Alternative titles; symbols
HGNC Approved Gene Symbol: PNMT
Cytogenetic location: 17q12 Genomic coordinates (GRCh38): 17:39,668,019-39,670,475 (from NCBI)
Phenylethanolamine N-methyltransferase (PNMT; EC 2.1.1.28) catalyzes the synthesis of epinephrine from norepinephrine, the last step of catecholamine biosynthesis. The enzyme is found predominantly in chromaffin cells of the adrenal medulla, in which epinephrine is synthesized as a hormone. It is also distributed in adrenergic neurons of the medulla oblongata as a neurotransmitter (summary by Kaneda et al., 1988).
To isolate a cDNA clone for human PNMT, Kaneda et al. (1988) first isolated a cDNA clone for bovine adrenal medulla PNMT using mixed oligodeoxyribonucleotide probes whose synthesis was based on the partial amino acid sequence of tryptic peptides from the bovine enzyme. Using a bovine cDNA as a probe, they screened a human pheochromocytoma cDNA library and isolated a cDNA clone with an insert of about 1.0 kb, which contained a complete coding region of the enzyme. Northern blot analysis of human pheochromocytoma polyadenylated RNA using this cDNA insert as the probe demonstrated a single RNA species of about 1,000 nucleotides, suggesting that this clone is a full-length cDNA. The nucleotide sequence showed that human PNMT has 282 amino acid residues with a predicted molecular weight of 30,853 Da, including the initial methionine. The amino acid sequence was 88% homologous to that of the bovine enzyme.
Baetge et al. (1988) showed that transgenic mice containing the human PNMT gene with either 2 or 8 kb of 5-prime flanking sequence expressed PNMT mRNA in the adrenal gland and eye. A chimeric gene consisting of 2 kb of human PNMT 5-prime flanking region fused to the simian virus 40 early region also resulted in tumor antigen mRNA expression in adrenal glands and eyes; furthermore, immunocytochemistry showed that the tumor antigen was localized in nuclei of adrenal medullary cells and cells of the inner nuclear cell layer of the retina, both prominent sites of epinephrine synthesis. The results indicate that the enhancer(s) for appropriate expression of the gene in these cell types are in the 2-kb 5-prime flanking region of the gene.
Baetge et al. (1988) found that the PNMT gene contains 3 exons and spans about 2.1 kb.
Kaneda et al. (1988) assigned the human PNMT gene to chromosome 17 by Southern blot analysis of DNA from mouse-human somatic cell hybrids. Hoehe et al. (1989) assigned PNMT to chromosome 17 by probing of DNA from somatic cell hybrids and demonstrated a RFLP. Hoehe et al. (1992) narrowed the localization to 17q21-q22 by linkage analysis using RFLPs related to the PNMT gene and several 17q DNA markers. However, Gross (2014) mapped the PNMT gene to chromosome 17q12 based on an alignment of the PNMT sequence (GenBank BC037246) with the genomic sequence (GRCh38).
Baetge, E. E., Behringer, R. R., Messing, A., Brinster, R. L., Palmiter, R. D. Transgenic mice express the human phenylethanolamine N-methyltransferase gene in adrenal medulla and retina. Proc. Nat. Acad. Sci. 85: 3648-3652, 1988. [PubMed: 2835776] [Full Text: https://doi.org/10.1073/pnas.85.10.3648]
Gross, M. B. Personal Communication. Baltimore, Md. 10/16/2014.
Hoehe, M. R., Berrettini, W. H., Baetge, E. E. A two allele DNA polymorphism of the human phenylethanolamine N-methyltransferase (hPNMT) gene identified by HGIA I. Nucleic Acids Res. 17: 828 only, 1989. [PubMed: 2563586] [Full Text: https://doi.org/10.1093/nar/17.2.828]
Hoehe, M. R., Plaetke, R., Otterud, B., Stauffer, D., Holik, J., Byerley, W. F., Baetge, E. E., Gershon, E. S., Lalouel, J.-M., Leppert, M. Genetic linkage of the human gene for phenylethanolamine N-methyltransferase (PNMT), the adrenaline-synthesizing enzyme, to DNA markers on chromosome 17q21-q22. Hum. Molec. Genet. 1: 175-178, 1992. [PubMed: 1303174] [Full Text: https://doi.org/10.1093/hmg/1.3.175]
Kaneda, N., Ichinose, H., Kobayashi, K., Oka, K., Kishi, F., Nakazawa, A., Kurosawa, Y., Fujita, K., Nagatsu, T. Molecular cloning of cDNA and chromosomal assignment of the gene for human phenylethanolamine N-methyltransferase, the enzyme for epinephrine biosynthesis. J. Biol. Chem. 263: 7672-7677, 1988. [PubMed: 3372503]