Ryanodine receptor 2

RYR2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesRYR2, ARVC2, ARVD2, RYR-2, RyR, VTSIP, ryanodine receptor 2
External IDsMGI: 99685 HomoloGene: 37423 GeneCards: RYR2
Gene location (Human)
Chr.Chromosome 1 (human)[1]
Band1q43Start237,042,205 bp[1]
End237,833,988 bp[1]
Orthologs
SpeciesHumanMouse
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 MbChr 13: 11.55 – 12.11 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Ryanodine receptor 2 (RYR2) is a protein found primarily in cardiac muscle. In humans, it is encoded by the RYR2 gene.[5][6][7] In the process of cardiac calcium-induced calcium release, RYR2 is the major mediator for sarcoplasmic release of stored calcium ions.

Structure

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.[8]

Function

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.[9] RYR2 channels are associated with many cellular functions, including mitochondrial metabolism, gene expression and cell survival, in addition to their role in cardiomyocyte contraction.[10]

Clinical significance

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."[11]

Mutations in the RYR2 gene are associated with catecholaminergic polymorphic ventricular tachycardia, stress-induced polymorphic ventricular tachycardia, and arrhythmogenic right ventricular dysplasia.[12]

Mice with genetically reduced RYR2 exhibit a lower basal heart rate and fatal arrythmias.[13]

Interactions

Ryanodine receptor 2 has been shown to interact with:

See also

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000198626 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000021313 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:".
  4. ↑ "Mouse PubMed Reference:".
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ "Q92736 - RYR2_HUMAN".
  10. ↑ 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. PMC 3696672. PMID 23678000.
  11. ↑ 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.
  12. ↑ "Entrez Gene: RYR2 ryanodine receptor 2 (cardiac)".
  13. ↑ 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. PMC 3500041. PMID 22869620.
  14. 1 2 3 4 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.
  15. ↑ 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.
  16. ↑ 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

  • Ogawa Y, Kurebayashi N, Murayama T (1999). "Ryanodine receptor isoforms in excitation-contraction coupling". Adv. Biophys. 36: 27–64. doi:10.1016/S0065-227X(99)80004-5. PMID 10463072.
  • Marks AR, Priori S, Memmi M, Kontula K, Laitinen PJ (2002). "Involvement of the cardiac ryanodine receptor/calcium release channel in catecholaminergic polymorphic ventricular tachycardia". J. Cell. Physiol. 190 (1): 1–6. doi:10.1002/jcp.10031. PMID 11807805.
  • Marks AR (2002). "Ryanodine receptors, FKBP12, and heart failure". Front. Biosci. 7: d970–7. doi:10.2741/marks. PMID 11897558.
  • Danieli GA, Rampazzo A (2002). "Genetics of arrhythmogenic right ventricular cardiomyopathy". Curr. Opin. Cardiol. 17 (3): 218–21. doi:10.1097/00001573-200205000-00002. PMID 12015469.
  • Ma J, Hayek SM, Bhat MB (2005). "Membrane topology and membrane retention of the ryanodine receptor calcium release channel". Cell Biochem. Biophys. 40 (2): 207–24. doi:10.1385/CBB:40:2:207. PMID 15054223.
  • Meyers MB, Pickel VM, Sheu SS, Sharma VK, Scotto KW, Fishman GI (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.
  • Rampazzo A, Nava A, Erne P, Eberhard M, Vian E, Slomp P, Tiso N, Thiene G, Danieli GA (1996). "A new locus for arrhythmogenic right ventricular cardiomyopathy (ARVD2) maps to chromosome 1q42-q43". Hum. Mol. Genet. 4 (11): 2151–4. doi:10.1093/hmg/4.11.2151. PMID 8589694.
  • Tunwell RE, Wickenden C, Bertrand BM, Shevchenko VI, Walsh MB, Allen PD, Lai FA (1996). "The human cardiac muscle ryanodine receptor-calcium release channel: identification, primary structure and topological analysis". Biochem. J. 318 (Pt 2): 477–87. PMC 1217646. PMID 8809036.
  • Awad SS, Lamb HK, Morgan JM, Dunlop W, Gillespie JI (1997). "Differential expression of ryanodine receptor RyR2 mRNA in the non-pregnant and pregnant human myometrium". Biochem. J. 322 (Pt 3): 777–83. PMC 1218255. PMID 9148749.
  • Martin C, Chapman KE, Seckl JR, Ashley RH (1998). "Partial cloning and differential expression of ryanodine receptor/calcium-release channel genes in human tissues including the hippocampus and cerebellum". Neuroscience. 85 (1): 205–16. doi:10.1016/S0306-4522(97)00612-X. PMID 9607712.
  • Chambers P, Neal DE, Gillespie JI (1999). "Ryanodine receptors in human bladder smooth muscle". Exp. Physiol. 84 (1): 41–6. doi:10.1111/j.1469-445x.1999.tb00070.x. PMID 10081705.
  • Mori F, Fukaya M, Abe H, Wakabayashi K, Watanabe M (2000). "Developmental changes in expression of the three ryanodine receptor mRNAs in the mouse brain". Neurosci. Lett. 285 (1): 57–60. doi:10.1016/S0304-3940(00)01046-6. PMID 10788707.
  • Marx SO, Reiken S, Hisamatsu Y, Jayaraman T, Burkhoff D, Rosemblit N, Marks AR (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.
  • Laitinen PJ, Brown KM, Piippo K, Swan H, Devaney JM, Brahmbhatt B, Donarum EA, Marino M, Tiso N, Viitasalo M, Toivonen L, Stephan DA, Kontula K (2001). "Mutations of the cardiac ryanodine receptor (RyR2) gene in familial polymorphic ventricular tachycardia". Circulation. 103 (4): 485–90. doi:10.1161/01.cir.103.4.485. PMID 11157710.
  • Priori SG, Napolitano C, Tiso N, Memmi M, Vignati G, Bloise R, Sorrentino V, Danieli GA (2004). "Mutations in the cardiac ryanodine receptor gene (hRyR2) underlie catecholaminergic polymorphic ventricular tachycardia". Circulation. 103 (2): 196–200. doi:10.1161/01.cir.103.2.196. PMID 11208676.
  • Jeyakumar LH, Ballester L, Cheng DS, McIntyre JO, Chang P, Olivey HE, Rollins-Smith L, Barnett JV, Murray K, Xin HB, Fleischer S (2001). "FKBP binding characteristics of cardiac microsomes from diverse vertebrates". Biochem. Biophys. Res. Commun. 281 (4): 979–86. doi:10.1006/bbrc.2001.4444. PMID 11237759.
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