Protein detail
RYR2
Ryanodine receptor 2 (RYR-2) (RyR2) (hRYR-2) (Cardiac muscle ryanodine receptor) (Cardiac muscle ryanodine receptor-calcium release channel) (Type 2 ryanodine receptor)
Entry name RYR2 | UniProt ID | EVMP score 0.50 |
Frequency 1 | Transmembrane count 6 | Protein classification Disease related genesFDA approved drug targetsHuman disease related genesPlasma proteinsPredicted intracellular proteinsPredicted membrane proteinsTransporters |
EVMP score: annotation confidence score.
Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40
Basic Information
Protein Names
Ryanodine receptor 2 (RYR-2) (RyR2) (hRYR-2) (Cardiac muscle ryanodine receptor) (Cardiac muscle ryanodine receptor-calcium release channel) (Type 2 ryanodine receptor)
Protein Class
Disease related genesFDA approved drug targetsHuman disease related genesPlasma proteinsPredicted intracellular proteinsPredicted membrane proteinsTransporters
Protein Function
- Predicted intracellular proteins
- Transporters:Transporter channels and pores
- Disease related genes
- Human disease related genes:Cardiovascular diseases:Cardiac diseases
- FDA approved drug targets:Small molecule drugs
Transmembrane
4282..4302; Helical; 4504..4524; Helical; 4580..4600; Helical; 4730..4750; Helical; 4769..4789; Helical; 4850..4870; Helical
Transmembrane Count
6
Ensembl
Entrez Gene Symbol
Gene Synonym
ARVC2ARVD2VTSIP
Gene Description
Ryanodine receptor 2
Chromosome
1
Position
237042184-237833988
Frequency
1
EVMP Score
0.50
Fluorescence & Localization
Tissue SpecificbrainCell SpecificMicrogliaSingle-Nuclei Brain Specificcentral nervous system macrophageBlood Cell Specificnon-classical monocyte
Function & Pathway
Protein Function
- Predicted intracellular proteins
- Transporters:Transporter channels and pores
- Disease related genes
- Human disease related genes:Cardiovascular diseases:Cardiac diseases
- FDA approved drug targets:Small molecule drugs
Cellular Component
- GO:0005790 smooth endoplasmic reticulum
- GO:0005886 plasma membrane
- GO:0014701 junctional sarcoplasmic reticulum membrane
- GO:0016020 membrane
- GO:0016529 sarcoplasmic reticulum
- GO:0030018 Z disc
- GO:0032991 protein-containing complex
- GO:0033017 sarcoplasmic reticulum membrane
- GO:0034704 calcium channel complex
- GO:0042383 sarcolemma
Molecular Function
- GO:0005219 ryanodine-sensitive calcium-release channel activity
- GO:0005262 calcium channel activity
- GO:0005509 calcium ion binding
- GO:0005515 protein binding
- GO:0005516 calmodulin binding
- GO:0015278 intracellularly gated calcium channel activity
- GO:0019899 enzyme binding
- GO:0034236 protein kinase A catalytic subunit binding
- GO:0034237 protein kinase A regulatory subunit binding
- GO:0042802 identical protein binding
- GO:0043924 suramin binding
- GO:0048763 calcium-induced calcium release activity
Biological Process
KEGG
- hsa04020 Calcium signaling pathway
- KEGG:hsa04024 cAMP signaling pathway
- KEGG:hsa04260 Cardiac muscle contraction
- KEGG:hsa04261 Adrenergic signaling in cardiomyocytes
- KEGG:hsa04371 Apelin signaling pathway
- KEGG:hsa04713 Circadian entrainment
- KEGG:hsa04911 Insulin secretion
- KEGG:hsa04921 Oxytocin signaling pathway
- KEGG:hsa04972 Pancreatic secretion
- KEGG:hsa05020 Prion disease
- KEGG:hsa05022 Pathways of neurodegeneration - multiple diseases
- KEGG:hsa05410 Hypertrophic cardiomyopathy
- KEGG:hsa05412 Arrhythmogenic right ventricular cardiomyopathy
- KEGG:hsa05414 Dilated cardiomyopathy
- KEGG:hsa05415 Diabetic cardiomyopathy
Reactome
Mediation Categories
Clinical-translation mediationFusion and delivery mediationMetabolism mediationReceptor-signaling mediation
Relations & Evidence
Enzyme-Mediated Modification
21 records.
| Substrate Gene Symbol | Enzyme Gene Symbol | Enzyme UniProt ID | Residue Type | Residue Offset | Modification | Database | References |
|---|---|---|---|---|---|---|---|
| RYR2 | RPS6KA3 | P51812 | S | 2,808 | phosphorylation | KEA | KEA:17570479 |
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Ligand-Receptor Signaling
17 records.
| Category | Parent | Database | Transmitter | Receiver | Secreted | Plasma Membrane (Transmembrane) | Plasma Membrane (Peripheral) |
|---|---|---|---|---|---|---|---|
| receptor | receptor | CellTalkDB | No | Yes | No | No | No |
| receptor | receptor | OmniPath | No | Yes | No | No | No |
| intracellular | intracellular | ComPPI | No | No | No | No | No |
| intracellular | intracellular | GO_Intercell | No | No | No | No | No |
| intracellular | intracellular | UniProt_location | No | No | No | No | No |
| intracellular | intracellular | OmniPath | No | No | No | No | No |
| transmembrane | transmembrane | UniProt_location | No | No | No | No | No |
| transmembrane | transmembrane | UniProt_topology | No | No | No | No | No |
| transmembrane | transmembrane | UniProt_keyword | No | No | No | No | No |
| transmembrane | transmembrane | TopDB | No | No | No | No | No |
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Regulatory Interaction Network
3 records.
| Source Protein Symbol | Source UniProt ID | Target Protein Symbol | Target UniProt ID | Is Directed | Is Stimulation | Is Inhibition | Database | References |
|---|---|---|---|---|---|---|---|---|
| SPEG | Q15772 | RYR2 | Q92736 | Yes | No | Yes | SIGNOR | SIGNOR:32683896 |
| KAPCA | P17612 | RYR2 | Q92736 | Yes | Yes | No | phosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPiPTMnetPhosphoPointSIGNORProtMapperHPRDPhosphoSite_KEAKEAHPRD_KEASIGNOR_ProtMapperPhosphoSiteHPRD-phosPhosphoSite_ProtMapper | HPRD:10830164HPRD-phos:10830164KEA:10830164KEA:14715536SIGNOR:14532276ProtMapper:10830164ProtMapper:14532276PhosphoSite:29760186 |
| KCC2A | Q9UQM7 | RYR2 | Q92736 | Yes | Yes | No | phosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPiPTMnetPhosphoPointProtMapperPhosphoSite_KEAKEAphosphoELM_KEAphosphoELMPhosphoSitePhosphoSite_ProtMapper | phosphoELM:14514795PhosphoSite:14532276PhosphoSite:14715536KEA:15790957KEA:14715536PhosphoSite:16709901KEA:14514795PhosphoSite:10830164KEA:17643448PhosphoSite:30571258PhosphoSite:23059182KEA:10830164PhosphoSite:14514795 |
Protein Complex Composition
8 records.
| Component Name | Component Gene Symbols | Component UniProt ID | Stoichiometry | Database | Database IDs | References |
|---|---|---|---|---|---|---|
| HT_DM_Cluster215 | DNAJC10RYR1RYR2RYR3 | P21817Q15413Q8IXB1Q92736 | 1:1:1:1 | Compleat | Compleat:HC3066 | 22036573 |
| Ryanodine 2 complex | RYR2 | Q92736 | 4 | ComplexPortalPDB | intact:EBI-9638199PDB:8uq5 | 209619761475529222822064152760121608439218003898 |
| calcium channel complex | AKAP6ATP2A1FKBP1BPTPARYR2SESTD1TRPC4TRPC5 | O14983P68106Q13023Q15257Q86VW0Q92736Q9UBN4Q9UL62 | 1:1:1:1:1:1:1:1 | Compleat | Compleat:HC436 | 1083016411402072 |
| CALM1FKBP1BRYR2 | P0DP23P68106Q92736 | 4:4:4 | PDB | PDB:8uxlPDB:7u9tPDB:7ua3PDB:8uxmPDB:7ua4 | ||
| CALM1RYR2 | P0DP23Q92736 | 1:1 | PDB | PDB:6y4oPDB:7kl5PDB:6y4p | ||
| GPKOWPRKACAPRKACBPRKAR1APRKAR2APRKXRYR2 | P10644P13861P17612P22694P51817Q92736Q92917 | 1:1:1:1:1:1:1 | NetworkBlastCompleat | Compleat:HC5629 | ||
| CDK17PPP1CBPRKACGPRKAR2APRKXRYR2 | P13861P22612P51817P62140Q00537Q92736 | 1:1:1:1:1:1 | NetworkBlastCompleat | Compleat:HC3994 | ||
| FKBP1BRYR2 | P68106Q92736 | 4:4 | PDB | PDB:8uxgPDB:7u9rPDB:8uxePDB:8uq2PDB:8uq3PDB:8uxfPDB:7u9zPDB:8uxcPDB:7ua9PDB:8uxiPDB:7u9qPDB:8uxhPDB:7ua5PDB:7ua1PDB:7u9xPDB:8uq4 |
Sequence, Structure & Domains
Sequences
Length
4,967
Mass
564,567
Sequence
MADGGEGEDEIQFLRTDDEVVLQCTATIHKEQQKLCLAAEGFGNRLCFLESTSNSKNVPPDLSICTFVLEQSLSVRALQEMLANTVEKSEGQVDVEKWKFMMKTAQGGGHRTLLYGHAILLRHSYSGMYLCCLSTSRSSTDKLAFDVGLQEDTTGEACWWTIHPASKQRSEGEKVRVGDDLILVSVSSERYLHLSYGNGSLHVDAAFQQTLWSVAPISSGSEAAQGYLIGGDVLRLLHGHMDECLTVPSGEHGEEQRRTVHYEGGAVSVHARSLWRLETLRVAWSGSHIRWGQPFRLRHVTTGKYLSLMEDKNLLLMDKEKADVKSTAFTFRSSKEKLDVGVRKEVDGMGTSEIKYGDSVCYIQHVDTGLWLTYQSVDVKSVRMGSIQRKAIMHHEGHMDDGISLSRSQHEESRTARVIRSTVFLFNRFIRGLDALSKKAKASTVDLPIESVSLSLQDLIGYFHPPDEHLEHEDKQNRLRALKNRQNLFQEEGMINLVLECIDRLHVYSSAAHFADVAGREAGESWKSILNSLYELLAALIRGNRKNCAQFSGSLDWLISRLERLEASSGILEVLHCVLVESPEALNIIKEGHIKSIISLLDKHGRNHKVLDVLCSLCVCHGVAVRSNQHLICDNLLPGRDLLLQTRLVNHVSSMRPNIFLGVSEGSAQYKKWYYELMVDHTEPFVTAEATHLRVGWASTEGYSPYPGGGEEWGGNGVGDDLFSYGFDGLHLWSGCIARTVSSPNQHLLRTDDVISCCLDLSAPSISFRINGQPVQGMFENFNIDGLFFPVVSFSAGIKVRFLLGGRHGEFKFLPPPGYAPCYEAVLPKEKLKVEHSREYKQERTYTRDLLGPTVSLTQAAFTPIPVDTSQIVLPPHLERIREKLAENIHELWVMNKIELGWQYGPVRDDNKRQHPCLVEFSKLPEQERNYNLQMSLETLKTLLALGCHVGISDEHAEDKVKKMKLPKNYQLTSGYKPAPMDLSFIKLTPSQEAMVDKLAENAHNVWARDRIRQGWTYGIQQDVKNRRNPRLVPYTLLDDRTKKSNKDSLREAVRTLLGYGYNLEAPDQDHAARAEVCSGTGERFRIFRAEKTYAVKAGRWYFEFETVTAGDMRVGWSRPGCQPDQELGSDERAFAFDGFKAQRWHQGNEHYGRSWQAGDVVGCMVDMNEHTMMFTLNGEILLDDSGSELAFKDFDVGDGFIPVCSLGVAQVGRMNFGKDVSTLKYFTICGLQEGYEPFAVNTNRDITMWLSKRLPQFLQVPSNHEHIEVTRIDGTIDSSPCLKVTQKSFGSQNSNTDIMFYRLSMPIECAEVFSKTVAGGLPGAGLFGPKNDLEDYDADSDFEVLMKTAHGHLVPDRVDKDKEATKPEFNNHKDYAQEKPSRLKQRFLLRRTKPDYSTSHSARLTEDVLADDRDDYDFLMQTSTYYYSVRIFPGQEPANVWVGWITSDFHQYDTGFDLDRVRTVTVTLGDEKGKVHESIKRSNCYMVCAGESMSPGQGRNNNGLEIGCVVDAASGLLTFIANGKELSTYYQVEPSTKLFPAVFAQATSPNVFQFELGRIKNVMPLSAGLFKSEHKNPVPQCPPRLHVQFLSHVLWSRMPNQFLKVDVSRISERQGWLVQCLDPLQFMSLHIPEENRSVDILELTEQEELLKFHYHTLRLYSAVCALGNHRVAHALCSHVDEPQLLYAIENKYMPGLLRAGYYDLLIDIHLSSYATARLMMNNEYIVPMTEETKSITLFPDENKKHGLPGIGLSTSLRPRMQFSSPSFVSISNECYQYSPEFPLDILKSKTIQMLTEAVKEGSLHARDPVGGTTEFLFVPLIKLFYTLLIMGIFHNEDLKHILQLIEPSVFKEAATPEEESDTLEKELSVDDAKLQGAGEEEAKGGKRPKEGLLQMKLPEPVKLQMCLLLQYLCDCQVRHRIEAIVAFSDDFVAKLQDNQRFRYNEVMQALNMSAALTARKTKEFRSPPQEQINMLLNFKDDKSECPCPEEIRDQLLDFHEDLMTHCGIELDEDGSLDGNSDLTIRGRLLSLVEKVTYLKKKQAEKPVESDSKKSSTLQQLISETMVRWAQESVIEDPELVRAMFVLLHRQYDGIGGLVRALPKTYTINGVSVEDTINLLASLGQIRSLLSVRMGKEEEKLMIRGLGDIMNNKVFYQHPNLMRALGMHETVMEVMVNVLGGGESKEITFPKMVANCCRFLCYFCRISRQNQKAMFDHLSYLLENSSVGLASPAMRGSTPLDVAAASVMDNNELALALREPDLEKVVRYLAGCGLQSCQMLVSKGYPDIGWNPVEGERYLDFLRFAVFCNGESVEENANVVVRLLIRRPECFGPALRGEGGNGLLAAMEEAIKIAEDPSRDGPSPNSGSSKTLDTEEEEDDTIHMGNAIMTFYSALIDLLGRCAPEMHLIHAGKGEAIRIRSILRSLIPLGDLVGVISIAFQMPTIAKDGNVVEPDMSAGFCPDHKAAMVLFLDRVYGIEVQDFLLHLLEVGFLPDLRAAASLDTAALSATDMALALNRYLCTAVLPLLTRCAPLFAGTEHHASLIDSLLHTVYRLSKGCSLTKAQRDSIEVCLLSICGQLRPSMMQHLLRRLVFDVPLLNEHAKMPLKLLTNHYERCWKYYCLPGGWGNFGAASEEELHLSRKLFWGIFDALSQKKYEQELFKLALPCLSAVAGALPPDYMESNYVSMMEKQSSMDSEGNFNPQPVDTSNITIPEKLEYFINKYAEHSHDKWSMDKLANGWIYGEIYSDSSKVQPLMKPYKLLSEKEKEIYRWPIKESLKTMLAWGWRIERTREGDSMALYNRTRRISQTSQVSVDAAHGYSPRAIDMSNVTLSRDLHAMAEMMAENYHNIWAKKKKMELESKGGGNHPLLVPYDTLTAKEKAKDREKAQDILKFLQINGYAVSRGFKDLELDTPSIEKRFAYSFLQQLIRYVDEAHQYILEFDGGSRGKGEHFPYEQEIKFFAKVVLPLIDQYFKNHRLYFLSAASRPLCSGGHASNKEKEMVTSLFCKLGVLVRHRISLFGNDATSIVNCLHILGQTLDARTVMKTGLESVKSALRAFLDNAAEDLEKTMENLKQGQFTHTRNQPKGVTQIINYTTVALLPMLSSLFEHIGQHQFGEDLILEDVQVSCYRILTSLYALGTSKSIYVERQRSALGECLAAFAGAFPVAFLETHLDKHNIYSIYNTKSSRERAALSLPTNVEDVCPNIPSLEKLMEEIVELAESGIRYTQMPHVMEVILPMLCSYMSRWWEHGPENNPERAEMCCTALNSEHMNTLLGNILKIIYNNLGIDEGAWMKRLAVFSQPIINKVKPQLLKTHFLPLMEKLKKKAATVVSEEDHLKAEARGDMSEAELLILDEFTTLARDLYAFYPLLIRFVDYNRAKWLKEPNPEAEELFRMVAEVFIYWSKSHNFKREEQNFVVQNEINNMSFLITDTKSKMSKAAVSDQERKKMKRKGDRYSMQTSLIVAALKRLLPIGLNICAPGDQELIALAKNRFSLKDTEDEVRDIIRSNIHLQGKLEDPAIRWQMALYKDLPNRTDDTSDPEKTVERVLDIANVLFHLEQKSKRVGRRHYCLVEHPQRSKKAVWHKLLSKQRKRAVVACFRMAPLYNLPRHRAVNLFLQGYEKSWIETEEHYFEDKLIEDLAKPGAEPPEEDEGTKRVDPLHQLILLFSRTALTEKCKLEEDFLYMAYADIMAKSCHDEEDDDGEEEVKSFEEKEMEKQKLLYQQARLHDRGAAEMVLQTISASKGETGPMVAATLKLGIAILNGGNSTVQQKMLDYLKEKKDVGFFQSLAGLMQSCSVLDLNAFERQNKAEGLGMVTEEGSGEKVLQDDEFTCDLFRFLQLLCEGHNSDFQNYLRTQTGNNTTVNIIISTVDYLLRVQESISDFYWYYSGKDVIDEQGQRNFSKAIQVAKQVFNTLTEYIQGPCTGNQQSLAHSRLWDAVVGFLHVFAHMQMKLSQDSSQIELLKELMDLQKDMVVMLLSMLEGNVVNGTIGKQMVDMLVESSNNVEMILKFFDMFLKLKDLTSSDTFKEYDPDGKGVISKRDFHKAMESHKHYTQSETEFLLSCAETDENETLDYEEFVKRFHEPAKDIGFNVAVLLTNLSEHMPNDTRLQTFLELAESVLNYFQPFLGRIEIMGSAKRIERVYFEISESSRTQWEKPQVKESKRQFIFDVVNEGGEKEKMELFVNFCEDTIFEMQLAAQISESDLNERSANKEESEKERPEEQGPRMAFFSILTVRSALFALRYNILTLMRMLSLKSLKKQMKKVKKMTVKDMVTAFFSSYWSIFMTLLHFVASVFRGFFRIICSLLLGGSLVEGAKKIKVAELLANMPDPTQDEVRGDGEEGERKPLEAALPSEDLTDLKELTEESDLLSDIFGLDLKREGGQYKLIPHNPNAGLSDLMSNPVPMPEVQEKFQEQKAKEEEKEEKEETKSEPEKAEGEDGEKEEKAKEDKGKQKLRQLHTHRYGEPEVPESAFWKKIIAYQQKLLNYFARNFYNMRMLALFVAFAINFILLFYKVSTSSVVEGKELPTRSSSENAKVTSLDSSSHRIIAVHYVLEESSGYMEPTLRILAILHTVISFFCIIGYYCLKVPLVIFKREKEVARKLEFDGLYITEQPSEDDIKGQWDRLVINTQSFPNNYWDKFVKRKVMDKYGEFYGRDRISELLGMDKAALDFSDAREKKKPKKDSSLSAVLNSIDVKYQMWKLGVVFTDNSFLYLAWYMTMSVLGHYNNFFFAAHLLDIAMGFKTLRTILSSVTHNGKQLVLTVGLLAVVVYLYTVVAFNFFRKFYNKSEDGDTPDMKCDDMLTCYMFHMYVGVRAGGGIGDEIEDPAGDEYEIYRIIFDITFFFFVIVILLAIIQGLIIDAFGELRDQQEQVKEDMETKCFICGIGNDYFDTVPHGFETHTLQEHNLANYLFFLMYLINKDETEHTGQESYVWKMYQERCWEFFPAGDCFRKQYEDQLN
Alternative Products
Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=Q92736-1; Sequence=Displayed; Name=2; IsoId=Q92736-2; Sequence=VSP_005953
Alternative Sequence
3715; E -> EVTGSQRSK (in isoform 2)
3D Structural Models
Turn
53..57; 108..110; 139..141; 186..188; 239..242; 283..286; 300..302; 356..358; 366..368
Helix
63..65; 256..258; 265..269; 271..273; 319..321; 324..327; 410..437; 442..444; 449..462; 472..491; 494..506; 511..518; 520..541; 3584..3604; 4247..4272
Beta Strand
19..28; 31..38; 48..51; 67..73; 118..127; 129..132; 145..151; 159..166; 180..185; 191..196; 198..208; 212..218; 233..238; 243..246; 250..252; 261..263; 275..280; 295..299; 305..308; 310..312; 314..317; 329..336; 340..342; 360..365; 371..375; 388..396; 403..407; 508..510
3D Structure
Electron microscopy (22); X-ray crystallography (4)
Domain & Motif Annotations
Compositional Bias
1863..1874; Basic and acidic residues; 1881..1891; Basic and acidic residues; 4211..4229; Basic and acidic residues; 4415..4459; Basic and acidic residues
Repeat
853..966; 1; 967..1080; 2; 2692..2810; 3; 2812..2925; 4
Coiled Coil
4412..4445
Domain (CC)
The calcium release channel activity resides in the C-terminal region while the remaining part of the protein resides in the cytoplasm.
Domain (FT)
110..165; MIR 1; 172..217; MIR 2; 225..280; MIR 3; 286..343; MIR 4; 351..408; MIR 5; 599..809; B30.2/SPRY 1; 1025..1222; B30.2/SPRY 2; 1337..1562; B30.2/SPRY 3
Region
853..2925; 4 X approximate repeats; 1856..1891; Disordered; 2354..2379; Disordered; 3581..3610; Interaction with CALM; 4210..4229; Disordered; 4415..4467; Disordered
Protein Families
- Ryanodine receptor (TC 1.A.3.1) family
- RYR2 subfamily
Sequence Similarities
Belongs to the ryanodine receptor (TC 1.A.3.1) family. RYR2 subfamily.
Clinical Relevance
Disease Involvement
CardiomyopathyDisease variantFDA approved drug targets
Drug Targets
FDA approved drug targets
Drugs
Antibody
Interaction Protein
ENSG00000119782
Interaction Count
1
Interaction Dataset
intact_biogrid