Ryanodine receptor 2

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Ryanodine receptor 2 (cardiac)
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols RYR2 ; ARVC2; ARVD2; RYR-2; RyR; VTSIP
External IDs OMIM180902 MGI99685 HomoloGene37423 IUPHAR: 748 ChEMBL: 4403 GeneCards: RYR2 Gene
Species Human Mouse
Entrez 6262 20191
Ensembl ENSG00000198626 ENSMUSG00000021313
UniProt Q92736 E9Q401
RefSeq (mRNA) NM_001035 NM_023868
RefSeq (protein) NP_001026 NP_076357
Location (UCSC) Chr 1:
237.04 – 237.83 Mb
Chr 13:
11.55 – 12.11 Mb
PubMed search [1] [2]

Ryanodine receptor 2 (RYR2) is a protein found primarily in cardiac muscle. In humans, it is encoded by the RYR2 gene.[1][2][3] In the process of cardiac calcium-induced calcium release, RYR2 is the major mediator for sarcoplasmic release of stored calcium ions.


The channel is composed of RYR2 homotetramers and FK506-binding proteins found in a 1:4 stoichiometric ratio. Calcium channel function is affected by the specific type of FK506 isomer interacting with the RYR2 protein, due to binding differences and other factors.[4]


The RYR2 protein functions as the major component of a calcium channel located in the sarcoplasmic reticulum that supplies ions to the cardiac muscle during systole. To enable cardiac muscle contraction, calcium influx through voltage-gated L-type calcium channels in the plasma membrane allows calcium ions to bind to RYR2 located on the sarcoplasmic reticulum. This binding causes the release of calcium through RYR2 from the sarcoplasmic reticulum into the cytosol, where it binds to the C domain of troponin, which shifts tropomyosin and allows the myosin ATPase to bind to actin, enabling cardiac muscle contraction.[5] RYR2 channels are associated with many cellular functions, including mitochondrial metabolism, gene expression and cell survival, in addition to their role in cardiomyocyte contraction.[6]

Clinical significance[edit]

Deleterious mutations of the ryanodine receptor family, and especially the RYR2 receptor, lead to a constellation of pathologies leading to both acute and chronic heart failure collectively known as "Ryanopathies."[7]

Mutations in the RYR2 gene are associated with catecholaminergic polymorphic ventricular tachycardia, stress-induced polymorphic ventricular tachycardia, and arrhythmogenic right ventricular dysplasia.[8]

Mice with genetically reduced RYR2 exhibit a lower basal heart rate and fatal arrythmias.[9]


Ryanodine receptor 2 has been shown to interact with:

See also[edit]


  1. ^ Otsu K, Willard HF, Khanna VK, Zorzato F, Green NM, MacLennan DH (September 1990). "Molecular cloning of cDNA encoding the Ca2+ release channel (ryanodine receptor) of rabbit cardiac muscle sarcoplasmic reticulum". J Biol Chem 265 (23): 13472–83. PMID 2380170. 
  2. ^ Otsu K, Fujii J, Periasamy M, Difilippantonio M, Uppender M, Ward DC, MacLennan DH (October 1993). "Chromosome mapping of five human cardiac and skeletal muscle sarcoplasmic reticulum protein genes". Genomics 17 (2): 507–9. doi:10.1006/geno.1993.1357. PMID 8406504. 
  3. ^ Tiso N, Stephan DA, Nava A, Bagattin A, Devaney JM, Stanchi F, Larderet G, Brahmbhatt B, Brown K, Bauce B, Muriago M, Basso C, Thiene G, Danieli GA, Rampazzo A (February 2001). "Identification of mutations in the cardiac ryanodine receptor gene in families affected with arrhythmogenic right ventricular cardiomyopathy type 2 (ARVD2)". Hum Mol Genet 10 (3): 189–94. doi:10.1093/hmg/10.3.189. PMID 11159936. 
  4. ^ Guo T, Cornea RL, Huke S, Camors E, Yang Y, Picht E, Fruen BR, Bers DM (June 2010). "Kinetics of FKBP12.6 binding to ryanodine receptors in permeabilized cardiac myocytes and effects on Ca sparks". Circ. Res. 106 (11): 1743–52. doi:10.1161/CIRCRESAHA.110.219816. PMC 2895429. PMID 20431056. 
  5. ^ "Q92736 - RYR2_HUMAN". 
  6. ^ Bround MJ, Wambolt R, Luciani DS, Kulpa JE, Rodrigues B, Brownsey RW, Allard MF, Johnson JD (15 May 2013). "Cardiomyocyte ATP production, metabolic flexibility, and survival require calcium flux through cardiac ryanodine receptors in vivo". Journal of Biological Chemistry 288 (26): 18975–86. doi:10.1074/jbc.M112.427062. PMID 23678000. 
  7. ^ Belevych AE, Radwański PB, Carnes CA, Györke S (2013). "'Ryanopathy': causes and manifestations of RyR2 dysfunction in heart failure". Cardiovasc. Res. 98 (2): 240–7. doi:10.1093/cvr/cvt024. PMC 3633158. PMID 23408344. 
  8. ^ "Entrez Gene: RYR2 ryanodine receptor 2 (cardiac)". 
  9. ^ Bround MJ, Asghari P, Wambolt RB, Bohunek L, Smits C, Philit M, Kieffer TJ, Lakatta EG, Boheler KR, Moore ED, Allard MF, Johnson JD (September 2012). "Cardiac ryanodine receptors control heart rate and rhythmicity in adult mice". Cardiovasc. Res. 96 (3): 372–80. doi:10.1093/cvr/cvs260. PMID 22869620. 
  10. ^ a b c d Marx SO, Reiken S, Hisamatsu Y, Jayaraman T, Burkhoff D, Rosemblit N, Marks AR (May 2000). "PKA phosphorylation dissociates FKBP12.6 from the calcium release channel (ryanodine receptor): defective regulation in failing hearts". Cell 101 (4): 365–76. doi:10.1016/S0092-8674(00)80847-8. PMID 10830164. 
  11. ^ Marx SO, Reiken S, Hisamatsu Y, Gaburjakova M, Gaburjakova J, Yang YM, Rosemblit N, Marks AR (May 2001). "Phosphorylation-dependent regulation of ryanodine receptors: a novel role for leucine/isoleucine zippers". J. Cell Biol. 153 (4): 699–708. doi:10.1083/jcb.153.4.699. PMC 2192391. PMID 11352932. 
  12. ^ Meyers MB, Pickel VM, Sheu SS, Sharma VK, Scotto KW, Fishman GI (November 1995). "Association of sorcin with the cardiac ryanodine receptor". J. Biol. Chem. 270 (44): 26411–8. doi:10.1074/jbc.270.44.26411. PMID 7592856. 

Further reading[edit]

External links[edit]