InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: RYR2

Summary

InnateDB Protein

IDBP-107651.6

Last Modified

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

Gene Symbol

RYR2

Protein Name

ryanodine receptor 2 (cardiac)

Synonyms

ARVC2; ARVD2; RyR; RYR-2; VTSIP;

Species

Homo sapiens

Ensembl Protein

ENSP00000355533

InnateDB Gene

IDBG-107649 (RYR2)

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 cardiac muscle contraction. Aberrant channel activation can lead to cardiac arrhythmia. In cardiac myocytes, calcium release is triggered by increased Ca(2+) levels due to activation of the L-type calcium channel CACNA1C. The calcium channel activity is modulated by formation of heterotetramers with RYR3. Required for cellular calcium ion homeostasis. Required for embryonic heart development. {ECO:0000269PubMed:10830164, ECO:0000269PubMed:20056922}.

Subcellular Localization

Sarcoplasmic reticulum membrane {ECO:0000269PubMed:10830164}; Multi-pass membrane protein {ECO:0000269PubMed:10830164}. Membrane {ECO:0000305PubMed:10830164}; Multi-pass membrane protein {ECO:0000305PubMed:10830164}. Note=The number of predicted transmembrane domains varies between orthologs, but both N- terminus and C-terminus seem to be cytoplasmic. {ECO:0000250}.

Disease Associations

Arrhythmogenic right ventricular dysplasia, familial, 2 (ARVD2) [MIM:600996]: A congenital heart disease characterized by infiltration of adipose and fibrous tissue into the right ventricle and loss of myocardial cells, resulting in ventricular and supraventricular arrhythmias. {ECO:0000269PubMed:11159936}. Note=The disease is caused by mutations affecting the gene represented in this entry.Ventricular tachycardia, catecholaminergic polymorphic, 1, with or without atrial dysfunction and/or dilated cardiomyopathy (CPVT1) [MIM:604772]: An arrhythmogenic disorder characterized by stress-induced, bidirectional ventricular tachycardia that may degenerate into cardiac arrest and cause sudden death. Patients present with recurrent syncope, seizures, or sudden death after physical activity or emotional stress. {ECO:0000269PubMed:11157710, ECO:0000269PubMed:12093772, ECO:0000269PubMed:12106942, ECO:0000269PubMed:15046072, ECO:0000269PubMed:15046073, ECO:0000269PubMed:15466642, ECO:0000269PubMed:15544015}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Detected in heart muscle (at protein level). Heart muscle, brain (cerebellum and hippocampus) and placenta. {ECO:0000269PubMed:10830164, ECO:0000269PubMed:9607712}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 34 experimentally validated interaction(s) in this database.
They are also associated with 8 interaction(s) predicted by orthology.

Experimentally validated
Total	34 [view]
Protein-Protein	34 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	8 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005216	ion channel activity
GO:0005218	intracellular ligand-gated calcium channel activity
GO:0005219	ryanodine-sensitive calcium-release channel activity
GO:0005262	calcium channel activity
GO:0005488	binding
GO:0005509	calcium ion binding
GO:0005515	protein binding
GO:0005516	calmodulin binding
GO:0015278	calcium-release channel activity
GO:0019899	enzyme binding
GO:0019901	protein kinase binding
GO:0034236	protein kinase A catalytic subunit binding
GO:0034237	protein kinase A regulatory subunit binding
GO:0042802	identical protein binding
GO:0043621	protein self-association
GO:0043924	suramin binding
GO:0044325	ion channel binding
GO:0048763	calcium-induced calcium release activity

Biological Process

GO:0001666	response to hypoxia
GO:0002027	regulation of heart rate
GO:0003143	embryonic heart tube morphogenesis
GO:0003220	left ventricular cardiac muscle tissue morphogenesis
GO:0003300	cardiac muscle hypertrophy
GO:0005513	detection of calcium ion
GO:0006811	ion transport
GO:0006816	calcium ion transport
GO:0006874	cellular calcium ion homeostasis
GO:0010460	positive regulation of heart rate
GO:0010881	regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion
GO:0014808	release of sequestered calcium ion into cytosol by sarcoplasmic reticulum
GO:0019722	calcium-mediated signaling
GO:0030509	BMP signaling pathway
GO:0031000	response to caffeine
GO:0034220	ion transmembrane transport
GO:0035584	calcium-mediated signaling using intracellular calcium source
GO:0051209	release of sequestered calcium ion into cytosol
GO:0051284	positive regulation of sequestering of calcium ion
GO:0051480	cytosolic calcium ion homeostasis
GO:0051775	response to redox state
GO:0055085	transmembrane transport
GO:0055117	regulation of cardiac muscle contraction
GO:0060048	cardiac muscle contraction
GO:0060070	canonical Wnt signaling pathway
GO:0060401	cytosolic calcium ion transport
GO:0060402	calcium ion transport into cytosol
GO:0070296	sarcoplasmic reticulum calcium ion transport
GO:0070588	calcium ion transmembrane transport
GO:0071313	cellular response to caffeine
GO:0071872	cellular response to epinephrine stimulus
GO:0072599	establishment of protein localization to endoplasmic reticulum
GO:0086005	ventricular cardiac muscle cell action potential
GO:0086029	Purkinje myocyte to ventricular cardiac muscle cell signaling
GO:0086064	cell communication by electrical coupling involved in cardiac conduction
GO:0086094	positive regulation of ryanodine-sensitive calcium-release channel activity by adrenergic receptor signaling pathway involved in positive regulation of cardiac muscle contraction
GO:0097050	type B pancreatic cell apoptotic process
GO:1901896	positive regulation of calcium-transporting ATPase activity

Cellular Component

GO:0005790	smooth endoplasmic reticulum
GO:0005886	plasma membrane
GO:0014701	junctional sarcoplasmic reticulum membrane
GO:0016020	membrane
GO:0016021	integral component of membrane
GO:0016529	sarcoplasmic reticulum
GO:0030017	sarcomere
GO:0030018	Z disc
GO:0033017	sarcoplasmic reticulum membrane
GO:0034704	calcium channel complex
GO:0043234	protein complex
GO:0070062	extracellular vesicular exosome

Protein Structure and Domains

PDB ID

InterPro

IPR000699 RIH (RyR and IP3R Homology) domain
IPR001870 B30.2/SPRY domain
IPR002048 EF-hand domain
IPR003032 Ryanodine receptor Ryr
IPR003877 SPRY domain
IPR005821 Ion transport domain
IPR008985 Concanavalin A-like lectin/glucanases superfamily
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