Ryanodine receptor 2
Ensembl | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| UniProt | |||||||||
| RefSeq (mRNA) | |||||||||
| RefSeq (protein) | |||||||||
| Location (UCSC) | Chr 1: 237.04 – 237.83 Mb | Chr 13: 11.55 – 12.11 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
Ryanodine receptor 2 (RYR2) is one of a class of
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
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
arrhythmogenic right ventricular dysplasia.[12]
Recently, sudden cardiac death in several young individuals in the Amish community (four of which were from the same family) was traced to homozygous duplication of a mutant RyR2 gene.[13] Normal (wild type) RyR2 functions primarily in the myocardium (heart muscle).
Mice with genetically reduced RYR2 exhibit a lower basal heart rate and fatal arrhythmias.[14]
Interactions
Ryanodine receptor 2 has been shown to
interact
with:
- Protein kinase A (AKAP6,[15][16] PRKACA,[15] PRKACB,[15] PRKACG,[15]) (phosphorylation at serine position S2808 in rodents[17])
- CaMKII (via phosphorylation at serine positions S2808 and S2814 in humans and rodents, S2809[18] and S2815[19] in rabbits)
- SRI[20]
- Protein phosphatase 1 (dephosphorylation at serine positions S2808 and S2814 in rodents[17])
- Protein phosphatase 2 (dephosphorylation at serine position S2814 in rodents<ref name = "Huke_2008" / >)
See also
References
- ^ 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:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 2380170.
- PMID 8406504.
- PMID 11159936.
- PMID 20431056.
- ^ "Q92736 - RYR2_HUMAN".
- PMID 23678000.
- PMID 23408344.
- ^ "Entrez Gene: RYR2 ryanodine receptor 2 (cardiac)".
- PMID 31913406.
- PMID 22869620.
- ^ S2CID 6496567.
- PMID 11352932.
- ^ PMID 18755143.
- PMID 1645727.
- PMID 15016728.
- PMID 7592856.
Further reading
- Ogawa Y, Kurebayashi N, Murayama T (1999). "Ryanodine receptor isoforms in excitation-contraction coupling". Advances in Biophysics. 36: 27–64. PMID 10463072.
- Marks AR, Priori S, Memmi M, Kontula K, Laitinen PJ (January 2002). "Involvement of the cardiac ryanodine receptor/calcium release channel in catecholaminergic polymorphic ventricular tachycardia". Journal of Cellular Physiology. 190 (1): 1–6. PMID 11807805.
- Marks AR (April 2002). "Ryanodine receptors, FKBP12, and heart failure". Frontiers in Bioscience. 7 (1–3): d970 – d977. PMID 11897558.
- Danieli GA, Rampazzo A (May 2002). "Genetics of arrhythmogenic right ventricular cardiomyopathy". Current Opinion in Cardiology. 17 (3): 218–221. PMID 12015469.
- Ma J, Hayek SM, Bhat MB (2005). "Membrane topology and membrane retention of the ryanodine receptor calcium release channel". Cell Biochemistry and Biophysics. 40 (2): 207–224. S2CID 25375622.
- Meyers MB, Pickel VM, Sheu SS, Sharma VK, Scotto KW, Fishman GI (November 1995). "Association of sorcin with the cardiac ryanodine receptor". The Journal of Biological Chemistry. 270 (44): 26411–26418. PMID 7592856.
- Rampazzo A, Nava A, Erne P, Eberhard M, Vian E, Slomp P, et al. (November 1995). "A new locus for arrhythmogenic right ventricular cardiomyopathy (ARVD2) maps to chromosome 1q42-q43". Human Molecular Genetics. 4 (11): 2151–2154. PMID 8589694.
- Tunwell RE, Wickenden C, Bertrand BM, Shevchenko VI, Walsh MB, Allen PD, et al. (September 1996). "The human cardiac muscle ryanodine receptor-calcium release channel: identification, primary structure and topological analysis". The Biochemical Journal. 318 ( Pt 2) (Pt 2): 477–487. PMID 8809036.
- Awad SS, Lamb HK, Morgan JM, Dunlop W, Gillespie JI (March 1997). "Differential expression of ryanodine receptor RyR2 mRNA in the non-pregnant and pregnant human myometrium". The Biochemical Journal. 322 ( Pt 3) (Pt 3): 777–783. PMID 9148749.
- Martin C, Chapman KE, Seckl JR, Ashley RH (July 1998). "Partial cloning and differential expression of ryanodine receptor/calcium-release channel genes in human tissues including the hippocampus and cerebellum". Neuroscience. 85 (1): 205–216. S2CID 25634042.
- Chambers P, Neal DE, Gillespie JI (January 1999). "Ryanodine receptors in human bladder smooth muscle". Experimental Physiology. 84 (1): 41–46. PMID 10081705.
- Mori F, Fukaya M, Abe H, Wakabayashi K, Watanabe M (May 2000). "Developmental changes in expression of the three ryanodine receptor mRNAs in the mouse brain". Neuroscience Letters. 285 (1): 57–60. S2CID 32514035.
- Marx SO, Reiken S, Hisamatsu Y, Jayaraman T, Burkhoff D, Rosemblit N, et al. (May 2000). "PKA phosphorylation dissociates FKBP12.6 from the calcium release channel (ryanodine receptor): defective regulation in failing hearts". Cell. 101 (4): 365–376. S2CID 6496567.
- Laitinen PJ, Brown KM, Piippo K, Swan H, Devaney JM, Brahmbhatt B, et al. (January 2001). "Mutations of the cardiac ryanodine receptor (RyR2) gene in familial polymorphic ventricular tachycardia". Circulation. 103 (4): 485–490. PMID 11157710.
- Priori SG, Napolitano C, Tiso N, Memmi M, Vignati G, Bloise R, et al. (January 2001). "Mutations in the cardiac ryanodine receptor gene (hRyR2) underlie catecholaminergic polymorphic ventricular tachycardia". Circulation. 103 (2): 196–200. PMID 11208676.
- Jeyakumar LH, Ballester L, Cheng DS, McIntyre JO, Chang P, Olivey HE, et al. (March 2001). "FKBP binding characteristics of cardiac microsomes from diverse vertebrates". Biochemical and Biophysical Research Communications. 281 (4): 979–986. PMID 11237759.
External links
- GeneReviews/NCBI/NIH/UW entry on Catecholaminergic Polymorphic Ventricular Tachycardia
- GeneReviews/NCBI/NIH/UW entry on Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy, Autosomal Dominant
- OMIM entries on Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy, Autosomal Dominant
- RYR2+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)