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Information on EC 2.1.1.8 - histamine N-methyltransferase and Organism(s) Homo sapiens

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EC Tree
     2 Transferases
         2.1 Transferring one-carbon groups
             2.1.1 Methyltransferases
                2.1.1.8 histamine N-methyltransferase
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This record set is specific for:
Homo sapiens
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
hnmt, histamine n-methyltransferase, histamine-n-methyltransferase, histamine methyltransferase, ntau-methyltransferase, histamine-methylating enzyme, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
histamine 1-methyltransferase
-
-
-
-
histamine methyltransferase
-
-
-
-
histamine N-methyltransferase
histamine-methylating enzyme
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-
-
-
histamine-N-methyltransferase
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-
imidazole methyltransferase
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-
-
-
imidazole N-methyltransferase
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-
-
-
imidazolemethyltransferase
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-
-
-
methyltransferase, histamine
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-
-
-
S-adenosylmethionine-histamine N-methyltransferase
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-
-
-
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
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-
-
-
N-methylation
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-
-
-
PATHWAY SOURCE
PATHWAYS
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-
SYSTEMATIC NAME
IUBMB Comments
S-adenosyl-L-methionine:histamine N-tele-methyltransferase
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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 + BI 187004
S-adenosyl-L-homocysteine + 1-(1-methyl-1H-benzimidazole-6-carbonyl)-1,2,3,4,5,5a,10,10a-octahydroindeno[2,1-b]azepine-7-carbonitrile
show the reaction diagram
BI 187004, i.e. an 11beta-hydroxysteroid dehydrogenase 1 inhibitor
-
-
?
S-adenosyl-L-methionine + histamine
S-adenosyl-L-homocysteine + Ntau-methylhistamine
show the reaction diagram
additional information
?
-
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
additional information
?
-
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(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-Methylhistamine
-
-
2-(4-hydroperoxyphenyl)-6-methyl-4H-chromen-4-one
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-
3,6-dimethyl-2-phenyl-4H-chromen-4-one
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-
3-bromo-6-chloro-2-phenyl-4H-chromen-4-one
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-
3-bromo-6-methyl-2-phenyl-4H-chromen-4-one
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-
3-chloro-6-methyl-2-phenyl-4H-chromen-4-one
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-
6-chloro-2-phenyl-4H-chromen-4-one
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-
6-methyl-2-phenyl-4H-chromen-4-one
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-
8-bromo-6-chloro-2-phenyl-4H-chromen-4-one
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-
8-bromo-6-methyl-2-phenyl-4H-chromen-4-one
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-
amodiaquine
diphenhydramine
potent HNMT inhibitor, occupies the histamine-binding site, thus blocks access to the enzyme’s active site
histamine
-
0.025-0.1 mM
Metoprine
potent HNMT inhibitor, occupies the histamine-binding site, thus blocks access to the enzyme’s active site
N-[2(benzhydryloxy)ethyl] N N-dimethylamine
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diphenhydramine, competitive inhibitor
S-adenosylhomocysteine
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-
SKF 91488
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-
tacrine
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0011 - 0.0042
histamine
0.0018 - 0.015
S-adenosyl-L-methionine
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.03 - 0.61
S-adenosyl-L-methionine
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0000186
amodiaquine
-
0.000091
Metoprine
-
0.0000382
tacrine
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
-
Manually annotated by BRENDA team
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
HNMT_HUMAN
292
0
33295
Swiss-Prot
Mitochondrion (Reliability: 5)
B4DWC1_HUMAN
161
0
18435
TrEMBL
Mitochondrion (Reliability: 5)
Q9P1Y0_HUMAN
117
0
13346
TrEMBL
other Location (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
33000
-
x * 33000, deduced from DNA sequence
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
-
x * 33000, deduced from DNA sequence
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
PROTEIN VARIANTS
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
L208D
mutant is severely compromised in its stability
L208F
21% of wild-type activtiy, Michaelis-Menten parameters for SAM and histamine similar to wild-type
L208H
mutant is severely compromised in its stability
L208K
substantial loss of enzymatic activity and binding affinity for histamine
L208N
mutant is severely compromised in its stability
L208R
substantial loss of enzymatic activity and binding affinity for histamine
L208T
mutant is severely compromised in its stability
L208V
48% of wild-type activity, Michaelis-Menten parameters for SAM and histamine similar to wild-type
T105I
additional information
-
the A939G polymorphism is significantly associated with the aspirin intolerant chronic urticaria phenotype, while no association is found with the C314T polymorphism, the 939A allele gives lower levels of HNMT mRNA stability, HNMT protein expression, and HNMT enzymatic activity and higher histamine release than the 939G allele, patients with the 939A allele have lower HNMT activity in red blood cell lysates and higher histamine release from their basophils
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
48.4
melting temperature, mutant L208R
53.7
melting temperature, mutant L208K
57.8
melting temperature, mutant L208V
60.4
melting temperature, wild-type, presence of histamine, and melting temeprature of mutant L208F
61.3
melting temperature, wild-type
61.5
melting temperature, wild-type, presence of S-adenosyl-L-methionine
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant protein
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in HMC-1 cells
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expression in Escherichia coli
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Francis, D.M.; Thompson, M.F.; Greaves, M.W.
The kinetic properties and reaction mechanism of histamine methyltransferase from human skin
Biochem. J.
187
819-828
1980
Homo sapiens
Manually annotated by BRENDA team
Scott, M.C.; Guerciolini, R.; Szumlanski, C.; Weinshilboum, R.M.
Mouse kidney histamine N-methyltransferase: assay conditions, biochemical properties and strain variation
Agents Actions
32
194-202
1991
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Horton, J.R.; Sawada, K.; Nishibori, M.; Zhang, X.; Cheng, X.
Two polymorphic forms of human histamine methyltransferase. Structural, thermal, and kinetic comparisons
Structure
9
837-849
2001
Homo sapiens (P50135), Homo sapiens
Manually annotated by BRENDA team
Yamauchi, K.; Sekizawa, K.; Suzuki, H.; Nakazawa, H.; Ohkawara, Y.; Katayose, D.; Ohtsu, H.; Tamura, G.; Shibahara, S.; et al.
Structure and function of human histamine N-methyltransferase: critical enzyme in histamine metabolism in airway
Am. J. Physiol.
267
L342-L349
1994
Homo sapiens
Manually annotated by BRENDA team
Preuss, C.V.; Wood, T.C.; Szumlanski, C.L.; Raftogianis, R.B.; Otterness, D.M.; Girard, B.; Scott, M.C.; Weinshilboum, R.M.
Human histamine N-methyltransferase pharmacogenetics: common genetic polymorphisms that alter activity
Mol. Pharmacol.
53
708-717
1998
Homo sapiens
Manually annotated by BRENDA team
Donatelli, P.; Marchi, G.; Giuliani, L.; Gustafsson, L.L.; Pacifici, G.M.
Stereoselective inhibition by chloroquine of histamine N-methyltransferase in the human liver and brain
Eur. J. Clin. Pharmacol.
47
345-349
1994
Homo sapiens
Manually annotated by BRENDA team
Pang, Y.P.; Zheng, X.E.; Weinshilboum, R.M.
Theoretical 3D model of histamine N-methyltransferase: Insights into the effects of a genetic polymorphism on enzymatic activity and thermal stability
Biochem. Biophys. Res. Commun.
287
204-208
2001
Homo sapiens (P50135), Homo sapiens
Manually annotated by BRENDA team
Oroszi, G.; Enoch, M.A.; Chun, J.; Virkkunen, M.; Goldman, D.
Thr105Ile, a functional polymorphism of histamine N-methyltransferase, is associated with alcoholism in two independent populations
Alcohol. Clin. Exp. Res.
29
303-309
2005
Homo sapiens
Manually annotated by BRENDA team
Kuefner, M.A.; Schwelberger, H.G.; Weidenhiller, M.; Hahn, E.G.; Raithel, M.
Both catabolic pathways of histamine via histamine-N-methyl-transferase and diamine oxidase are diminished in the colonic mucosa of patients with food allergy
Inflamm. Res.
53
S31-S32
2004
Homo sapiens
-
Manually annotated by BRENDA team
Taraschenko, O.D.; Barnes, W.G.; Herrick-Davis, K.; Yokoyama, Y.; Boyd, D.L.; Hough, L.B.
Actions of tacrine and galanthamine on histamine-N-methyltransferase
Methods Find. Exp. Clin. Pharmacol.
27
161-165
2005
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Horton, J.R.; Sawada, K.; Nishibori, M.; Cheng, X.
Structural basis for inhibition of histamine N-methyltransferase by diverse drugs
J. Mol. Biol.
353
334-344
2005
Homo sapiens (P50135)
Manually annotated by BRENDA team
Rutherford, K.; Parson, W.W.; Daggett, V.
The histamine N-methyltransferase T105I polymorphism affects active site structure and dynamics
Biochemistry
47
893-901
2008
Homo sapiens (P50135), Homo sapiens
Manually annotated by BRENDA team
Cao, H.; Mei, Q.; Zhang, L.; Xu, J.
C314T polymorphism in histamine N-methyltransferase gene and susceptibility to duodenal ulcer in Chinese population.
Clin. Chim. Acta
391
130
2008
Homo sapiens
-
Manually annotated by BRENDA team
Reuter, M.; Jeste, N.; Klein, T.; Hennig, J.; Goldman, D.; Enoch, M.; Oroszi, G.
Association of THR105Ile, a functional polymorphism of histamine N-methyltransferase (HNMT), with alcoholism in German Caucasians
Drug Alcohol Depend.
87
69-75
2007
Homo sapiens
Manually annotated by BRENDA team
Ledesma, M.C.; Garcia-Martin, E.; Alonso-Navarro, H.; Martinez, C.; Jimenez-Jimenez, F.J.; Benito-Leon, J.; Puertas, I.; Rubio, L.; Lopez-Alburquerque, T.; Agundez, J.A.
The Nonsynonymous Thr105Ile Polymorphism of the Histamine N-Methyltransferase is Associated to the Risk of Developing Essential Tremor
Neuromolecular Med.
10
356-361
2008
Homo sapiens
Manually annotated by BRENDA team
Kim, S.H.; Kang, Y.M.; Kim, S.H.; Cho, B.Y.; Ye, Y.M.; Hur, G.Y.; Park, H.S.
Histamine N-methyltransferase 939A>G polymorphism affects mRNA stability in patients with acetylsalicylic acid-intolerant chronic urticaria
Allergy
64
213-221
2009
Homo sapiens
Manually annotated by BRENDA team
Dave, S.; Rahatgaonkar, A.
Computational evaluation of 2-phenyl-4H-chromen-4-one analogues as antihistamines: Potential histamine N-methyltransferase (HMT) inhibitors
E-J. Chem.
6
1009-1016
2009
Homo sapiens
-
Manually annotated by BRENDA team
von Mach-Szczypi?ski, J.; Stanosz, S.; Sieja, K.; Stanosz, M.
Histamine and its metabolizing enzymes in tissues of primary ductal breast cancer
Eur. J. Gynaecol. Oncol.
30
509-511
2009
Homo sapiens
Manually annotated by BRENDA team
Agundez, J.; Luengo, A.; Herraez, O.; Martinez, C.; Alonso-Navarro, H.; Jimenez-Jimenez, F.; Garcia-Martin, E.
Nonsynonymous polymorphisms of histamine-metabolising enzymes in patients with Parkinsons disease
Neuromolecular Med.
10
10-16
2008
Homo sapiens (P50135), Homo sapiens
Manually annotated by BRENDA team
Palada, V.; Terzi?, J.; Mazzulli, J.; Bwala, G.; Hagenah, J.; Peterlin, B.; Hung, A.Y.; Klein, C.; Krainc, D.
Histamine N-methyltransferase Thr105Ile polymorphism is associated with Parkinsons disease
Neurobiol. Aging
33
836.e1-3
2012
Homo sapiens
Manually annotated by BRENDA team
Kuefner, M.A.; Feurle, J.; Petersen, J.; Uder, M.; Schwelberger, H.G.
Influence of iodinated contrast media on the activities of histamine inactivating enzymes diamine oxidase and histamine N-methyltransferase in vitro
Allergol. Immunopathol. (Madr.)
42
324-328
2014
Homo sapiens (P50135), Homo sapiens
Manually annotated by BRENDA team
Tongsook, C.; Niederhauser, J.; Kronegger, E.; Straganz, G.; Macheroux, P.
Leucine 208 in human histamine N-methyltransferase emerges as a hotspot for protein stability rationalizing the role of the L208P variant in intellectual disability
Biochim. Biophys. Acta
1863
188-199
2017
Homo sapiens (P50135), Homo sapiens
Manually annotated by BRENDA team
Jia, H.Z.; Liu, S.L.; Zou, Y.F.; Chen, X.F.; Yu, L.; Wan, J.; Zhang, H.Y.; Chen, Q.; Xiong, Y.; Yu, B.; Zhang, W.
MicroRNA-223 is involved in the pathogenesis of atopic dermatitis by affecting histamine-N-methyltransferase
Cell. Mol. Biol. (Noisy-le-grand)
64
103-107
2018
Homo sapiens (P50135), Homo sapiens
Manually annotated by BRENDA team
Maw, H.H.; Zeng, X.; Campbell, S.; Taub, M.E.; Teitelbaum, A.M.
N-Methylation of BI 187004 by thiol S-methyltransferase
Drug Metab. Dispos.
46
770-778
2018
Homo sapiens (P50135), Homo sapiens
Manually annotated by BRENDA team