RYR1

Identifiers

RYR1, CCO, MHS, MHS1, PPP1R137, RYDR, RYR, RYR-1, SKRR, ryanodine receptor 1

External IDs

MGI: 99659 HomoloGene: 68069 GeneCards: RYR1

Targeted by Drug

adenosine triphosphate, caffeine, suramin, dantrolene, procaine^[1]

Gene ontology
Molecular function	• ryanodine-sensitive calcium-release channel activity • calcium ion binding • voltage-gated calcium channel activity • calcium channel activity • calmodulin binding • protease binding • ion channel activity • protein binding • enzyme binding • calcium-release channel activity
Cellular component	• cytoplasm • integral component of membrane • membrane • I band • T-tubule • plasma membrane • integral component of plasma membrane • sarcoplasmic reticulum • junctional sarcoplasmic reticulum membrane • terminal cisterna • smooth endoplasmic reticulum • protein complex • cell cortex • sarcoplasmic reticulum membrane • junctional membrane complex • extracellular exosome
Biological process	• ossification involved in bone maturation • release of sequestered calcium ion into cytosol • regulation of cardiac conduction • response to hypoxia • muscle contraction • release of sequestered calcium ion into cytosol by sarcoplasmic reticulum • regulation of cytosolic calcium ion concentration • outflow tract morphogenesis • cellular calcium ion homeostasis • ion transport • multicellular organism development • ion transmembrane transport • skeletal muscle fiber development • calcium ion transmembrane transport • cellular response to caffeine • transport • response to caffeine • calcium ion transport • skin development • transmembrane transport
Sources:Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

Entrez


6261


20190

Ensembl


ENSG00000196218


ENSMUSG00000030592

UniProt


P21817


E9PZQ0

RefSeq (mRNA)


NM_000540 NM_001042723


NM_009109

RefSeq (protein)


NP_000531.2 NP_001036188.1


NP_033135.2

Location (UCSC)

Chr 19: 38.43 – 38.59 Mb

Chr 7: 29 – 29.13 Mb

PubMed search

^[2]

^[3]

Wikidata

View/Edit Human

View/Edit Mouse

Ryanodine receptor 1 (RYR-1) also known as skeletal muscle calcium release channel or skeletal muscle-type ryanodine receptor is a protein found primarily in skeletal muscle. In humans, it is encoded by the RYR1 gene.^[4]^[5]

Function

RYR1 functions as a calcium release channel in the sarcoplasmic reticulum, as well as a connection between the sarcoplasmic reticulum and the transverse tubule.^[6] RYR1 is associated with the dihydropyridine receptor (L-type calcium channels) within the sarcolemma of the T-tubule, which opens in response to depolarization, and thus effectively means that the RYR1 channel opens in response to depolarization of the cell.

Clinical significance

Mutations in the RYR1 gene are associated with malignant hyperthermia susceptibility, central core disease, minicore myopathy with external ophthalmoplegia and samaritan myopathy, a benign congenital myopathy.^[7] Alternatively spliced transcripts encoding different isoforms have been demonstrated.^[6] Dantrolene may be the only known drug that is effective during cases of malignant hyperthermia.

Interactions

RYR1 has been shown to interact with:

References

↑ "Drugs that physically interact with Ryanodine receptor 1 view/edit references on wikidata".
↑ "Human PubMed Reference:".
↑ "Mouse PubMed Reference:".
↑ Fujii J, Otsu K, Zorzato F, de Leon S, Khanna VK, Weiler JE, O'Brien PJ, MacLennan DH (Jul 1991). "Identification of a mutation in porcine ryanodine receptor associated with malignant hyperthermia". Science. 253 (5018): 448–51. doi:10.1126/science.1862346. PMID 1862346.
↑ Wu S, Ibarra MC, Malicdan MC, Murayama K, Ichihara Y, Kikuchi H, Nonaka I, Noguchi S, Hayashi YK, Nishino I (Jun 2006). "Central core disease is due to RYR1 mutations in more than 90% of patients". Brain. 129 (Pt 6): 1470–80. doi:10.1093/brain/awl077. PMID 16621918.
1 2 "Entrez Gene: RYR1 ryanodine receptor 1 (skeletal)".
↑ Böhm J, Leshinsky-Silver E, Vassilopoulos S, Le Gras S, Lerman-Sagie T, Ginzberg M, Jost B, Lev D, Laporte J (Oct 2012). "Samaritan myopathy, an ultimately benign congenital myopathy, is caused by a RYR1 mutation". Acta Neuropathologica. 124 (4): 575–81. doi:10.1007/s00401-012-1007-3. PMID 22752422.
↑ Fruen BR, Balog EM, Schafer J, Nitu FR, Thomas DD, Cornea RL (Jan 2005). "Direct detection of calmodulin tuning by ryanodine receptor channel targets using a Ca2+-sensitive acrylodan-labeled calmodulin". Biochemistry. 44 (1): 278–84. doi:10.1021/bi048246u. PMID 15628869.
↑ Cornea RL, Nitu F, Gruber S, Kohler K, Satzer M, Thomas DD, Fruen BR (Apr 2009). "FRET-based mapping of calmodulin bound to the RyR1 Ca2+ release channel". Proceedings of the National Academy of Sciences of the United States of America. 106 (15): 6128–33. doi:10.1073/pnas.0813010106. PMC 2662960. PMID 19332786.
↑ Avila G, Lee EH, Perez CF, Allen PD, Dirksen RT (Jun 2003). "FKBP12 binding to RyR1 modulates excitation-contraction coupling in mouse skeletal myotubes". The Journal of Biological Chemistry. 278 (25): 22600–8. doi:10.1074/jbc.M205866200. PMID 12704193.
↑ Bultynck G, De Smet P, Rossi D, Callewaert G, Missiaen L, Sorrentino V, De Smedt H, Parys JB (Mar 2001). "Characterization and mapping of the 12 kDa FK506-binding protein (FKBP12)-binding site on different isoforms of the ryanodine receptor and of the inositol 1,4,5-trisphosphate receptor". The Biochemical Journal. 354 (Pt 2): 413–22. doi:10.1042/bj3540413. PMC 1221670. PMID 11171121.
↑ 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.
↑ Hwang SY, Wei J, Westhoff JH, Duncan RS, Ozawa F, Volpe P, Inokuchi K, Koulen P (Aug 2003). "Differential functional interaction of two Vesl/Homer protein isoforms with ryanodine receptor type 1: a novel mechanism for control of intracellular calcium signaling". Cell Calcium. 34 (2): 177–84. doi:10.1016/S0143-4160(03)00082-4. PMID 12810060.
1 2 3 Feng W, Tu J, Yang T, Vernon PS, Allen PD, Worley PF, Pessah IN (Nov 2002). "Homer regulates gain of ryanodine receptor type 1 channel complex". The Journal of Biological Chemistry. 277 (47): 44722–30. doi:10.1074/jbc.M207675200. PMID 12223488.
↑ Lee JM, Rho SH, Shin DW, Cho C, Park WJ, Eom SH, Ma J, Kim DH (Feb 2004). "Negatively charged amino acids within the intraluminal loop of ryanodine receptor are involved in the interaction with triadin". The Journal of Biological Chemistry. 279 (8): 6994–7000. doi:10.1074/jbc.M312446200. PMID 14638677.
↑ Caswell AH, Motoike HK, Fan H, Brandt NR (Jan 1999). "Location of ryanodine receptor binding site on skeletal muscle triadin". Biochemistry. 38 (1): 90–7. doi:10.1021/bi981306+. PMID 9890886.
↑ Guo W, Campbell KP (Apr 1995). "Association of triadin with the ryanodine receptor and calsequestrin in the lumen of the sarcoplasmic reticulum". The Journal of Biological Chemistry. 270 (16): 9027–30. doi:10.1074/jbc.270.16.9027. PMID 7721813.
↑ Groh S, Marty I, Ottolia M, Prestipino G, Chapel A, Villaz M, Ronjat M (Apr 1999). "Functional interaction of the cytoplasmic domain of triadin with the skeletal ryanodine receptor". The Journal of Biological Chemistry. 274 (18): 12278–83. doi:10.1074/jbc.274.18.12278. PMID 10212196.

External links

RYR1 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
GeneReviews/NIH/UW entry on Multiminicore Disease
GeneReviews/NCBI/NIH/UW entry on Malignant Hyperthermia Susceptibility
RYR1 Variation Database

PDB gallery

2bcx: Crystal structure of calmodulin in complex with a ryanodine receptor peptide

Membrane transport protein: ion channels (TC 1A)

Ca²⁺: Calcium channel

Ligand-gated	Inositol trisphosphate receptor 1 2 3 Ryanodine receptor 1 2 3

Voltage-gated	L-type/Ca_vα 1.1 1.2 1.3 1.4 N-type/Ca_vα2.2 P-type/Ca_vα 2.1 Q-type/Ca_vα2.1 R-type/Ca_vα2.3 T-type/Ca_vα 3.1 3.2 3.3 α₂δ-subunits 1 2 β-subunits β1 β2 β3 β4 γ-subunits γ1 γ2 γ3 γ4 Cation channels of sperm 1 2 3 4 Two-pore channel 1 2

Na⁺: Sodium channel

Constitutively active	Epithelial sodium channel α β γ δ

Proton-gated	Amiloride-sensitive cation channel 1 2 3 4

Voltage-gated	Na_vα 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 7A Na_vβ 1 2 3 4

K⁺: Potassium channel

Calcium-activated	BK channel α1 β1 β2 β3 β4 SK channel SK1 SK2 SK3 IK channel IK1 K_Ca 1.1 2.1 2.2 2.3 3.1 4.1 4.2 5.1

Inward-rectifier	K_ATP K_ir 1.1 2.1 2.2 2.3 2.4 2.6 GIRK/K_ir 3.1 3.2 3.3 3.4 K_ir 4.1 4.2 5.1 6.1 6.2 7.1

Tandem pore domain	K2P 1 2 3 4 5 6 7 9 10 12 13 15 16 17 18

Voltage-gated	K_vα1-6 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 2.1 2.2 3.1 3.2 3.3 3.4 4.1 4.2 4.3 5.1 6.1 6.2 6.3 6.4 K_vα7-12 7.1 7.2 7.3 7.4 7.5 8.1 8.2 9.1 9.2 9.3 10.1 10.2 11.1/hERG 11.2 11.3 12.1 12.2 12.3 K_vβ 1 2 3 KCNIP 1 2 3 4 minK/ISK minK/ISK-like MiRP 1 2 3 Shaker gene

Miscellaneous

Cl⁻: Chloride channel	Calcium-activated chloride channels Anoctamin ANO1 Bestrophin 1 2 Chloride Channel Accessory 1 2 3 4 CFTR CLCN 1 2 3 4 5 6 7 KA KB CLIC 1 2 3 4 5 6 L1 CLNS 1A 1B

H⁺: Proton channel	HVCN1

M⁺: CNG cation channel	α 1 2 3 4 β 1 2 3 HCN FC 1 2 3 4

M⁺: TRP cation channel	TRPA (1) TRPC 1 2 3 4 4AP 5 6 7 TRPM 1 2 3 4 5 6 7 8 TRPML 1 2 3 TRPN TRPP 1 2 TRPV 1 2 3 4 5 6

H₂O (+ solutes): Porin	Aquaporin 0 1 2 3 4 5 6 7 8 9 Voltage-dependent anion channel 1 2 3 General bacterial porin family

Cytoplasm: Gap junction	Connexin: A GJA1 GJA3 GJA4 GJA5 GJA8 GJA9 GJA10 B GJB1 GJB2 GJB3 GJB4 GJB5 GJB6 GJB7 C GJC1 GJC2 GJC3 D GJD2 GJD3 GJD4) Innexin

By gating mechanism

Ion channel class	Ligand-gated Light-gated Voltage-gated Stretch-activated

see also disorders

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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