RYR1

This gene encodes a ryanodine receptor found in skeletal muscle. The encoded protein functions as a calcium release channel in the sarcoplasmic reticulum but also serves to connect the sarcoplasmic reticulum and transverse tubule. Mutations in this gene are associated with malignant hyperthermia susceptibility, central core disease, and minicore myopathy with external ophthalmoplegia. Alternatively spliced transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

RYR1

Calcium channel that mediates the release of Ca2+ from the sarcoplasmic reticulum into the cytoplasm and thereby plays a key role in triggering muscle contraction following depolarization of T-tubules (PubMed:11741831, PubMed:16163667).
Repeated very high-level exercise increases the open probability of the channel and leads to Ca2+ leaking into the cytoplasm (PubMed:18268335).
Can also mediate the release of Ca2+ from intracellular stores in neurons, and may thereby promote prolonged Ca2+ 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).

Biological Process calcium ion transportISS:BHF-UCL
Biological Process cellular response to caffeineManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process cellular response to calcium ionISS:UniProtKB
Biological Process muscle contractionISS:UniProtKB
Biological Process ossification involved in bone maturationISS:UniProtKB
Biological Process outflow tract morphogenesisISS:UniProtKB
Biological Process protein homotetramerizationISS:UniProtKB
Biological Process regulation of cytosolic calcium ion concentrationISS:BHF-UCL
Biological Process release of sequestered calcium ion into cytosolManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process release of sequestered calcium ion into cytosol by sarcoplasmic reticulumISS:UniProtKB
Biological Process response to caffeineISS:BHF-UCL
Biological Process response to hypoxiaManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process skeletal muscle fiber developmentISS:UniProtKB
Biological Process skin developmentISS:UniProtKB

Sarcoplasmic reticulum membrane
Sarcoplasmic reticulum
The number of predicted transmembrane domains varies between orthologs, but the 3D-structures show the presence of six transmembrane regions. Both N-terminus and C-terminus are cytoplasmic.

Malignant hyperthermia 1 (MHS1):
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).
Central core disease of muscle (CCD):
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.
Multiminicore disease with external ophthalmoplegia (MMDO):
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.
King-Denborough syndrome (KDS):
An autosomal dominant disorder characterized by the triad of dysmorphic features, congenital myopathy, and susceptibility to malignant hyperthermia. Variable expressivity has been reported in several cases.

Cytoplasmic: 1-4559
Helical: 4560-4580
Lumenal: 4581-4641
Helical: 4642-4662
Cytoplasmic: 4663-4780
Helical: 4781-4803
Lumenal: 4804
Helical: 4805-4821
Cytoplasmic: 4822-4836
Helical: 4837-4857
Lumenal: 4858-4880
Helical: 4881-4900
Cytoplasmic: 4901-4920
Helical: 4921-4941
Lumenal: 4942-5038

Channel activity is modulated by phosphorylation. Phosphorylation at Ser-2843 may increase channel activity. Repeated very high-level exercise increases phosphorylation at Ser-2843.
Activated by reversible S-nitrosylation (By similarity).
Repeated very high-level exercise increases S-nitrosylation (PubMed:18268335).