Histamine N-methyltransferase

histamine N-methyltransferase
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1JQD, 1JQE, 2AOT, 2AOU, 2AOV, 2AOW, 2AOX
Identifiers
Aliases	HNMT, HMT, HNMT-S1, HNMT-S2, MRT51
External IDs	OMIM: 605238; MGI: 2153181; HomoloGene: 5032; GeneCards: HNMT; OMA:HNMT - orthologs
EC number	2.1.1.8
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2q22.1 Start 137,964,020 bp[1] End 138,016,364 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2|2 A3 Start 23,892,922 bp[2] End 23,939,406 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in gallbladder monocyte mucosa of sigmoid colon rectum kidney tubule liver Achilles tendon skin of hip left ovary bronchial epithelial cell Top expressed in parotid gland granulocyte ventral tegmental area intercostal muscle white adipose tissue habenula dorsomedial hypothalamic nucleus right kidney dorsal tegmental nucleus Epithelium of choroid plexus More reference expression data BioGPS n/a
Gene ontology Molecular function methyltransferase activity transferase activity N-methyltransferase activity histamine N-methyltransferase activity Cellular component cytoplasm cytosol neuron projection extracellular exosome Biological process response to immobilization stress response to interleukin-1 positive regulation of protein targeting to mitochondrion response to glucocorticoid hyperosmotic response respiratory gaseous exchange by respiratory system response to tumor cell brain development response to amine histidine catabolic process response to cocaine histamine catabolic process methylation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3176 140483 Ensembl ENSG00000150540 ENSMUSG00000026986 UniProt P50135 Q91VF2 RefSeq (mRNA) NM_001024074 NM_001024075 NM_006895 NM_080462 RefSeq (protein) NP_001019245 NP_001019246 NP_008826 NP_536710 Location (UCSC) Chr 2: 137.96 – 138.02 Mb Chr 2: 23.89 – 23.94 Mb PubMed search [3] [4]
Wikidata
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Histamine N-methyltransferase (HNMT) is a protein encoded by the HNMT gene in humans. It belongs to the methyltransferases superfamily of enzymes and plays a role in the inactivation of histamine, a biomolecule that is involved in various physiological processes. Methyltransferases are present in every life form including archaeans, with 230 families of methyltransferases found across species.

Specifically, HNMT transfers a methyl (-CH₃) group from S-adenosyl-L-methionine (SAM-e) to histamine, forming an inactive metabolite called N^τ-methylhistamine, in a chemical reaction called N^τ-methylation. In mammals, HNMT operates alongside diamine oxidase (DAO) as the only two enzymes responsible for histamine metabolism; however, what sets HNMT apart is its unique presence within the central nervous system (CNS), where it governs histaminergic neurotransmission, that is a process where histamine acts as a messenger molecule between the neurons—nerve cells—in the brain. By degrading and regulating levels of histamine specifically within the CNS, HNMT ensures the proper functioning of neural pathways related to arousal, appetite regulation, sleep-wake cycles, and other essential brain functions.

Research on knockout mice—that are genetically modified mice lacking the Hnmt gene—has revealed that the absence of this enzyme leads to increased brain histamine concentrations and behavioral changes such as heightened aggression and disrupted sleep patterns. These findings highlight the critical role played by HNMT in maintaining normal brain function through precise regulation of neuronal signaling involving histamine. Genetic variants affecting HNMT activity have also been implicated in various neurological disorders like Parkinson's disease and attention deficit disorder.