CADPR
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CADPR
Cyclic ADP Ribose, frequently abbreviated as cADPR, is a cyclic adenine nucleotide (like cAMP) with two phosphate groups present on 5' OH of the adenosine (like ADP), further connected to another ribose at the 5' position, which, in turn, closes the cycle by glycosidic bonding to the nitrogen 1 (N1) of the same adenine base (whose position N9 has the glycosidic bond to the other ribose). The N1-glycosidic bond to adenine is what distinguishes cADPR from ADP-ribose (ADPR), the non-cyclic analog. cADPR is produced from nicotinamide adenine dinucleotide (NAD+) by ADP-ribosyl cyclases ( EC 3.2.2.5) as part of a second messenger system. Function cADPR is a cellular messenger for calcium signaling. It stimulates calcium-induced calcium release at lower cytosolic concentrations of Ca2+. The primary target of cADPR is the endoplasmic reticulum Ca2+ uptake mechanism. cADPR mobilizes Ca2+ from the endoplasmic reticulum by activation of ryanodine receptors, a critical step in muscle contracti ...
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CD38
CD38 (cluster of differentiation 38), also known as cyclic ADP ribose hydrolase is a glycoprotein found on the surface of many immune cells (white blood cells), including CD4+, CD8+, B lymphocytes and natural killer cells. CD38 also functions in cell adhesion, signal transduction and calcium signaling. In humans, the CD38 protein is encoded by the CD38 gene which is located on chromosome 4. CD38 is a paralog of CD157, which is also located on chromosome 4 (4p15) in humans. History CD38 was first identified in 1980 as a surface marker (cluster of differentiation) of thymus cell lymphocytes. In 1992 it was additionally described as a surface marker on B cells, monocytes, and natural killer cells (NK cells). About the same time, CD38 was discovered to be not simply a marker of cell types, but an activator of B cells and T cells. In 1992 the enzymatic activity of CD38 was discovered, having the capacity to synthesize the calcium-releasing second messengers cyclic ADP-ribose (cA ...
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NAADP
Nicotinic acid adenine dinucleotide phosphate, (NAADP), is a Ca2+-mobilizing second messenger synthesised in response to extracellular stimuli. Like its mechanistic cousins, IP3 and cyclic adenosine diphosphoribose (Cyclic ADP-ribose), NAADP binds to and opens Ca2+ channels on intracellular organelles, thereby increasing the intracellular Ca2+ concentration which, in turn, modulates sundry cellular processes (see Calcium signalling). Structurally, it is a dinucleotide that only differs from the house-keeping enzyme cofactor, NADP by a hydroxyl group (replacing the nicotinamide amino group) and yet this minor modification converts it into the most potent Ca2+-mobilizing second messenger yet described. NAADP acts across phyla from plants to humans. Discovery In their landmark 1987 paper, Hon Cheung Lee and colleagues discovered not one but two Ca2+-mobilizing second messengers, cADPR and NAADP from the effects of nucleotides on Ca2+ release in sea urchin egg homogenates. It turns ...
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SARM1
Sterile alpha and TIR motif containing 1 Is an enzyme that in humans is encoded by the ''SARM1'' gene. It is the most evolutionarily conserved member of the Toll/Interleukin receptor-1 (TIR) family. SARM1's TIR domain has intrinsic NADase enzymatic activity that is highly conserved from archaea, plants, nematode worms, fruit flies, and humans. In mammals, SARM1 is highly expressed in neurons, where it resides in both cell bodies and axons, and can be associated with mitochondria. Function While SARM1 has been studied as a Toll-like receptor adaptor protein in an immune context, its most well-studied function in mammals is as a sensor of metabolic stress and an executioner of neuronal cell body and axon death. Because SARM1 is highly expressed in the nervous system, most studies of SARM1 focus on neuron degeneration, but some SARM1 can be found in other tissues, notably macrophages and T cells. By generating cADPR or NAADP, SARM1 may function as a Ca2+-signaling enzyme sim ...
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BST1
Bst1 (Bone marrow stromal cell antigen 1, ADP-ribosyl cyclase 2, CD157) is an enzyme that in humans is encoded by the ''BST1'' gene. CD157 is a Gene duplication#Identifying duplications in sequenced_genomes, paralog of CD38, both of which are located on chromosome 4 (4p15) in humans. Bst1 is a stromal cell line-derived glycosylphosphatidylinositol-anchored molecule that facilitates pre-B-cell growth. The deduced amino acid sequence exhibits 33% similarity with CD38. BST1 expression is enhanced in bone marrow stromal cell lines derived from patients with rheumatoid arthritis. The polyclonal B-cell abnormalities in rheumatoid arthritis may be, at least in part, attributed to BST1 overexpression in the stromal cell population. CD157 and CD38 are both members of the ADP-ribosyl cyclase family of enzymes that Catalysis, catalyze the formation of nicotinamide and adenosine diphosphate ribose (ADPR) or cyclic ADP-ribose (cADPR) from Nicotinamide adenine dinucleotide, NAD+, although CD157 ...
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Nicotinamide Adenine Dinucleotide
Nicotinamide adenine dinucleotide (NAD) is a coenzyme central to metabolism. Found in all living cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an adenine nucleobase and the other nicotinamide. NAD exists in two forms: an oxidized and reduced form, abbreviated as NAD and NADH (H for hydrogen), respectively. In metabolism, nicotinamide adenine dinucleotide is involved in redox reactions, carrying electrons from one reaction to another. The cofactor is, therefore, found in two forms in cells: NAD is an oxidizing agent – it accepts electrons from other molecules and becomes reduced. This reaction, also with H+, forms NADH, which can then be used as a reducing agent to donate electrons. These electron transfer reactions are the main function of NAD. However, it is also used in other cellular processes, most notably as a substrate of enzymes in adding or removing chemical groups to ...
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Adenosine Diphosphate Ribose
Adenosine diphosphate ribose (ADPR) is an ester molecule formed into chains by the enzyme poly ADP ribose polymerase. ADPR is created from cyclic ADP-ribose (cADPR) by the CD38 enzyme using nicotinamide adenine dinucleotide (NAD+) as a cofactor. ADPR binds to and activates the TRPM2 ion channel. ADPR is the most potent agonist of the TRPM2 channel. cADPR also binds to TPRM2, and the action of both molecules is synergistic, with both molecules enhancing the action of the other molecule in activating the TRPM2 channel. See also * Adenosine diphosphate * ADP-ribosylation * Ribose Ribose is a simple sugar and carbohydrate with molecular formula C5H10O5 and the linear-form composition H−(C=O)−(CHOH)4−H. The naturally-occurring form, , is a component of the ribonucleotides from which RNA is built, and so this compo ... References Nucleotides Organophosphates NADH dehydrogenase inhibitors Phosphate esters {{biochemistry-stub ...
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ADP-ribose
Adenosine diphosphate ribose (ADPR) is an ester molecule formed into chains by the enzyme poly ADP ribose polymerase. ADPR is created from cyclic ADP-ribose (cADPR) by the CD38 enzyme using nicotinamide adenine dinucleotide (NAD+) as a cofactor. ADPR binds to and activates the TRPM2 ion channel. ADPR is the most potent agonist of the TRPM2 channel. cADPR also binds to TPRM2, and the action of both molecules is synergistic, with both molecules enhancing the action of the other molecule in activating the TRPM2 channel. See also * Adenosine diphosphate * ADP-ribosylation * Ribose Ribose is a simple sugar and carbohydrate with molecular formula C5H10O5 and the linear-form composition H−(C=O)−(CHOH)4−H. The naturally-occurring form, , is a component of the ribonucleotides from which RNA is built, and so this compo ... References Nucleotides Organophosphates NADH dehydrogenase inhibitors Phosphate esters {{biochemistry-stub ...
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Ryanodine Receptor
Ryanodine receptors (RyR for short) form a class of intracellular calcium channels in various forms of excitable animal tissue like muscles and neurons. There are three major isoforms of the ryanodine receptor, which are found in different tissues and participate in different signaling pathways involving calcium release from intracellular organelles. The RYR2 ryanodine receptor isoform is the major cellular mediator of calcium-induced calcium release (CICR) in animal cells. Etymology The ryanodine receptors are named after the plant alkaloid ryanodine which shows a high affinity to them. Isoforms There are multiple isoforms of ryanodine receptors: * RyR1 is primarily expressed in skeletal muscle * RyR2 is primarily expressed in myocardium (heart muscle) * RyR3 is expressed more widely, but especially in the brain. * Non-mammalian vertebrates typically express two RyR isoforms, referred to as RyR-alpha and RyR-beta. * Many invertebrates, including the model organisms Dros ...
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Aplysia
''Aplysia'' () is a genus of medium-sized to extremely large sea slugs, specifically sea hares, which are one clade of large sea slugs, marine gastropod mollusks. These benthic herbivorous creatures can become rather large compared with most other mollusks. They graze in tidal and subtidal zones of tropical waters, mostly in the Indo-Pacific Ocean (23 species); but they can also be found in the Atlantic Ocean (12 species), with a few species occurring in the Mediterranean. ''Aplysia'' species, when threatened, frequently release clouds of ink, it is believed in order to blind the attacker (though they are in fact considered edible by relatively few species). Following the lead of Eric R. Kandel, the genus has been studied as a model organism by neurobiologists, because its gill and siphon withdrawal reflex, as studied in ''Aplysia californica'', is mediated by electrical synapses, which allow several neurons to fire synchronously. This quick neural response is necessary f ...
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Glycophosphatidylinositol
Glycosylphosphatidylinositol (), or glycophosphatidylinositol, or GPI in short, is a phosphoglyceride that can be attached to the C-terminus of a protein during posttranslational modification. The resulting GPI-anchored proteins play key roles in a wide variety of biological processes. GPI is composed of a phosphatidylinositol group linked through a carbohydrate-containing linker (glucosamine and mannose glycosidically bound to the inositol residue) and via an ethanolamine phosphate (EtNP) bridge to the C-terminal amino acid of a mature protein. The two fatty acids within the hydrophobic phosphatidyl-inositol group anchor the protein to the cell membrane. Synthesis Glycosylated (GPI-anchored) proteins contain a signal sequence, thus directing them to the endoplasmic reticulum (ER). The protein is co-translationally inserted in the ER membrane via a translocon and is attached to the ER membrane by its hydrophobic C terminus; the majority of the protein extends into the ER lumen ...
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TIR Domain
Members of the very wide interleukin-1 receptor (IL-1R) family are characterized by extracellular immunoglobulin-like domains and intracellular Toll/Interleukin-1R (TIR) domain. It is a group of structurally homologous proteins, conserved throughout the species as it was identified from plants to mammals. Proteins of this family play important role in host defence, injury and stress. There are four main groups of TIR domain-containing proteins in animals; Toll-like receptors, Interleukin-1 receptor (IL-1R), cytosolic adaptor proteins (such as MyD88 adaptor protein) and insect and nematode Toll. Each of these groups is involved mainly in host defence; Toll receptors are also involved in embryogenesis. TIR domain The TIR domain is about 200 amino acids long and consists of 3 conserved boxes and between these boxes there are regions of variable length. If due to some mutation all of the three boxes are damaged, there is no surface expression of the protein. If only boxes one and ...
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Adenosine Triphosphate
Adenosine triphosphate (ATP) is an organic compound that provides energy to drive many processes in living cells, such as muscle contraction, nerve impulse propagation, condensate dissolution, and chemical synthesis. Found in all known forms of life, ATP is often referred to as the "molecular unit of currency" of intracellular energy transfer. When consumed in metabolic processes, it converts either to adenosine diphosphate (ADP) or to adenosine monophosphate (AMP). Other processes regenerate ATP. The human body recycles its own body weight equivalent in ATP each day. It is also a precursor to DNA and RNA, and is used as a coenzyme. From the perspective of biochemistry, ATP is classified as a nucleoside triphosphate, which indicates that it consists of three components: a nitrogenous base (adenine), the sugar ribose, and the Polyphosphate, triphosphate. Structure ATP consists of an adenine attached by the 9-nitrogen atom to the 1′ carbon atom of a sugar (ribose), which i ...
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