D.J.;
RT "S100A1 and calmodulin compete for the same binding site on ryanodine
RT receptor.";
RL J. Biol. Chem. 283:26676-26683(2008).
CC -!- FUNCTION: Calcium channel that mediates the release of Ca(2+) from the
CC sarcoplasmic reticulum into the cytoplasm and thereby plays a key role
CC in triggering cardiac muscle contraction. Aberrant channel activation
CC can lead to cardiac arrhythmia. In cardiac myocytes, calcium release is
CC triggered by increased Ca(2+) levels due to activation of the L-type
CC calcium channel CACNA1C. The calcium channel activity is modulated by
CC formation of heterotetramers with RYR3. Required for cellular calcium
CC ion homeostasis. Required for embryonic heart development (By
CC similarity). {ECO:0000250|UniProtKB:Q92736,
CC ECO:0000269|PubMed:20431056, ECO:0000269|PubMed:20471962}.
CC -!- ACTIVITY REGULATION: Channel activity is modulated by the alkaloid
CC ryanodine that binds to the open Ca-release channel with high affinity.
CC At low concentrations, ryanodine maintains the channel in an open
CC conformation. High ryanodine concentrations inhibit channel activity.
CC Channel activity is regulated by calmodulin (CALM). The calcium release
CC is activated by increased cytoplasmic calcium levels, by nitric oxyde
CC (NO), caffeine and ATP. Channel activity is inhibited by magnesium
CC ions, possibly by competition for calcium binding sites (By
CC similarity). {ECO:0000250|UniProtKB:P11716}.
CC -!- SUBUNIT: Homotetramer. Can also form heterotetramers with RYR3.
CC Identified in a complex composed of RYR2, FKBP1B, PKA catalytic
CC subunit, PRKAR2A, AKAP6, and the protein phosphatases PP2A and PP1.
CC Interacts directly with FKBP1B, PKA, PP1 and PP2A (By similarity).
CC Interacts with FKBP1A and FKBP1B; these interactions may stabilize the
CC channel in its closed state and prevent Ca(2+) leaks. Interacts with
CC CALM and S100A1; these interactions regulate channel activity.
CC Interacts with SELENON (By similarity). In cardiac muscles, identified
CC in a complex composed of FSD2, CMYA5 and RYR2 (By similarity).
CC {ECO:0000250|UniProtKB:E9Q401, ECO:0000250|UniProtKB:P30957,
CC ECO:0000250|UniProtKB:Q92736, ECO:0000269|PubMed:18650434,
CC ECO:0000269|PubMed:20431056}.
CC -!- SUBCELLULAR LOCATION: Sarcoplasmic reticulum membrane {ECO:0000305};
CC Multi-pass membrane protein {ECO:0000305}. Membrane {ECO:0000305};
CC Multi-pass membrane protein {ECO:0000305}. Sarcoplasmic reticulum
CC {ECO:0000250|UniProtKB:P30957}. Note=The number of predicted
CC transmembrane domains varies between orthologs, but both N-terminus and
CC C-terminus seem to be cytoplasmic. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=B0LPN4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=B0LPN4-2; Sequence=VSP_042299, VSP_042300;
CC -!- TISSUE SPECIFICITY: Detected in heart muscle myocytes (at protein
CC level). Widely expressed. Detected in heart muscle and cerebral artery
CC smooth muscle. Detected in pancreatic islet cells.
CC {ECO:0000269|PubMed:18755143, ECO:0000269|PubMed:20431056,
CC ECO:0000269|PubMed:20445169, ECO:0000269|PubMed:20471962}.
CC -!- DOMAIN: The calcium release channel activity resides in the C-terminal
CC region while the remaining part of the protein resides in the
CC cytoplasm. {ECO:0000305}.
CC -!- PTM: Channel activity is modulated by phosphorylation. Phosphorylation
CC at Ser-2798 and Ser-2804 increases the open probability of the calcium
CC channel. Phosphorylation is increased in failing heart, leading to
CC calcium leaks and increased cytoplasmic Ca(2+) levels (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Phosphorylation at Ser-2021 by PKA enhances the response to
CC lumenal calcium. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the ryanodine receptor (TC 1.A.3.1) family. RYR2
CC subfamily. {ECO:0000305}.
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DR EMBL; EU346200; ABY79796.1; -; mRNA.
DR EMBL; AB204523; BAJ10276.1; -; mRNA.
DR RefSeq; NP_001177972.1; NM_001191043.1. [B0LPN4-2]
DR RefSeq; NP_114467.1; NM_032078.2.
DR PDB; 2K2F; NMR; -; C/D=3561-3572.
DR PDBsum; 2K2F; -.
DR SMR; B0LPN4; -.
DR BioGRID; 604379; 4.
DR CORUM; B0LPN4; -.
DR IntAct; B0LPN4; 1.
DR STRING; 10116.ENSRNOP00000059019; -.
DR BindingDB; B0LPN4; -.
DR ChEMBL; CHEMBL3388; -.
DR DrugCentral; B0LPN4; -.
DR CarbonylDB; B0LPN4; -.
DR iPTMnet; B0LPN4; -.
DR PhosphoSitePlus; B0LPN4; -.
DR PaxDb; B0LPN4; -.
DR PeptideAtlas; B0LPN4; -.
DR PRIDE; B0LPN4; -.
DR ABCD; B0LPN4; 1 sequenced antibody.
DR GeneID; 689560; -.
DR KEGG; rno:689560; -.
DR CTD; 6262; -.
DR RGD; 620314; Ryr2.
DR eggNOG; KOG2243; Eukaryota.
DR InParanoid; B0LPN4; -.
DR OrthoDB; 5161at2759; -.
DR Reactome; R-RNO-2672351; Stimuli-sensing channels.
DR Reactome; R-RNO-5578775; Ion homeostasis.
DR EvolutionaryTrace; B0LPN4; -.
DR PRO; PR:B0LPN4; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0031672; C:A band; IDA:RGD.
DR GO; GO:0034704; C:calcium channel complex; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:RGD.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IDA:RGD.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0043005; C:neuron projection; IDA:RGD.
DR GO; GO:0005635; C:nuclear envelope; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0042383; C:sarcolemma; IDA:RGD.
DR GO; GO:0030017; C:sarcomere; ISO:RGD.
DR GO; GO:0016529; C:sarcoplasmic reticulum; IDA:BHF-UCL.
DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; IDA:BHF-UCL.
DR GO; GO:0005790; C:smooth endoplasmic reticulum; ISO:RGD.
DR GO; GO:0030018; C:Z disc; IDA:BHF-UCL.
DR GO; GO:0005262; F:calcium channel activity; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central.
DR GO; GO:0048763; F:calcium-induced calcium release activity; IDA:RGD.
DR GO; GO:0015278; F:calcium-release channel activity; ISS:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; ISS:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0097159; F:organic cyclic compound binding; ISO:RGD.
DR GO; GO:0034236; F:protein kinase A catalytic subunit binding; ISO:RGD.
DR GO; GO:0034237; F:protein kinase A regulatory subunit binding; ISO:RGD.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0043621; F:protein self-association; ISO:RGD.
DR GO; GO:0005219; F:ryanodine-sensitive calcium-release channel activity; IDA:RGD.
DR GO; GO:0097110; F:scaffold protein binding; IPI:BHF-UCL.
DR GO; GO:0043924; F:suramin binding; ISO:RGD.
DR GO; GO:0097553; P:calcium ion transmembrane import into cytosol; ISO:RGD.
DR GO; GO:0070588; P:calcium ion transmembrane transport; IMP:RGD.
DR GO; GO:0006816; P:calcium ion transport; ISS:UniProtKB.
DR GO; GO:0060402; P:calcium ion transport into cytosol; ISO:RGD.
DR GO; GO:0019722; P:calcium-mediated signaling; ISS:UniProtKB.
DR GO; GO:0035584; P:calcium-mediated signaling using intracellular calcium source; ISO:RGD.
DR GO; GO:0060048; P:cardiac muscle contraction; ISO:RGD.
DR GO; GO:0003300; P:cardiac muscle hypertrophy; ISO:RGD.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; ISS:UniProtKB.
DR GO; GO:0071313; P:cellular response to caffeine; ISS:UniProtKB.
DR GO; GO:0071872; P:cellular response to epinephrine stimulus; ISO:RGD.
DR GO; GO:0005513; P:detection of calcium ion; ISO:RGD.
DR GO; GO:0003143; P:embryonic heart tube morphogenesis; ISS:UniProtKB.
DR GO; GO:0072599; P:establishment of protein localization to endoplasmic reticulum; ISO:RGD.
DR GO; GO:0034220; P:ion transmembrane transport; IMP:RGD.
DR GO; GO:0003220; P:left ventricular cardiac muscle tissue morphogenesis; ISO:RGD.
DR GO; GO:0071421; P:manganese ion transmembrane transport; IMP:RGD.
DR GO; GO:0051481; P:negative regulation of cytosolic calcium ion concentration; IDA:RGD.
DR GO; GO:1901896; P:positive regulation of ATPase-coupled calcium transmembrane transporter activity; ISO:RGD.
DR GO; GO:0010460; P:positive regulation of heart rate; ISO:RGD.
DR GO; GO:0051284; P:positive regulation of sequestering of calcium ion; ISO:RGD.
DR GO; GO:0098735; P:positive regulation of the force of heart contraction; ISO:RGD.
DR GO; GO:0086029; P:Purkinje myocyte to ventricular cardiac muscle cell signaling; ISO:RGD.
DR GO; GO:0098910; P:regulation of atrial cardiac muscle cell action potential; ISO:RGD.
DR GO; GO:0098904; P:regulation of AV node cell action potential; ISO:RGD.
DR GO; GO:0055117; P:regulation of cardiac muscle contraction; ISO:RGD.
DR GO; GO:0010882; P:regulation of cardiac muscle contraction by calcium ion signaling; ISO:RGD.
DR GO; GO:0010881; P:regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion; ISO:RGD.
DR GO; GO:0051480; P:regulation of cytosolic calcium ion concentration; IMP:RGD.
DR GO; GO:0002027; P:regulation of heart rate; ISO:RGD.
DR GO; GO:0098907; P:regulation of SA node cell action potential; ISO:RGD.
DR GO; GO:0098911; P:regulation of ventricular cardiac muscle cell action potential; ISO:RGD.
DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; ISO:RGD.
DR GO; GO:0014808; P:release of sequestered calcium ion into cytosol by sarcoplasmic reticulum; ISO:RGD.
DR GO; GO:0031000; P:response to caffeine; ISO:RGD.
DR GO; GO:0051592; P:response to calcium ion; IDA:RGD.
DR GO; GO:0001666; P:response to hypoxia; ISO:RGD.
DR GO; GO:0032026; P:response to magnesium ion; IDA:RGD.
DR GO; GO:0014850; P:response to muscle activity; ISO:RGD.
DR GO; GO:0035994; P:response to muscle stretch; ISO:RGD.
DR GO; GO:0007584; P:response to nutrient; IEP:RGD.
DR GO; GO:0051775; P:response to redox state; ISO:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0070296; P:sarcoplasmic reticulum calcium ion transport; IMP:RGD.
DR GO; GO:0097050; P:type B pancreatic cell apoptotic process; ISO:RGD.
DR GO; GO:0086005; P:ventricular cardiac muscle cell action potential; ISO:RGD.
DR CDD; cd12877; SPRY1_RyR; 1.
DR CDD; cd12878; SPRY2_RyR; 1.
DR CDD; cd12879; SPRY3_RyR; 1.
DR Gene3D; 2.60.120.920; -; 3.
DR InterPro; IPR001870; B30.2/SPRY.
DR InterPro; IPR043136; B30.2/SPRY_sf.
DR InterPro; IPR013320; ConA-like_dom_sf.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR014821; Ins145_P3_rcpt.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR036300; MIR_dom_sf.
DR InterPro; IPR016093; MIR_motif.
DR InterPro; IPR013662; RIH_assoc-dom.
DR InterPro; IPR000699; RIH_dom.
DR InterPro; IPR013333; Ryan_recept.
DR InterPro; IPR003032; Ryanodine_rcpt.
DR InterPro; IPR009460; Ryanrecept_TM4-6.
DR InterPro; IPR035910; RyR/IP3R_RIH_dom_sf.
DR InterPro; IPR035761; SPRY1_RyR.
DR InterPro; IPR035764; SPRY2_RyR.
DR InterPro; IPR035762; SPRY3_RyR.
DR InterPro; IPR003877; SPRY_dom.
DR Pfam; PF08709; Ins145_P3_rec; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR Pfam; PF02815; MIR; 1.
DR Pfam; PF08454; RIH_assoc; 1.
DR Pfam; PF06459; RR_TM4-6; 1.
DR Pfam; PF01365; RYDR_ITPR; 2.
DR Pfam; PF02026; RyR; 4.
DR Pfam; PF00622; SPRY; 3.
DR PRINTS; PR00795; RYANODINER.
DR SMART; SM00472; MIR; 4.
DR SMART; SM00449; SPRY; 3.
DR SUPFAM; SSF100909; SSF100909; 2.
DR SUPFAM; SSF47473; SSF47473; 1.
DR SUPFAM; SSF49899; SSF49899; 2.
DR SUPFAM; SSF82109; SSF82109; 2.
DR PROSITE; PS50188; B302_SPRY; 3.
DR PROSITE; PS50919; MIR; 5.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calcium; Calcium channel;
KW Calcium transport; Calmodulin-binding; Developmental protein; Ion channel;
KW Ion transport; Ligand-gated ion channel; Membrane; Phosphoprotein;
KW Receptor; Reference proteome; Repeat; Sarcoplasmic reticulum;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..4953
FT /note="Ryanodine receptor 2"
FT /id="PRO_0000415583"
FT TOPO_DOM 1..4218
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 4219..4239
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 4265..4285
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 4489..4509
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 4566..4586
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 4716..4736
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 4755..4775
FT /note="Helical"
FT /evidence="ECO:0000255"
FT INTRAMEM 4806..4815
FT /note="Pore-forming"
FT /evidence="ECO:0000250"
FT TRANSMEM 4836..4856
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 4857..4953
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 103..158
FT /note="MIR 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT DOMAIN 165..210
FT /note="MIR 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT DOMAIN 218..273
FT /note="MIR 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT DOMAIN 279..336
FT /note="MIR 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT DOMAIN 344..401
FT /note="MIR 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT DOMAIN 592..802
FT /note="B30.2/SPRY 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT REPEAT 846..959
FT /note="1"
FT REPEAT 960..1073
FT /note="2"
FT DOMAIN 1018..1215
FT /note="B30.2/SPRY 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT DOMAIN 1350..1556
FT /note="B30.2/SPRY 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT REPEAT 2682..2800
FT /note="3"
FT REPEAT 2802..2915
FT /note="4"
FT REGION 846..2915
FT /note="4 X approximate repeats"
FT REGION 1349..1370
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2344..2369
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3559..3588
FT /note="Interaction with CALM"
FT /evidence="ECO:0000250"
FT REGION 3679..3705
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 4196..4215
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 4322..4349
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 4406..4450
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3690..3705
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 4198..4215
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 4330..4349
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1334
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1863
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 2021
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 2359
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:E9Q401"
FT MOD_RES 2687
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 2787
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:E9Q401"
FT MOD_RES 2798
FT /note="Phosphoserine; by CaMK2D and PKA"
FT /evidence="ECO:0000269|PubMed:18755143,
FT ECO:0007744|PubMed:22673903"
FT MOD_RES 2801
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 2804
FT /note="Phosphoserine; by CaMK2D"
FT /evidence="ECO:0000269|PubMed:18755143,
FT ECO:0007744|PubMed:22673903"
FT MOD_RES 2937
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:E9Q401"
FT VAR_SEQ 1952
FT /note="R -> RKT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:20471962"
FT /id="VSP_042299"
FT VAR_SEQ 3694..3701
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:20471962"
FT /id="VSP_042300"
FT CONFLICT 40
FT /note="E -> G (in Ref. 1; ABY79796)"
FT /evidence="ECO:0000305"
FT CONFLICT 364
FT /note="W -> R (in Ref. 1; ABY79796)"
FT /evidence="ECO:0000305"
FT CONFLICT 1838
FT /note="Q -> R (in Ref. 1; ABY79796)"
FT /evidence="ECO:0000305"
FT CONFLICT 2691
FT /note="F -> S (in Ref. 1; ABY79796)"
FT /evidence="ECO:0000305"
FT CONFLICT 3216
FT /note="I -> T (in Ref. 1; ABY79796)"
FT /evidence="ECO:0000305"
FT CONFLICT 3226
FT /note="E -> G (in Ref. 1; ABY79796)"
FT /evidence="ECO:0000305"
FT CONFLICT 3355
FT /note="D -> N (in Ref. 1; ABY79796)"
FT /evidence="ECO:0000305"
FT CONFLICT 3541
FT /note="V -> I (in Ref. 1; ABY79796)"
FT /evidence="ECO:0000305"
FT CONFLICT 3751
FT /note="I -> T (in Ref. 1; ABY79796)"
FT /evidence="ECO:0000305"
FT CONFLICT 3885
FT /note="D -> G (in Ref. 1; ABY79796)"
FT /evidence="ECO:0000305"
FT CONFLICT 3990
FT /note="V -> A (in Ref. 1; ABY79796)"
FT /evidence="ECO:0000305"
FT CONFLICT 4196
FT /note="D -> G (in Ref. 1; ABY79796)"
FT /evidence="ECO:0000305"
FT CONFLICT 4262
FT /note="V -> A (in Ref. 1; ABY79796)"
FT /evidence="ECO:0000305"
FT CONFLICT 4536
FT /note="S -> G (in Ref. 1; ABY79796)"
FT /evidence="ECO:0000305"
FT CONFLICT 4667
FT /note="D -> G (in Ref. 1; ABY79796)"
FT /evidence="ECO:0000305"
FT CONFLICT 4930
FT /note="Y -> H (in Ref. 1; ABY79796)"
FT /evidence="ECO:0000305"
FT HELIX 3562..3571
FT /evidence="ECO:0007829|PDB:2K2F"
SQ SEQUENCE 4953 AA; 562955 MW; 2C2798E8A2C4564A CRC64;
MADAGEGEDE IQFLRTDDEV VLQCTATIHK EQQKLCLAAE GFGNRLCFLE STSNSKNVPP
DLSICTFVLE QSLSVRALQE MLANTVEKSE GKFMMKTAQG GGHRTLLYGH AILLRHSYSG
MYLCCLSTSR SSTDKLAFDV GLQEDTTGEA CWWTIHPASK QRSEGEKVRV GDDLILVSVS
SERYLHLSYG NSSWRVDAAF QQTLWSVAPI SSGSEAAQGY LIGGDVLRLL HGHMDECLTV
PSGEHGEEQR RTVHYEGGAV SVHARSLWRL ETLRVAWSGS HIRWGQPFRL RHVTTGKYLS
LMEDKNLLLM DKEKADVKST AFAFRSSKEK LDAGVRKEVD GMGTSEIKYG DSICYIQHVD
TGLWLTYQAV DVKSARMGSI QRKAIMHHEG HMDDGLNLSR SQHEESRTAR VIRSTVFLFN
RFIRGLDALS KRAKLPTVDL PIESVSLSLQ DLIGYFHPPD EHLEHEDKQN RLRALKNRQN
LFQEEGMINL VLECIDRLHV YSSAAHFADV AGREAGESWK SILNSLYELL AALIRGNRKN
CAQFSGSLDW LISRLERLEA SSGILEVLHC VLVESPEALN IIKEGHIKSI ISLLDKHGRN
HKVLDVLCSL CVCHGVAVRS NQHLICDNLL PGRDLLLQTR LVNHVSSMRP NIFLGVSEGS
AQYKKWYYEL MVDHTEPFVT AEATHLRVGW ASTEGYSPYP GGGEEWGGNG VGDDLFSYGF
DGLHLWSGCI ARTVSSPNQH LLRTDDVISC CLDLSAPSIS FRINGQPVQG MFENFNIDGL
FFPVVSFSAG IKVRFLLGGR HGEFKFLPPP GYAACYEAVL PKEKLKVEHS REYKQERTYT
RDLLGPTVSL TQAAFTPVPV DTSQIVLPPH LERIRERLAE NIHELWVMNK IELGWQYGPV
RDDNKRQHPC LVEFCKLPEQ ERNYNLQMSL ETLKTLLALG CHVGIADEHA EEKVKKMKLP
KNYQLTSGYK PAPMDLSFIK LTPSQEAMVD KLAENAHNVW ARDRIRQGWT YGIQQDVKNR
RNPRLVPYTL LDDRTKKSNK DSLREAVRTL LGYGYHLEAP DQDHASRAEV CSGTGERFRI
FRAEKTYAVK AGRWYFEFEA VTAGDMRVGW SRPGCQPDLE LGSDERAFAF DGFKAQRWHQ
GNEHYGRSWQ AGDVVGCMVD MNEHTMMFTL NGEILLDDSG SELAFKDFDV GDGFIPVCSL
GVAQVGRMNF GKDVSTLKYF TICGLQEGYE PFAVNTNRDI TMWLSKRLPQ FLQVPSNHEH
IEVTRIDGTI DSSPCLKVTQ KSFGSQNSNT DIMFYRLSMP IECAEVFSKS VAGGIPGAGF
YGPKNDLEDF DVDSDFEVLM KTAHGHLVPD RMDKDKETPK PEFNNHKDYA QEKPSRLKQR
FLLRRTKPDY STSHSARLTE DVLADDRDDY EYLMQTSTYY YSVRIFPGQE PANVWVGWIT
SDFHQYDTGF DLDRVRTVTV TLGDEKGKVH ESIKRSNCYM VCAGESMSPG QGRNNSNGLE
IGCVVDAASG LLTFIANGKE LSTYYQVEPS TKLFPAVFAQ ATSPNVFQFE LGRIKNVMPL
SAGLFKSEHK NPVPQCPPRL HVQFLSHVLW SRMPNQFLKV DVSRISERQG WLVQCLDPLQ
FMSLHIPEEN RSVDILELTE QEELLQFHYH TLRLYSAVCA LGNHRVAHAL CSHVDEPQLL
YAIENKYMPG LLRAGYYDLL IDIHLSSYAT ARLMMNNEFI VPMTEETKSI TLFPDENKKH
GLPGIGLSTS LRPRMCFSSP SFVSISNECY QYSPEFPLDI LKAKTIQMLT EAVKEGSLHA
RDPVGGTTEF LFVPLIKLFY TLLIMGIFHN EDLKHILQLI EPSVFKEAAT PEEEGGAPEK
EISIDDSKLE VKEEAKAGKR PKEGLLQMKL PEPVKLQMCL LLQYLCDCQV RHRIEAIVAF
SDDFVAKLQD NQRFRYNEVM QALNMSAALT ARKEFRSPPQ EQINMLLNFK DDKSECPCPE
EIRDQLLDFH EDLMTHCGIE LDEDGSLDGS NDLTIRGRLL SLVEKVTYLK KKQAEKPVAS
DSRKSSSLQQ LISETMVRWA QESVIEDPEL VRAMFVLLHR QYDGIGGLVR ALPKTYTING
VSVEDTINLL ASLGQIRSLL SVRMGKEEEK LMIRGLGDIM NNKVFYQHPN LMRALGMHET
VMEVMVNVLG GGESKEITFP KMVANCCRFL CYFCRISRQN QKAMFDHLSY LLENSSVGLA
SPAMRGSTPL DVAAASVMDN NELALALREP DLEKVVRYLA GCGLQSCQML VSKGYPDIGW
NPVEGERYLD FLRFAVFCNG ESVEENANVV VRLLIRRPEC FGPALRGEGG NGLLAAMEEA
IKIAEDPSRD GPSPTSGSSK TLDAEEEEDD TIHMGNAIMT FYAALIDLLG RCAPEMHLIH
AGKGEAIRIR SILRSLIPLG DLVGVISIAF QMPTIAKDGK VVEPDMSAGF CPDHKAAMVL
FLDRVYGIEV QDFLLHLLEV GFLPDLRAAA SLDTAALSAT DMALALNRYL CTAVLPLLTR
CAPLFAGTEH HASLIDSLLH TVYRLSKGCS LTKAQRDSIE VCLLSICGQL RPSMMQHLLR
RLVFDVPLLN EHAKMPLKLL TNHYERCWKY YCLPGGWSNF GAASEEELHL SRKLFWGIFD
ALSQKKYEQE LFKLALPCLS AVAGALPPDY MESNYVSMME KQSSMDSEGN FNPQPVDTSN
ITIPEKLEYF INKYAEHSHD KWSMDKLANG WIYGEIYSDS SKIQPLMKPY KLLSEKEKEI
YRWPIKESLK TMLAWGWRIE RTREGDSMAL YNRTRRISQT SQVSIDAAHG YSPRAIDMSN
VTLSRDLHAM AEMMAENYHN IWAKKKKMEL ESKGGGNHPL LVPYDTLTAK EKAKDREKAQ
DIFKFLQISG YAVSRGFKDL DLDTPSIEKR FAYSFLQQLI RYVDEAHQYI LEFDGGSRSK
GEHFPYEQEI KFFAKVVLPL IDQYFKNHRL YFLSAASRPL CTGGHASNKE KEMVTSLFCK
LGVLVRHRIS LFGNDATSIV NCLHILGQTL DARTVMKTGL DSVKSALRAF LDNAAEDLEK
TMENLKQGQF THTRSQPKGV TQIINYTTVA LLPMLSSLFE HIGQHQFGED LILEDVQVSC
YRILTSLYAL GTSKSIYVER QRSALGECLA AFAGAFPIAF LETHLDKHNV YSIYNTRSSR
ERAALSLPAN VEDVCPNIPS LEKLMTEIIE LAESGIRYTQ MPHMMEVVLP MLCSYMSRWW
EHGPENHPER AEMCCTALNS EHMNTLLGNI LKIIYNNLGI DEGAWMKRLA VFSQPIINKV
KPQLLKTHFL PLMEKLKKKA AMVVSEEDHL KAEARGDMSE AELLILDEFT TLARDLYAFY
PLLIRFVDYN RAKWLKEPNP EAEELFRMVA EVFIYWSKSH NFKREEQNFV VQNEINNMSF
LITDTKSKMS KAAISDQERK KMKRKGDRYS MQTSLIVAAL KRLLPIGLNI CAPGDQELIA
LAKNRFSLKD TEEEVRDVIR SNIHLQGKLE DPAIRWQMAL YKDLPNRAED TSDPERTVER
VLDIANVLFH LEQVEHPQRS KKAVWHKLLS KQRKRAVVAC FRMAPLYNLP RHRAVNLFLQ
GYEKSWIETE EHYFEDKLIE DLAKPGSELP EEDEAMKRVD PLHQLILLFS RTALTEKCKL
EEDFLYMAYA DIMAKSCHDE EDDDGEEEVK SFEVTGSQRS KEKEMEKQKL LYQQARLHDR
GAAEMVLQTF SASKGETGPM VAATLKLGIA ILNGGNSTVQ QKMLDYLKEK KDVGFFQSLA
GLMQSCSVLD LNAFERQNKA EGLGMVTEEG SGEKVLQDDE FTCDLFRFLQ LLCEGHNSDF
QNYLRTQTGN NTTVNIIIST VDYLLRVQES ISDFYWYYSG KDIIDEQGQR NFSKAIQVAK
QVFNTLTEYI QGPCTGNQQS LAHSRLWDAV VGFLHVFAHM QMKLSQDSSQ IELLKELMDL
QKDMVVMLLS MLEGNVVNGT IGKQMVDMLV ESSNNVEMIL KFFDMFLKLK DLTSSDTFKE
YDPDGKGVIS KRDFHKAMES HKHYTQSETE FLLSCAETDE NETLDYEEFV KRFHEPAKDI
GFNVAVLLTN LSEHMPNDTR LQTFLELAES VLNYFQPFLG RIEIMGSAKR IERVYFEISE
SSRTQWEKPQ VKESKRQFIF DVVNEGGEKE KMELFVNFCE DTIFEMQLAA QISESDLNER
SANKEESEKE RPEEQAPRMG FFSLLTVQSA LFALRYNVLT LVRMLSLKSL KKQMKRMKKM
TVKDMVSAFF SSYWSVFVTL LHFVASVCRG FFRIVSSLLL GGSLVEGAKK IKVAELLANM
PDPTQDEVRG DEEEGERKPL ESALPSEDLT DLKELTEESD LLSDIFGLDL KREGGQYKLI
PHNPNAGLSD LMTNPIPVPE VQEKFQEQKV KEEKEGKEET KSEPEKAEGE DGEKEEKAKD
DKGKQKLRQL HTHRYGEPEV PESAFWKKII AYQQKLLNYF ARNFYNMRML ALFVAFAINF
ILLFYKVSTS SVVEGKELPT RTSSDAAKVT TSLDSSPHRI IAVHYVLEES SGYMEPTLRI
LAILHTIISF FCIIGYYCLK VPLVIFKREK EVARKLEFDG LYITEQPSED DIKGQWDRLV
INTQSFPNNY WDKFVKRKVM DKYGEFYGRD RISELLGMDK AALDFSDARE KKKPKKDSSL
SAVLNSIDVK YQMWKLGVVF TDNSFLYLAW YMTMSVLGHY NNFFFAAHLL DIAMGFKTLR
TILSSVTHNG KQLVLTVGLL AVVVYLYTVV AFNFFRKFYN KSEDGDTPDM KCDDMLTCYM
FHMYVGVRAG GGIGDEIEDP AGDEYEIYRI IFDITFFFFV IVILLAIIQG LIIDAFGELR
DQQEQVKEDM ETKCFICGIG NDYFDTVPHG FETHTLQEHN LANYLFFLMY LINKDETEHT
GQESYVWKMY QERCWEFFPA GDCFRKQYED QLN
