Nicotinamide N-methyltransferase (EC 2.1.1.1)
1_MESGF 6_ TSKDT 11_ YLSHF 16_ NPRDY 21_ LEKYY 26_ KFGSR 31_ HSAES 36_ QILKH 41_ LLKNL 46_ FKIFC 51_ LDGVK 56_ GDLLI 61_ DIGSG 66_ PTIYQ 71_ LLSAC 76_ ESFKE 81_ IVVTD 86_ YSDQN 91_ LQELE 96_ KWLKK 101_ EPEAF 106_ DWSPV 111_ VTYVC 116_ DLEGN 121_ RVKGP 126_ EKEEK 131_ LRQAV 136_ KQVLK 141_ CDVTQ 146_ SQPLG 151_ AVPLP 156_ PADCV 161_ LSTLC 166_ LDAAC 171_ PDLPT 176_ YCRAL 181_ RNLGS 186_ LLKPG 191_ GFLVI 196_ MDALK 201_ SSYYM 206_ IGEQK 211_ FSSLP 216_ LGREA 221_ VEAAV 226_ KEAGY 231_ TIEWF 236_ EVISQ 241_ SYSST 246_ MANNE 251_ GLFSL 256_VARKL
1: 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:21823666, PubMed:23455543, PubMed:8182091). 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:23455543, PubMed:26571212, 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)