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Information on EC 2.3.1.6 - choline O-acetyltransferase and Organism(s) Homo sapiens and UniProt Accession P28329

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     2 Transferases
         2.3 Acyltransferases
             2.3.1 Transferring groups other than aminoacyl groups
                2.3.1.6 choline O-acetyltransferase
IUBMB Comments
Propanoyl-CoA can act, more slowly, in place of acetyl-CoA.
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This record set is specific for:
Homo sapiens
UNIPROT: P28329
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The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
choline acetyltransferase, choline acetyl transferase, pchat, choline-acetyltransferase, cchat, choline acetylase, choline o-acetyltransferase, acetyl-coa:choline o-acetyltransferase, peripheral type of choline acetyltransferase, acetyl-coa:choline-o-acetyltransferase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
choline acetyltransferase
-
choline-acetyltransferase
-
acetyl CoA:choline-O-acetyltransferase
-
-
-
-
acetyl-CoA:choline-O-acetyltransferase
-
-
-
-
acetyltransferase, choline
-
-
-
-
chAcT
-
-
-
-
choline acetyl transferase
-
-
-
-
choline acetylase
-
-
-
-
choline acetyltransferase
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Acyl group transfer
-
-
-
-
PATHWAY SOURCE
PATHWAYS
SYSTEMATIC NAME
IUBMB Comments
acetyl-CoA:choline O-acetyltransferase
Propanoyl-CoA can act, more slowly, in place of acetyl-CoA.
CAS REGISTRY NUMBER
COMMENTARY hide
9012-78-6
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
acetyl-CoA + choline
CoA + O-acetylcholine
show the reaction diagram
acetyl-CoA + choline
acetylcholine + CoA
show the reaction diagram
acetyl-CoA + choline
CoA + O-acetylcholine
show the reaction diagram
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
acetyl-CoA + choline
CoA + O-acetylcholine
show the reaction diagram
acetyl-CoA + choline
acetylcholine + CoA
show the reaction diagram
acetyl-CoA + choline
CoA + O-acetylcholine
show the reaction diagram
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
acetyl-CoA
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
K+
-
highest activity at 10-20 mM K+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1-(azepan-1-yl)-3-[(8-ethyl-4a,5-dihydro-4H-[1,2,4]triazino[5,6-b]indol-3-yl)sulfanyl]propan-1-one
the amide carbonyl of the compound forms a hydrogen bond with the Ser540 amino acid residue of ChAT with a distance of 2.15 A. The 5H-[1,2,4]triazino[5,6-b]indole nucleus forms a hydrogen bond with the Gly329 amino acid residue of ChAT active site
1-[2-[(naphthalen-1-yl)amino]-1,3-thiazole-4-carbonyl]-N-(propan-2-yl)piperidine-4-carboxamide
the terminal amide carbonyl forms a hydrogen bond with Ser438 at a distance of 1.88 A, while the thiazole nucleus forms pi_pi interactions with the Tyr436 amino acid residue of the active site of ChAT
2-(alpha-naphthoyl) ethyltrimethylammonium iodide
i.e. alpha-NETA, commercially available inhibitor. The naphthyl group forms pi-pi interaction with residue Tyr552, while the quaternary trimethyl ammonium moiety is closely surrounded by His324, Pro98, Asp328 residues. The naphthyl moiety is accommodated in a pocket consisting of Asn95, Pro554, Gly553, Thr539, and Ser538 residues. The determined IC50 values are 34.18 microM for acetylcholinesterase and 33.30 microM for butanoylcholinesterase
2-[[5-(furan-2-yl)-1H-1,2,4-triazol-3-yl]sulfanyl]-1-[4-(propan-2-yl)phenyl]ethan-1-one
compound makes the His324 residue inaccessible for the catalysis
beta-amyloid
-
-
3-Bromoacetonyltrimethylammonium bromide
-
-
3-Chloro-4-stilbazole
-
-
4-(1-Naphthylvinyl)pyridine
-
-
5,5'-dithiobis(2-nitrobenzoate)
-
-
Acetylaminocholine
-
-
Acetylcholine
-
-
Acyloylcholine
-
-
bromo-acetylcholine
-
-
bromoacetylcholine
-
-
Chlorocholine
-
-
choline
-
-
Choline mustard aziridinium salt
-
-
Diethylaminoethanol
-
-
N-ethylmaleimide
-
-
N-Methyl-4-(1-naphthylvinyl)pyridine
-
-
ocadaic acid
-
-
p-chloromercuribenzoate
-
-
phenylacetate
-
-
phenylacetyl-CoA
-
-
phenylbutyrate
-
-
Styrylpyridinium salts
-
-
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Abeta42 peptide
acts as allosteric enhancer
-
LiCl
-
-
Na2HPO4
-
-
Na2SO4
-
-
NaBr
-
-
NaCl
-
-
NGFI-A
-
NGF activates transcriptional factors which influence the promotor region of the enzyme
-
NGFI-C
-
NGF activates transcriptional factors which influence the promotor region of the enzyme
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NH4Cl
-
-
Sodium acetate
-
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.055
acetyl-CoA
-
-
4.4
choline
-
-
additional information
additional information
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00031
phenylacetyl-CoA
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.007
1-(azepan-1-yl)-3-[(8-ethyl-4a,5-dihydro-4H-[1,2,4]triazino[5,6-b]indol-3-yl)sulfanyl]propan-1-one
Homo sapiens
pH 7.4, 37°C
0.0165
1-[2-[(naphthalen-1-yl)amino]-1,3-thiazole-4-carbonyl]-N-(propan-2-yl)piperidine-4-carboxamide
Homo sapiens
pH 7.4, 37°C
0.000088
2-(alpha-naphthoyl) ethyltrimethylammonium iodide
Homo sapiens
pH 7.4, 23°C
0.0254
2-[[5-(furan-2-yl)-1H-1,2,4-triazol-3-yl]sulfanyl]-1-[4-(propan-2-yl)phenyl]ethan-1-one
Homo sapiens
pH 7.4, 37°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
50
-
purified enzyme, pH 7.4
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.3
-
without NaCl in assay medium
7 - 8
-
presence of NaCl
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
lung, fetal lung fibroblasts, HFL-1
Manually annotated by BRENDA team
-
autonomic
Manually annotated by BRENDA team
-
increased ChAT activity in some brain regions, notably the hippocampus, of patients diagnosed with mild cognitive impairment
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
-
preganglionic
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
nuclei of cholinergic neurons
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
the reduction in levels of O-acetylcholine is one of the most significant physiological symptoms of Alzheimer's disease
physiological function
malfunction
physiological function
-
acetylcholine, synthesized by ChAT, and muscarinic M1, M2, and M3 receptors are involved in fibroblast proliferation
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
CLAT_HUMAN
748
0
82536
Swiss-Prot
other Location (Reliability: 3)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
65000
x * 65000, SDS-PAGE
62000
-
x * 62000, form 1, x * 67000, form 2, SDS-PAGE
66000
-
1 * 66000, SDS-PAGE
67000
-
x * 62000, form 1, x * 67000, form 2, SDS-PAGE
67000 - 69000
-
gel filtration
additional information
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
-
x * 62000, form 1, x * 67000, form 2, SDS-PAGE
monomer
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
-
serine 440 of the recombinant human 69-kDa protein is the phoshorylation site
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A513T
mutant associated with congenital myasthenic syndrome, shows enhanced interaction with heat shock proteins HSC/HSP70 and HSP90 and increased sensitivity to heat shock protein inhibition
P17A/P19A
mutant shows enhanced interaction with heat shock proteins HSC/HSP70 and HSP90 and increased sensitivity to heat shock protein inhibition
V18M
mutant associated with congenital myasthenic syndrome, shows enhanced interaction with heat shock proteins HSC/HSP70 and HSP90 and increased sensitivity to heat shock protein inhibition
S440A
-
the wild-type enzyme is distributed predominantly in cytoplasm (88%), with the remainder (12%) bound to cellular membranes, mutation S440A results in localization of the enzyme entirely in cytoplasm
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
increasing ionic strength increases susceptibility to thermal degradation
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
acetyl-CoA stabilizes
-
choline chloride stabilizes
-
increasing ionic strength increases susceptibility to proteolysis and thermal degradation
-
OXIDATION STABILITY
ORGANISM
UNIPROT
LITERATURE
extremely sensitive to oxidation due to its cysteine-rich nature, oxidation causes formation of dimers and loss of activity
-
660442
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, partially purified preparation, several months stable, less stable in purified state
-
-20°C, several months
-
4°C, 24 h, less than 10% loss of activity
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
placental acidic and basic form
-
recombinant proteins using His-tag or chitin-binding-domain
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in HEK-293 cell
expression of wild-type- and S440A mutant-enzyme in HEK293 cells
-
large-scale expression as His-tag or chitin-binding-domain fusion protein in Escherichia coli, His-tag fusion protein expresses in inclusion bodies at 37°C growth temperature and in soluble form at 20°C, chitin-binding-domain fusion protein expressed at 15°C but not at 37°C
-
two fragments of the hChAT gene are used for functional analysis carrying 944 bp (P1) and 4000 bp (P2) of the 5' flanking region in front of the chloramphenicol acetyltransferase (CAT) reporter gene. They are transfected in NG108-15, SN6 and COS-1 cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
cerebral spinal fluid enzyme is upregulated in autoimmune neuroinflammation
enzyme activity is reduced significantly when neurons are exposed to high levels of beta-amyloid aggregates
interleukin-1beta induces the enzyme in HFL-1 cells
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
investigation of three ChAt gene polymorphisms in schizophrenia. Evidence for an influence of a 5' promoter polymorphism, rs1880676A/G, on susceptibility to the disorder among individuals of Basque origin. Evidence for a similar though less significant, influence for a second polymorphism of putative function, rs3810950
analysis
-
real-time multiplex PCR technique can be carried out in a single tube and can differentiate between the polymorphic sites of the ChAT gene associated with Alzheimer’s disease
medicine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
McGeer, P.L.; McGeer, E.G.; Peng, J.H.
Choline acetyltransferase: purification and immunohistochemical localization
Life Sci.
34
2319-2336
1984
Bos taurus, Gallus gallus, Drosophila sp. (in: flies), Homo sapiens, Rattus norvegicus, Torpedo sp.
Manually annotated by BRENDA team
Chao, L.P.
Choline acetyltransferase: purification and characterization
J. Neurosci. Res.
5
85-115
1980
Bos taurus, Drosophila melanogaster, Homo sapiens, Rattus norvegicus, Tetronarce californica
Manually annotated by BRENDA team
Haubrich, D.R.
Choline acetyltransferase and its inhibitors
Biol. of Cholinergic Funct. (Goldberg, A. M. , Hanin, I. , eds. )
1976
239-266
1976
Bos taurus, Cavia porcellus, Columba livia, Oryctolagus cuniculus, Homo sapiens, Musa domestica, Rattus norvegicus
-
Manually annotated by BRENDA team
Peng, J.H.; McGeer, P.L.; McGeer, E.G.
Membrane-bound choline acetyltransferase from human brain: purification and properties
Neurochem. Res.
11
959-971
1986
Homo sapiens
Manually annotated by BRENDA team
Froissart, C.; Massarelli, R.
Placental choline acetyltransferase purification and properties
Adv. Behav. Biol.
25
91-95
1981
Homo sapiens
-
Manually annotated by BRENDA team
Roskoski, R.; Lim, C.T.; Roskoski, L.M.
Human brain and placental choline acetyltransferase: purification and properties
Biochemistry
14
5105-5110
1975
Homo sapiens
Manually annotated by BRENDA team
Hersh L.B.; Peet, M.
Re-evaluation of the kinetic mechanism of the choline acetyltransferase reaction
J. Biol. Chem.
252
4796-4802
1977
Homo sapiens
Manually annotated by BRENDA team
Hersh, L.B.; Peet, M.
Effect of salts on the physical and kinetic properties of human placental choline acetyltransferase
J. Neurochem.
30
1087-1093
1978
Homo sapiens
Manually annotated by BRENDA team
Schuberth, J.
Choline acetyltransferase. Purification and effect of salts on the mechanism of the enzyme-catalyzed reaction
Biochim. Biophys. Acta
122
470-481
1966
Homo sapiens
-
Manually annotated by BRENDA team
Potempska, A.; Loo, Y.H.; Wisniewski, M.M.
On the possible mechanism of phenylacetate neurotoxicity: inhibition of choline acetyltransferase by phenylacetyl-CoA
J. Neurochem.
42
1499-1501
1984
Homo sapiens
Manually annotated by BRENDA team
Quirin-Stricker, C.; Mauvais, C.; Schmitt, M.
Transcriptional activation of human choline acetyltransferase by AP2- and NGF-induced factors
Mol. Brain Res.
49
165-174
1997
Homo sapiens
Manually annotated by BRENDA team
Dobransky, T.; Davis, W.L.; Rylett, R.J.
Functional characterization of phosphorylation of 69-kDa human choline acetyltransferase at serine 440 by protein kinase C
J. Biol. Chem.
276
22244-22250
2001
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Sigle, J.P.; Zander, J.; Ehret, A.; Honegger, J.; Jackisch, R.; Feuerstein, T.J.
High potassium-induced activation of choline-acetyltransferase in human neocortex: implications and species differences
Brain Res. Bull.
60
255-262
2003
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Kim, A.R.; Doherty-Kirby, A.; Lajoie, G.; Rylett, R.J.; Shilton, B.H.
Two methods for large-scale purification of recombinant human choline acetyltransferase
Protein Expr. Purif.
40
107-117
2005
Homo sapiens
Manually annotated by BRENDA team
Mancama, D.; Mata, I.; Kerwin, R.W.; Arranz, M.J.
Choline acetyltransferase variants and their influence in schizophrenia and olanzapine response
Am. J. Med. Genet. B Neuropsychiatr. Genet.
144B
849-853
2007
Homo sapiens (P28329), Homo sapiens
Manually annotated by BRENDA team
Park, H.D.; Park, K.U.; Kim, K.W.; Song, J.; Chang, H.E.; Heo, S.R.; Lee, H.J.; Kim, J.Q.
Real-time multiplex PCR assay for genotyping of three apolipoprotein E alleles and two choline acetyltransferase alleles with three hybridization probes
Clin. Chem. Lab. Med.
45
346-350
2007
Homo sapiens
Manually annotated by BRENDA team
Tang, M.; Rao, D.; Ma, C.; Guo, Y.; Han, H.; Ling, K.; Ling, Y.
Evaluation of choline acetyltransferase gene polymorphism (2384 G/A) in Alzheimers disease and mild cognitive impairment
Dement. Geriatr. Cogn. Disord.
26
9-14
2008
Homo sapiens
Manually annotated by BRENDA team
Yeung, W.L.; Lam, C.W.; Fung, L.W.; Hon, K.L.; Ng, P.C.
Severe congenital myasthenia gravis of the presynaptic type with choline acetyltransferase mutation in a Chinese infant with respiratory failure
Neonatology
95
183-186
2009
Homo sapiens
Manually annotated by BRENDA team
Contestabile, A.; Ciani, E.; Contestabile, A.
The place of choline acetyltransferase activity measurement in the "cholinergic hypothesis" of neurodegenerative diseases
Neurochem. Res.
33
318-327
2008
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Counts, S.E.; He, B.; Che, S.; Ginsberg, S.D.; Mufson, E.J.
Galanin hyperinnervation upregulates choline acetyltransferase expression in cholinergic basal forebrain neurons in Alzheimers disease
Neurodegener. Dis.
5
228-231
2008
Homo sapiens
Manually annotated by BRENDA team
Murphy, E.M.; Defontgalland, D.; Costa, M.; Brookes, S.J.; Wattchow, D.A.
Quantification of subclasses of human colonic myenteric neurons by immunoreactivity to Hu, choline acetyltransferase and nitric oxide synthase
Neurogastroenterol. Motil.
19
126-134
2007
Homo sapiens
Manually annotated by BRENDA team
Ray, B.; Simon, J.R.; Lahiri, D.K.
Determination of high-affinity choline uptake (HACU) and choline acetyltransferase (ChAT) activity in the same population of cultured cells
Brain Res.
1297
160-168
2009
Homo sapiens
Manually annotated by BRENDA team
Profita, M.; Bonanno, A.; Siena, L.; Bruno, A.; Ferraro, M.; Montalbano, A.M.; Albano, G.D.; Riccobono, L.; Casarosa, P.; Pieper, M.P.; Gjomarkaj, M.
Smoke, choline acetyltransferase, muscarinic receptors, and fibroblast proliferation in chronic obstructive pulmonary disease
J. Pharmacol. Exp. Ther.
329
753-763
2009
Homo sapiens
Manually annotated by BRENDA team
Fgaier, H.; Mustafa, I.H.; Awad, A.A.; Elkamel, A.
Modeling the interaction between beta-amyloid aggregates and choline acetyltransferase activity and its relation with cholinergic dysfunction through two-enzyme/two-compartment model
Comput. Math. Methods Med.
2015
923762
2015
Homo sapiens (P28329), Homo sapiens
Manually annotated by BRENDA team
Mukaetova-Ladinska, E.; Andras, A.; Milne, J.; Abdel-All, Z.; Borr, I.; Jaros, E.; Perry, R.; Honer, W.; Cleghorn, A.; Doherty, J.; Mcintosh, G.; Perry, E.; Kalaria, R.; Mckeith, I.
Synaptic proteins and choline acetyltransferase loss in visual cortex in dementia with Lewy Bodies
J. Neuropathol. Exp. Neurol.
72
53-60
2013
Homo sapiens
Manually annotated by BRENDA team
Vijayaraghavan, S.; Karami, A.; Aeinehband, S.; Behbahani, H.; Grandien, A.; Nilsson, B.; Ekdahl, K.N.; Lindblom, R.P.; Piehl, F.; Darreh-Shori, T.
Regulated extracellular choline acetyltransferase activity - the plausible missing link of the distant action of acetylcholine in the cholinergic anti-inflammatory pathway
PLoS ONE
8
e65936
2013
Homo sapiens (P28329), Homo sapiens
Manually annotated by BRENDA team
Morey, T.; Winick-Ng, W.; Seah, C.; Jane Rylett, R.
Chaperone-mediated regulation of choline acetyltransferase protein stability and activity by HSC/HSP70, HSP90, and p97/VCP
Front. Mol. Neurosci.
10
415
2017
Homo sapiens (P28329)
Manually annotated by BRENDA team
Kumar, A.; Lana, E.; Kumar, R.; Lithner, C.U.; Darreh-Shori, T.
Soluble Abeta42 acts as allosteric activator of the core cholinergic enzyme choline acetyltransferase
Front. Mol. Neurosci.
11
327
2018
Homo sapiens (P28329), Homo sapiens
Manually annotated by BRENDA team
Winick-Ng, W.; Caetano, F.A.; Winick-Ng, J.; Morey, T.M.; Heit, B.; Rylett, R.J.
82-kDa choline acetyltransferase and SATB1 localize to beta-amyloid induced matrix attachment regions
Sci. Rep.
6
23914
2016
Homo sapiens (P28329), Homo sapiens
Manually annotated by BRENDA team
Kumar, R.; Langstroem, B.; Darreh-Shori, T.
Novel ligands of Choline acetyltransferase designed by in silico molecular docking, hologram QSAR and lead optimization
Sci. Rep.
6
31247
2016
Homo sapiens (P28329)
Manually annotated by BRENDA team
Kumar, R.; Kumar, A.; Langstroem, B.; Darreh-Shori, T.
Discovery of novel choline acetyltransferase inhibitors using structure-based virtual screening
Sci. Rep.
7
16287
2017
Homo sapiens (P28329)
Manually annotated by BRENDA team