Ryanodine receptor 2

RYR2
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	4JKQ
Identifiers
Aliases	RYR2, ARVC2, ARVD2, RYR-2, RyR, VTSIP, ryanodine receptor 2
External IDs	MGI: 99685 HomoloGene: 37423 GeneCards: RYR2
Gene location (Human)
Chr.	Chromosome 1 (human)
End	237,833,988 bp
Gene location (Mouse)
Chr.	Chromosome 13 (mouse)
End	12,106,945 bp
Gene ontology
Molecular function	• ion channel binding; • calcium channel activity; • calcium-induced calcium release activity; • protein kinase A catalytic subunit binding; • organic cyclic compound binding; • protein self-association; • ion channel activity; • protein binding; • identical protein binding; • enzyme binding; • suramin binding; • protein kinase A regulatory subunit binding; • protein kinase binding; • calcium-release channel activity; • ryanodine-sensitive calcium-release channel activity; • calcium ion binding; • calmodulin binding;
Cellular component	• integral component of membrane; • calcium channel complex; • membrane; • sarcomere; • junctional sarcoplasmic reticulum membrane; • sarcoplasmic reticulum; • Z disc; • sarcoplasmic reticulum membrane; • smooth endoplasmic reticulum; • plasma membrane; • macromolecular complex; • cytoplasmic vesicle membrane; • sarcolemma;
Biological process	• response to muscle stretch; • cytosolic calcium ion transport; • release of sequestered calcium ion into cytosol; • calcium ion transport into cytosol; • regulation of cardiac conduction; • regulation of cardiac muscle contraction by calcium ion signaling; • release of sequestered calcium ion into cytosol by sarcoplasmic reticulum; • response to hypoxia; • cardiac muscle contraction; • regulation of cytosolic calcium ion concentration; • positive regulation of the force of heart contraction; • regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion; • cardiac muscle hypertrophy; • ventricular cardiac muscle cell action potential; • cell communication by electrical coupling involved in cardiac conduction; • cellular calcium ion homeostasis; • establishment of protein localization to endoplasmic reticulum; • ion transport; • BMP signaling pathway; • left ventricular cardiac muscle tissue morphogenesis; • regulation of heart rate; • positive regulation of heart rate; • detection of calcium ion; • response to redox state; • cellular response to epinephrine stimulus; • multicellular organism development; • ion transmembrane transport; • positive regulation of sequestering of calcium ion; • embryonic heart tube morphogenesis; • calcium ion transmembrane transport; • cellular response to caffeine; • sarcoplasmic reticulum calcium ion transport; • canonical Wnt signaling pathway; • regulation of SA node cell action potential; • response to caffeine; • regulation of cardiac muscle contraction; • regulation of ventricular cardiac muscle cell action potential; • regulation of AV node cell action potential; • calcium-mediated signaling using intracellular calcium source; • response to muscle activity; • calcium ion transport; • calcium-mediated signaling; • type B pancreatic cell apoptotic process; • regulation of atrial cardiac muscle cell action potential; • positive regulation of calcium-transporting ATPase activity; • Purkinje myocyte to ventricular cardiac muscle cell signaling; • transmembrane transport;
	Sources:Amigo / QuickGO
Orthologs
	6262
	20191
	ENSG00000198626
	ENSMUSG00000021313
	Q92736
	E9Q401
	NM_001035
	NM_023868
	NP_001026
	NP_076357
	Wikidata
View/Edit Human	View/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[edit]

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[edit]

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[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."^[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[edit]

Ryanodine receptor 2 has been shown to interact with:

References[edit]

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000198626 - Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000021313 - Ensembl, May 2017
^ "Human PubMed Reference:".
^ "Mouse PubMed Reference:".
^ 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.
^ 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.
^ 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.
^ 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.
^ "Q92736 - RYR2_HUMAN".
^ 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.
^ 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.
^ "Entrez Gene: RYR2 ryanodine receptor 2 (cardiac)".
^ 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.
^ ^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.
^ 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.
^ 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.

External links[edit]

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000198626 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000021313 - Ensembl, May 2017

[3] "Human PubMed Reference:".

[4] "Mouse PubMed Reference:".

[pmid2380170-5] 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.

[pmid8406504-6] 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.

[pmid11159936-7] 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.

[pmid2043105622-8] 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.

[Uniprot2-9] "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.

[pmid23408344-11] 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.

[entrez-12] "Entrez Gene: RYR2 ryanodine receptor 2 (cardiac)".

[pmid22869620-13] 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.

[pmid10830164-14] 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.

[pmid11352932-15] 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.

[pmid7592856-16] 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.

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Ryanodine receptor 2

Contents

Structure[edit]

Function[edit]

Clinical significance[edit]

Interactions[edit]

See also[edit]

References[edit]

Further reading[edit]

External links[edit]

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