Thr17

Site Information
SAIRRAstIEMPQQA SwissProt Entrez-Gene
Blast this site against: NCBI SwissProt PDB
Site Group ID: 448115

In vivo Characterization
Methods used to characterize site in vivo:	[32P] bio-synthetic labeling ( 29 ) , mass spectrometry ( 11 ) , mutation of modification site ( 23 ) , phospho-antibody ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ) , western blotting ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 22 , 24 , 25 , 27 , 28 )
Relevant cell line - cell type - tissue:	'heart, ventricle' ( 1 , 5 ) , 'muscle, smooth'-thoracic aorta ( 22 ) , H9c2 (myoblast) ( 7 ) , heart ( 4 , 6 , 8 , 9 , 10 , 11 , 12 , 13 , 15 , 18 , 19 , 25 , 29 ) , intestine ( 11 ) , lung ( 11 ) , muscle ( 2 , 11 ) , myocardium ( 6 ) , myocyte ( 5 ) , myocyte-heart ( 1 , 3 , 7 , 12 , 14 , 16 , 17 , 21 , 23 , 24 , 26 , 27 , 28 ) , stomach ( 11 )

Upstream Regulation
Regulatory protein:	ADCY6 (human) ( 14 ) , ADCY6 (mouse) ( 14 ) , Calmodulin (human) ( 24 ) , CAMK2A (human) ( 2 ) , CAMK2B (human) ( 2 )
Putative in vivo kinases:	CAMK2D (rat) ( 17 , 22 )
Putative upstream phosphatases:	PPP1CA (human) ( 12 )
Treatments:	5-Methoxytryptophan ( 3 ) , acidosis ( 25 ) , aortic banding ( 6 ) , autocamtide_inhibitory_peptide ( 24 ) , Ba(2+) ( 7 ) , Bay 60-7550 ( 5 ) , bradykinin ( 20 ) , Ca(2+) ( 25 ) , calyculin_A ( 16 ) , ciclosporin ( 12 ) , cigarette smoke extract ( 1 ) , colforsin ( 14 , 15 ) , electrical_stimulation ( 16 , 19 , 27 ) , exercise ( 2 , 18 ) , exercise training ( 8 ) , FK506 ( 12 ) , Go_6976 ( 12 ) , H-89 ( 15 , 25 ) , hypertension ( 26 ) , ibrutinib ( 3 ) , inhibitor-1 ( 10 ) , ionomycin ( 22 ) , ischemia ( 12 ) , ischemia/reperfusion ( 7 , 13 ) , isoproterenol ( 5 , 14 , 15 , 16 , 19 , 25 ) , KBR ( 13 ) , KN-93 ( 7 , 13 , 22 , 24 ) , liothyronine ( 28 ) , low_Ca(2+) ( 25 ) , myocarditis ( 9 ) , nifedipine ( 13 , 25 ) , norepinephrine ( 21 , 27 ) , okadaic_acid ( 25 ) , prazosin ( 21 , 27 ) , prednisolone ( 9 ) , pressure ( 8 ) , W-7 ( 25 ) , zacopride ( 7 )

Downstream Regulation
Effects of modification on PLB:	activity, induced ( 1 , 12 , 25 )

Disease / Diagnostics Relevance
Relevant diseases:	diabetes mellitus ( 4 )

References
1	Matsumura S, et al. (2024) Direct toxicity of cigarette smoke extract on cardiac function mediated by mitochondrial dysfunction in Sprague-Dawley rat ventricular myocytes and human induced pluripotent stem cell-derived cardiomyocytes. PLoS One 19, e0295737 38165883 Curated Info
2	Flück M, et al. (2023) Enhanced capacity for CaMKII signaling mitigates calcium release related contractile fatigue with high intensity exercise. Biochim Biophys Acta Mol Cell Res 1871, 119610 37913845 Curated Info
3	Shuai W, et al. (2023) 5-Methoxytryptophan alleviates atrial structural remodeling in ibrutinib-associated atrial fibrillation. Heliyon 9, e19501 37810107 Curated Info
4	Chaoul V, et al. (2023) Differential changes in cyclic adenosine 3'-5' monophosphate (cAMP) effectors and major Ca handling proteins during diabetic cardiomyopathy. J Cell Mol Med 36967707 Curated Info
5	Wang YW, et al. (2021) Bay 60-7550, a PDE2 inhibitor, exerts positive inotropic effect of rat heart by increasing PKA-mediated phosphorylation of phospholamban. Eur J Pharmacol 901, 174077 33798601 Curated Info
6	Mazeto IFS, et al. (2021) Calcium homeostasis behavior and cardiac function on left ventricular remodeling by pressure overload. Braz J Med Biol Res 54, e10138 33624728 Curated Info
7	Liu Q, et al. (2021) The Agonist of Inward Rectifier Potassium Channel (I) Attenuates Rat Reperfusion Arrhythmias Linked to CaMKII Signaling. Int Heart J 62, 1348-1357 34853227 Curated Info
8	de Souza SLB, et al. (2020) Adjustments in ¿¿-Adrenergic Signaling Contribute to the Amelioration of Cardiac Dysfunction by Exercise Training in Supravalvular Aortic Stenosis. Cell Physiol Biochem 32639114 Curated Info
9	Park H, et al. (2014) Increased phosphorylation of ca(2+) handling proteins as a proarrhythmic mechanism in myocarditis. Circ J 78, 2292-301 25056499 Curated Info
10	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
11	Lundby A, et al. (2012) Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues. Nat Commun 3, 876 22673903 Curated Info
12	Shintani-Ishida K, Yoshida K (2011) Ischemia induces phospholamban dephosphorylation via activation of calcineurin, PKC-α, and protein phosphatase 1, thereby inducing calcium overload in reperfusion. Biochim Biophys Acta 1812, 743-51 21447388 Curated Info
13	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
14	Gao MH, et al. (2008) Adenylyl cyclase type VI increases Akt activity and phospholamban phosphorylation in cardiac myocytes. J Biol Chem 283, 33527-35 18838385 Curated Info
15	Ferrero P, et al. (2007) Ca2+/calmodulin kinase II increases ryanodine binding and Ca2+-induced sarcoplasmic reticulum Ca2+ release kinetics during beta-adrenergic stimulation. J Mol Cell Cardiol 43, 281-91 17643448 Curated Info
16	Huke S, Bers DM (2007) Temporal dissociation of frequency-dependent acceleration of relaxation and protein phosphorylation by CaMKII. J Mol Cell Cardiol 42, 590-9 17239900 Curated Info
17	Yang D, et al. (2007) Ca2+/calmodulin kinase II-dependent phosphorylation of ryanodine receptors suppresses Ca2+ sparks and Ca2+ waves in cardiac myocytes. Circ Res 100, 399-407 17234969 Curated Info
18	Kolwicz SC, et al. (2007) Effects of forskolin on inotropic performance and phospholamban phosphorylation in exercise-trained hypertensive myocardium. J Appl Physiol 102, 628-33 17082376 Curated Info
19	Valverde CA, et al. (2005) Frequency-dependent acceleration of relaxation in mammalian heart: a property not relying on phospholamban and SERCA2a phosphorylation. J Physiol 562, 801-13 15528241 Curated Info
20	Tschöpe C, et al. (2004) Improvement of defective sarcoplasmic reticulum Ca2+ transport in diabetic heart of transgenic rats expressing the human kallikrein-1 gene. FASEB J 18, 1967-9 15448111 Curated Info
21	Wang W, et al. (2004) Sustained beta1-adrenergic stimulation modulates cardiac contractility by Ca2+/calmodulin kinase signaling pathway. Circ Res 95, 798-806 15375008 Curated Info
22	Pfleiderer PJ, et al. (2004) Modulation of vascular smooth muscle cell migration by calcium/ calmodulin-dependent protein kinase II-delta 2. Am J Physiol Cell Physiol 286, C1238-45 14761894 Curated Info
23	Said M, et al. (2003) Role of dual-site phospholamban phosphorylation in the stunned heart: insights from phospholamban site-specific mutants. Am J Physiol Heart Circ Physiol 285, H1198-205 12763747 Curated Info
24	Yang D, et al. (2003) Calmodulin regulation of excitation-contraction coupling in cardiac myocytes. Circ Res 92, 659-67 12609973 Curated Info
25	Said M, Mundiña-Weilenmann C, Vittone L, Mattiazzi A (2002) The relative relevance of phosphorylation of the Thr(17) residue of phospholamban is different at different levels of beta-adrenergic stimulation. Pflugers Arch 444, 801-9 12355181 Curated Info
26	Bokník P, et al. (2001) Enhanced protein phosphorylation in hypertensive hypertrophy. Cardiovasc Res 51, 717-28 11530105 Curated Info
27	Hagemann D, et al. (2000) Frequency-encoding Thr17 phospholamban phosphorylation is independent of Ser16 phosphorylation in cardiac myocytes. J Biol Chem 275, 22532-6 10825152 Curated Info
28	Ojamaa K, Kenessey A, Klein I (2000) Thyroid hormone regulation of phospholamban phosphorylation in the rat heart. Endocrinology 141, 2139-44 10830301 Curated Info
29	Vittone L, Mundiña-Weilenmann C, Said M, Mattiazzi A (1998) Mechanisms involved in the acidosis enhancement of the isoproterenol-induced phosphorylation of phospholamban in the intact heart. J Biol Chem 273, 9804-11 9545319 Curated Info