Information on EC 2.1.1.8 - histamine N-methyltransferase

New: Word Map on EC 2.1.1.8
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Mark a special word or phrase in this record:
Search Reference ID:
Select one or more organisms in this record:
Show additional data
Do not include text mining results
Include (text mining) results (more...)
Include results (AMENDA + additional results, but less precise; more...)


The expected taxonomic range for this enzyme is: Euteleostomi

EC NUMBER
COMMENTARY hide
2.1.1.8
-
RECOMMENDED NAME
GeneOntology No.
histamine N-methyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
S-adenosyl-L-methionine + histamine = S-adenosyl-L-homocysteine + Ntau-methylhistamine
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
methyl group transfer
-
-
-
-
N-methylation
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
histamine degradation
-
-
Histidine metabolism
-
-
SYSTEMATIC NAME
IUBMB Comments
S-adenosyl-L-methionine:histamine N-tele-methyltransferase
-
CAS REGISTRY NUMBER
COMMENTARY hide
9029-80-5
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
S-adenosyl-L-methionine + (+/-)beta-methylhistamine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + (R)-alpha-methylhistamine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
S-adenosyl-L-methionine + (S)-alpha-methylhistamine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
S-adenosyl-L-methionine + histamine
S-adenosyl-L-homocysteine + N-methylhistamine
show the reaction diagram
S-adenosyl-L-methionine + histamine
S-adenosyl-L-homocysteine + Ntau-methylhistamine
show the reaction diagram
S-adenosyl-L-methionine + homohistamine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
additional information
?
-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(5'-amino-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-yl)-[4-(3-piperidin-1-yl-propoxy)-phenyl]-methanone
-
50% inhibition at 0.0020 mM, simultaneously a highly potent H3 receptor ligand
(5'-nitro-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-yl)-[4-(3-piperidin-1-yl-propoxy)-phenyl]-methanone
-
50% inhibition at 0.0015 mM, simultaneously a highly potent H3 receptor ligand
(5-nitro-pyridin-2-yl)-[4-(3-piperidin-1-yl-propoxy)-benzyl]-amine
-
50% inhibition at 0.0042 mM, simultaneously a highly potent H3 receptor ligand
(5-nitro-pyridin-2-yl)-{2-[4-(3-piperidin-1-yl-propoxy)-phenyl]-ethyl}-amine
-
50% inhibition at 0.0028 mM, simultaneously a highly potent H3 receptor ligand
(5-nitro-pyridin-2-yl)-{3-[4-(3-piperidin-1-yl-propoxy)-phenyl]-propyl}-amine
-
50% inhibition at 0.0017 mM, simultaneously a highly potent H3 receptor ligand
(5-nitro-pyridin-2-yl)-{4-[4-(3-piperidin-1-yl-propoxy)-phenyl]-butyl}-amine
-
50% inhibition at 0.0017 mM, simultaneously a highly potent H3 receptor ligand
(R)-chloroquine
-
50% inhibition at 0.018 mM, liver enzyme, 50% inhibition at 0.0022 mM, brain enzyme
(S)-chloroquine
-
50% inhibition at 0.005 mM, liver enzyme, 50% inhibition at 0.007 mM, brain enzyme
1-(3-(4-(3,4-dihydro-2H-pyrrol-5-yl)phenoxy)propyl)piperidine
-
50% inhibition at 0.0090 mM, simultaneously a highly potent H3 receptor ligand
1-Methylhistamine
2-(3-piperidin-1-ylpropoxy)-1,3-benzothiazole quinoline
-
50% inhibition at 0.021 mM, simultaneously a highly potent H3 receptor ligand
-
2-(4-hydroperoxyphenyl)-6-methyl-4H-chromen-4-one
-
-
2-Bromolysergic acid diethylamide
-
-
2-Methylhistamine
-
strong
3,6-dimethyl-2-phenyl-4H-chromen-4-one
-
-
3-bromo-6-chloro-2-phenyl-4H-chromen-4-one
-
-
3-bromo-6-methyl-2-phenyl-4H-chromen-4-one
-
-
3-chloro-6-methyl-2-phenyl-4H-chromen-4-one
-
-
3-Methylhistamine
-
strong
4-(dimethylamino)butyl carbamimidothioate
-
SKF-91488
5-Methylhistamine
-
weak
5-nitro-2-(3-piperidin-1-ylpropoxy)pyridine
-
50% inhibition at 0.034 mM, simultaneously a highly potent H3 receptor ligand
5-nitro-N-(4-(3-piperidin-1-ylpropoxy)phenyl)pyridin-2-amine
-
50% inhibition at 0.0038 mM, simultaneously a highly potent H3 receptor ligand
6-(3-piperidin-1-ylpropoxy)pyridin-3-amine
-
50% inhibition at 0.053 mM, simultaneously a potent H3 receptor ligand
6-chloro-2-phenyl-4H-chromen-4-one
-
-
6-methyl-2-phenyl-4H-chromen-4-one
-
-
6-piperidin-1-yl-1-[4-(3-piperidin-1-yl-propoxy)-phenyl]-hexan-1-one
-
50% inhibition at 0.0089 mM, simultaneously a highly potent H3 receptor ligand
7-chloro-4-(3-piperidin-1-ylpropoxy)quinoline
-
50% inhibition at 0.0026 mM, simultaneously a potent H3 receptor ligand
8-(3-(1H-imidazol-4-yl)propoxy)-5-nitroquinoline
-
50% inhibition at 0.0117 mM, simultaneously a highly potent H3 receptor ligand
8-bromo-6-chloro-2-phenyl-4H-chromen-4-one
-
-
8-bromo-6-methyl-2-phenyl-4H-chromen-4-one
-
-
amodiaquine
Biogenic amines
-
-
-
bromo-lysergic acid diethylamide
-
55% inhibition at 0.005 mM
Bufotenine
-
-
chlorpromazine
d-Chlorpheniramine
-
-
Dimaprit
-
-
diphenhydramine
-
potent HNMT inhibitor, occupies the histamine-binding site, thus blocks access to the enzyme’s active site
ethylamine
-
-
histamine
Impromidine
-
competitive, reversible
iodoacetamide
Methylhistamine
methylthioadenosine
-
-
Metoprine
N-(2-(1H-imidazol-4-yl)ethyl)-1,2,3,4-tetrahydroacridin-9-amine
-
50% inhibition at 0.000086 mM, simultaneously a highly potent H3 receptor ligand
N-(2-(1H-imidazol-4-yl)ethyl)-N-methylquinolin-4-amine
-
50% inhibition at 0.000079 mM, simultaneously a highly potent H3 receptor ligand
N-(2-(1H-imidazol-4-yl)ethyl)quinolin-4-amine
-
50% inhibition at 0.000055 mM, simultaneously a highly potent H3 receptor ligand
N-(3-(1H-imidazol-4-yl)propyl)-1,2,3,4-tetrahydroacridin-9-amine
-
50% inhibition at 0.000035 mM, simultaneously a highly potent H3 receptor ligand
N-(3-(1H-imidazol-4-yl)propyl)-2-methylquinolin-4-amine
-
50% inhibition at 0.000054 mM, simultaneously a highly potent H3 receptor ligand
N-(3-(1H-imidazol-4-yl)propyl)-N-methylquinolin-4-amine
-
50% inhibition at 0.000035 mM, simultaneously a highly potent H3 receptor ligand
N-(3-(1H-imidazol-4-yl)propyl)quinolin-4-amine
-
50% inhibition at 0.000024 mM, simultaneously a highly potent H3 receptor ligand
N-ethylmaleimide
-
-
N-[2(benzhydryloxy)ethyl] N N-dimethylamine
-
diphenhydramine, competitive inhibitor
N2-[2-[4-(3-piperidin-1-yl-propoxy)-phenyl]-ethyl]-pyridine-2,5-diamine
-
50% inhibition at 0.00031 mM, simultaneously a highly potent H3 receptor ligand
N2-[3-[4-(3-piperidin-1-yl-propoxy)-phenyl]-propyl]-pyridine-2,5-diamine
-
50% inhibition at 0.0013 mM, simultaneously a highly potent H3 receptor ligand
N2-[4-[4-(3-piperidin-1-yl-propoxy)-phenyl]-butyl]-pyridine-2,5-diamine
-
50% inhibition at 0.00034 mM, simultaneously a highly potent H3 receptor ligand
Nalpha-methylhistamine
-
weak
p-chloromercuribenzoate
p-hydroxymercuribenzoate
-
complete inhibition at 0.1 mM
S-adenosylhomocysteine
serotonin
SKF 91488
tacrine
tryptamine
-
and the hydroxyl derivative
Tubocurare
-
-
tyramine
-
and the hydroxyl derivative
[4-(3-piperidin-1-yl-propoxy)-phenyl]-(1-quinolin-4-yl-piperidin-4-yl)-methanone
-
50% inhibition at 0.00031 mM, simultaneously a highly potent H3 receptor ligand
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
5-Methylhistamine
-
0.001-0.5 mM, activation
alpha,Nalpha-Dimethylhistamine
-
activation
iodoacetamide
iodoacetic acid
-
activation
N',N'-dimethylhistamine
-
0.001-0.5 mM, activation
Nalpha-methylhistamine
-
0.001-0.5 mM, activation
Succinic anhydride
-
activation
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0042 - 0.043
histamine
0.0017 - 0.38
S-adenosyl-L-methionine
additional information
additional information
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00005
Amodiaquin
-
-
0.0000186
amodiaquine
-
-
0.0007
d-Chlorpheniramine
-
-
0.008
Dimaprit
-
-
0.000091
Metoprine
-
-
0.001
SKF 91488
-
-
0.0000382
tacrine
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.000022
-
large intestine, saline treated
0.000028
-
large intestine, amitriptyline treated
0.000036
-
kidney, saline treated
0.000038
-
lung, saline treated
0.000052
-
lung, amitriptyline treated
0.000054
-
kidney, amitriptyline treated
0.00008
-
cerebrum, saline treated
0.000101
-
small intestine, saline treated
0.000121
-
cerebrum, amitriptyline treated
0.000132
-
spleen, saline treated
0.000163
-
small intestine, amitriptyline treated
0.000165
-
spleen, amitriptyline treated
0.517
-
-
4.47
-
37°C
10.4
-
-
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.2 - 7.4
8.3
-
N-methylhistamine
8.5 - 9
-
kidney enzyme
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.5 - 10.5
-
about 50% of maximum activity at pH 6.5 and pH 10.5, N-methylhistamine
7.3 - 10.3
-
about 50% of maximum activity at pH 7.3 and pH 10.3
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
HMT activity comparable to activity in the jejunum
Manually annotated by BRENDA team
-
columnar epithelium
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
29000
-
gel filtration, SDS-PAGE
31500
-
SDS-PAGE, gel filtration
34800
-
gel filtration
36000
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
additional information
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
by hanging-drop method, HNMT bound to four different inhibitors at resolution limits of 1.9 A (diphenhydramine), 2.3 A (amodiaquine), 2.48 A (metoprine), and 2.97 A (tacrine) and in complex with S-adenosyl-L-homocysteine
-
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
90 min, 1 mM dithiothreitol, stable, 40% loss of activity without addition of dithiothreitol
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
dithiothreitol, 1 mM, stabilizes
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-80°C, 10 mM potassium phosphate buffer, pH 7.4, 10% glycerol, 1 mM dithiothreitol, 8 months, 16% loss of activity
-
-80°C, 3 months
-80°C, 5 months
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant protein
-
simultaneous purification of enzyme and diamine oxidase
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
by molecular cloning
-
expressed in HMC-1 cells
-
kidney, intestine
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
HMT expression is elevated in reg6 mutants
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C314T
-
PCR reaction-restriction fragment length polymorphism assay is used to identify the polymorphism of the point mutation C314T of HNMT gene of 498 Chinese patients with duodenal ulcer and 151 healthy individuals. In normal controls, the allele frequency of HNMT T314 is 3.3%, which is significantly lower than American Caucasians. The HNMT T314 allele is detected in 3.5% of the duodenal ulcer patients. In cases and controls, the frequency of C/C genotypes are 93.0% and 93.4%, respectively. The HNMT T/T genotype is not found in this population. No significant differences is seen in both genotype frequencies and allele frequencies between duodenal ulcer groups and controls
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
-
guinea-pig HNMT has 292 amino acid residues, its sequences are more similar to the human and pig sequences than to the mouse and rat sequences, respectively
degradation
-
higher HMT activity seems to be linked to reduced histamine catabolism, percentage of catabolized histamine is not correlated to individual mannitol fluxes and appears to be independent of paracellular permeability
medicine