Ryanodine receptor 2: Difference between revisions

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{{Infobox_gene}}
{{PBB_Controls
'''Ryanodine receptor 2''' (RYR2) is a [[protein]] found primarily in [[Myocardium|cardiac muscle]]. In humans, it is encoded by the ''RYR2'' [[gene]].<ref name="pmid2380170">{{cite journal | vauthors = Otsu K, Willard HF, Khanna VK, Zorzato F, Green NM, MacLennan DH | title = Molecular cloning of cDNA encoding the Ca2+ release channel (ryanodine receptor) of rabbit cardiac muscle sarcoplasmic reticulum | journal = J Biol Chem | volume = 265 | issue = 23 | pages = 13472–83 | date = September 1990 | pmid = 2380170 | pmc =  | doi =  }}</ref><ref name="pmid8406504">{{cite journal | vauthors = Otsu K, Fujii J, Periasamy M, Difilippantonio M, Uppender M, Ward DC, MacLennan DH | title = Chromosome mapping of five human cardiac and skeletal muscle sarcoplasmic reticulum protein genes | journal = Genomics | volume = 17 | issue = 2 | pages = 507–9 | date = October 1993 | pmid = 8406504 | pmc =  | doi = 10.1006/geno.1993.1357 }}</ref><ref name="pmid11159936">{{cite journal | vauthors = 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 | title = Identification of mutations in the cardiac ryanodine receptor gene in families affected with arrhythmogenic right ventricular cardiomyopathy type 2 (ARVD2) | journal = Hum Mol Genet | volume = 10 | issue = 3 | pages = 189–94 | date = February 2001 | pmid = 11159936 | pmc = | doi = 10.1093/hmg/10.3.189 }}</ref> In the process of cardiac [[calcium-induced calcium release]], RYR2 is the major mediator for sarcoplasmic release of stored calcium ions.
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Structure ==
{{GNF_Protein_box
| image =
| image_source =
| PDB =  
| Name = Ryanodine receptor 2 (cardiac)
| HGNCid = 10484
| Symbol = RYR2
| AltSymbols =; ARVD2; ARVC2; VTSIP
| OMIM = 180902
| ECnumber = 
| Homologene = 37423
| MGIid = 99685
| Function = {{GNF_GO|id=GO:0004872 |text = receptor activity}} {{GNF_GO|id=GO:0005216 |text = ion channel activity}} {{GNF_GO|id=GO:0005219 |text = ryanodine-sensitive calcium-release channel activity}} {{GNF_GO|id=GO:0005509 |text = calcium ion binding}} {{GNF_GO|id=GO:0005516 |text = calmodulin binding}} {{GNF_GO|id=GO:0015278 |text = calcium-release channel activity}}
| Component = {{GNF_GO|id=GO:0005886 |text = plasma membrane}} {{GNF_GO|id=GO:0005887 |text = integral to plasma membrane}}
| Process = {{GNF_GO|id=GO:0006811 |text = ion transport}} {{GNF_GO|id=GO:0006816 |text = calcium ion transport}} {{GNF_GO|id=GO:0006874 |text = cellular calcium ion homeostasis}} {{GNF_GO|id=GO:0006936 |text = muscle contraction}} {{GNF_GO|id=GO:0007165 |text = signal transduction}} {{GNF_GO|id=GO:0008016 |text = regulation of heart contraction}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 6262
    | Hs_Ensembl = ENSG00000198626
    | Hs_RefseqProtein = NP_001026
    | Hs_RefseqmRNA = NM_001035
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 1
    | Hs_GenLoc_start = 235272128
    | Hs_GenLoc_end = 236063911
    | Hs_Uniprot = Q92736
    | Mm_EntrezGene = 20191
    | Mm_Ensembl = ENSMUSG00000021313
    | Mm_RefseqmRNA = NM_023868
    | Mm_RefseqProtein = NP_076357
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 13
    | Mm_GenLoc_start = 11608677
    | Mm_GenLoc_end = 12000036
    | Mm_Uniprot = 
  }}
}}
'''Ryanodine receptor 2 (cardiac)''', also known as '''RYR2''', is a human [[gene]].


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
The channel is composed of RYR2 homotetramers and&nbsp;[[FK506 binding protein|FK506-binding proteins]]&nbsp;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.<ref name="pmid2043105622">{{cite journal | vauthors = Guo T, Cornea RL, Huke S, Camors E, Yang Y, Picht E, Fruen BR, Bers DM | title = Kinetics of FKBP12.6 binding to ryanodine receptors in permeabilized cardiac myocytes and effects on Ca sparks | journal = Circ. Res. | volume = 106 | issue = 11 | pages = 1743–52 | date = June 2010 | pmid = 20431056 | pmc = 2895429 | doi = 10.1161/CIRCRESAHA.110.219816 }}</ref>
{{PBB_Summary
| section_title =
| summary_text = This gene encodes a ryanodine receptor found in cardiac muscle sarcoplasmic reticulum. The encoded protein is one of the components of a calcium channel, composed of a tetramer of the ryanodine receptor proteins and a tetramer of FK506 binding protein 1B proteins, that supplies calcium to cardiac muscle. Mutations in this gene are associated with stress-induced polymorphic ventricular tachycardia and arrhythmogenic right ventricular dysplasia.<ref name="entrez">{{cite web | title = Entrez Gene: RYR2 ryanodine receptor 2 (cardiac)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6262| accessdate = }}</ref>
}}


==See also==
== Function ==
 
The RYR2 protein functions as the major component of a calcium channel located in the [[sarcoplasmic reticulum]] that supplies ions to the [[Myocardium|cardiac muscle]] during [[systole]].&nbsp;To enable cardiac muscle contraction, calcium influx through voltage-gated&nbsp;[[L-type calcium channel]]s&nbsp;in the plasma membrane allows calcium ions to bind to RYR2 located on the&nbsp;[[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&nbsp;[[troponin]], which shifts [[tropomyosin]] and allows the [[myosin]] [[ATPase]] to bind to [[actin]], enabling cardiac muscle contraction.<ref name="Uniprot2">{{cite web | title = Q92736 - RYR2_HUMAN| url = http://www.uniprot.org/uniprot/Q92736}}</ref> RYR2 channels are associated with many cellular functions, including mitochondrial metabolism, gene expression and cell survival, in addition to their role in cardiomyocyte contraction.<ref>{{cite journal | vauthors = Bround MJ, Wambolt R, Luciani DS, Kulpa JE, Rodrigues B, Brownsey RW, Allard MF, Johnson JD | title = Cardiomyocyte ATP production, metabolic flexibility, and survival require calcium flux through cardiac ryanodine receptors in vivo | journal = Journal of Biological Chemistry | volume = 288 | issue = 26 | pages = 18975–86 | date = 15 May 2013 | pmid = 23678000 | doi = 10.1074/jbc.M112.427062 | pmc=3696672}}</ref>
 
== 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."<ref name="pmid23408344">{{cite journal | vauthors = Belevych AE, Radwański PB, Carnes CA, Györke S | title = 'Ryanopathy': causes and manifestations of RyR2 dysfunction in heart failure | journal = Cardiovasc. Res. | volume = 98 | issue = 2 | pages = 240–7 | year = 2013 | pmid = 23408344 | pmc = 3633158 | doi = 10.1093/cvr/cvt024 }}</ref>
 
Mutations in the ''RYR2'' gene are associated with [[catecholaminergic polymorphic ventricular tachycardia]], [[stress-induced polymorphic ventricular tachycardia]], and [[arrhythmogenic right ventricular dysplasia]].<ref name="entrez">{{cite web | title = Entrez Gene: RYR2 ryanodine receptor 2 (cardiac)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6262| accessdate = }}</ref>
 
Mice with genetically reduced RYR2 exhibit a lower basal heart rate and fatal arrythmias.<ref name="pmid22869620">{{cite journal | vauthors = Bround MJ, Asghari P, Wambolt RB, Bohunek L, Smits C, Philit M, Kieffer TJ, Lakatta EG, Boheler KR, Moore ED, Allard MF, Johnson JD | title = Cardiac ryanodine receptors control heart rate and rhythmicity in adult mice | journal = Cardiovasc. Res. | volume = 96 | issue = 3 | pages = 372–80 | date = September 2012 | pmid = 22869620 | doi = 10.1093/cvr/cvs260 }}</ref>
 
== Interactions ==
 
Ryanodine receptor 2 has been shown to [[Protein-protein interaction|interact]] with:
 
* [[AKAP6]],<ref name=pmid10830164/><ref name="pmid11352932">{{cite journal | vauthors = Marx SO, Reiken S, Hisamatsu Y, Gaburjakova M, Gaburjakova J, Yang YM, Rosemblit N, Marks AR | title = Phosphorylation-dependent regulation of ryanodine receptors: a novel role for leucine/isoleucine zippers | journal = J. Cell Biol. | volume = 153 | issue = 4 | pages = 699–708 | date = May 2001 | pmid = 11352932 | pmc = 2192391 | doi = 10.1083/jcb.153.4.699 }}</ref>
* [[PRKACA]],<ref name="pmid10830164">{{cite journal | vauthors = Marx SO, Reiken S, Hisamatsu Y, Jayaraman T, Burkhoff D, Rosemblit N, Marks AR | title = PKA phosphorylation dissociates FKBP12.6 from the calcium release channel (ryanodine receptor): defective regulation in failing hearts | journal = Cell | volume = 101 | issue = 4 | pages = 365–76 | date = May 2000 | pmid = 10830164 | doi = 10.1016/S0092-8674(00)80847-8 }}</ref>
* [[PRKACB]],<ref name=pmid10830164/>
* [[PRKACG]],<ref name=pmid10830164/> and
* [[SRI (gene)|SRI]].<ref name="pmid7592856">{{cite journal | vauthors = Meyers MB, Pickel VM, Sheu SS, Sharma VK, Scotto KW, Fishman GI | title = Association of sorcin with the cardiac ryanodine receptor | journal = J. Biol. Chem. | volume = 270 | issue = 44 | pages = 26411–8 | date = November 1995 | pmid = 7592856 | doi = 10.1074/jbc.270.44.26411 }}</ref>
 
== See also ==
*[[Ryanodine receptor]]
*[[Ryanodine receptor]]


==References==
== References ==
{{reflist|2}}
{{Reflist|35em}}
==Further reading==
 
{{refbegin | 2}}
== Further reading ==
{{PBB_Further_reading
{{Refbegin|35em}}
| citations =
* {{cite journal | vauthors = Ogawa Y, Kurebayashi N, Murayama T | title = Ryanodine receptor isoforms in excitation-contraction coupling | journal = Adv. Biophys. | volume = 36 | issue =  | pages = 27–64 | year = 1999 | pmid = 10463072 | doi = 10.1016/S0065-227X(99)80004-5 }}
*{{cite journal | author=Ogawa Y, Kurebayashi N, Murayama T |title=Ryanodine receptor isoforms in excitation-contraction coupling. |journal=Adv. Biophys. |volume=36 |issue=  |pages= 27-64 |year= 1999 |pmid= 10463072 |doi= }}
* {{cite journal | vauthors = Marks AR, Priori S, Memmi M, Kontula K, Laitinen PJ | title = Involvement of the cardiac ryanodine receptor/calcium release channel in catecholaminergic polymorphic ventricular tachycardia | journal = J. Cell. Physiol. | volume = 190 | issue = 1 | pages = 1–6 | year = 2002 | pmid = 11807805 | doi = 10.1002/jcp.10031 }}
*{{cite journal | author=Marks AR, Priori S, Memmi M, ''et al.'' |title=Involvement of the cardiac ryanodine receptor/calcium release channel in catecholaminergic polymorphic ventricular tachycardia. |journal=J. Cell. Physiol. |volume=190 |issue= 1 |pages= 1-6 |year= 2002 |pmid= 11807805 |doi= 10.1002/jcp.10031 }}
* {{cite journal | vauthors = Marks AR | title = Ryanodine receptors, FKBP12, and heart failure | journal = Front. Biosci. | volume = 7 | issue =  | pages = d970–7 | year = 2002 | pmid = 11897558 | doi = 10.2741/marks }}
*{{cite journal | author=Marks AR |title=Ryanodine receptors, FKBP12, and heart failure. |journal=Front. Biosci. |volume=7 |issue=  |pages= d970-7 |year= 2002 |pmid= 11897558 |doi= }}
* {{cite journal | vauthors = Danieli GA, Rampazzo A | title = Genetics of arrhythmogenic right ventricular cardiomyopathy | journal = Curr. Opin. Cardiol. | volume = 17 | issue = 3 | pages = 218–21 | year = 2002 | pmid = 12015469 | doi = 10.1097/00001573-200205000-00002 }}
*{{cite journal | author=Danieli GA, Rampazzo A |title=Genetics of arrhythmogenic right ventricular cardiomyopathy. |journal=Curr. Opin. Cardiol. |volume=17 |issue= 3 |pages= 218-21 |year= 2002 |pmid= 12015469 |doi= }}
* {{cite journal | vauthors = Ma J, Hayek SM, Bhat MB | title = Membrane topology and membrane retention of the ryanodine receptor calcium release channel | journal = Cell Biochem. Biophys. | volume = 40 | issue = 2 | pages = 207–24 | year = 2005 | pmid = 15054223 | doi = 10.1385/CBB:40:2:207 }}
*{{cite journal | author=Ma J, Hayek SM, Bhat MB |title=Membrane topology and membrane retention of the ryanodine receptor calcium release channel. |journal=Cell Biochem. Biophys. |volume=40 |issue= 2 |pages= 207-24 |year= 2005 |pmid= 15054223 |doi= }}
* {{cite journal | vauthors = Meyers MB, Pickel VM, Sheu SS, Sharma VK, Scotto KW, Fishman GI | title = Association of sorcin with the cardiac ryanodine receptor | journal = J. Biol. Chem. | volume = 270 | issue = 44 | pages = 26411–8 | year = 1995 | pmid = 7592856 | doi = 10.1074/jbc.270.44.26411 }}
*{{cite journal  | author=Otsu K, Willard HF, Khanna VK, ''et al.'' |title=Molecular cloning of cDNA encoding the Ca2+ release channel (ryanodine receptor) of rabbit cardiac muscle sarcoplasmic reticulum. |journal=J. Biol. Chem. |volume=265 |issue= 23 |pages= 13472-83 |year= 1990 |pmid= 2380170 |doi=  }}
* {{cite journal | vauthors = Rampazzo A, Nava A, Erne P, Eberhard M, Vian E, Slomp P, Tiso N, Thiene G, Danieli GA | title = A new locus for arrhythmogenic right ventricular cardiomyopathy (ARVD2) maps to chromosome 1q42-q43 | journal = Hum. Mol. Genet. | volume = 4 | issue = 11 | pages = 2151–4 | year = 1996 | pmid = 8589694 | doi = 10.1093/hmg/4.11.2151 }}
*{{cite journal | author=Meyers MB, Pickel VM, Sheu SS, ''et al.'' |title=Association of sorcin with the cardiac ryanodine receptor. |journal=J. Biol. Chem. |volume=270 |issue= 44 |pages= 26411-8 |year= 1995 |pmid= 7592856 |doi=  }}
* {{cite journal | vauthors = Tunwell RE, Wickenden C, Bertrand BM, Shevchenko VI, Walsh MB, Allen PD, Lai FA | title = The human cardiac muscle ryanodine receptor-calcium release channel: identification, primary structure and topological analysis | journal = Biochem. J. | volume = 318 | issue = Pt 2 | pages = 477–87 | year = 1996 | pmid = 8809036 | pmc = 1217646 | doi =  }}
*{{cite journal  | author=Otsu K, Fujii J, Periasamy M, ''et al.'' |title=Chromosome mapping of five human cardiac and skeletal muscle sarcoplasmic reticulum protein genes. |journal=Genomics |volume=17 |issue= 2 |pages= 507-9 |year= 1993 |pmid= 8406504 |doi= 10.1006/geno.1993.1357 }}
* {{cite journal | vauthors = Awad SS, Lamb HK, Morgan JM, Dunlop W, Gillespie JI | title = Differential expression of ryanodine receptor RyR2 mRNA in the non-pregnant and pregnant human myometrium | journal = Biochem. J. | volume = 322 | issue = Pt 3 | pages = 777–83 | year = 1997 | pmid = 9148749 | pmc = 1218255 | doi =  }}
*{{cite journal | author=Rampazzo A, Nava A, Erne P, ''et al.'' |title=A new locus for arrhythmogenic right ventricular cardiomyopathy (ARVD2) maps to chromosome 1q42-q43. |journal=Hum. Mol. Genet. |volume=4 |issue= 11 |pages= 2151-4 |year= 1996 |pmid= 8589694 |doi= }}
* {{cite journal | vauthors = Martin C, Chapman KE, Seckl JR, Ashley RH | title = Partial cloning and differential expression of ryanodine receptor/calcium-release channel genes in human tissues including the hippocampus and cerebellum | journal = Neuroscience | volume = 85 | issue = 1 | pages = 205–16 | year = 1998 | pmid = 9607712 | doi = 10.1016/S0306-4522(97)00612-X }}
*{{cite journal | author=Tunwell RE, Wickenden C, Bertrand BM, ''et al.'' |title=The human cardiac muscle ryanodine receptor-calcium release channel: identification, primary structure and topological analysis. |journal=Biochem. J. |volume=318 ( Pt 2) |issue= |pages= 477-87 |year= 1996 |pmid= 8809036 |doi=  }}
* {{cite journal | vauthors = Chambers P, Neal DE, Gillespie JI | title = Ryanodine receptors in human bladder smooth muscle | journal = Exp. Physiol. | volume = 84 | issue = 1 | pages = 41–6 | year = 1999 | pmid = 10081705 | doi =  10.1111/j.1469-445x.1999.tb00070.x}}
*{{cite journal | author=Awad SS, Lamb HK, Morgan JM, ''et al.'' |title=Differential expression of ryanodine receptor RyR2 mRNA in the non-pregnant and pregnant human myometrium. |journal=Biochem. J. |volume=322 ( Pt 3) |issue= |pages= 777-83 |year= 1997 |pmid= 9148749 |doi=  }}
* {{cite journal | vauthors = Mori F, Fukaya M, Abe H, Wakabayashi K, Watanabe M | title = Developmental changes in expression of the three ryanodine receptor mRNAs in the mouse brain | journal = Neurosci. Lett. | volume = 285 | issue = 1 | pages = 57–60 | year = 2000 | pmid = 10788707 | doi = 10.1016/S0304-3940(00)01046-6 }}
*{{cite journal | author=Martin C, Chapman KE, Seckl JR, Ashley RH |title=Partial cloning and differential expression of ryanodine receptor/calcium-release channel genes in human tissues including the hippocampus and cerebellum. |journal=Neuroscience |volume=85 |issue= 1 |pages= 205-16 |year= 1998 |pmid= 9607712 |doi= }}
* {{cite journal | vauthors = Marx SO, Reiken S, Hisamatsu Y, Jayaraman T, Burkhoff D, Rosemblit N, Marks AR | title = PKA phosphorylation dissociates FKBP12.6 from the calcium release channel (ryanodine receptor): defective regulation in failing hearts | journal = Cell | volume = 101 | issue = 4 | pages = 365–76 | year = 2000 | pmid = 10830164 | doi = 10.1016/S0092-8674(00)80847-8 }}
*{{cite journal | author=Chambers P, Neal DE, Gillespie JI |title=Ryanodine receptors in human bladder smooth muscle. |journal=Exp. Physiol. |volume=84 |issue= 1 |pages= 41-6 |year= 1999 |pmid= 10081705 |doi=  }}
* {{cite journal | vauthors = 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 | title = Mutations of the cardiac ryanodine receptor (RyR2) gene in familial polymorphic ventricular tachycardia | journal = Circulation | volume = 103 | issue = 4 | pages = 485–90 | year = 2001 | pmid = 11157710 | doi = 10.1161/01.cir.103.4.485 }}
*{{cite journal | author=Mori F, Fukaya M, Abe H, ''et al.'' |title=Developmental changes in expression of the three ryanodine receptor mRNAs in the mouse brain. |journal=Neurosci. Lett. |volume=285 |issue= 1 |pages= 57-60 |year= 2000 |pmid= 10788707 |doi= }}
* {{cite journal | vauthors = Priori SG, Napolitano C, Tiso N, Memmi M, Vignati G, Bloise R, Sorrentino V, Danieli GA | title = Mutations in the cardiac ryanodine receptor gene (hRyR2) underlie catecholaminergic polymorphic ventricular tachycardia | journal = Circulation | volume = 103 | issue = 2 | pages = 196–200 | year = 2004 | pmid = 11208676 | doi = 10.1161/01.cir.103.2.196 }}
*{{cite journal | author=Marx SO, Reiken S, Hisamatsu Y, ''et al.'' |title=PKA phosphorylation dissociates FKBP12.6 from the calcium release channel (ryanodine receptor): defective regulation in failing hearts. |journal=Cell |volume=101 |issue= 4 |pages= 365-76 |year= 2000 |pmid= 10830164 |doi= }}
* {{cite journal | vauthors = Jeyakumar LH, Ballester L, Cheng DS, McIntyre JO, Chang P, Olivey HE, Rollins-Smith L, Barnett JV, Murray K, Xin HB, Fleischer S | title = FKBP binding characteristics of cardiac microsomes from diverse vertebrates | journal = Biochem. Biophys. Res. Commun. | volume = 281 | issue = 4 | pages = 979–86 | year = 2001 | pmid = 11237759 | doi = 10.1006/bbrc.2001.4444 }}
*{{cite journal | author=Laitinen PJ, Brown KM, Piippo K, ''et al.'' |title=Mutations of the cardiac ryanodine receptor (RyR2) gene in familial polymorphic ventricular tachycardia. |journal=Circulation |volume=103 |issue= 4 |pages= 485-90 |year= 2001 |pmid= 11157710 |doi= }}
{{Refend}}
*{{cite journal  | author=Tiso N, Stephan DA, Nava A, ''et al.'' |title=Identification of mutations in the cardiac ryanodine receptor gene in families affected with arrhythmogenic right ventricular cardiomyopathy type 2 (ARVD2). |journal=Hum. Mol. Genet. |volume=10 |issue= 3 |pages= 189-94 |year= 2001 |pmid= 11159936 |doi=  }}
 
*{{cite journal | author=Priori SG, Napolitano C, Tiso N, ''et al.'' |title=Mutations in the cardiac ryanodine receptor gene (hRyR2) underlie catecholaminergic polymorphic ventricular tachycardia. |journal=Circulation |volume=103 |issue= 2 |pages= 196-200 |year= 2004 |pmid= 11208676 |doi= }}
== External links ==
*{{cite journal | author=Jeyakumar LH, Ballester L, Cheng DS, ''et al.'' |title=FKBP binding characteristics of cardiac microsomes from diverse vertebrates. |journal=Biochem. Biophys. Res. Commun. |volume=281 |issue= 4 |pages= 979-86 |year= 2001 |pmid= 11237759 |doi= 10.1006/bbrc.2001.4444 }}
* [https://www.ncbi.nlm.nih.gov/books/NBK1289/  GeneReviews/NCBI/NIH/UW entry on Catecholaminergic Polymorphic Ventricular Tachycardia]
}}
* [https://www.ncbi.nlm.nih.gov/books/NBK1131/  GeneReviews/NCBI/NIH/UW entry on Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy, Autosomal Dominant]
{{refend}}
* [https://www.ncbi.nlm.nih.gov/omim/604772,605676,601214,107970,125645,125647,125671,173325,180902,190230,600996,602086,602087,602861,604400,604401,607450,609040,609160,610193,610476,611528,612048,107970,125645,125647,125671,173325,180902,190230,600996,602086,602087,602861,604400,604401,607450,609040,609160,610193,610476,611528,612048  OMIM entries on Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy, Autosomal Dominant]
* {{MeshName|RYR2+protein,+human}}
 
{{Ion channels|g1}}


{{protein-stub}}
[[Category:Ion channels]]
[[Category:EF-hand-containing proteins]]

Revision as of 05:26, 11 September 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
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View/Edit Human

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.

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.[4]

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.[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

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]

Interactions

Ryanodine receptor 2 has been shown to interact with:

See also

References

  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. PMC 3696672. 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. ↑ 10.0 10.1 10.2 10.3 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

External links

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