Coding
HNMT

Part:BBa_K3647777

Designed by: Natalia Savinkova, Ida Berghten, Astrid Welin, Thalia Rodriquez, Osamudiamen Iyere, Frida Haugskott, Oliver Hild Walett   Group: iGEM20_Linkoping   (2020-08-20)
Revision as of 09:00, 18 October 2020 by Nataliasavinkova (Talk | contribs)

Histamine N-methyltransferase (N-term. 6XHIS, TEV)


For information and characterization of this part please see: BBa_K3647666

Sequence and Features


Assembly Compatibility:
  • 10
    COMPATIBLE WITH RFC[10]
  • 12
    COMPATIBLE WITH RFC[12]
  • 21
    INCOMPATIBLE WITH RFC[21]
    Illegal BamHI site found at 40
  • 23
    COMPATIBLE WITH RFC[23]
  • 25
    COMPATIBLE WITH RFC[25]
  • 1000
    INCOMPATIBLE WITH RFC[1000]
    Illegal BsaI.rc site found at 394
    Illegal BsaI.rc site found at 778

General information

Histamine N-methyltransferase is one of the two enzymes involved in the metabolism of histamine in mammals, this is known as the N(tau)-methylation pathway. The second pathway is oxidative deamination via diamine oxidase (DAO). This protein is encoded by the gene HNMT and it can be found in the cytosol intracellular fluid. HNMT is expressed in many organs like liver, kidney and brain, being found in most of the body tissues, except for serum. (Yoshikawa, 2019)

Funtion of HNMT is catalyzation of histamine methylation in the presence of S-adenosylmethionine (SAM-e) yielding N-methylhistamine. Histamine (HA) is inactivated by using S-adenosylmethionine (SAM-e) as a methyl donor. This occurs, as an example, during the termination process of neurotransmission actions of HA in the mammalian central nervous system. (Heidari et al, 2015) (Yoshikawa, 2019)

Figure 1. Structure of histamine N-methyltransferase. PBD code 1JQD
Human Histamine N-methyltransferase is a monomeric protein. It consists of 292 amino acids, of chains A and B and has a weight of 33,33 kDa. It is a two-domain structure, the large domain is a MTase fold, defined by 20 MTases and the S domain. The MTase domain is the one that participates in histamine binding. The polymorphic amino acid 105 is located on the outer surface of the MTase domain. The HNMT gene is located on chromosome 2q22.1 and has six exons of 50kb.(Horton, 2001)

HNMT is released via mast cells degranulation upon bronchoconstriction thus contributing to the asthmatic symptoms. The enzyme Histamine N-methyl transferase catalyzes N-methylation which means that it inactivates and degrades histamine. Since histamine is a key ingredient in allergic asthma, it works as a mediator with information from the mast cells. In allergic asthma, IgE antibodies will be released in response to the antibody-mediated cell degranulation. The gene coding for the HNMT protein is stated to be a candidate for inherited asthma due to the human polymorphism and primary biotransformation of histamine in the bronchial epithelium. Histamine N-methyltransferase is one of two enzymes involved in the metabolism of histamine, the second being diamine oxidase. Low levels of HNMT expression in numerous tissues points to an increased risk of asthma development. (Yan, 2000), (Yamauchi, 2019)




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