Ryanodine receptor-related (IPR015925)

Short name: Ryanodine_recept-rel

Overlapping homologous superfamilies

Family relationships


The ryanodine and inositol 1,4,5-triphosphate (IP3) receptors are intracellular Ca2+ release channels characterised by their large size and 4-fold symmetry [PMID: 2660829]. In excitation-contraction coupling of skeletal and heart muscle, the ryanodine receptor serves as a Ca2+ release channel of sarcoplasmic reticulum (SR) and is morphologically identical to the foot structure spanning the gap between terminal cisternae of SR and sarcolemma/transverse tubules. The IP3 receptor acts as a Ca2+ release channel of non-mitochondrial intracellular Ca2+ stores in smooth muscle and in non-muscle tissues.

The so-called excitation-contraction coupling phenomenon in muscle cells takes place in a highly specialised junctional region that arise from close proximity between plasma membrane (PM) and SR. More precisely, transverse tubular invaginations of the PM touch the terminal cisternae of SR to form a unique anatomical structure known as the triad junction [PMID: 12765683, PMID: 8010750, PMID: 1426638]. In skeletal muscle, dihydropyridine receptors (DHPRs) located in the transverse tubule membrane function mainly as the voltage sensor which sends an orthograde signal to control opening of the ryanodine receptor/Ca2+ release channel [PMID: 1562172, PMID: 1648106]. There appears to a physical interaction between DHPRs and ryanodine receptors in the triad junction without requiring the movement of extracellular Ca2+ through DHPRs in the PM [PMID: 2455801].

IP3 receptors are large (~1200 kDa) tetrameric proteins, each subunit of which projects an amino-terminal domain into the cytoplasm, their membrane-spanning carboxy-terminal regions forming an integral Ca2+ channel. IP3 binding by the amino-terminal domains causes a conformational change that promotes channel opening. Between the IP3 binding site and the transmembrane regions is a large stretch of amino acids where a significant proportion of regulatory interactions occur. Although IP3 is necessary to open native IP3 receptors, activation of these channels is complex and their open probability actually depends on the ambient Ca2+ concentration. Up to ~ 500 nM, Ca2+ works synergistically with IP3 to activate IP3 receptors. At higher concentrations, cytosolic Ca2+ inhibits IP3 receptor opening. The inhibition of IP3 receptors by Ca2+ is thought to be a crucial mechanism for terminating channel activity and thus preventing pathological Ca2+ rises.

GO terms

Biological Process

GO:0006816 calcium ion transport

Molecular Function

No terms assigned in this category.

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.