1VZJ
28-400: 8292 382864 ENSG00000206561 ENSMUSG00000057606 Q9Y215 O35348 NM_080541 NM_080542 NM_080543 NM_009937 NP_005668 NP_536799 NP_536800 NP_034067 Acetylcholinesterase collagenic tail peptide also known as AChE Q subunit , acetylcholinesterase-associated collagen , or ColQ is the collagen-tail subunit of acetylcholinesterase found in
56-436: A gorge leading to the active site. All 14 amino acids in the aromatic gorge are highly conserved across different species. Among the aromatic amino acids, tryptophan 84 is critical and its substitution with alanine results in a 3000-fold decrease in reactivity. The gorge is approximately 20 angstroms deep and five angstroms wide. The esteratic subsite, where acetylcholine is hydrolyzed to acetate and choline, contains
84-426: A study on Solanum lycopersicum (tomato) identified 87 SlAChE genes containing GDSL lipase/acylhydrolase domain. The study also showed up-and down-regulation of SlAChE genes under salinity stress condition. Some marine fungi have been found to produce compounds that inhibit AChE. However, the specific role and mechanisms of AChE in fungi are not as well-studied as in mammals. The presence and role of AChE in bacteria
112-506: Is Mir-132 microRNA , which may limit inflammation in the brain by silencing the expression of this protein and allowing ACh to act in an anti-inflammatory capacity. It has also been shown that the main active ingredient in cannabis, tetrahydrocannabinol , is a competitive inhibitor of acetylcholinesterase. AChE is found in many types of conducting tissue: nerve and muscle, central and peripheral tissues, motor and sensory fibers, and cholinergic and noncholinergic fibers. The activity of AChE
140-515: Is a committee of the Human Genome Organisation (HUGO) that sets the standards for human gene nomenclature . The HGNC approves a unique and meaningful name for every known human gene , based on a query of experts. In addition to the name, which is usually 1 to 10 words long, the HGNC also assigns a symbol (a short group of characters) to every gene. As with an SI symbol, a gene symbol
168-584: Is encoded by a single AChE gene while some invertebrates have multiple acetylcholinesterase genes. Note higher vertebrates also encode a closely related paralog BCHE (butyrylcholinesterase) with 50% amino acid identity to ACHE. Diversity in the transcribed products from the sole mammalian gene arises from alternative mRNA splicing and post-translational associations of catalytic and structural subunits. There are three known forms: T (tail), R (read through), and H (hydrophobic). The major form of acetylcholinesterase found in brain, muscle, and other tissues, known as
196-460: Is higher in motor neurons than in sensory neurons. Acetylcholinesterase is also found on the red blood cell membranes, where different forms constitute the Yt blood group antigens . Acetylcholinesterase exists in multiple molecular forms, which possess similar catalytic properties, but differ in their oligomeric assembly and mode of attachment to the cell surface. In mammals, acetylcholinesterase
224-618: Is hypothesized in other species. It is thought to be involved in the stress response and, possibly, inflammation. The nomenclatural variations of ACHE and of cholinesterases generally are discussed at Cholinesterase § Types and nomenclature . For acetylcholine esterase (AChE), reversible inhibitors are those that do not irreversibly bond to and deactivate AChE. Drugs that reversibly inhibit acetylcholine esterase are being explored as treatments for Alzheimer's disease and myasthenia gravis , among others. Examples include tacrine and donepezil . Exposure to acetylcholinesterase inhibitors
252-468: Is like an abbreviation but is more than that, being a second unique name that can stand on its own just as much as substitute for the longer name. It may not necessarily "stand for" the initials of the name, although many gene symbols do reflect that origin. Full gene names, and especially gene abbreviations and symbols, are often not specific to a single gene. A marked example is CAP which can refer to any of 6 different genes ( BRD4 Archived 2013-10-27 at
280-402: Is not well-documented. During neurotransmission , ACh is released from the presynaptic neuron into the synaptic cleft and binds to ACh receptors on the post-synaptic membrane, relaying the signal from the nerve. AChE is concentrated in the synaptic cleft, where it terminates the signal transmission by hydrolyzing ACh. The liberated choline is taken up again by the pre-synaptic neuron and ACh
308-643: Is one of several studied explanations for the chronic cognitive symptoms veterans displayed after returning from the Gulf War . Soldiers were dosed with AChEI pyridostigmine bromide (PB) as protection from nerve agent weapons. Studying acetylcholine levels using microdialysis and HPLC -ECD, researchers at the University of South Carolina School of Medicine determined PB, when combined with a stress element can lead to cognitive responses. HUGO Gene Nomenclature Committee The HUGO Gene Nomenclature Committee ( HGNC )
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#1732868972658336-517: Is primarily involved in the termination of impulse transmission at cholinergic synapses by rapid hydrolysis of the neurotransmitter acetylcholine. In non-vertebrates, AChE plays a similar role in nerve conduction processes at the neuromuscular junction. It is usually located in the membranes of these animals and controls ionic currents in excitable membranes. In plants, the biological functions of AChE are less clear, and its existence has been recognized by indirect evidence of its activity. For instance,
364-487: Is referred to. The HGNC published its latest human gene naming guidelines in 2020. These may be summarized as: The HGNC states that "gene nomenclature should evolve with new technology rather than be restrictive, as sometimes occurs when historical and single gene nomenclature systems are applied." The HGNC has also issued guides to specific locus types such as endogenous retroviral loci, structural variants and non-coding RNAs. When assigning new gene nomenclature
392-406: Is synthesized by combining with acetyl-CoA through the action of choline acetyltransferase . A cholinomimetic drug disrupts this process by acting as a cholinergic neurotransmitter that is impervious to acetylcholinesterase's lysing action. Drugs or toxins that inhibit AChE lead to persistence of high concentrations of ACh within synapses, leading to increased cholinergic signaling within
420-474: Is the hydrophilic species, which forms disulfide-linked oligomers with collagenous , or lipid -containing structural subunits. In the neuromuscular junctions AChE expresses in asymmetric form which associates with ColQ or subunit. In the central nervous system it is associated with PRiMA which stands for Proline Rich Membrane anchor to form symmetric form. In either case, the ColQ or PRiMA anchor serves to maintain
448-421: Is the primary cholinesterase in the body. It is an enzyme that catalyzes the breakdown of acetylcholine and some other choline esters that function as neurotransmitters : It is found at mainly neuromuscular junctions and in chemical synapses of the cholinergic type, where its activity serves to terminate cholinergic synaptic transmission . It belongs to the carboxylesterase family of enzymes. It
476-434: Is the primary target of inhibition by organophosphorus compounds such as nerve agents and pesticides . AChE is a hydrolase that hydrolyzes choline esters. It has a very high catalytic activity—each molecule of AChE degrades about 5,000 molecules of acetylcholine (ACh) per second, approaching the limit allowed by diffusion of the substrate . The active site of AChE comprises two subsites—the anionic site and
504-612: The Wayback Machine , CAP1 Archived 2013-11-02 at the Wayback Machine , HACD1 Archived 2013-10-07 at the Wayback Machine , LNPEP Archived 2012-09-13 at the Wayback Machine , SERPINB6 Archived 2013-10-08 at the Wayback Machine , and SORBS1 Archived 2012-10-12 at the Wayback Machine ). The HGNC short gene names, or gene symbols, unlike previously used or published symbols, are specifically assigned to one gene only. This can result in less common abbreviations being selected but reduces confusion as to which gene
532-430: The catalytic triad of three amino acids: serine 203, histidine 447 and glutamate 334. These three amino acids are similar to the triad in other serine proteases except that the glutamate is the third member rather than aspartate . Moreover, the triad is of opposite chirality to that of other proteases. The hydrolysis reaction of the carboxyl ester leads to the formation of an acyl-enzyme and free choline . Then,
560-423: The central nervous system , autonomic ganglia and neuromuscular junctions . Irreversible inhibitors of AChE may lead to muscular paralysis , convulsions, bronchial constriction, and death by asphyxiation . Organophosphates (OP), esters of phosphoric acid, are a class of irreversible AChE inhibitors. Cleavage of OP by AChE leaves a phosphoryl group in the esteratic site, which is slow to be hydrolyzed (on
588-456: The neuromuscular junction . In humans it is encoded by the COLQ gene . This gene encodes the subunit of a collagen -like molecule associated with acetylcholinesterase in skeletal muscle. Each molecule is composed of three identical subunits. Each subunit contains a proline -rich attachment domain (PRAD) that binds an acetylcholinesterase tetramer to anchor the catalytic subunit of the enzyme to
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#1732868972658616-421: The HGNC make efforts to contact authors who have published on the human gene in question by email, and their responses to the proposed nomenclature are requested. HGNC also coordinates with the related Mouse and Rat Genomic Nomenclature Committees, other database curators, and experts for given specific gene families or sets of genes. The gene name revision procedure is similar to the naming procedure, but changing
644-464: The acyl-enzyme undergoes nucleophilic attack by a water molecule, assisted by the histidine 440 group, liberating acetic acid and regenerating the free enzyme. AChE is found in many biological species, including humans and other mammals, non-vertebrates, and plants. In humans, AChE is a cholinergic enzyme involved in the hydrolysis of the neurotransmitter acetylcholine (ACh) into its constituents, choline, and acetate. Overall, in mammals, AChE
672-1021: The basal lamina. Multiple transcript variants encoding different isoforms have been found for this gene. Mutations in this gene are associated with endplate acetylcholinesterase deficiency and one of the causes of the neuromuscular disease, congenital myasthenia gravis . This article on a gene on human chromosome 3 is a stub . You can help Misplaced Pages by expanding it . Acetylcholinesterase 4EY7 , 4PQE , 1F8U , 3LII , 4BDT , 4M0E , 4M0F , 1VZJ , 2X8B , 1B41 , 4EY4 , 4EY5 , 4EY6 , 4EY8 , 5FOQ , 5HF9 , 5HF6 , 5FPQ , 5HF8 , 5HFA 43 11423 ENSG00000087085 ENSMUSG00000023328 P22303 P21836 NM_001367915 NM_001367917 NM_001367918 NM_001367919 NM_001290010 NM_009599 NP_001354846 NP_001354847 NP_001354848 NP_001276939 NP_033729 Acetylcholinesterase ( HGNC symbol ACHE ; EC 3.1.1.7; systematic name acetylcholine acetylhydrolase ), also known as AChE, AChase or acetylhydrolase ,
700-584: The enzyme in the intercellular junction, ColQ for the neuromuscular junction and PRiMA for synapses. The other, alternatively spliced form expressed primarily in the erythroid tissues, differs at the C-terminus , and contains a cleavable hydrophobic peptide with a PI-anchor site. It associates with membranes through the phosphoinositide (PI) moieties added post-translationally. The third type has, so far, only been found in Torpedo sp. and mice although it
728-497: The esteratic site for short periods of time (seconds to minutes) and are used to treat of a range of central nervous system diseases. Tetrahydroaminoacridine (THA) and donepezil are FDA-approved to improve cognitive function in Alzheimer's disease . Rivastigmine is also used to treat Alzheimer's and Lewy body dementia , and pyridostigmine bromide is used to treat myasthenia gravis . An endogenous inhibitor of AChE in neurons
756-421: The esteratic subsite. The structure and mechanism of action of AChE have been elucidated from the crystal structure of the enzyme. The anionic subsite accommodates the positive quaternary amine of acetylcholine as well as other cationic substrates and inhibitors . The cationic substrates are not bound by a negatively charged amino acid in the anionic site, but by interaction of 14 aromatic residues that line
784-417: The order of days) and can become covalently bound. Irreversible AChE inhibitors have been used in insecticides (e.g., malathion ) and nerve gases for chemical warfare (e.g., Sarin and VX ). Carbamates , esters of N-methyl carbamic acid, are AChE inhibitors that hydrolyze in hours and have been used for medical purposes (e.g., physostigmine for the treatment of glaucoma ). Reversible inhibitors occupy
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