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768  structures 728  species 0  interactions 9927  sequences 247  architectures

Family: RyR (PF02026)

Summary: RyR domain

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Ryanodine-Inositol 1,4,5-triphosphate receptor calcium channels". More...

Ryanodine-Inositol 1,4,5-triphosphate receptor calcium channels Edit Wikipedia article

Ryanodine receptor 2
Identifiers
SymbolRYR2
PfamPF02026
InterProIPR003032
SMARTSM00054
PROSITEPS50188
TCDB1.A.3
OPM superfamily8
OPM protein6dr2

The ryanodine-inositol 1,4,5-triphosphate receptor Ca2+ channel (RIR-CaC) family includes Ryanodine receptors and Inositol trisphosphate receptors. Members of this family are large proteins, some exceeding 5000 amino acyl residues in length. This family belongs to the Voltage-gated ion channel (VIC) superfamily. Ry receptors occur primarily in muscle cell sarcoplasmic reticular (SR) membranes, and IP3 receptors occur primarily in brain cell endoplasmic reticular (ER) membranes where they effect release of Ca2+ into the cytoplasm upon activation (opening) of the channel. They are redox sensors, possibly providing a partial explanation for how they control cytoplasmic Ca2+. Ry receptors have been identified in heart mitochondria where they provide the main pathway for Ca2+ entry.[1] Sun et al. (2011) have demonstrated oxygen-coupled redox regulation of the skeletal muscle ryanodine receptor-Ca2+ release channel (RyR1;TC# 1.A.3.1.2) by NADPH oxidase 4.[2]

Function

Ryanodine (Ry)-sensitive and inositol 1,4,5-triphosphate (IP3)-sensitive Ca2+-release channels function in the release of Ca2+ from intracellular storage sites in animal cells and thereby regulate various Ca2+-dependent physiological processes.[3] The Ry receptors are activated as a result of the activity of dihydropyridine-sensitive Ca2+ channels. Ry receptors, IP3 receptors, and dihydropyridine-sensitive Ca2+ channels (TC#1.A.1.11.2) are members of the voltage-sensitive ion channel (VIC) superfamily (TC# 1.A.1). Dihydropyridine-sensitive channels are present in the T-tubular systems of muscle tissues. Ry receptor 2 dysfunction leads to arrhythmias, altered myocyte contraction during the process of EC (excitation-contraction) coupling, and sudden cardiac death.[4] Neomycin is a RyR blocker which serves as a pore plug and a competitive antagonist at a cytoplasmic Ca2+ binding site that causes allosteric inhibition.[5]

The generalized transport reaction catalyzed by members of the RIR-CaC family following channel activation is:[6]

Ca2+ (out, or sequestered in the ER or SR) → Ca2+ (cell cytoplasm).

Structure

Ry and IP3 receptors consist of (1) an N-terminal ligand binding domain, (2) a central modulatory domain and (3) a C-terminal channel-forming domain. The 3-D structure (2.2 Å) of the inositol 1,3,5-triphosphate receptor of an IP3 receptor has been solved (PDB: 1N4K​).[7] Structural and functional conservation of key domains in IP3 and ryanodine receptors has been reviewed by Seo et al. (2012).[8] Members of the VIC (TC# 1.A.1), RIR-CaC (TC# 2.A.3) and TRP-CC (TC# 1.A.4) families have similar transmembrane domain structures, but very different cytosolic domain structures.[9]

The channel domains of the Ry and IP3 receptors comprise a coherent family that shows apparent structural similarities as well as sequence similarity with proteins of the VIC family (TC #1.A.1). The Ry receptors and the IP3 receptors cluster separately on the RIR-CaC family tree. They both have homologues in Drosophila. Based on the phylogenetic tree for the family, the family probably evolved in the following sequence:

  1. A gene duplication event occurred that gave rise to Ry and IP3 receptors in invertebrates.
  2. Vertebrates evolved from invertebrates.
  3. The three isoforms of each receptor arose as a result of two distinct gene duplication events.
  4. These isoforms were transmitted to mammals before divergence of the mammalian species.

Ry receptors

Ry receptors are homotetrameric complexes with each subunit exhibiting a molecular size of over 500,000 daltons (about 5,000 amino acyl residues). They possess C-terminal domains with six putative transmembrane α-helical spanners (TMSs). Putative pore-forming sequences occur between the fifth and sixth TMSs as suggested for members of the VIC family. Recently an 8 TMS topology with four hairpin loops has been suggested.[10] The large N-terminal hydrophilic domains and the small C-terminal hydrophilic domains are localized to the cytoplasm. Mammals possess at least three isoforms which probably arose by gene duplication and divergence before divergence of the mammalian species. Homologues are present in Drosophila melanogaster and Caenorabditis elegans.

Tetrameric cardiac and skeletal muscle sarcoplasmic reticular ryanodine receptors (RyR) are large (~2.3 MDa). The complexes include signaling proteins such as 4 FKBP12 molecules, protein kinases, phosphatases, etc. They modulate the activity of and the binding of immunophilin to the channel. FKBP12 is required for normal gating as well as coupled gating between neighboring channels. PKA phosphorylation of RyR dissociates FKBP12 yielding increased Ca2+ sensitivity for activation, part of the excitation-contraction (fight or flight) response.[11]

IP3 receptors

IP3 receptors resemble Ry receptors in many respects.[12]

  1. They are homotetrameric complexes with each subunit exhibiting a molecular size of over 300,000 daltons (about 2,700 amino acyl residues).
  2. They possess C-terminal channel domains that are homologous to those of the Ry receptors.
  3. The channel domains possess six putative TMSs and a putative channel lining region between TMSs 5 and 6.
  4. Both the large N-terminal domains and the smaller C-terminal tails face the cytoplasm.
  5. They possess covalently linked carbohydrate on extracytoplasmic loops of the channel domains.
  6. They have three currently recognized isoforms (types 1, 2, and 3) in mammals which are subject to differential regulation and have different tissue distributions. They co-localize with Orai channels (TC# 1.A.52) in pancreatic acinar cells.[13]

IP3 receptors possess three domains:

  1. N-terminal IP3-binding domains,
  2. central coupling or
  3. regulatory domains and C-terminal channel domains.

Channels are activated by IP3 binding, and like the Ry receptors, the activities of the IP3 receptor channels are regulated by phosphorylation of the regulatory domains, catalyzed by various protein kinases. They predominate in the endoplasmic reticular membranes of various cell types in the brain but have also been found in the plasma membranes of some nerve cells derived from a variety of tissues.

Specific residues in the putative pore helix, selectivity filter and S6 transmembrane helix of the IP3 receptor, have been mutated in order to examine their effects on channel function.[14] Mutation of 5 of 8 highly conserved residues in the pore helix/selectivity filter region inactivated the channel. Channel function was also inactivated by G2586P and F2592D mutations. These studies defined the pore-forming segment in IP3.[14]

See also

References

  1. ^ Beutner G, Sharma VK, Giovannucci DR, Yule DI, Sheu SS (June 2001). "Identification of a ryanodine receptor in rat heart mitochondria". The Journal of Biological Chemistry. 276 (24): 21482–8. doi:10.1074/jbc.M101486200. PMID 11297554.
  2. ^ Sun QA, Hess DT, Nogueira L, Yong S, Bowles DE, Eu J, Laurita KR, Meissner G, Stamler JS (September 2011). "Oxygen-coupled redox regulation of the skeletal muscle ryanodine receptor-Ca2+ release channel by NADPH oxidase 4". Proceedings of the National Academy of Sciences of the United States of America. 108 (38): 16098–103. Bibcode:2011PNAS..10816098S. doi:10.1073/pnas.1109546108. PMC 3179127. PMID 21896730.
  3. ^ Santulli, Gaetano; Marks, Andrew (2015). "Essential Roles of Intracellular Calcium Release Channels in Muscle, Brain, Metabolism, and Aging". Current Molecular Pharmacology. 8 (2): 206–222. doi:10.2174/1874467208666150507105105. ISSN 1874-4672. PMID 25966694.
  4. ^ Thomas NL, George CH, Williams AJ, Lai FA (November 2007). "Ryanodine receptor mutations in arrhythmias: advances in understanding the mechanisms of channel dysfunction". Biochemical Society Transactions. 35 (Pt 5): 946–51. doi:10.1042/BST0350946. PMID 17956252.
  5. ^ Laver DR, Hamada T, Fessenden JD, Ikemoto N (December 2007). "The ryanodine receptor pore blocker neomycin also inhibits channel activity via a previously undescribed high-affinity Ca(2+) binding site". The Journal of Membrane Biology. 220 (1–3): 11–20. doi:10.1007/s00232-007-9067-3. PMID 17879109. S2CID 38255566.
  6. ^ "1.A.3 The Ryanodine-Inositol 1,4,5-triphosphate Receptor Ca2+ Channel (RIR-CaC) Family". TCDB. Retrieved 2016-04-10.
  7. ^ Bosanac I, Alattia JR, Mal TK, Chan J, Talarico S, Tong FK, Tong KI, Yoshikawa F, Furuichi T, Iwai M, Michikawa T, Mikoshiba K, Ikura M (December 2002). "Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand". Nature. 420 (6916): 696–700. Bibcode:2002Natur.420..696B. doi:10.1038/nature01268. PMID 12442173. S2CID 4422308.
  8. ^ Seo MD, Velamakanni S, Ishiyama N, Stathopulos PB, Rossi AM, Khan SA, Dale P, Li C, Ames JB, Ikura M, Taylor CW (January 2012). "Structural and functional conservation of key domains in InsP3 and ryanodine receptors". Nature. 483 (7387): 108–12. Bibcode:2012Natur.483..108S. doi:10.1038/nature10751. PMC 3378505. PMID 22286060.
  9. ^ Mio K, Ogura T, Sato C (May 2008). "Structure of six-transmembrane cation channels revealed by single-particle analysis from electron microscopic images". Journal of Synchrotron Radiation. 15 (Pt 3): 211–4. doi:10.1107/S0909049508004640. PMC 2394823. PMID 18421141.
  10. ^ Du GG, Sandhu B, Khanna VK, Guo XH, MacLennan DH (December 2002). "Topology of the Ca2+ release channel of skeletal muscle sarcoplasmic reticulum (RyR1)". Proceedings of the National Academy of Sciences of the United States of America. 99 (26): 16725–30. Bibcode:2002PNAS...9916725D. doi:10.1073/pnas.012688999. PMC 139211. PMID 12486242.
  11. ^ Gaburjakova M, Gaburjakova J, Reiken S, Huang F, Marx SO, Rosemblit N, Marks AR (May 2001). "FKBP12 binding modulates ryanodine receptor channel gating". The Journal of Biological Chemistry. 276 (20): 16931–5. doi:10.1074/jbc.M100856200. PMID 11279144.
  12. ^ Mikoshiba, Katsuhiko; Furuichi, Teiichi; Miyawaki, Atsushi (1997-01-01). "IP3-sensitive calcium channel". In Lee, A. G. (ed.). Transmembrane Receptors and Channels. Transmembrane Receptors and Channels. 6. JAI. pp. 273–289. doi:10.1016/s1874-5342(96)80040-7. ISBN 9781559386630.
  13. ^ Lur G, Sherwood MW, Ebisui E, Haynes L, Feske S, Sutton R, Burgoyne RD, Mikoshiba K, Petersen OH, Tepikin AV (June 2011). "InsP₃receptors and Orai channels in pancreatic acinar cells: co-localization and its consequences". The Biochemical Journal. 436 (2): 231–9. doi:10.1042/BJ20110083. PMC 3262233. PMID 21568942.
  14. ^ a b Schug ZT, da Fonseca PC, Bhanumathy CD, Wagner L, Zhang X, Bailey B, Morris EP, Yule DI, Joseph SK (February 2008). "Molecular characterization of the inositol 1,4,5-trisphosphate receptor pore-forming segment". The Journal of Biological Chemistry. 283 (5): 2939–48. doi:10.1074/jbc.M706645200. PMID 18025085.

As of this edit, this article uses content from "1.A.3 The Ryanodine-Inositol 1,4,5-triphosphate Receptor Ca2+ Channel (RIR-CaC) Family", which is licensed in a way that permits reuse under the Creative Commons Attribution-ShareAlike 3.0 Unported License, but not under the GFDL. All relevant terms must be followed.

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This is the Wikipedia entry entitled "Ryanodine receptor". More...

Ryanodine receptor Edit Wikipedia article

RyR domain
Identifiers
SymbolRyR
PfamPF02026
InterProIPR003032
TCDB1.A.3
OPM superfamily8
OPM protein5gl0

Ryanodine receptors (RyR for short) form a class of intracellular calcium channels in various forms of excitable animal tissue like muscles and neurons.[1] There are three major isoforms of the ryanodine receptor, which are found in different tissues and participate in different signaling pathways involving calcium release from intracellular organelles. The RYR2 ryanodine receptor isoform is the major cellular mediator of calcium-induced calcium release (CICR) in animal cells.

Etymology

Ryanodine

The ryanodine receptors are named after the plant alkaloid ryanodine which shows a high affinity to them.

Isoforms

There are multiple isoforms of ryanodine receptors:

  • RyR1 is primarily expressed in skeletal muscle
  • RyR2 is primarily expressed in myocardium (heart muscle)
  • RyR3 is expressed more widely, but especially in the brain.[2]
  • Non-mammalian vertebrates typically express two RyR isoforms, referred to as RyR-alpha and RyR-beta.
  • Many invertebrates, including the model organisms Drosophila melanogaster (fruitfly) and Caenorhabditis elegans, only have a single isoform. In non-metazoan species, calcium-release channels with sequence homology to RyRs can be found, but they are shorter than the mammalian ones and may be closer to IP3 Receptors.
ryanodine receptor 1 (skeletal)
Identifiers
SymbolRYR1
Alt. symbolsMHS, MHS1, CCO
NCBI gene6261
HGNC10483
OMIM180901
RefSeqNM_000540
UniProtP21817
Other data
LocusChr. 19 q13.1
ryanodine receptor 2 (cardiac)
Identifiers
SymbolRYR2
NCBI gene6262
HGNC10484
OMIM180902
RefSeqNM_001035
UniProtQ92736
Other data
LocusChr. 1 q42.1-q43
ryanodine receptor 3
Identifiers
SymbolRYR3
NCBI gene6263
HGNC10485
OMIM180903
RefSeqNM_001036
UniProtQ15413
Other data
LocusChr. 15 q14-q15

Physiology

Ryanodine receptors mediate the release of calcium ions from the sarcoplasmic reticulum and endoplasmic reticulum, an essential step in muscle contraction.[1] In skeletal muscle, activation of ryanodine receptors occurs via a physical coupling to the dihydropyridine receptor (a voltage-dependent, L-type calcium channel), whereas, in cardiac muscle, the primary mechanism of activation is calcium-induced calcium release, which causes calcium outflow from the sarcoplasmic reticulum.[3]

It has been shown that calcium release from a number of ryanodine receptors in a ryanodine receptor cluster results in a spatiotemporally restricted rise in cytosolic calcium that can be visualised as a calcium spark.[4] Ryanodine receptors are very close to mitochondria and calcium release from RyR has been shown to regulate ATP production in heart and pancreas cells.[5][6][7]

Ryanodine receptors are similar to the inositol trisphosphate (IP3) receptor, and stimulated to transport Ca2+ into the cytosol by recognizing Ca2+ on its cytosolic side, thus establishing a positive feedback mechanism; a small amount of Ca2+ in the cytosol near the receptor will cause it to release even more Ca2+ (calcium-induced calcium release/CICR).[1] However, as the concentration of intracellular Ca2+ rises, this can trigger closing of RyR, preventing the total depletion of SR. This finding therefore indicates that a plot of opening probability for RyR as a function of Ca2+ concentration is a bell-curve.[8] Furthermore, RyR can sense the Ca2+ concentration inside the ER/SR and spontaneously open in a process known as store overload-induced calcium release (SOICR).[9]

RyRs are especially important in neurons and muscle cells. In heart and pancreas cells, another second messenger (cyclic ADP-ribose) takes part in the receptor activation.

The localized and time-limited activity of Ca2+ in the cytosol is also called a Ca2+ wave. The building of the wave is done by

Associated proteins

RyRs form docking platforms for a multitude of proteins and small molecule ligands.[1] The cardiac-specific isoform of the receptor (RyR2) is known to form a quaternary complex with luminal calsequestrin, junctin, and triadin.[10] Calsequestrin has multiple Ca2+ binding sites and binds Ca2+ ions with very low affinity so they can be easily released.


Pharmacology

  • Antagonists:[11]
  • Activators:[12]
    • Agonist: 4-chloro-m-cresol and suramin are direct agonists, i.e., direct activators.
    • Xanthines like caffeine and pentifylline activate it by potentiating sensitivity to native ligand Ca.
    • Physiological agonist: Cyclic ADP-ribose can act as a physiological gating agent. It has been suggested that it may act by making FKBP12.6 (12.6 kilodalton FK506 binding protein, as opposed to 12 kDa FKBP12 which binds to RyR1) which normally bind (and blocks) RyR2 channel tetramer in an average stoichiometry of 3.6, to fall off RyR2 (which is the predominant RyR in pancreatic beta cells, cardiomyocytes and smooth muscles).[13]

A variety of other molecules may interact with and regulate ryanodine receptor. For example: dimerized Homer physical tether linking inositol trisphosphate receptors (IP3R) and ryanodine receptors on the intracellular calcium stores with cell surface group 1 metabotropic glutamate receptors and the Alpha-1D adrenergic receptor[14]

Ryanodine

The plant alkaloid ryanodine, for which this receptor was named, has become an invaluable investigative tool. It can block the phasic release of calcium, but at low doses may not block the tonic cumulative calcium release. The binding of ryanodine to RyRs is use-dependent, that is the channels have to be in the activated state. At low (<10 micromolar, works even at nanomolar) concentrations, ryanodine binding locks the RyRs into a long-lived subconductance (half-open) state and eventually depletes the store, while higher (~100 micromolar) concentrations irreversibly inhibit channel-opening.

Caffeine

RyRs are activated by millimolar caffeine concentrations. High (greater than 5 mmol/L) caffeine concentrations cause a pronounced increase (from micromolar to picomolar) in the sensitivity of RyRs to Ca2+ in the presence of caffeine, such that basal Ca2+ concentrations become activatory. At low millimolar caffeine concentrations, the receptor opens in a quantal way, but has complicated behavior in terms of repeated use of caffeine or dependence on cytosolic or luminal calcium concentrations.

Role in disease

RyR1 mutations are associated with malignant hyperthermia and central core disease. RyR2 mutations play a role in stress-induced polymorphic ventricular tachycardia (a form of cardiac arrhythmia) and ARVD.[2] It has also been shown that levels of type RyR3 are greatly increased in PC12 cells overexpressing mutant human Presenilin 1, and in brain tissue in knockin mice that express mutant Presenilin 1 at normal levels,[15] and thus may play a role in the pathogenesis of neurodegenerative diseases, like Alzheimer's disease.[16]

The presence of antibodies against ryanodine receptors in blood serum has also been associated with myasthenia gravis.[1]

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 (Ryanodine Receptor) gene.[17] Normal (wild type) ryanodine receptors are involved in CICR in heart and other muscles, and RyR2 functions primarily in the myocardium (heart muscle).

Structure

RyR1 cryo-EM structure revealed a large cytosolic assembly built on an extended α-solenoid scaffold connecting key regulatory domains to the pore. The RyR1 pore architecture shares the general structure of the six-transmembrane ion channel superfamily. A unique domain inserted between the second and third transmembrane helices interacts intimately with paired EF-hands originating from the α-solenoid scaffold, suggesting a mechanism for channel gating by Ca2+.[1][18]

See also

  • Ryanoid, a class of insecticide that act through ryanodine receptors

References

  1. ^ a b c d e f Santulli G, Marks AR (2015). "Essential Roles of Intracellular Calcium Release Channels in Muscle, Brain, Metabolism, and Aging". Current Molecular Pharmacology. 8 (2): 206–22. doi:10.2174/1874467208666150507105105. PMID 25966694.
  2. ^ a b Zucchi R, Ronca-Testoni S (March 1997). "The sarcoplasmic reticulum Ca2+ channel/ryanodine receptor: modulation by endogenous effectors, drugs and disease states". Pharmacological Reviews. 49 (1): 1–51. PMID 9085308.
  3. ^ Fabiato A (July 1983). "Calcium-induced release of calcium from the cardiac sarcoplasmic reticulum". The American Journal of Physiology. 245 (1): C1-14. doi:10.1152/ajpcell.1983.245.1.C1. PMID 6346892.
  4. ^ Cheng H, Lederer WJ, Cannell MB (October 1993). "Calcium sparks: elementary events underlying excitation-contraction coupling in heart muscle". Science. 262 (5134): 740–4. Bibcode:1993Sci...262..740C. doi:10.1126/science.8235594. PMID 8235594.
  5. ^ Bround MJ, Wambolt R, Luciani DS, Kulpa JE, Rodrigues B, Brownsey RW, et al. (June 2013). "Cardiomyocyte ATP production, metabolic flexibility, and survival require calcium flux through cardiac ryanodine receptors in vivo". The Journal of Biological Chemistry. 288 (26): 18975–86. doi:10.1074/jbc.M112.427062. PMC 3696672. PMID 23678000.
  6. ^ Tsuboi T, da Silva Xavier G, Holz GG, Jouaville LS, Thomas AP, Rutter GA (January 2003). "Glucagon-like peptide-1 mobilizes intracellular Ca2+ and stimulates mitochondrial ATP synthesis in pancreatic MIN6 beta-cells". The Biochemical Journal. 369 (Pt 2): 287–99. doi:10.1042/BJ20021288. PMC 1223096. PMID 12410638.
  7. ^ Dror V, Kalynyak TB, Bychkivska Y, Frey MH, Tee M, Jeffrey KD, et al. (April 2008). "Glucose and endoplasmic reticulum calcium channels regulate HIF-1beta via presenilin in pancreatic beta-cells". The Journal of Biological Chemistry. 283 (15): 9909–16. doi:10.1074/jbc.M710601200. PMID 18174159.
  8. ^ Meissner G, Darling E, Eveleth J (January 1986). "Kinetics of rapid Ca2+ release by sarcoplasmic reticulum. Effects of Ca2+, Mg2+, and adenine nucleotides". Biochemistry. 25 (1): 236–44. doi:10.1021/bi00349a033. PMID 3754147.
  9. ^ Van Petegem F (September 2012). "Ryanodine receptors: structure and function". The Journal of Biological Chemistry. 287 (38): 31624–32. doi:10.1074/jbc.r112.349068. PMC 3442496. PMID 22822064.
  10. ^ Kranias E. "Dr. Evangelia Kranias Lab: Calsequestrin". Retrieved 22 May 2014.
  11. ^ Vites AM, Pappano AJ (March 1994). "Distinct modes of inhibition by ruthenium red and ryanodine of calcium-induced calcium release in avian atrium". The Journal of Pharmacology and Experimental Therapeutics. 268 (3): 1476–84. PMID 7511166.
  12. ^ Xu L, Tripathy A, Pasek DA, Meissner G (September 1998). "Potential for pharmacology of ryanodine receptor/calcium release channels". Annals of the New York Academy of Sciences. 853 (1): 130–48. Bibcode:1998NYASA.853..130T. doi:10.1111/j.1749-6632.1998.tb08262.x. PMID 10603942. S2CID 86436194.
  13. ^ Wang YX, Zheng YM, Mei QB, Wang QS, Collier ML, Fleischer S, et al. (March 2004). "FKBP12.6 and cADPR regulation of Ca2+ release in smooth muscle cells". American Journal of Physiology. Cell Physiology. 286 (3): C538-46. doi:10.1152/ajpcell.00106.2003. PMID 14592808.
  14. ^ Tu JC, Xiao B, Yuan JP, Lanahan AA, Leoffert K, Li M, et al. (October 1998). "Homer binds a novel proline-rich motif and links group 1 metabotropic glutamate receptors with IP3 receptors". Neuron. 21 (4): 717–26. doi:10.1016/S0896-6273(00)80589-9. PMID 9808459. S2CID 2851554.
  15. ^ Chan SL, Mayne M, Holden CP, Geiger JD, Mattson MP (June 2000). "Presenilin-1 mutations increase levels of ryanodine receptors and calcium release in PC12 cells and cortical neurons". The Journal of Biological Chemistry. 275 (24): 18195–200. doi:10.1074/jbc.M000040200. PMID 10764737.
  16. ^ Gong S, Su BB, Tovar H, Mao C, Gonzalez V, Liu Y, et al. (June 2018). "Polymorphisms Within RYR3 Gene Are Associated With Risk and Age at Onset of Hypertension, Diabetes, and Alzheimer's Disease". American Journal of Hypertension. 31 (7): 818–826. doi:10.1093/ajh/hpy046. PMID 29590321.
  17. ^ Tester DJ, Bombei HM, Fitzgerald KK, Giudicessi JR, Pitel BA, Thorland EC, et al. (January 2020). "Identification of a Novel Homozygous Multi-Exon Duplication in RYR2 Among Children With Exertion-Related Unexplained Sudden Deaths in the Amish Community". JAMA Cardiology. 5 (3): 13–18. doi:10.1001/jamacardio.2019.5400. PMC 6990654. PMID 31913406.
  18. ^ Zalk R, Clarke OB, des Georges A, Grassucci RA, Reiken S, Mancia F, et al. (January 2015). "Structure of a mammalian ryanodine receptor". Nature. 517 (7532): 44–9. Bibcode:2015Natur.517...44Z. doi:10.1038/nature13950. PMC 4300236. PMID 25470061.

External links

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

RyR domain Provide feedback

This domain is called RyR for Ryanodine receptor [1]. The domain is found in four copies in the ryanodine receptor. The function of this domain is unknown.

Literature references

  1. Ponting CP; , Trends Biochem Sci 2000;25:48-50.: Novel repeats in ryanodine and IP3 receptors and protein O-mannosyltransferases. PUBMED:10664581 EPMC:10664581


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR003032

This domain is called RyR for Ryanodine receptor [ PUBMED:10664581 ]. The domain is found in four copies in the ryanodine receptor. A single copy of this domain encodes an unknown protein from Bacteroides thetaiotamicron, and and suggests that the repeats in RyRs may have a prokaryotic origin [ PUBMED:22453942 ]. The function of this domain is unknown.

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Curation View help on the curation process

Seed source: [1]
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Bateman A
Number in seed: 103
Number in full: 9927
Average length of the domain: 87.80 aa
Average identity of full alignment: 37 %
Average coverage of the sequence by the domain: 7.64 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 27.4 27.4
Trusted cut-off 27.4 27.4
Noise cut-off 27.3 27.3
Model length: 91
Family (HMM) version: 19
Download: download the raw HMM for this family

Species distribution

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Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence

Selections

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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

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Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the RyR domain has been found. There are 768 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A2R8QEE5 View 3D Structure Click here