Ser2813
Javascript is not enabled on this browser. This site will not work properly without Javascript.
PhosphoSitePlus Homepage PhosphoSitePlus® v6.7.4
Powered by Cell Signaling Technology
Home > Phosphorylation Site Page: > Ser2813  -  RYR2 (mouse)

Site Information
IsQtsQVsIDAAHGY   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 458801

In vivo Characterization
Methods used to characterize site in vivo:
immunoassay ( 23 ) , immunoprecipitation ( 42 ) , mass spectrometry ( 10 , 22 , 29 , 34 , 35 , 39 , 43 , 44 , 45 , 46 , 48 , 49 ) , mutation of modification site ( 3 , 4 , 13 , 16 , 18 , 19 , 23 , 24 , 30 , 31 , 37 , 38 , 40 , 42 ) , phospho-antibody ( 2 , 3 , 5 , 6 , 7 , 8 , 9 , 11 , 12 , 13 , 14 , 15 , 17 , 18 , 19 , 20 , 21 , 23 , 24 , 25 , 26 , 27 , 28 , 31 , 32 , 33 , 38 , 40 , 41 , 47 , 50 ) , western blotting ( 2 , 3 , 5 , 6 , 7 , 8 , 9 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 23 , 24 , 25 , 26 , 27 , 28 , 31 , 32 , 33 , 38 , 40 , 41 , 47 )
Disease tissue studied:
pancreatic cancer ( 31 ) , pancreatic carcinoma ( 31 ) , cardiomyopathy ( 16 )
Relevant cell line - cell type - tissue:
'brain, cerebellum' ( 48 ) , 'brain, cerebral cortex' ( 48 ) , 'brain, hippocampus, dentate gyrus' ( 48 ) , 'brain, midbrain' ( 48 ) , 'heart, ventricle' ( 4 , 5 , 6 , 19 , 23 ) , 'muscle, skeletal' ( 31 ) , 293 (epithelial) ( 15 , 24 ) , brain ( 31 , 34 , 35 ) , cardiac-heart ( 24 ) , heart ( 2 , 7 , 8 , 9 , 10 , 20 , 26 , 29 , 31 , 32 , 38 , 39 , 40 , 41 , 42 , 45 , 46 , 49 , 50 ) , HL-1 (myocyte) [Akt1 (mouse), knockdown, stable lentiviral expression of Akt1 shRNA] ( 22 ) , HL-1 (myocyte) [Akt2 (mouse), knockdown, stable lentiviral expression of Akt2 shRNA] ( 22 ) , HL-1 (myocyte) ( 17 , 22 ) , INS-1 (pancreatic) ( 31 ) , lung ( 39 ) , myocardium ( 12 ) , myocyte ( 6 , 37 ) , myocyte-heart ( 3 , 5 , 11 , 12 , 13 , 14 , 15 , 16 , 18 , 19 , 21 , 23 , 25 , 27 , 28 , 33 , 47 ) , myocyte-heart [CAMK2D (mouse), homozygous knockout] ( 30 ) , pancreas [RYR2 (mouse), genetic knockin] ( 31 ) , thymus ( 43 , 44 )

Upstream Regulation
Regulatory protein:
CAMK2A (mouse) ( 24 ) , nNOS (mouse) ( 25 ) , PKACA (human) ( 12 ) , plakophilin 2 (mouse) ( 9 ) , Spinophilin (mouse) ( 24 ) , tafazzin (human) ( 5 ) , tafazzin (mouse) ( 5 ) , TRPC7 (human) ( 6 )
Putative in vivo kinases:
CAMK2A (mouse) ( 2 , 5 , 7 , 19 , 28 , 31 , 38 , 40 ) , CAMK2D (mouse) ( 23 , 30 , 42 )
Kinases, in vitro:
CAMK2A (mouse) ( 40 ) , CAMK2D (human) ( 42 )
Putative upstream phosphatases:
PPP1CA (mouse) ( 24 )
Phosphatases, in vitro:
PPP1CA (mouse) ( 24 )
Treatments:
adriamycin ( 11 ) , autocamtide_inhibitory_peptide ( 5 , 24 , 26 ) , bisindolylmaleimide ( 47 ) , calyculin_A ( 33 ) , cpTOME ( 47 ) , fructose-rich diet ( 15 ) , GLP-1 ( 17 ) , glucose ( 31 ) , glutathione ( 19 ) , H2O2 ( 19 ) , heart failure ( 42 ) , high_glucose ( 15 ) , hydroxyurea ( 20 ) , imatinib ( 21 ) , increased heart rate ( 42 ) , inhibitor-1 ( 32 ) , ionizing_radiation ( 28 ) , ischemia/reperfusion ( 23 , 38 , 41 ) , isoproterenol ( 3 , 12 , 25 , 27 , 33 ) , KN-93 ( 15 , 19 , 24 , 38 , 40 , 42 ) , LPS ( 2 ) , mutation ( 14 ) , ouabain ( 33 ) , pyridostigmine_bromide ( 7 ) , resatorvid ( 2 ) , TAC ( 7 ) , wheel running test ( 9 )

Downstream Regulation
Effects of modification on RYR2:
activity, induced ( 6 , 7 , 23 , 38 , 40 ) , molecular association, regulation ( 4 , 16 ) , protein conformation ( 16 )
Effects of modification on biological processes:
apoptosis, induced ( 15 , 23 ) , signaling pathway regulation ( 25 )
Inhibit interaction with:
Calmodulin (mouse) ( 16 ) , IDH3B (mouse) ( 4 ) , PDCD8 (mouse) ( 4 )

Disease / Diagnostics Relevance
Relevant diseases:
atrial fibrillation ( 24 , 37 ) , ventricular tachycardia ( 38 , 40 ) , type 2 diabetes ( 31 ) , FHC ( 14 )

References 

1

Zhou D, et al. (2024) mROS‑calcium feedback loop promotes lethal ventricular arrhythmias and sudden cardiac death in early myocardial ischemia. Int J Mol Med 53
37997788   Curated Info

2

Matsuo I, et al. (2022) Role of TLR4 signaling on Porphyromonas gingivalis LPS-induced cardiac dysfunction in mice. PLoS One 17, e0258823
35648750   Curated Info

3

Baier MJ, et al. (2021) Phosphorylation of RyR2 Ser-2814 by CaMKII mediates β1-adrenergic stress induced Ca -leak from the sarcoplasmic reticulum. FEBS Open Bio
34403217   Curated Info

4

Chiang DY, et al. (2021) Phosphorylation-Dependent Interactome of Ryanodine Receptor Type 2 in the Heart. Proteomes 9
34200203   Curated Info

5

Liu X, et al. (2021) Increased Reactive Oxygen Species-Mediated Ca/Calmodulin-Dependent Protein Kinase II Activation Contributes to Calcium Handling Abnormalities and Impaired Contraction in Barth Syndrome. Circulation 143, 1894-1911
33793303   Curated Info

6

Liu X, et al. (2021) TRPC7 regulates the electrophysiological functions of embryonic stem cell-derived cardiomyocytes. Stem Cell Res Ther 12, 262
33941260   Curated Info

7

Baine S, et al. (2021) Pyridostigmine improves cardiac function and rhythmicity through RyR2 stabilization and inhibition of STIM1-mediated calcium entry in heart failure. J Cell Mol Med
33755308   Curated Info

8

Sun B, et al. (2021) Cardiac ryanodine receptor calcium release deficiency syndrome. Sci Transl Med 13
33536282   Curated Info

9

Hammer KP, et al. (2021) Beneficial effect of voluntary physical exercise in Plakophilin2 transgenic mice. PLoS One 16, e0252649
34086773   Curated Info

10

Campbell HM, et al. (2020) Loss of SPEG Inhibitory Phosphorylation of RyR2 Promotes Atrial Fibrillation. Circulation
32683896   Curated Info

11

Llach A, et al. (2019) Progression of excitation-contraction coupling defects in doxorubicin cardiotoxicity. J Mol Cell Cardiol 126, 129-139
30500377   Curated Info

12

Potenza DM, et al. (2018) Phosphorylation of the ryanodine receptor 2 at serine 2030 is required for a complete β-adrenergic response. J Gen Physiol
30541771   Curated Info

13

Valverde CA, et al. (2018) Ablation of PLN rescues reperfusion arrhythmias but exacerbates myocardium infarction in hearts with Ca2+/calmodulin kinase II constitutive phosphorylation of ryanodine receptors. Cardiovasc Res
30169578   Curated Info

14

Okuda S, et al. (2018) CaMKII-mediated phosphorylation of RyR2 plays a crucial role in aberrant Carelease as an arrhythmogenic substrate in cardiac troponin T-related familial hypertrophic cardiomyopathy. Biochem Biophys Res Commun 496, 1250-1256
29402414   Curated Info

15

Federico M, et al. (2017) Calcium-calmodulin-dependent protein kinase mediates the intracellular signalling pathways of cardiac apoptosis in mice with impaired glucose tolerance. J Physiol 595, 4089-4108
28105734   Curated Info

16

Uchinoumi H, et al. (2016) CaMKII-dependent phosphorylation of RyR2 promotes targetable pathological RyR2 conformational shift. J Mol Cell Cardiol 98, 62-72
27318036   Curated Info

17

Huang JH, et al. (2016) Glucagon-like peptide-1 regulates calcium homeostasis and electrophysiological activities of HL-1 cardiomyocytes. Peptides 78, 91-8
26930508   Curated Info

18

Wang Q, et al. (2015) Crosstalk between RyR2 oxidation and phosphorylation contributes to cardiac dysfunction in mice with Duchenne muscular dystrophy. J Mol Cell Cardiol 89, 177-84
26555638   Curated Info

19

Shirokova N, et al. (2014) Oxidative stress and ca(2+) release events in mouse cardiomyocytes. Biophys J 107, 2815-27
25517148   Curated Info

20

Respress JL, et al. (2014) Long-term simulated microgravity causes cardiac RyR2 phosphorylation and arrhythmias in mice. Int J Cardiol 176, 994-1000
25227892   Curated Info

21

Barr LA, et al. (2014) Imatinib activates pathological hypertrophy by altering myocyte calcium regulation. Clin Transl Sci 7, 360-7
24931551   Curated Info

22

Reinartz M, Raupach A, Kaisers W, Gödecke A (2014) AKT1 and AKT2 induce distinct phosphorylation patterns in HL-1 cardiac myocytes. J Proteome Res 13, 4232-45
25162660   Curated Info

23

Di Carlo MN, et al. (2014) CaMKII-dependent phosphorylation of cardiac ryanodine receptors regulates cell death in cardiac ischemia/reperfusion injury. J Mol Cell Cardiol 74, 274-83
24949568   Curated Info

24

Chiang DY, et al. (2014) Impaired local regulation of ryanodine receptor type 2 by protein phosphatase 1 promotes atrial fibrillation. Cardiovasc Res 103, 178-87
24812280   Curated Info

25

Curran J, et al. (2014) Nitric Oxide-Dependent Activation of CaMKII Increases Diastolic Sarcoplasmic Reticulum Calcium Release in Cardiac Myocytes in Response to Adrenergic Stimulation. PLoS One 9, e87495
24498331   Curated Info

26

Chakraborty A, et al. (2014) Inhibition of CaMKII Does Not Attenuate Cardiac Hypertrophy in Mice with Dysfunctional Ryanodine Receptor. PLoS One 9, e104338
25093823   Curated Info

27

Besser J, et al. (2014) MiRNA-1/133a Clusters Regulate Adrenergic Control of Cardiac Repolarization. PLoS One 9, e113449
25415383   Curated Info

28

Sag CM, et al. (2013) Ionizing radiation regulates cardiac Ca handling via increased ROS and activated CaMKII. Basic Res Cardiol 108, 385
24068185   Curated Info

29

Lundby A, et al. (2013) In vivo phosphoproteomics analysis reveals the cardiac targets of β-adrenergic receptor signaling. Sci Signal 6, rs11
23737553   Curated Info

30

Pereira L, et al. (2013) Epac2 Mediates Cardiac β1-Adrenergic-Dependent Sarcoplasmic Reticulum Ca2+ Leak and Arrhythmia. Circulation 127, 913-22
23363625   Curated Info

31

Dixit SS, et al. (2013) Effects of CaMKII-Mediated Phosphorylation of Ryanodine Receptor Type 2 on Islet Calcium Handling, Insulin Secretion, and Glucose Tolerance. PLoS One 8, e58655
23516528   Curated Info

32

Pritchard TJ, et al. (2013) Active inhibitor-1 maintains protein hyper-phosphorylation in aging hearts and halts remodeling in failing hearts. PLoS One 8, e80717
24312496   Curated Info

33

Sacherer M, et al. (2012) JTV519 (K201) reduces sarcoplasmic reticulum Ca²⁺ leak and improves diastolic function in vitro in murine and human non-failing myocardium. Br J Pharmacol 167, 493-504
22509897   Curated Info

34

Trinidad JC, et al. (2012) Global identification and characterization of both O-GlcNAcylation and phosphorylation at the murine synapse. Mol Cell Proteomics 11, 215-29
22645316   Curated Info

35

Goswami T, et al. (2012) Comparative phosphoproteomic analysis of neonatal and adult murine brain. Proteomics 12, 2185-9
22807455   Curated Info

36

Respress JL, et al. (2012) Role of RyR2 Phosphorylation at S2814 During Heart Failure Progression. Circ Res 110, 1474-83
22511749   Curated Info

37

Li N, et al. (2012) Inhibition of CaMKII Phosphorylation of RyR2 Prevents Induction of Atrial Fibrillation in FKBP12.6 Knockout Mice. Circ Res 110, 465-70
22158709   Curated Info

38

Said M, et al. (2011) Calcium-calmodulin dependent protein kinase II (CaMKII): a main signal responsible for early reperfusion arrhythmias. J Mol Cell Cardiol 51, 936-44
21888910   Curated Info

39

Huttlin EL, et al. (2010) A tissue-specific atlas of mouse protein phosphorylation and expression. Cell 143, 1174-89
21183079   Curated Info

40

van Oort RJ, et al. (2010) Ryanodine receptor phosphorylation by calcium/calmodulin-dependent protein kinase II promotes life-threatening ventricular arrhythmias in mice with heart failure. Circulation 122, 2669-79
21098440   Curated Info

41

Salas MA, et al. (2010) The signalling pathway of CaMKII-mediated apoptosis and necrosis in the ischemia/reperfusion injury. J Mol Cell Cardiol 48, 1298-306
20060004   Curated Info

42

Kushnir A, et al. (2010) Role of CaMKIIdelta phosphorylation of the cardiac ryanodine receptor in the force frequency relationship and heart failure. Proc Natl Acad Sci U S A 107, 10274-9
20479242   Curated Info

43

Guo A (2009) CST Curation Set: 8170; Year: 2009; Biosample/Treatment: tissue, thymus/untreated; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: (F/Y/M)Xp[ST](L/I/M)
Curated Info

44

Guo A (2009) CST Curation Set: 8169; Year: 2009; Biosample/Treatment: tissue, thymus/untreated; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: (F/Y/M)Xp[ST](L/I/M)
Curated Info

45

Zhou J (2009) CST Curation Set: 7385; Year: 2009; Biosample/Treatment: tissue, heart/untreated; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: QXp[ST]
Curated Info

46

Zhou J (2009) CST Curation Set: 7386; Year: 2009; Biosample/Treatment: tissue, heart/untreated; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: QXp[ST]
Curated Info

47

Oestreich EA, et al. (2009) Epac and phospholipase Cepsilon regulate Ca2+ release in the heart by activation of protein kinase Cepsilon and calcium-calmodulin kinase II. J Biol Chem 284, 1514-22
18957419   Curated Info

48

Trinidad JC, et al. (2008) Quantitative analysis of synaptic phosphorylation and protein expression. Mol Cell Proteomics 7, 684-96
18056256   Curated Info

49

Guo A (2007) CST Curation Set: 2922; Year: 2007; Biosample/Treatment: tissue, heart/-; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]Q Antibodies Used to Purify Peptides prior to LCMS: Phospho-(Ser/Thr) ATM/ATR Substrate Antibody Cat#: 2851
Curated Info

50

Wehrens XH, et al. (2006) Ryanodine receptor/calcium release channel PKA phosphorylation: a critical mediator of heart failure progression. Proc Natl Acad Sci U S A 103, 511-8
16407108   Curated Info