NNMT

N-methylation is one method by which drug and other xenobiotic compounds are metabolized by the liver. This gene encodes the protein responsible for this enzymatic activity which uses S-adenosyl methionine as the methyl donor. [provided by RefSeq, Jul 2008]

Full Name

Nicotinamide N-Methyltransferase

Function

Catalyzes the N-methylation of nicotinamide using the universal methyl donor S-adenosyl-L-methionine to form N1-methylnicotinamide and S-adenosyl-L-homocysteine, a predominant nicotinamide/vitamin B3 clearance pathway (PubMed:8182091. PubMed:21823666, PubMed:23455543).
Plays a central role in regulating cellular methylation potential, by consuming S-adenosyl-L-methionine and limiting its availability for other methyltransferases. Actively mediates genome-wide epigenetic and transcriptional changes through hypomethylation of repressive chromatin marks, such as H3K27me3 (PubMed:26571212, PubMed:23455543, PubMed:31043742).
In a developmental context, contributes to low levels of the repressive histone marks that characterize pluripotent embryonic stem cell pre-implantation state (PubMed:26571212).
Acts as a metabolic regulator primarily on white adipose tissue energy expenditure as well as hepatic gluconeogenesis and cholesterol biosynthesis. In white adipocytes, regulates polyamine flux by consuming S-adenosyl-L-methionine which provides for propylamine group in polyamine biosynthesis, whereas by consuming nicotinamide controls NAD+ levels through the salvage pathway (By similarity).
Via its product N1-methylnicotinamide regulates protein acetylation in hepatocytes, by repressing the ubiquitination and increasing the stability of SIRT1 deacetylase (By similarity).
Can also N-methylate other pyridines structurally related to nicotinamide and play a role in xenobiotic detoxification (PubMed:30044909).

Biological Process

Animal organ regenerationIEA:Ensembl
MethylationTAS:Reactome
NAD biosynthesis via nicotinamide riboside salvage pathwayTAS:Reactome
Nicotinamide metabolic processManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of gluconeogenesisISS:UniProtKB
Positive regulation of protein deacetylationISS:UniProtKB
Regulation of histone H3-K4 methylationIEA:Ensembl
Regulation of histone methylationManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of polyamine biosynthetic processIEA:Ensembl
Response to organonitrogen compoundIEA:Ensembl
Response to xenobiotic stimulusIEA:Ensembl

Cellular Location

Cytoplasm

PTM

Deiminated by PADI1 and PADI2.