TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
*1.A.3.1.1









Ryanodine receptor Ca2+ release channel, RyR2.  Causes Ca2+ release from the E.R. and consequent cardiac arrhythmia (Chelu and Wehrens, 2007). Associates with FKBP12.6, but phosphorylation by protein kinase A on serine-2030 causes dissociation (Jones et al., 2008).  Enhanced binding of calmodulin corrects arrhythmogenic channel disorder in myocytes (Fukuda et al. 2014).  RyR2s can open spontaneously, giving rise to spatially-confined Ca2+ release events known as "sparks." They are organized in a lattice to form clusters in the junctional sarcoplasmic reticulum membrane. The spatial arrangement of RyR2s within clusters strongly influences the frequency of Ca2+ sparks (Walker et al. 2015).  Structures of RyR2 from porcine heart in both the open and closed states at near atomic resolutions have been determined using single-particle electron cryomicroscopy (Peng et al. 2016). Structural comparisons revealed breathing motions of the overall cytoplasmic region resulting from the interdomain movements of amino-terminal domains (NTDs), Helical domains, and Handle domains, whereas little intradomain shifts are observed in these armadillo repeat-containing domains. Outward rotations of the central domains, which integrate the conformational changes of the cytoplasmic region, lead to the dilation of the cytoplasmic gate through coupled motions. These observations provide insight into the gating mechanism of RyRs (Peng et al. 2016). RyR2 is subject ot regulation by cytoplasmic Zn2+ (>1nM), and this regulation plays a key role in diastolic SR Ca2+ leakage in cardiac muscle (Reilly-O'Donnell et al. 2017).

Eukaryota
Metazoa
Cardiac muscle RyR-CaC of Homo sapiens
*1.A.3.1.2









The Ryanodine receptor Ca2+/K+ release tetrameric channel, RyR1, present in skeletal muscle, is 5038 aas long. Mutants are linked to core myopathies such as Central Core Disease, Malignant Hyperthermia and Multiple Minicore Disease) (Xu et al., 2008). RyR1 interacts with CLIC2 to modulate its channel activity (Meng et al., 2009).  A model pf RyR1 has been constructed encompassing the six transmembrane helices to calculate the RyR1 pore region conductance, to analyze its structural stability, and to hypothesize the mechanism of the Ile4897 CCD-associated mutation. The calculated conductance of the wild-type RyR1 suggests that the pore structure can sustain ion currents measured in single-channel experiments. Shirvanyants et al. 2014 observed a stable pore structure with multiple cations occupying the selectivity filter and cytosolic vestibule, but not the inner chamber. Stability of the selectivity filter depends on interactions between the I4897 residue and several hydrophobic residues of the neighboring subunit. Loss of these interactions in the case of the polar substitution, I4897T, results in destabilization of the selectivity filter, a possible cause of the CCD-specific reduced Ca2+ conductance.  A 4.8 Å structure of the rabbit orthologue in the closed state of this 2.3 MDa tetramer (3757 aas/protomer) reveals the pore, the VIC superfamily fold and a potential mechanism of Ca2+ gating (Zalk et al. 2015).  A cryo-electron microscopy analysis revealed the structure at 6.1 Å resolution (Efremov et al. 2015). The transmembrane domain represents a chimaera of voltage-gated sodium and pH-activated ion channels. They identified the calcium-binding EF-hand domain and showed that it functions as a conformational switch, allosterically gating the channel.  Malignant hyperthermia-associated RyR1 mutations in the S2-S3 loop confer RyR2-type Ca2+- and Mg2+-dependent channel regulation (Gomez et al. 2016).  Structural analyses have elucidated a novel channel-gating mechanism and a novel ion selectivity mechanism for RyR1 (Wei et al. 2016).  Samsó 2016 reviewed structural determinations of RyR by cryoEM and  analyzed the first near-atomic structures, revealing a complex orchestration of domains controlling channel function.  The structural basis for gating and activation have been determined (des Georges et al. 2016). Junctin and triadin bind to different sites on RyR1; triadin plays an important role in ensuring rapid Ca2+ release during excitation-contraction coupling in skeletal muscle.  RyR1 structure/functioin has been reviewed (Zalk and Marks 2017).

Eukaryota
Metazoa
RyR1 of Homo sapiens (P21817)
*1.A.3.1.3









The Ryanodine Receptor homologue, RyRi (5,101 aas; 77% identical to the A gambiae RyR) of the aphid, Myzus persicae, is the tartet of diamide insecticides and is made without alternative splicing (Troczka et al. 2015). The almost identical well characterized orthologue from the oriential fruit fly, Bactrocera dorsalis also has its 6 TMSs C-terminal (Yuan et al. 2014).

Eukaryota
Metazoa
RyRi of Anopheles gambiae (Q7PMK5)
*1.A.3.1.4









Ryanodine receptor (RyR) of 5107 aas.  Flubendiamine, a RyR-activating insecticide, induced Ca2+ release in hemocytes (Kato et al. 2009; Wu et al. 2013).

Eukaryota
Metazoa
RyR of Pieris rapae (white cabbage butterfly)
*1.A.3.1.5









Ryanodine receptor (RyR) of 5127 aas and 6 TMSs. Intracellular calcium channel that is required for proper muscle function during embryonic development and may be essential for excitation-contraction coupling in larval body wall muscles. Mediates general anaesthesia by halothane (Gao et al. 2013) and confers sensitivity to diamide insecticides (Tao et al. 2013).

Eukaryota
Metazoa
RyR of Drosophila melanogaster (Fruit fly)
*1.A.3.1.6









Ryanodine-sensitive calcium release channel receptor, RyR of 5071 aas and 6 putative TMSs.  The tissue lecalization has been described (Hamada et al. 2002).  Required for neuronal regeneration (Sun et al. 2014).

Eukaryota
Metazoa
RyR of Caenorhabditis elegans
*1.A.3.1.7









Aphid ryanodine receptor RyR) of 5105 aas and 6 TMSs, a target of insecticides.  The sequence of the Acyrthosiphon pisum (Pea aphid) is provided below, but the Toxoptera citricida (98% identiy; Brown citrus aphid; Aphis citricidus) RyR was studied (Wang et al. 2015).

Aphid RyR of Acyrthosiphon pisum (Pea aphid)
*1.A.3.2.1









Inositol 1,4,5-trisphosphate receptor-2 with 2701 aas and 6 TMSs.  Mediates release of intracellular calcium which is regulated by cAMP both dependently and independently of PKA and plays a critical role in cell cycle regulation and cell proliferation.  High level expression in humans is an indication of cytogenetically normal acute myeloid leukemia (CN-AML) (Shi et al. 2015).

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Eukaryota
Metazoa
Brain IP3-CaC of Rattus norvegicus
*1.A.3.2.2









The Inositol 1,4,5- triphosphate (InsP3)-like receptor (2838aas). Receptor for inositol 1,4,5-trisphosphate, a second messenger that mediates the release of intracellular calcium. May be involved in visual and olfactory transduction as well as myoblast proliferation.   Loss in adult neurons results in obesity in adult flies (Subramanian et al. 2013).

Eukaryota
Metazoa
InsP3l receptor Drosophila melanogaster (P29993)
*1.A.3.2.3









The cation channel family protein, IsnP3-like protein (2872aas)
Eukaryota
Intramacronucleata
InsP3-like protein of Tetrahymena themophila (Q23K98)
*1.A.3.2.4









The Inositol 1,4,5- triphosphate (InsP3)-like receptor (3036aas) (Ladenburger et al. 2009; Docampo et al. 2013Docampo et al. 2013).

Eukaryota
Intramacronucleata
InsP3l receptor of Paramecium tetraaurelia (A0CX44)
*1.A.3.2.5









Inositol 1,4,5-triphosphate receptor type 1 splice variant, IP(3)R1 (Subedi et al., 2012).  The human orthologue, IP3R3, is regulated at the ER-mitochondrion interface by BCL-XL (TC# 1.A.21.1.6) (Williams et al. 2016).

Eukaryota
Metazoa
IP(3)R1 of Rattus norvegicus (Q63269)
*1.A.3.2.6









Inositol 1,4,5-trisphosphate receptor type 1 (IP3 receptor isoform 1) (IP3R 1) (InsP3R1) (Type 1 inositol 1,4,5-trisphosphate receptor) (Type 1 InsP3 receptor)
Eukaryota
Metazoa
ITPR1 of Homo sapiens
*1.A.3.2.7









Contractile vacuole complex calcium release channel (CRC)II; IP3Rn (Ladenburger et al. 2006).  Functions in osmoregulation by promoting expulsion of water and some ions including Ca2+.  Also functions in calcium homeostasis (Ladenburger et al. 2006; Docampo et al. 2013Docampo et al. 2013).

Eukaryota
Intramacronucleata
IP3Rn or CRCII of Paramecium trtraurelia
*1.A.3.2.8









Putative IP3R calcium-release channel VI-3 of 2021 aas (Docampo et al., 2013).

Eukaryota
Intramacronucleata
Calcium-release channel VI-3 of Paramecium tetraurelia
*1.A.3.2.9









CRCI-1a; IP3R.  Functions similarly to TC# 1.A.3.2.7 (Docampo et al. 2013).  Cortical Ca2+ stores (alveolar sacs) are activated during stimulated trichocyst exocytosis, mediating store-operated Ca2+ entry (SOCE). Ca2+ release channels (CRCs) localise to alveoli and are Ryanodine receptor-like proteins (RyR-LPs) as well as inositol 1,4,5-trisphosphate receptors (IP3Rs), members of the CRC family with 6 subfamilies (Plattner 2014).

Eukaryota
Intramacronucleata
CRCI-1a of Paramecium tetraurelia
*1.A.3.2.10









Calcium release channel III, CRCIII1a of 2598 aas.  Associated with recycling vesicles engaged in phagosome formation (Ladenburger and Plattner 2011).

Eukaryota
Intramacronucleata
CRCIII1a of Paramecium tetraurelia
*1.A.3.2.11









Calcium release channel IV3b, CRCIV3b, of 3127 aas.  Display structural and functional properties of ryanodine receptors (Ladenburger et al. 2009).  Localized to the alveolar sacs of the cortical subplasmalemmal Ca2+-stores (Plattner et al. 2012).  Involved in exocytosis in response to ryanodine receptor agonists (Docampo et al. 2013).

Eukaryota
Intramacronucleata
CRCIV3b of Paramecium tetraurelia
*1.A.3.2.12









Calcium release channel V-4b, CRCV4b of 2589 aas.  Occurs in parasomal (alveolar) sacs (clathrin coated pits) (Docampo et al. 2013).

Eukaryota
Intramacronucleata
CRCV4b of Paramecium tetraurelia
*1.A.3.2.13









Calcium release channel VI-2b, CRCVI2b.  Localized to the contractile vacuole (Docampo et al. 2013).

Eukaryota
Intramacronucleata
CRCVI2b of Paramecium tetraurelia
*1.A.3.2.14









Endoplasmic reticular inositol triphosphate receptor, IP3R of 3099 aas (Docampo et al. 2013).

Eukaryota
Kinetoplastida
IP3R of Trypanosoma brucei
*1.A.3.2.16









Inositol triphosphate receptor, IP3R, also called Itr-1, Dec-4 and Ife-1, of 2892 aas and 6 TMSs (Baylis and Vázquez-Manrique 2012).  Receptor for inositol 1,4,5-trisphosphate, a second messenger that regulates intracellular calcium homeostasis. Binds in vitro to both 1,4,5-InsP3 and 2,4,5-InsP3 with high affinity and does not discriminate between the phosphate at the 1 or 2 position. Can also bind inositol 1,3,4,5-tetrakisphosphate (1,3,4,5-InsP4) and inositol 4,5-bisphosphate (4,5-InsP2), but with lower affinity. Acts as a timekeeper/rhythm generator via calcium signaling, affecting the defecation cycle and pharyngeal pumping (Dal Santo et al. 1999). Affects normal hermaphrodite and male fertility as a participant in intracellular signaling by acting downstream of let-23/lin-3 which regulates ovulation, spermathecal valve dilation and male mating behavior (Walker et al. 2002Gower et al. 2005). Important for early embryonic development; controls epidermal cell migration and may also regulate filopodial protrusive activity during epithelial morphogenesis (Thomas-Virnig et al. 2004; ). Component of inositol trisphosphate (IP3)-mediated downstream signaling pathways that controls amphid sensory neuronal (ASH)-mediated response to nose touch and benzaldehyde (Walker et al. 2009).

Eukaryota
Metazoa
IP3 receptor of Caenorhabditis elegans
*1.A.3.2.17









IP3R of 3140 aas, RyR1 (Wheeler and Brownlee 2008).

IP3R of Chlamydomonas reinhardtii