Go Annotations as Summary Text (Tabular View) (GO Graph)

GO curators for mouse genes have assigned the following annotations to the gene product of Ryr2. (This text reflects annotations as of Wednesday, January 23, 2013.)

---

Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a ryanodine receptor found in cardiac muscle sarcoplasmic reticulum. The encoded protein is one of the components of a calcium channel, composed of a tetramer of the ryanodine receptor proteins and a tetramer of FK506 binding protein 1B proteins, that supplies calcium to cardiac muscle. Mutations in this gene are associated with stress-induced polymorphic ventricular tachycardia and arrhythmogenic right ventricular dysplasia. [provided by RefSeq, Jul 2008]

---

Summary text based on GO annotations supported by experimental evidence in mouse

• Researchers have inferred from direct assay, that the gene product of Ryr2
  • participates in the following biological processes:
    • BMP signaling pathway ^[7]
    • calcium ion transmembrane transport ^{[9, 10, 13, 15]}
    • calcium ion transport ^{[10, 15]}
    • canonical Wnt receptor signaling pathway ^[7]
    • cellular response to caffeine ^{[9, 14]}
    • response to caffeine ^{[10, 15]}
    • response to hypoxia ^[6]
  • performs the following molecular functions:
    • calcium channel activity ^[9]
    • calmodulin binding ^[13]
    • intracellular ligand-gated calcium channel activity ^[15]
    • ryanodine-sensitive calcium-release channel activity ^{[10, 13]}
  • is located in the following cellular components:
    • membrane ^[13]
    • sarcoplasmic reticulum ^[3]
    • sarcoplasmic reticulum membrane ^{[5, 11]}
    • Z disc ^{[2, 8]}
• The gene product of Ryr2 has been shown to bind to the gene products of Fkbp1b. ^[3] Researchers have inferred, based on physical interactions, that the gene product of Ryr2
  • participates in the following biological processes:
    • calcium ion transport ^[8]
  • performs the following molecular functions:
    • binding ^[13]
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Ryr2
  • participates in the following biological processes:
    • calcium ion transmembrane transport ^[4]
    • calcium ion transport ^[9]
    • calcium-mediated signaling ^[9]
    • cardiac muscle hypertrophy ^[13]
    • cellular calcium ion homeostasis ^[9]
    • cytosolic calcium ion transport ^[13]
    • embryonic heart tube morphogenesis ^[9]
    • left ventricular cardiac muscle tissue morphogenesis ^[13]
    • positive regulation of heart rate ^{[13, 14]}
    • positive regulation of ryanodine-sensitive calcium-release channel activity by adrenergic receptor signaling pathway involved in positive regulation of cardiac muscle contraction ^[1]
    • Purkinje myocyte to ventricular cardiac muscle cell signaling ^[1]
    • regulation of heart rate ^[1]
    • regulation of ventricular cardiac muscle cell action potential ^[1]
    • release of sequestered calcium ion into cytosol by sarcoplasmic reticulum ^[14]
  • performs the following molecular functions:
    • protein self-association ^[15]
• Researchers have inferred, based on genetic interactions, that the gene product of Ryr2
  • participates in the following biological processes:
    • regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion based on interactions with Fkbp1b ^[12]
  • is located in the following cellular components:
    • intracellular based on interactions with Fkbp1b ^[12]
• Based on the experimental annotations above, MGI curators have inferred, that the gene product of Ryr2
  • is located in the following cellular components:
    • integral to membrane ^[10]

---

Summary text based on GO annotations supported by experimental evidence in other organisms

• From comparative sequence analysis (see table for details), MGI curators have determined that the gene product of Ryr2:
  • participates in the following biological processes:
    • calcium ion transport
    • cardiac muscle contraction
    • cytosolic calcium ion homeostasis
    • detection of calcium ion
    • intrinsic apoptotic signaling pathway in response to osmotic stress
    • reduction of cytosolic calcium ion concentration
    • response to caffeine
    • response to calcium ion
    • response to magnesium ion
    • response to redox state
    • sarcoplasmic reticulum calcium ion transport
  • performs the following molecular functions:
    • calcium-induced calcium release activity
    • calcium-release channel activity
    • calmodulin binding
    • identical protein binding
    • protein kinase A catalytic subunit binding
    • protein kinase A regulatory subunit binding
    • ryanodine-sensitive calcium-release channel activity
    • suramin binding
  • is located in the following cellular components:
    • A band
    • calcium channel complex
    • endoplasmic reticulum
    • neuron projection
    • protein complex
    • sarcolemma
    • sarcoplasmic reticulum
    • sarcoplasmic reticulum membrane
    • Z disc

---

Summary text based on GO annotations supported by structural data

• Ryr2 encodes a protein or proteins that contain the following InterPro domains: B30.2/SPRY domain, Calcium-binding EF-hand, Concanavalin A-like lectin/glucanases superfamily, EF-HAND 2, EF-hand-like domain, Inositol 1,4,5-trisphosphate/ryanodine receptor, Intracellular calcium-release channel, Ion transport domain, MIR motif, Ryanodine receptor, Ryanodine receptor Ryr, Ryanodine Receptor TM 4-6, Ryanodine receptor-related, RyR/IP3R Homology associated domain, SPla/RYanodine receptor SPRY, SPla/RYanodine receptor subgroup, indicating that the gene product:
  • participates in the following biological processes:
    • ion transmembrane transport
    • ion transport
    • transmembrane transport
  • performs the following molecular functions:
    • calcium ion binding
    • ion channel activity

---

Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Ryr2 indicates that it:
  • participates in the following biological processes:
    • ion transmembrane transport
    • ion transport
    • multicellular organismal development
    • transport
  • performs the following molecular functions:
    • ion channel activity

---

References

1. Cerrone M et al. (2007) Arrhythmogenic mechanisms in a mouse model of catecholaminergic polymorphic ventricular tachycardia. Circ Res, 101:1039-48. (PubMed:17872467)
2. Chopra N et al. (2009) Ablation of triadin causes loss of cardiac Ca2+ release units, impaired excitation-contraction coupling, and cardiac arrhythmias. Proc Natl Acad Sci U S A, 106:7636-41. (PubMed:19383796)
3. Fauconnier J et al. (2011) Ryanodine receptor leak mediated by caspase-8 activation leads to left ventricular injury after myocardial ischemia-reperfusion. Proc Natl Acad Sci U S A, 108:13258-63. (PubMed:21788490)
4. Fernandez-Velasco M et al. (2011) RyRCa2+ leak limits cardiac Ca2+ window current overcoming the tonic effect of calmodulinin mice. PLoS One, 6:e20863. (PubMed:21673970)
5. Huang F et al. (2006) Analysis of calstabin2 (FKBP12.6)-ryanodine receptor interactions: rescue of heart failure by calstabin2 in mice. Proc Natl Acad Sci U S A, 103:3456-61. (PubMed:16481613)
6. Jurkovicova D et al. (2008) Hypoxia differently modulates gene expression of inositol 1,4,5-trisphosphate receptors in mouse kidney and HEK 293 cell line. Ann N Y Acad Sci, 1148:421-7. (PubMed:19120137)
7. Liu Y et al. (2007) Sox17 is essential for the specification of cardiac mesoderm in embryonic stem cells. Proc Natl Acad Sci U S A, 104:3859-64. (PubMed:17360443)
8. Takeda T et al. (2005) Presenilin 2 regulates the systolic function of heart by modulating Ca2+ signaling. FASEB J, 19:2069-71. (PubMed:16204356)
9. Takeshima H et al. (1998) Embryonic lethality and abnormal cardiac myocytes in mice lacking ryanodine receptor type 2. EMBO J, 17:3309-16. (PubMed:9628868)
10. Wang R et al. (2004) The predicted TM10 transmembrane sequence of the cardiac Ca2+ release channel (ryanodine receptor) is crucial for channel activation and gating. J Biol Chem, 279:3635-42. (PubMed:14593104)
11. Wang YX et al. (2004) FKBP12.6 and cADPR regulation of Ca2+ release in smooth muscle cells. Am J Physiol Cell Physiol, 286:C538-46. (PubMed:14592808)
12. Wehrens XH et al. (2003) FKBP12.6 deficiency and defective calcium release channel (ryanodine receptor) function linked to exercise-induced sudden cardiac death. Cell, 113:829-40. (PubMed:12837242)
13. Yamaguchi N et al. (2007) Early cardiac hypertrophy in mice with impaired calmodulin regulation of cardiac muscle Ca release channel. J Clin Invest, 117:1344-53. (PubMed:17431507)
14. Yang HT et al. (2002) The ryanodine receptor modulates the spontaneous beating rate of cardiomyocytes during development. Proc Natl Acad Sci U S A, 99:9225-30. (PubMed:12089338)
15. Zhao M et al. (1999) Molecular identification of the ryanodine receptor pore-forming segment. J Biol Chem, 274:25971-4. (PubMed:10473538)

---

---

Gene Ontology Evidence Code Abbreviations:

EXP Inferred from experiment

IC Inferred by curator

IDA Inferred from direct assay

IEA Inferred from electronic annotation

IGI Inferred from genetic interaction

IMP Inferred from mutant phenotype

IPI Inferred from physical interaction

ISS Inferred from sequence or structural similarity

ISO Inferred from sequence orthology

ISA Inferred from sequence alignment

ISM Inferred from sequence model

NAS Non-traceable author statement

ND No biological data available

RCA Reviewed computational analysis

TAS Traceable author statement

---