Amine N-methyltransferase

INMT
Identifiers
Aliases	INMT, TEMT, indolethylamine N-methyltransferase
External IDs	OMIM: 604854; MGI: 102963; GeneCards: INMT
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2A14
Enzyme activity
Gene location (Human)
Chr.	Chromosome 7 (human)
End	30,757,602 bp
Gene location (Mouse)
Chr.	Chromosome 6 (mouse)
End	55,152,028 bp
RNA expression pattern
	Top expressed in
	right lung; ; upper lobe of left lung; ; right coronary artery; ; left coronary artery; ; cardiac muscle tissue of right atrium; ; right auricle of heart; ; apex of heart; ; right adrenal gland; ; right adrenal cortex; ; left adrenal cortex;
	Top expressed in
	right lung lobe; ; right kidney; ; left lobe of liver; ; olfactory epithelium; ; carotid body; ; human kidney; ; tunica adventitia of aorta; ; left lung; ; choroid plexus of fourth ventricle; ; intercostal muscle;
	More reference expression data
	n/a
Gene ontology
Molecular function	amine N-methyltransferase activity; methyltransferase activity; transferase activity; thioether S-methyltransferase activity; protein binding; S-adenosyl-L-methionine:beta-alanine N-methyltransferase activity;
Cellular component	cytoplasm; cytosol;
Biological process	methylation; amine metabolic process; response to toxic substance;
	Sources:Amigo / QuickGO
Orthologs
Databases	NCBI: entry; OMA: entry
	11185
	21743
	ENSG00000241644
	ENSMUSG00000003477
	O95050
	P40936
	NM_006774; NM_001199219
	NM_009349
	NP_001186148; NP_006765
	NP_033375
	Wikidata
View/Edit Human	View/Edit Mouse

Search
PMC	articles
PubMed	articles
NCBI	proteins

amine N-methyltransferase
amine N-methyltransferase
	indolethylamine N-methyltransferase (with slight variation on CPK coloration) – See PDB 2A14
Identifiers
EC no.	2.1.1.49
CAS no.	51377-47-0
Databases
BRENDA	enzyme data
ExPASy	NiceZyme view
KEGG	enzyme entry
MetaCyc	metabolic pathway
Rhea	reactions
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / QuickGO
PMC
Search
PMC	articles
PubMed	articles
NCBI	proteins

Amine N-methyltransferase (EC 2.1.1.49), also called indolethylamine N-methyltransferase, and thioether S-methyltransferase, is an enzyme that in humans is encoded by the INMT gene. It is ubiquitously present in non-neural tissues and catalyzes the N-methylation of tryptamine and structurally related compounds. It can also catalyze the methylation of thioether and selenoether compounds, although the physiological significance of this biotransformation is not yet known.

The general reaction taking place is:

S-adenosyl-L-methionine + an amine

\rightleftharpoons

S-adenosyl-L-homocysteine + a methylated amine

Function

Important reactions known to be catalysed by the enzyme include the dimethylation of tryptamine and serotonin, which are transformed to N,N-dimethyltryptamine (DMT) and bufotenine respectively, for example:

serotonin

+ 2 SAM

bufotenin

+ 2 SAH

A wide range of primary, secondary and tertiary amines can act as substrates, including tryptamine, aniline, nicotine and a variety of drugs and other xenobiotics.

The enzyme can also transfer methyl groups to atoms other than nitrogen, for example sulfur and selenium.

Nomenclature

This enzyme belongs to the family of transferases, specifically those transferring one-carbon group methyltransferases. The systematic name of this enzyme class is S-adenosyl-L-methionine:amine N-methyltransferase. Other names in common use include nicotine N-methyltransferase, tryptamine N-methyltransferase, indolethylamine N-methyltransferase, and arylamine N-methyltransferase.

Structural studies

As of late 2007, only one structure has been solved for this class of enzymes, with the PDB accession code PDB: 2A14.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000241644 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000003477 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ Ansher SS, Jakoby WB (1986). "Amine N-methyltransferases from rabbit liver". J. Biol. Chem. 261 (9): 3996–4001. doi:10.1016/S0021-9258(17)35612-0. PMID 3949799.
1 2 tryptamine+N-methyltransferase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
1 2 Chu, Uyen; Mavlyutov, Timur; Schulman, Amanda; Baker, Erin; Raj, Rebecca; Epstein, Miles; Guo, Lian; Ruoho, Arnold (April 2015). "Methylation of Thiols and Thioethers by Human Indolethylamine-N Methyl Transferase". The FASEB Journal. 29 (S1) 1022.7. doi:10.1096/fasebj.29.1_supplement.1022.7. ISSN 0892-6638.
1 2 Mozier, N M; McConnell, K P; Hoffman, J L (April 1988). "S-adenosyl-L-methionine:thioether S-methyltransferase, a new enzyme in sulfur and selenium metabolism". Journal of Biological Chemistry. 263 (10): 4527–4531. doi:10.1016/s0021-9258(18)68814-3. ISSN 0021-9258. PMID 3350800.
↑ Boarder MR, Rodnight R (1976). "Tryptamine-N-methyltransferase activity in brain tissue: a re-examination". Brain Res. 114 (2): 359–64. doi:10.1016/0006-8993(76)90680-6. PMID 963555. S2CID 36334101.
↑ J., Kärkkäinen; T. Forsström; J. Tornaeus; K. Wähälä; P. Kiuru; A. Honkanen; U. -H. Stenman; U. Turpeinen; A. Hesso (April 2005). "Potentially hallucinogenic 5-hydroxytryptamine receptor ligands bufotenine and dimethyltryptamine in blood and tissues". Scandinavian Journal of Clinical and Laboratory Investigation. 65 (3): 189–199. doi:10.1080/00365510510013604. PMID 16095048. S2CID 20005294.
↑ Lyon ES, Jakoby WB (1981). "Arylamine N-methyltransferase". Detoxication and Drug Metabolism: Conjugation and Related Systems. Methods in Enzymology. Vol. 77. pp. 263–6. doi:10.1016/S0076-6879(81)77035-6. ISBN 9780121819774. PMID 6276654.
↑ Crooks PA, Godin CS, Damani LA, Ansher SS, Jakoby WB (1988). "Formation of quaternary amines by N-methylation of azaheterocycles with homogeneous amine N-methyltransferases". Biochem. Pharmacol. 37 (9): 1673–7. doi:10.1016/0006-2952(88)90426-1. PMID 3377829.
↑ Enzyme 2.1.1.49 at KEGG Pathway Database.

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000241644 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000003477 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[5] Ansher SS, Jakoby WB (1986). "Amine N-methyltransferases from rabbit liver". J. Biol. Chem. 261 (9): 3996–4001. doi:10.1016/S0021-9258(17)35612-0. PMID 3949799.

[MeshName-6] 1 2 tryptamine+N-methyltransferase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

[Chu-7] 1 2 Chu, Uyen; Mavlyutov, Timur; Schulman, Amanda; Baker, Erin; Raj, Rebecca; Epstein, Miles; Guo, Lian; Ruoho, Arnold (April 2015). "Methylation of Thiols and Thioethers by Human Indolethylamine-N Methyl Transferase". The FASEB Journal. 29 (S1) 1022.7. doi:10.1096/fasebj.29.1_supplement.1022.7. ISSN 0892-6638.

[Mozier-8] 1 2 Mozier, N M; McConnell, K P; Hoffman, J L (April 1988). "S-adenosyl-L-methionine:thioether S-methyltransferase, a new enzyme in sulfur and selenium metabolism". Journal of Biological Chemistry. 263 (10): 4527–4531. doi:10.1016/s0021-9258(18)68814-3. ISSN 0021-9258. PMID 3350800.

[9] Boarder MR, Rodnight R (1976). "Tryptamine-N-methyltransferase activity in brain tissue: a re-examination". Brain Res. 114 (2): 359–64. doi:10.1016/0006-8993(76)90680-6. PMID 963555. S2CID 36334101.

[10] J., Kärkkäinen; T. Forsström; J. Tornaeus; K. Wähälä; P. Kiuru; A. Honkanen; U. -H. Stenman; U. Turpeinen; A. Hesso (April 2005). "Potentially hallucinogenic 5-hydroxytryptamine receptor ligands bufotenine and dimethyltryptamine in blood and tissues". Scandinavian Journal of Clinical and Laboratory Investigation. 65 (3): 189–199. doi:10.1080/00365510510013604. PMID 16095048. S2CID 20005294.

[11] Lyon ES, Jakoby WB (1981). "Arylamine N-methyltransferase". Detoxication and Drug Metabolism: Conjugation and Related Systems. Methods in Enzymology. Vol. 77. pp. 263–6. doi:10.1016/S0076-6879(81)77035-6. ISBN 9780121819774. PMID 6276654.

[12] Crooks PA, Godin CS, Damani LA, Ansher SS, Jakoby WB (1988). "Formation of quaternary amines by N-methylation of azaheterocycles with homogeneous amine N-methyltransferases". Biochem. Pharmacol. 37 (9): 1673–7. doi:10.1016/0006-2952(88)90426-1. PMID 3377829.

[13] Enzyme 2.1.1.49 at KEGG Pathway Database.

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)