InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: RYR1

Summary

InnateDB Protein

IDBP-48913.7

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

RYR1

Protein Name

ryanodine receptor 1 (skeletal)

Synonyms

CCO; MHS; MHS1; PPP1R137; RYDR; RYR; RYR-1; SKRR;

Species

Homo sapiens

Ensembl Protein

ENSP00000354254

InnateDB Gene

IDBG-48907 (RYR1)

Protein Structure

UniProt Annotation

Function

Calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytoplasm and thereby plays a key role in triggering muscle contraction following depolarization of T-tubules. Repeated very high-level exercise increases the open probability of the channel and leads to Ca(2+) leaking into the cytoplasm. Can also mediate the release of Ca(2+) from intracellular stores in neurons, and may thereby promote prolonged Ca(2+) signaling in the brain. Required for normal embryonic development of muscle fibers and skeletal muscle. Required for normal heart morphogenesis, skin development and ossification during embryogenesis (By similarity). {ECO:0000250}.

Subcellular Localization

Sarcoplasmic reticulum membrane; Multi-pass membrane protein. Membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}. Note=The number of predicted transmembrane domains varies between orthologs, but both N-terminus and C- terminus seem to be cytoplasmic.

Disease Associations

Malignant hyperthermia 1 (MHS1) [MIM:145600]: Autosomal dominant pharmacogenetic disorder of skeletal muscle and is one of the main causes of death due to anesthesia. In susceptible people, an MH episode can be triggered by all commonly used inhalational anesthetics such as halothane and by depolarizing muscle relaxants such as succinylcholine. The clinical features of the myopathy are hyperthermia, accelerated muscle metabolism, contractures, metabolic acidosis, tachycardia and death, if not treated with the postsynaptic muscle relaxant, dantrolene. Susceptibility to MH can be determined with the 'in vitro' contracture test (IVCT): observing the magnitude of contractures induced in strips of muscle tissue by caffeine alone and halothane alone. Patients with normal response are MH normal (MHN), those with abnormal response to caffeine alone or halothane alone are MH equivocal (MHE(C) and MHE(H) respectively). {ECO:0000269PubMed:10051009, ECO:0000269PubMed:10484775, ECO:0000269PubMed:10612851, ECO:0000269PubMed:10823104, ECO:0000269PubMed:10888602, ECO:0000269PubMed:11241852, ECO:0000269PubMed:11389482, ECO:0000269PubMed:11525881, ECO:0000269PubMed:11575529, ECO:0000269PubMed:11928716, ECO:0000269PubMed:12059893, ECO:0000269PubMed:12066726, ECO:0000269PubMed:12123492, ECO:0000269PubMed:12208234, ECO:0000269PubMed:12411788, ECO:0000269PubMed:12709367, ECO:0000269PubMed:12883402, ECO:0000269PubMed:1354642, ECO:0000269PubMed:14732627, ECO:0000269PubMed:14985404, ECO:0000269PubMed:15221887, ECO:0000269PubMed:15448513, ECO:0000269PubMed:16163667, ECO:0000269PubMed:1774074, ECO:0000269PubMed:19191329, ECO:0000269PubMed:20142353, ECO:0000269PubMed:7751854, ECO:0000269PubMed:7849712, ECO:0000269PubMed:7881417, ECO:0000269PubMed:8012359, ECO:0000269PubMed:9066328, ECO:0000269PubMed:9138151, ECO:0000269PubMed:9389851, ECO:0000269PubMed:9450902, ECO:0000269PubMed:9497245}. Note=The disease is caused by mutations affecting the gene represented in this entry.Central core disease of muscle (CCD) [MIM:117000]: Autosomal dominant congenital myopathy, but a severe autosomal recessive form also exists. Both clinical and histological variability is observed. Affected individuals typically display hypotonia and proximal muscle weakness in infancy, leading to the delay of motor milestones. The clinical course of the disorder is usually slow or nonprogressive in adulthood, and the severity of the symptoms may vary from normal to significant muscle weakness. Microscopic examination of CCD-affected skeletal muscle reveals a predominance of type I fibers containing amorphous-looking areas (cores) that do not stain with oxidative and phosphorylase histochemical techniques. {ECO:0000269PubMed:10051009, ECO:0000269PubMed:10097181, ECO:0000269PubMed:11113224, ECO:0000269PubMed:11709545, ECO:0000269PubMed:11741831, ECO:0000269PubMed:12112081, ECO:0000269PubMed:12136074, ECO:0000269PubMed:12565913, ECO:0000269PubMed:12566385, ECO:0000269PubMed:12937085, ECO:0000269PubMed:14670767, ECO:0000269PubMed:14985404, ECO:0000269PubMed:17204054, ECO:0000269PubMed:17226826, ECO:0000269PubMed:18253926, ECO:0000269PubMed:18312400, ECO:0000269PubMed:20142353, ECO:0000269PubMed:21674524, ECO:0000269PubMed:7829078, ECO:0000269PubMed:8220422, ECO:0000269PubMed:8220423, ECO:0000269PubMed:9497245}. Note=The disease is caused by mutations affecting the gene represented in this entry.Multiminicore disease with external ophthalmoplegia (MMDO) [MIM:255320]: Clinically heterogeneous neuromuscular disorder. General features include neonatal hypotonia, delayed motor development, and generalized muscle weakness and amyotrophy, which may progress slowly or remain stable. Muscle biopsy shows multiple, poorly circumscribed, short areas of sarcomere disorganization and mitochondria depletion (areas termed minicores) in most muscle fibers. Typically, no dystrophic signs, such as muscle fiber necrosis or regeneration or significant endomysial fibrosis, are present in multiminicore disease. {ECO:0000269PubMed:12719381, ECO:0000269PubMed:16380615}. Note=The disease is caused by mutations affecting the gene represented in this entry.Myopathy, congenital, with fiber-type disproportion (CFTD) [MIM:255310]: A genetically heterogeneous disorder in which there is relative hypotrophy of type 1 muscle fibers compared to type 2 fibers on skeletal muscle biopsy. However, these findings are not specific and can be found in many different myopathic and neuropathic conditions. {ECO:0000269PubMed:20583297}. Note=The disease is caused by mutations affecting the gene represented in this entry.Note=Defects in RYR1 may be a cause of Samaritan myopathy, a congenital myopathy with benign course. Patients display severe hypotonia and respiratory distress at birth. Unlike other congenital myopathies, the health status constantly improves and patients are minimally affected at adulthood.

Tissue Specificity

Skeletal muscle and brain (cerebellum and hippocampus). {ECO:0000269PubMed:9607712}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 18 experimentally validated interaction(s) in this database.
They are also associated with 16 interaction(s) predicted by orthology.

Experimentally validated
Total	18 [view]
Protein-Protein	18 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	16 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005216	ion channel activity
GO:0005219	ryanodine-sensitive calcium-release channel activity
GO:0005245	voltage-gated calcium channel activity
GO:0005262	calcium channel activity
GO:0005509	calcium ion binding
GO:0005515	protein binding
GO:0005516	calmodulin binding
GO:0015278	calcium-release channel activity

Biological Process

GO:0001666	response to hypoxia
GO:0003151	outflow tract morphogenesis
GO:0006811	ion transport
GO:0006816	calcium ion transport
GO:0006874	cellular calcium ion homeostasis
GO:0006936	muscle contraction
GO:0014808	release of sequestered calcium ion into cytosol by sarcoplasmic reticulum
GO:0031000	response to caffeine
GO:0034220	ion transmembrane transport
GO:0043588	skin development
GO:0043931	ossification involved in bone maturation
GO:0048741	skeletal muscle fiber development
GO:0051209	release of sequestered calcium ion into cytosol
GO:0051480	cytosolic calcium ion homeostasis
GO:0055085	transmembrane transport
GO:0070588	calcium ion transmembrane transport
GO:0071313	cellular response to caffeine

Cellular Component

GO:0005737	cytoplasm
GO:0005790	smooth endoplasmic reticulum
GO:0005886	plasma membrane
GO:0005887	integral component of plasma membrane
GO:0005938	cell cortex
GO:0014701	junctional sarcoplasmic reticulum membrane
GO:0014802	terminal cisterna
GO:0016020	membrane
GO:0016021	integral component of membrane
GO:0016529	sarcoplasmic reticulum
GO:0031674	I band
GO:0033017	sarcoplasmic reticulum membrane
GO:0070062	extracellular vesicular exosome

Protein Structure and Domains

PDB ID

InterPro

IPR000699 RIH (RyR and IP3R Homology) domain
IPR001870 B30.2/SPRY domain
IPR003032 Ryanodine receptor Ryr
IPR003877 SPRY domain
IPR005821 Ion transport domain
IPR008985 Concanavalin A-like lectin/glucanases superfamily
IPR009066 Alpha-2-macroglobulin receptor-associated protein, domain 1
IPR009460 Ryanodine Receptor TM 4-6
IPR013333 Ryanodine receptor
IPR013662 RyR/IP3R Homology associated domain
IPR014821 Inositol 1,4,5-trisphosphate/ryanodine receptor
IPR016093 MIR motif

PFAM