E9PZQ0 · RYR1_MOUSE

  • Protein
    Ryanodine receptor 1
  • Gene
    Ryr1
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Cytosolic calcium-activated calcium channel that mediates the release of Ca2+ from the sarcoplasmic reticulum into the cytosol and thereby plays a key role in triggering muscle contraction following depolarization of T-tubules (PubMed:18003898, PubMed:21156754, PubMed:7515481, PubMed:7621815).
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 (PubMed:22036948).
Required for normal embryonic development of muscle fibers and skeletal muscle (PubMed:7515481).
Required for normal heart morphogenesis, skin development and ossification during embryogenesis (PubMed:18003898, PubMed:7515481).

Catalytic activity

Activity regulation

The calcium release is activated by increased cytosolic calcium levels, by nitric oxyde (NO), caffeine and ATP (PubMed:21156754, PubMed:22036948, PubMed:7621815).
Channel activity is modulated by the alkaloid ryanodine that binds to the open Ca-release channel with high affinity. At low concentrations, ryanodine maintains the channel in an open conformation. High ryanodine concentrations inhibit channel activity (PubMed:7621815).
Channel activity is regulated by calmodulin (CALM). Channel activity is inhibited by magnesium ions, possibly by competition for calcium binding sites

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site3896Ca2+ (UniProtKB | ChEBI)
Binding site3970Ca2+ (UniProtKB | ChEBI)
Binding site4214-4218ATP (UniProtKB | ChEBI)
Binding site4714caffeine (UniProtKB | ChEBI)
Binding site4952-4957ATP (UniProtKB | ChEBI)
Binding site4977-4983ATP (UniProtKB | ChEBI)
Binding site4999Ca2+ (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentcalcium channel complex
Cellular Componentcytoplasm
Cellular Componentcytoplasmic side of plasma membrane
Cellular Componentextrinsic component of cytoplasmic side of plasma membrane
Cellular Componentjunctional membrane complex
Cellular Componentmembrane
Cellular Componentorganelle membrane
Cellular Componentperinuclear region of cytoplasm
Cellular Componentprotein-containing complex
Cellular Componentryanodine receptor complex
Cellular Componentsarcolemma
Cellular Componentsarcomere
Cellular Componentsarcoplasmic reticulum
Cellular Componentsarcoplasmic reticulum membrane
Cellular Componentsmooth endoplasmic reticulum
Cellular ComponentT-tubule
Cellular Componentterminal cisterna
Cellular Componentvesicle
Cellular ComponentZ disc
Molecular FunctionATP binding
Molecular Functioncalcium channel activity
Molecular Functioncalcium ion binding
Molecular Functioncalmodulin binding
Molecular Functionenzyme binding
Molecular Functionprotease binding
Molecular Functionryanodine-sensitive calcium-release channel activity
Molecular Functionvoltage-gated calcium channel activity
Biological Processcalcium ion transport
Biological Processcellular response to ATP
Biological Processcellular response to caffeine
Biological Processcellular response to calcium ion
Biological Processmuscle contraction
Biological Processnegative regulation of transforming growth factor beta receptor signaling pathway
Biological Processossification involved in bone maturation
Biological Processoutflow tract morphogenesis
Biological Processprotein homotetramerization
Biological Processregulation of cytosolic calcium ion concentration
Biological Processregulation of muscle contraction
Biological Processregulation of response to osmotic stress
Biological Processrelease of sequestered calcium ion into cytosol
Biological Processrelease of sequestered calcium ion into cytosol by sarcoplasmic reticulum
Biological Processresponse to caffeine
Biological Processsarcoplasmic reticulum calcium ion transport
Biological Processskeletal muscle fiber development
Biological Processskin development
Biological Processstriated muscle contraction

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Ryanodine receptor 1
  • Short names
    RYR-1; RyR1
  • Alternative names
    • Skeletal muscle calcium release channel
    • Skeletal muscle ryanodine receptor
    • Skeletal muscle-type ryanodine receptor
    • Type 1 ryanodine receptor

Gene names

    • Name
      Ryr1

Organism names

  • Taxonomic identifier
  • Strains
    • 129
    • BALB/c X CD-1
    • C57BL/6J
    • 129/J
    • BALB/cJ
    • FVB/N-3
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    E9PZQ0
  • Secondary accessions
    • Q60834
    • Q61779
    • Q61780
    • Q62173
    • Q62196

Proteomes

Organism-specific databases

Subcellular Location

Features

Showing features for topological domain, transmembrane, intramembrane.

TypeIDPosition(s)Description
Topological domain1-4556Cytoplasmic
Transmembrane4557-4577Helical; Name=1
Topological domain4578-4638Lumenal
Transmembrane4639-4659Helical; Name=2
Topological domain4660-4777Cytoplasmic
Transmembrane4778-4800Helical; Name=3
Topological domain4801Lumenal
Transmembrane4802-4818Helical; Name=4
Topological domain4819-4833Cytoplasmic
Transmembrane4834-4854Helical; Name=5
Topological domain4855-4877Lumenal
Intramembrane4878-4897Pore-forming
Topological domain4898-4917Lumenal
Transmembrane4918-4938Helical; Name=6
Topological domain4939-5035Cytoplasmic

Keywords

Phenotypes & Variants

Disruption phenotype

Perinatal lethality, due to severe defects in skeletal muscle development. Neonates do not breathe and do not move. Mutant mice show defects in muscle fiber development. Their muscles do not show a contractile response to electrical stimulation. In addition, mice display abnormal curvature of the spine, thin limbs, and an abnormal rib cage.

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis165Increased channel activity, leading to permanently increased cytoplasmic Ca2+ levels. Increased activation by calcium, and increased ryanodine binding.
Mutagenesis4895Causes paralysis and perinatal death in homozygous mice, apparently due to asphyxia. Mutant mice have greatly reduced and amorphous skeletal muscle.

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 211 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Chemistry

PTM/Processing

Features

Showing features for chain, modified residue.

TypeIDPosition(s)Description
ChainPRO_00004155661-5035Ryanodine receptor 1
Modified residue1339Phosphoserine
Modified residue2346Phosphoserine
Modified residue2844Phosphoserine; by PKA and PKG
Modified residue3636S-nitrosocysteine
Modified residue4464Phosphothreonine
Modified residue4468Phosphoserine
Modified residue4861Phosphotyrosine
Modified residue4864Phosphoserine

Post-translational modification

Channel activity is modulated by phosphorylation. Phosphorylation at Ser-2844 may increase channel activity. Repeated very high-level exercise increases phosphorylation at Ser-2844.
Activated by reversible S-nitrosylation (PubMed:22036948).
Repeated very high-level exercise increases S-nitrosylation

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Detected in muscle and myotubes (at protein level) (PubMed:18003898).
Ubiquitous. Detected in diaphragm, skeletal muscle, esophagus, spleen, submaxillary gland, adrenal gland, cerebellum, brain and in testis germ cells

Gene expression databases

Interaction

Subunit

Homotetramer (PubMed:18003898).
Can also form heterotetramers with RYR2 (By similarity).
Identified in a complex composed of RYR1, PDE4D, PKA, FKBP1A and protein phosphatase 1 (PP1) (PubMed:18268335).
Repeated very high-level exercise decreases interaction with PDE4D and protein phosphatase 1 (PP1) (PubMed:18268335).
Interacts with CALM; CALM with bound calcium inhibits the RYR1 channel activity (By similarity).
Interacts with S100A1 (By similarity).
Interacts with FKBP1A; this stabilizes the closed conformation of the channel. Interacts with CACNA1S; interaction with CACNA1S is important for activation of the RYR1 channel. Interacts with CACNB1. Interacts with TRDN and ASPH; these interactions stimulate RYR1 channel activity. Interacts with SELENON (By similarity).
Interacts with scorpion calcins (AC P0DPT1; AC P0DM30; AC A0A1L4BJ42; AC P59868; AC P60254; AC B8QG00; AC L0GBR1; AC P60252; AC P60253) (By similarity).

Binary interactions

TypeEntry 1Entry 2Number of experimentsIntact
BINARY E9PZQ0Bsg O551083EBI-642079, EBI-643315
BINARY E9PZQ0Camlg P490703EBI-642079, EBI-309114
BINARY E9PZQ0Fkbp1a P268832EBI-642079, EBI-6379901

Protein-protein interaction databases

Chemistry

Miscellaneous

Family & Domains

Features

Showing features for domain, region, repeat, compositional bias, motif.

TypeIDPosition(s)Description
Domain99-154MIR 1
Domain161-206MIR 2
Domain212-266MIR 3
Domain272-329MIR 4
Domain337-394MIR 5
Domain583-799B30.2/SPRY 1
Region671-682Interaction with FKBP1A
Repeat843-9561
Region843-29606 X approximate repeats
Repeat957-10702
Domain1015-1210B30.2/SPRY 2
Region1309-1387Disordered
Repeat1346-13613; truncated
Domain1359-1572B30.2/SPRY 3
Compositional bias1372-1387Basic and acidic residues
Repeat1374-13894; truncated
Region1873-1928Disordered
Compositional bias1874-1923Acidic residues
Region2391-2414Disordered
Repeat2727-28465
Compositional bias2828-2844Basic and acidic residues
Region2828-2859Disordered
Repeat2847-29606
Region3479-3502Disordered
Region3615-3644Interaction with CALM
Domain4078-4106EF-hand
Region4255-4283Disordered
Compositional bias4257-4274Acidic residues
Region4378-4531Disordered
Compositional bias4402-4418Acidic residues
Compositional bias4482-4496Acidic residues
Compositional bias4497-4513Basic and acidic residues
Compositional bias4514-4528Pro residues
Region4586-4618Disordered
Motif4892-4898Selectivity filter

Domain

The calcium 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 sarcoplasmic reticulum (SR) and the T-tubule (PubMed:7621815, PubMed:7724570).
Pore opening is mediated via the cytoplasmic calcium-binding domains that mediate a small rotation of the channel-forming transmembrane regions that then leads to channel opening (By similarity).

Sequence similarities

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    5,035
  • Mass (Da)
    565,039
  • Last updated
    2011-04-05 v1
  • Checksum
    D15D2E764B445573

Computationally mapped potential isoform sequences

There is 1 potential isoform mapped to this entry

View all
EntryEntry nameGene nameLength
A0A1L1SQG7A0A1L1SQG7_MOUSERyr15061

Features

Showing features for sequence conflict, compositional bias.

TypeIDPosition(s)Description
Sequence conflict616in Ref. 5; CAC34624
Compositional bias1372-1387Basic and acidic residues
Sequence conflict1380in Ref. 1; AAP29981
Compositional bias1874-1923Acidic residues
Compositional bias2828-2844Basic and acidic residues
Sequence conflict3484in Ref. 1; AAP29981
Compositional bias4257-4274Acidic residues
Compositional bias4402-4418Acidic residues
Compositional bias4482-4496Acidic residues
Compositional bias4497-4513Basic and acidic residues
Compositional bias4514-4528Pro residues
Sequence conflict4766in Ref. 8; AAA64955
Sequence conflict4821in Ref. 7; CAA58784
Sequence conflict4888in Ref. 7; CAA58784

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AY268935
EMBL· GenBank· DDBJ
AAP29981.1
EMBL· GenBank· DDBJ
mRNA
AC164564
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
AC165142
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
D21798
EMBL· GenBank· DDBJ
BAA21010.1
EMBL· GenBank· DDBJ
Genomic DNA
D21796
EMBL· GenBank· DDBJ
BAA04821.1
EMBL· GenBank· DDBJ
mRNA
D21797
EMBL· GenBank· DDBJ
BAA04822.1
EMBL· GenBank· DDBJ
Genomic DNA
AJ308737
EMBL· GenBank· DDBJ
CAC34624.1
EMBL· GenBank· DDBJ
Genomic DNA
BC051248
EMBL· GenBank· DDBJ
AAH51248.1
EMBL· GenBank· DDBJ
mRNA
BC055487
EMBL· GenBank· DDBJ
AAH55487.1
EMBL· GenBank· DDBJ
mRNA
X83932
EMBL· GenBank· DDBJ
CAA58784.1
EMBL· GenBank· DDBJ
mRNA
U23754
EMBL· GenBank· DDBJ
AAA64955.1
EMBL· GenBank· DDBJ
mRNA
D38216
EMBL· GenBank· DDBJ
BAA07391.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

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