Ryanodine receptor 3; RYR-3; RyR3; brain-type ryanodine receptor; brain ryanodine receptor-Ca+2 release channel (RYR3, HBRR)

Function

• Ca+2 channel
  • mediates release of Ca+2 from the sarcoplasmic reticulum into the cytoplasm in muscle, thus plays a role in triggering muscle contraction
  • mediates Ca+2-induced Ca+2 release from the endoplasmic reticulum in non-muscle cells
• may regulate Ca+2 release by other Ca+2 channels
• contributes to cellular Ca+2 homeostasis (putative)
• role in cellular Ca+2 signaling
• communication between transverse-tubules & sarcoplasmic reticulum
• contraction of skeletal muscle is triggered by release of Ca+2 from SR following depolarization of T-tubules (putative)
• Ca+2 release channel is modulated by Ca+2, Mg+2, ATP & calmodulin
• channel activity is modulated by the alkaloid ryanodine
  • ryanodine binds to the open Ca+2-release channel with high affinity
    • at low concentrations, ryanodine maintains the channel in an open conformation
    • at high concentrations, ryanodine inhibits channel activity
• channel activity is regulated by calmodulin
• the Ca+2 release is activated by elevated cytoplasmic Ca+2 levels in the micromolar range, by caffeine & adenine nucleotides, such as AMP & ATP
• homotetramer, heterotetramer with RYR2
• interacts with CALM (putative)
• interacts with FKBP1A

Inhibition:

• inhibited by Mg+2 & ruthenium red (putative)

Structure

• homotetramer (putative)
• belongs to the ryanodine receptor family
• contains 3 B30.2/SPRY domains
• contains 1 EF-hand domain
• contains 5 MIR domains
• Ca+2 release channel activity resides in the C-terminal region while the remaining part of the protein constitutes the 'foot' structure spanning the junctional gap between the SR & the T-tubule; it is possible that the foot structure interacts with the cytoplasmic region of the dihydropyridine receptor

Compartment

• sarcoplasmic reticulum membrane
• microsome membrane
• multi-pass membrane protein
  • the number of predicted transmembrane domains varies between orthologs, but both N-terminus & C-terminus seem to be cytoplasmic (putative)

Alternative splicing

named isoforms=3

Expression

• expressed in brain, skeletal muscle, placenta & possibly liver & kidney
• in brain, highest levels are found in the cerebellum, hippocampus, caudate nucleus & amygdala, with lower levels in the corpus callosum, substantia nigra & thalamus

More general terms

• ryanodine receptor (RyR)
• glycoprotein
• human longevity protein

Additional terms

• ryanodine

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=6263
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:6263
• OMIM: https://mirror.omim.org/entry/180903
• Kegg: http://www.genome.jp/dbget-bin/www_bget?PKKEGG; -.
• UniProt: http://www.uniprot.org/uniprot/Q15413.html