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Information on EC 2.3.1.87 - aralkylamine N-acetyltransferase and Organism(s) Homo sapiens and UniProt Accession Q16613
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2.3.1.87 aralkylamine N-acetyltransferaseIUBMB Comments
Narrow specificity towards 2-arylethylamines, including serotonin (5-hydroxytryptamine), tryptamine, 5-methoxytryptamine and phenylethylamine. This is the penultimate enzyme in the production of melatonin (5-methoxy-N-acetyltryptamine) and controls its synthesis (cf. EC 2.1.1.4, acetylserotonin O-methyltransferase). Differs from EC 2.3.1.5 arylamine N-acetyltransferase.
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Word Map
- 2.3.1.87
- melatonin
-
pineal
- rhythm
-
circadian
- clock
- retina
-
night
-
nocturnal
- norepinephrine
- hiomt
- pinealocytes
-
arylalkylamine-n-acetyltransferase
- hydroxyindole-o-methyltransferase
- photoreceptors
-
oscillator
- n-acetylserotonin
-
diurnal
-
suprachiasmatic
-
photoperiodic
-
snats
-
light-dark
-
sodium-coupled
-
adrenergic
- tryptamine
-
entrain
-
photoreceptive
- synthesis
- n-acetyl-5-methoxytryptamine
-
gcn5-related
-
photic
-
zeitgeber
-
clockwork
-
day-night
- octopamine
-
night-time
-
clock-controlled
- medicine
- analysis
-
ne-stimulated
-
hydroxyindole
-
meaib
-
melatoninergic
-
rhythm-generating
-
extrapineal
-
slc38a2
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
aanat, aa-nat, snat2, arylalkylamine n-acetyltransferase, snat1, aanat2, aanat1, serotonin-n-acetyltransferase, aralkylamine n-acetyltransferase, bm-iaanat, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
AA-NAT
-
-
-
-
AANAT
acetyl-CoA:aralkylamine N-acetyltransferase
-
-
-
-
acetyltransferase, arylalkylamine N-
-
-
-
-
arylalkylamine N-acetyltransferase
N-acetyltransferase
-
-
-
-
serotonin acetylase
-
-
-
-
serotonin acetyltransferase
-
-
-
-
AANAT
-
-
-
-
arylalkylamine N-acetyltransferase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Acyl group transfer
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
-
-
SYSTEMATIC NAME
IUBMB Comments
acetyl-CoA:2-arylethylamine N-acetyltransferase
Narrow specificity towards 2-arylethylamines, including serotonin (5-hydroxytryptamine), tryptamine, 5-methoxytryptamine and phenylethylamine. This is the penultimate enzyme in the production of melatonin (5-methoxy-N-acetyltryptamine) and controls its synthesis (cf. EC 2.1.1.4, acetylserotonin O-methyltransferase). Differs from EC 2.3.1.5 arylamine N-acetyltransferase.
CAS REGISTRY NUMBER
COMMENTARY
92941-56-5
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
acetyl-CoA + 2,5-dimethoxyphenylethylamine
CoA + ?
24% of the activity with 2-phenylethylamine
-
-
?
acetyl-CoA + 2-(2,3-dichlorophenyl)-ethylamine
CoA + N-acetyl-2-(2,3-dichlorophenyl)-ethylamine
78% of the activity with 2-phenylethylamine
-
-
?
acetyl-CoA + 2-(2-chlorophenyl)-ethylamine
CoA + N-acetyl-2-(2-chlorophenyl)-ethylamine
130% of the activity with 2-phenylethylamine
-
-
?
acetyl-CoA + 2-(3,4-dihydroxyphenyl)-ethylamine
CoA + N-acetyl-2-(3,4-dihydroxyphenyl)-ethylamine
7% of the activity with 2-phenylethylamine
-
-
?
acetyl-CoA + 2-(3,4-dimethoxyphenyl)-ethylamine
CoA + N-acetyl-2-(3,4-dimethoxyphenyl)-ethylamine
4.4% of the activity with 2-phenylethylamine
-
-
?
acetyl-CoA + 2-(3-chlorophenyl)-ethylamine
CoA + N-acetyl-2-(3-chlorophenyl)-ethylamine
67% of the activity with 2-phenylethylamine
-
-
?
acetyl-CoA + 2-(3-fluorophenyl)-ethylamine
CoA + N-acetyl-2-(3-fluorophenyl)-ethylamine
65% of the activity with 2-phenylethylamine
-
-
?
acetyl-CoA + 2-(4-bromophenyl)-ethylamine
CoA + N-acetyl-2-(4-bromophenyl)-ethylamine
48% of the activity with 2-phenylethylamine
-
-
?
acetyl-CoA + 2-(4-chlorophenyl)ethylamine
CoA + N-acetyl-2-(4-chlorophenyl)ethylamine
68% of the activity with 2-phenylethylamine
-
-
?
acetyl-CoA + 2-(4-fluorophenyl)-ethylamine
CoA + N-acetyl-2-(4-fluorophenyl)-ethylamine
116% of the activity with 2-phenylethylamine
-
-
?
acetyl-CoA + 2-(p-fluorophenyl)-ethylamine
CoA + N-acetyl-2-(p-fluorophenyl)-ethylamine
56% of the activity with 2-phenylethylamine
-
-
?
acetyl-CoA + 2-(p-nitrophenyl)-ethylamine
CoA + N-acetyl-2-(p-nitrophenyl)-ethylamine
9% of the activity with 2-phenylethylamine
-
-
?
acetyl-CoA + 2-(p-tolyl)-ethylamine
CoA + N-acetyl-2-(p-tolyl)-ethylamine
60% of the activity with 2-phenylethylamine
-
-
?
acetyl-CoA + 2-fluorophenylethylamine
CoA + ?
69% of the activity with 2-phenylethylamine
-
-
?
acetyl-CoA + 2-methoxyphenylethylamine
CoA + N-acetyl-2-methoxyphenylethylamine
52% of the activity with 2-phenylethylamine
-
-
?
acetyl-CoA + 2-phenylethylamine
CoA + N-acetyl-2-phenylethylamine
-
-
-
?
acetyl-CoA + 3-hydroxy-4-methoxyphenethylamine
CoA + ?
1% of the activity with 2-phenylethylamine
-
-
?
acetyl-CoA + 3-hydroxyphenethylamine
CoA + ?
24% of the activity with 2-phenylethylamine
-
-
?
acetyl-CoA + 3-methoxy-2-phenylethylamine
CoA + ?
23% of the activity with 2-phenylethylamine
-
-
?
acetyl-CoA + 3-methoxytyramine
CoA + ?
17% of the activity with 2-phenylethylamine
-
-
?
acetyl-CoA + 4-(2-aminoethyl)-benzenesulfonyl fluoride
CoA + ?
8% of the activity with 2-phenylethylamine
-
-
?
acetyl-CoA + 4-methoxyphenylethylamine
CoA + N-acetyl-4-methoxyphenylethylamine
11% of the activity with 2-phenylethylamine
-
-
?
acetyl-CoA + 6-hydroxydopamine
CoA + ?
51% of the activity with 2-phenylethylamine
-
-
?
acetyl-CoA + tyramine
CoA + ?
8% of the activity with 2-phenylethylamine
-
-
?
acetyl-CoA + serotonin
CoA + N-acetylserotonin
-
rate-limiting in melatonin synthesis
-
-
?
additional information
?
-
no activity with 2-(4-aminophenyl)-ethylamine, 3,4-(dibenzyloxy)phenethylamine, 5-hydroxydopamine, 4-(2-aminoethyl)-benzenesulfonamide or 2-(p-chlorophenoxy)-2-methylpropionic acid
-
-
?
additional information
?
-
-
no activity with 2-(4-aminophenyl)-ethylamine, 3,4-(dibenzyloxy)phenethylamine, 5-hydroxydopamine, 4-(2-aminoethyl)-benzenesulfonamide or 2-(p-chlorophenoxy)-2-methylpropionic acid
-
-
?
additional information
?
-
-
further substrates: selected synthetic amines
-
-
?
additional information
?
-
-
the enzyme catalyzes the rate-limiting step in melatonin synthesis
-
-
?
additional information
?
-
-
enzyme light and diurnal regulation involves phosphorylation on key AANAT Ser and Thr residues, which results in 14-3-3 protein recruitment and changes in catalytic activity and protein stability
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
acetyl-CoA + serotonin
CoA + N-acetylserotonin
-
rate-limiting in melatonin synthesis
-
-
?
additional information
?
-
-
the enzyme catalyzes the rate-limiting step in melatonin synthesis
-
-
?
additional information
?
-
-
enzyme light and diurnal regulation involves phosphorylation on key AANAT Ser and Thr residues, which results in 14-3-3 protein recruitment and changes in catalytic activity and protein stability
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
methyl 3-[2-[(bromoacetyl)amino]ethyl]-1-benzothiophene-5-carboxylate
-
IC50: 0.00225 mM
N-[2-(7-ethyl-1,2,3,4-tetrahydronapht-1-yl)ethyl]iodooacetamide
-
IC50: above 0.1 mM
N-[2-(7-methoxy-3-(3-trifluoromethylphenyl)-napht-1-yl)ethyl]iodoacetamide
-
IC50: 0.045 mM
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
14-3-3 protein
-
14-3-3zeta, interaction with the phosphorylated enzyme activates activity, binding analysis, overview
-
additional information
-
the enzyme is activated by Ser and Thr phosphorylations, e.g. AANAT Thr31 phosphorylation on its own can enhance catalytic efficiency up to 7fold
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
kinetics of recombinant partially phosphorylated wild-type and mutant enzymes, overview
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00039
2-bromo-N-[2-(5-fluoro-1-benzothien-3-yl)ethyl]acetamide
Homo sapiens
-
IC50: 0.00039 mM
0.00225
methyl 3-[2-[(bromoacetyl)amino]ethyl]-1-benzothiophene-5-carboxylate
Homo sapiens
-
IC50: 0.00225 mM
0.0087
N-[2-(2-benzyl-5-methoxy-benzofuran-3-yl)ethyl]iodoacetamide
Homo sapiens
-
IC50: 0.0087 mM
0.001
N-[2-(2-phenyl-benzo [b]thiophen-3-yl)ethyl]bromoacetamide
Homo sapiens
-
IC50: 0.001 mM
0.00378
N-[2-(5-bromo-benzo[b]thiophen-3-yl)ethyl]bromoacetamide
Homo sapiens
-
IC50: 0.00378 mM
0.00018
N-[2-(5-chloro-benzo[b]thiophen-3-yl)ethyl]bromoacetamide
Homo sapiens
-
IC50: 0.00018 mM
0.00071
N-[2-(5-ethyl-benzo[b]thiophen-3-yl)ethyl]bromoacetamide
Homo sapiens
-
IC50: 0.00071 mM
0.00018
N-[2-(5-hydroxy-benzo[b]thiophen-3-yl)ethyl]bromoacetamide
Homo sapiens
-
IC50: 0.00018 mM
0.1
N-[2-(7-ethyl-1,2,3,4-tetrahydronapht-1-yl)ethyl]iodooacetamide
Homo sapiens
-
IC50: above 0.1 mM
0.045
N-[2-(7-methoxy-3-(3-trifluoromethylphenyl)-napht-1-yl)ethyl]iodoacetamide
Homo sapiens
-
IC50: 0.045 mM
0.1
N-[2-(7-methoxy-8-propenyl-napht-1-yl)ethyl]-iodoacetamide
Homo sapiens
-
IC50: above 0.1 mM
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
the N-terminal sequence of human AANAT differs from that of rodent AANATs. The human enzyme is longer-lived than its rat counterpart and appears to be refractory to degradation by the N-end rule pathway
physiological function
AANAT levels and melatonin synthesis increase after TRPV4 channel stimulation in ciliary body epithelium
metabolism
physiological function
metabolism
-
serotonin N-acetyltransferase is a rate-limiting enzyme in melatonin biosynthesis in vertebrates
physiological function
-
AANAT is a key circadian rhythm enzyme that drives the nocturnal production of melatonin in the pineal
physiological function
-
serotonin N-acetyltransferase is responsible for the production of N-acetylserotonin, an intermediate of melatonin biosynthesis. Melatonin, i.e. N-acetyl-5-methoxytryptamine, has multiple functions in vertebrates, including the regulation of circadian rhythms and photoperiodism. Plant melatonin is involved in cold stress
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). SNAT_HUMAN
207
0
23344
Swiss-Prot
other Location (Reliability: 4)
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
-
phosphorylation on key AANAT Ser and Thr residues by protein kinase A results in 14-3-3 protein recruitment and changes in catalytic activity and protein stability. AANAT Thr31 phosphorylation on its own can enhance catalytic efficiency up to 7fold, but the catalytic profile is largely abolished by double phosphorylation at Thr31 and Ser205. Influence of phosphorylations on enzyme activity, overview
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
molecular modeling, docking of N-acetylserotonin and screening for potential ligands. N-[2-(5-hydroxy-1H-indol-3-yl)ethy1]-3-(4-hydroxyphenyl)-2-propenamide show least binding energy, i.e. -9.38 Kcal/mol
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
construction of truncation mutants AANAT 1-197(DELTAC8) and GST-AANAT 34-197 (DELTAN33, DELTAC8). Production of partially and differentially phosphorylated enzymes by semiprotein synthesis, overview
additional information
-
single-nucleotide polymorphisms in AANAT found in Japanese population cannot be found in Caucasian population, genotyping, overview
additional information
-
enhanced production of melatonin by ectopic overexpression of human serotonin N-acetyltransferase plays a role in cold resistance in transgenic rice seedlings. Leaves of transgenic lines S9 and S10 contain approximately 2.5fold and 1.9fold more chlorophyll, respectively, than those of the wild type
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
denaturation/renaturation process in which the enzyme is immobilized on an affinity chromatography column
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
functional ectopic overexpression of human serotonin N-acetyltransferase under the constitutive ubiquitin promoter in transgenic Oryza sativa cv. Dongjin seedlings using Agrobacterium-mediated gene transformation leading to elevated synthesis of N-acetylserotonin and melatonin in the transgenic rice plants, phenotype, overview
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
after 18 h incubation with TRPV4 channel agonist GSK1016790A, AANAT level increases 2.4fold
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Ferry, G.; Loynel, A.; Kucharczyk, N.; Bertin, S.; Rodriguez, M.; Delagrange, P.; Galizzi, J.P.; Jacoby, E.; Volland, J.P.; Lesieur, D.; Renard, P.; Canet, E.; Fauchere, J.L.; Boutin, J.A.
Substrate specificity and inhibition studies of human serotonin N-acetyltransferase
J. Biol. Chem.
275
8794-8805
2000
Ovis aries, Homo sapiens
Ferry, G.; Ubeaud, C.; Mozo, J.; Pean, C.; Hennig, P.; Rodriguez, M.; Scoul, C.; Bonnaud, A.; Nosjean, O.; Galizzi, J.P.; Delagrange, P.; Renard, P.; Volland, J.P.; Yous, S.; Lesieur, D.; Boutin, J.A.
New substrate analogues of human serotonin N-acetyltransferase produce in situ specific and potent inhibitors
Eur. J. Biochem.
271
418-428
2004
Homo sapiens
Ferry, G.; Ubeaud, C.; Dauly, C.; Mozo, J.; Guillard, S.; Berger, S.; Jimenez, S.; Scoul, C.; Leclerc, G.; Yous, S.; Delagrange, P.; Boutin, J.A.
Purification of the recombinant human serotonin N-acetyltransferase (EC 2.3.1.87): further characterization of and comparison with AANAT from other species
Protein Expr. Purif.
38
84-98
2004
Ovis aries, Homo sapiens (Q16613), Homo sapiens, Rattus norvegicus (Q64666)
Szewczuk, L.M.; Tarrant, M.K.; Sample, V.; Drury, W.J.; Zhang, J.; Cole, P.A.
Analysis of serotonin N-acetyltransferase regulation in vitro and in live cells using protein semisynthesis
Biochemistry
47
10407-10419
2008
Homo sapiens
Bloemeke, B.; Golka, K.; Griefahn, B.; Roemer, H.C.
Arylalkylamine N-acetyltransferase (AANAT) genotype as a personal trait in melatonin synthesis
J. Toxicol. Environ. Health
71
874-876
2008
Homo sapiens
Kang, K.; Lee, K.; Park, S.; Kim, Y.S.; Back, K.
Enhanced production of melatonin by ectopic overexpression of human serotonin N-acetyltransferase plays a role in cold resistance in transgenic rice seedlings
J. Pineal Res.
49
176-182
2010
Homo sapiens
Prashant, K.; Kumar, H.; Prasad, C.V.
In-silico study of arylalkylamine-nacetyltransferase enzyme to regulate circadian rhythmicity
Bioinformation
9
771-776
2013
Homo sapiens (Q16613), Homo sapiens
Alkozi, H.; de Lara, M.; Sanchez-Naves, J.; Pintor, J.
TRPV4 stimulation induced melatonin secretion by increasing arylalkymine N-acetyltransferase (AANAT) protein level
Int. J. Mol. Sci.
18
746
2017
Homo sapiens (Q16613), Homo sapiens
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