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Enzyme Nomenclature
Information on EC 2.1.1.8 - histamine N-methyltransferase and Organism(s) Homo sapiens
for references in articles please use BRENDA:EC2.1.1.8
Word Map on EC 2.1.1.8
- 2.1.1.8
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diamine
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histaminergic
- metoprine
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thr105ile
- l-histidine
- aminoguanidine
- thioperamide
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tele-methylhistamine
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radioenzymatic
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histamine-induced
- s-adenosyl-l-homocysteine
- amodiaquine
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n-myristoyltransferase
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tau-methylhistamine
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histamine-degrading
- histaminase
- dimaprit
- phenylethanolamine
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mepyramine
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pyrilamine
- pentagastrin
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r-alpha-methylhistamine
- medicine
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histamine-related
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gene-dose
- analysis
- degradation
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Specify your search results
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
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EC NUMBER 
COMMENTARY 
2.1.1.8
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RECOMMENDED NAME
GeneOntology No.
histamine N-methyltransferase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
S-adenosyl-L-methionine + histamine = S-adenosyl-L-homocysteine + Ntau-methylhistamine
ordered sequential bi bi reaction mechanism with S-adenosylmethionine as the first substrate and histamine as the second substrate, 1-methylhistamine is the first product to leave and S-adenosylhomocysteine the second; sequential reaction mechanism
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
methyl group transfer
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N-methylation
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
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SYSTEMATIC NAME
IUBMB Comments
S-adenosyl-L-methionine:histamine N-tele-methyltransferase
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CAS REGISTRY NUMBER
COMMENTARY
9029-80-5
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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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
S-adenosyl-L-methionine + histamine
S-adenosyl-L-homocysteine + Ntau-methylhistamine
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?
S-adenosyl-L-methionine + histamine
S-adenosyl-L-homocysteine + Ntau-methylhistamine
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-
-
?
S-adenosyl-L-methionine + histamine
S-adenosyl-L-homocysteine + Ntau-methylhistamine
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-
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?
additional information
?
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possible role in modulation of histamine mediated reactions in skin
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additional information
?
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major enzyme for histamine inactivation in mammalian tissues
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NATURAL SUBSTRATES
NATURAL PRODUCTS
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
additional information
?
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possible role in modulation of histamine mediated reactions in skin
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additional information
?
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major enzyme for histamine inactivation in mammalian tissues
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INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(R)-chloroquine
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50% inhibition at 0.018 mM, liver enzyme, 50% inhibition at 0.0022 mM, brain enzyme
(S)-chloroquine
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50% inhibition at 0.005 mM, liver enzyme, 50% inhibition at 0.007 mM, brain enzyme
amodiaquine
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potent HNMT inhibitor, occupies the histamine-binding site, thus blocks access to the enzymes active site
diphenhydramine
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potent HNMT inhibitor, occupies the histamine-binding site, thus blocks access to the enzymes active site
Metoprine
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potent HNMT inhibitor, occupies the histamine-binding site, thus blocks access to the enzymes active site
N-[2(benzhydryloxy)ethyl] N N-dimethylamine
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diphenhydramine, competitive inhibitor
tacrine
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50% inhibition at 0.00046 mM for enzyme of embryonic kidney, at 0.0007 mM for recombinant brain enzyme
tacrine
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potent HNMT inhibitor, occupies the histamine-binding site, thus blocks access to the enzymes active site
additional information
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near the N-terminus of HNMT, several aromatic residues (Phe9, Tyr15, and Phe19) adopt different rotamer conformations or become disordered in the enzyme-inhibitor complexes, accommodating the diverse, rigid hydrophobic groups of the inhibitors, maximized shape complementarity between the protein aromatic side-chains and aromatic rings of the inhibitors are responsible for the tight binding of the different inhibitors
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
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PDB
SCOP
CATH
UNIPROT
ORGANISM
Homo sapiens;
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
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two polymorphic forms, Thr105 corresponds to high activity, Ile105 corresponds to low activity phenotype
additional information
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theoretical 3D model of isoforms, Ile105 energetically destabilizes
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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
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C314T
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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
T105I
additional information
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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
T105I
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common threonine-isoleucine polymorphism at residue 105, showing decreased activity and lower protein levels than the 105T protein. Molecular dynamic simulations at 37°C indicate that replacing Thr with the larger Ile residue leads to greater burial of residue 105 and heightened intramolecular interactions between residue 105 and residues within helix R3 and strand a3. This altered, tighter packing is translated to the active site, resulting in the reorientation of several cosubstrate-binding residues
T105I
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Thr105Ile polymorphism is analyzed whether it is associated with alcoholism in German Caucasians. No significant difference is found in the frequency of the Ile105 allele between alcoholics and controls. Likewise, genotype distributions does not differ significantly. Frequency of the Ile105 allele is significantly lower in male alcoholics with a family history of alcoholism compared to that in male alcoholics without a family history of alcoholism
T105I
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Thr105Ile polymorphism of the HNMT enzyme is analyzed in patients with essential tremor. Leukocytary DNA from 204 essential tremor patients and a control group of 295 unrelated healthy individuals is studied for the nonsynonymous HNMT Thr105Ile polymorphism by using amplification-restriction analyses. Patients with essential tremor show a higher frequency of homozygous HNMT 105Thr genotypes leading to high metabolic activity with a statistically significant gene-dose effect, as compared to healthy subjects
T105I
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an association of the HNMT Thr105Ile polymorphism with Parkinsons disease is observed
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
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T105I mutation is more abundant among alcoholics from Finnish Caucasion and Plains Indian American populations. Decreased histamine level in central nervous system may be a risk factor in alcoholism and associated with higher levels of trait anxiety
medicine
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in patients with food allergy, median enzyme activity, as well as median diamone oxidase activity, are significantly decreased compared to controls. Histamine content is elevated
medicine
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the HNMT T314 allele frequency is lower in Chinese population than in American Caucasians. No association can be found in the involvement of HNMT C314T polymorphism in the susceptibility to duodenal ulcer
medicine
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in German Caucasians the association of the HNMT Thr105Ile polymorphism with alcoholism is not replicated, but a congruent association is found between the Ile105 allele and family history of alcoholism supporting the protective role of the Ile105 allele against alcoholism
medicine
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results suggest that alterations of histamine homeostasis are associated with the risk of movement disorders
medicine
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Iodinated contrast media can cause pseudoallergic reactions associated with histamine release in significant numbers of patients. The iodinated contrast media tested in vitro do not exhibit inhibition of histamine inactivating enzymes diamine oxidase and histamine N-methyltransferase at physiologically relevant concentrations
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