Ryanodine receptor 2

Function

Cytosolic calcium-activated calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytosol and thereby plays a key role in triggering cardiac muscle contraction. Aberrant channel activation can lead to cardiac arrhythmia. In cardiac myocytes, calcium release is triggered by increased Ca(2+) cytosolic levels due to activation of the L-type calcium channel CACNA1C. The calcium channel activity is modulated by formation of heterotetramers with RYR3. Required for cellular calcium ion homeostasis. Required for embryonic heart development.

Classification

Family (Pfam)

PF13499 EF-hand_7, PF08709 Ins145_P3_rec, PF00520 Ion_trans, PF02815 MIR, PF08454 RIH_assoc, PF06459 RR_TM4-6, PF01365 RYDR_ITPR, PF21119 RYDR_Jsol, PF02026 RyR, PF00622 SPRY

InterPro

B30.2/SPRY, B30.2/SPRY_sf, ConA-like_dom_sf, EF-hand-dom_pair, EF_hand_dom, Ins145_P3_rcpt, Ion_trans_dom, MIR_dom_sf, MIR_motif, RIH_assoc-dom, RIH_dom, Ryan_recept, Ryanodine_IP3_receptor, Ryanodine_rcpt, Ryanrecept_TM4-6, RYDR_Jsol, RyR/IP3R_RIH_dom_sf, SPRY1_RyR, SPRY2_RyR, SPRY3_RyR, SPRY_dom

Functional cluster

S-Adenosylmethionine Synthases & related

Experimental structures · PDB · 26

• 4JKQ X-ray 2.39A
• 6Y4O X-ray 1.84A
• 6Y4P X-ray 2.13A
• 7KL5 X-ray 1.65A
• 7U9Q EM 3.11A
• 7U9R EM 3.69A
• 7U9T EM 2.68A
• 7U9X EM 2.58A
• 7U9Z EM 3.29A
• 7UA1 EM 2.99A
• 7UA3 EM 2.97A
• 7UA4 EM 2.93A
• … and 14 more

A predicted model is available from AlphaFold.

Gene Ontology · 57

• GO:0034704 calcium channel complex
• GO:0014701 junctional sarcoplasmic reticulum membrane
• GO:0016020 membrane
• GO:0005886 plasma membrane
• GO:0032991 protein-containing complex
• GO:0042383 sarcolemma
• GO:0016529 sarcoplasmic reticulum
• GO:0033017 sarcoplasmic reticulum membrane
• GO:0005790 smooth endoplasmic reticulum
• GO:0030018 Z disc
• GO:0005262 calcium channel activity
• GO:0005509 calcium ion binding
• GO:0048763 calcium-induced calcium release activity
• GO:0005516 calmodulin binding
• GO:0019899 enzyme binding
• GO:0042802 identical protein binding
• GO:0015278 intracellularly gated calcium channel activity
• GO:0034236 protein kinase A catalytic subunit binding
• GO:0034237 protein kinase A regulatory subunit binding
• GO:0005219 ryanodine-sensitive calcium-release channel activity
• GO:0043924 suramin binding
• GO:0044325 transmembrane transporter binding
• GO:0006816 calcium ion transport
• GO:0060402 calcium ion transport into cytosol
• GO:0019722 calcium-mediated signaling
• GO:0060048 cardiac muscle contraction
• GO:0003300 cardiac muscle hypertrophy
• GO:0086064 cell communication by electrical coupling involved in cardiac conduction
• GO:0071313 cellular response to caffeine
• GO:0071872 cellular response to epinephrine stimulus
• GO:0005513 detection of calcium ion
• GO:0003143 embryonic heart tube morphogenesis
• GO:0006874 intracellular calcium ion homeostasis
• GO:0003220 left ventricular cardiac muscle tissue morphogenesis
• GO:0010460 positive regulation of heart rate
• GO:0098735 positive regulation of the force of heart contraction
• GO:0086029 Purkinje myocyte to ventricular cardiac muscle cell signaling
• GO:0098910 regulation of atrial cardiac muscle cell action potential
• GO:0098904 regulation of AV node cell action potential
• GO:0055117 regulation of cardiac muscle contraction
• GO:0010882 regulation of cardiac muscle contraction by calcium ion signaling
• GO:0010881 regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion
• GO:0051480 regulation of cytosolic calcium ion concentration
• GO:0002027 regulation of heart rate
• GO:0098907 regulation of SA node cell action potential
• GO:0098911 regulation of ventricular cardiac muscle cell action potential
• GO:0051209 release of sequestered calcium ion into cytosol
• GO:0014808 release of sequestered calcium ion into cytosol by sarcoplasmic reticulum
• GO:0031000 response to caffeine
• GO:0001666 response to hypoxia
• GO:0014850 response to muscle activity
• GO:0035994 response to muscle stretch
• GO:0051775 response to redox state
• GO:0070296 sarcoplasmic reticulum calcium ion transport
• GO:0006941 striated muscle contraction
• GO:0097050 type B pancreatic cell apoptotic process
• GO:0086005 ventricular cardiac muscle cell action potential

Disease associations

• ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome MONDO:0020745
• catecholaminergic polymorphic ventricular tachycardia 1 MONDO:0011484

Neighborhood · nearest proteins

Related proteins · sequence + function similarity

• Ryanodine receptor 2 1.00
• Ryanodine receptor 2 1.00
• Ryanodine receptor 2 1.00
• Ryanodine receptor 3 0.98
• Ryanodine receptor 3 0.98
• Ryanodine receptor 3 0.97
• Ryanodine receptor 1 0.95
• Ryanodine receptor 1 0.95
• Ryanodine receptor 1 0.95
• Ryanodine receptor 1 0.95
• Ryanodine receptor 1 0.94
• Ryanodine receptor 0.93

Co-cited proteins · studied together in the literature

• Peptidyl-prolyl cis-trans isomerase FKBP1B 1 shared papers
• Calsequestrin-2 1 shared papers
• Ryanodine receptor 1 3 shared papers
• Calcium/calmodulin-dependent protein kinase type II subunit delta 1 shared papers
• Ryanodine receptor 2 1 shared papers
• Ryanodine receptor 3 1 shared papers
• Ryanodine receptor 2 1 shared papers
• Protein S100-A1 1 shared papers
• Calmodulin-2 1 shared papers
• Calmodulin-3 1 shared papers
• Protein S100-A1 1 shared papers
• Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform 1 shared papers

Literature · 30 cited papers

• Cardiac ryanodine receptor calcium release deficiency syndrome. Sci. Transl. Med. · 2021
• Enhanced cytosolic Ca2+ activation underlies a common defect of central domain cardiac ryanodine receptor mutations linked to arrhythmias. J. Biol. Chem. · 2016
• The H29D mutation does not enhance cytosolic Ca2+ activation of the cardiac ryanodine receptor. PLoS ONE · 2015
• Short-coupled polymorphic ventricular tachycardia at rest linked to a novel ryanodine receptor (RyR2) mutation: leaky RyR2 channels under non-stress conditions. Int. J. Cardiol. · 2015
• Structural insights into the human RyR2 N-terminal region involved in cardiac arrhythmias. Acta Crystallogr. D · 2014
• De novo mutations in moderate or severe intellectual disability. PLoS Genet. · 2014
• A novel RyR2 mutation in a 2-year-old baby presenting with atrial fibrillation, atrial flutter, and atrial ectopic tachycardia. Heart Rhythm · 2014
• Modulation of ryanodine receptor Ca2+ channels. Mol. Med. Report. · 2010
• Ryanodine receptors: structure, expression, molecular details, and function in calcium release. Cold Spring Harb. Perspect. Biol. · 2010
• CaMKII-dependent diastolic SR Ca2+ leak and elevated diastolic Ca2+ levels in right atrial myocardium of patients with atrial fibrillation. Circ. Res. · 2010
• Cardiac ryanodine receptor phosphorylation by CaM Kinase II: keeping the balance right. Front. Biosci. · 2009
• S100A1 and calmodulin compete for the same binding site on ryanodine receptor. J. Biol. Chem. · 2008
• … and 18 more in the literature graph