Search Results

Overview

Uniprot ID	P40261
Protein Name	Nicotinamide N-methyltransferase
Gene Name	NNMT
Organism	Homo sapiens

Kla Sites from experimental identification

Position	Flanking peptide
136	EKLRQAVKQVLKCDV
210	YYMIGEQKFSSLPLG
39	SAESQILKHLLKNLF
43	QILKHLLKNLFKIFC
8	MESGFTSKDTYLSHF

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: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)

Protein Sequence

10 MESGFTSKDT 20 YLSHFNPRDY 30 LEKYYKFGSR 40 HSAESQILKH 50 LLKNLFKIFC 60 LDGVKGDLLI 70 DIGSGPTIYQ 80 LLSACESFKE 90 IVVTDYSDQN 100 LQELEKWLKK 110 EPEAFDWSPV 120 VTYVCDLEGN 130 RVKGPEKEEK 140 LRQAVKQVLK 150 CDVTQSQPLG 160 AVPLPPADCV 170 LSTLCLDAAC 180 PDLPTYCRAL 190 RNLGSLLKPG 200 GFLVIMDALK 210 SSYYMIGEQK 220 FSSLPLGREA 230 VEAAVKEAGY 240 TIEWFEVISQ 250 SYSSTMANNE 260 GLFSLVARKL SRPL

Gene Ontology

Classification	GO ID	Description
Cellular Component	GO:0005829	cytosol
Molecular Function	GO:0008112	nicotinamide N-methyltransferase activity
Molecular Function	GO:0030760	pyridine N-methyltransferase activity
Biological Process	GO:0032259	methylation
Biological Process	GO:0019677	NAD+ catabolic process
Biological Process	GO:0006769	nicotinamide metabolic process
Biological Process	GO:1901847	nicotinate metabolic process
Biological Process	GO:0045722	positive regulation of gluconeogenesis
Biological Process	GO:0090312	positive regulation of protein deacetylation

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[2] Lin Y, Chen M, Wang D, Yu Y, Chen R et al.. Multi-Proteomic Analysis Reveals the Effect of Protein Lactylation on Matrix and Cholesterol Metabolism in Tendinopathy.. J Proteome Res 22(6):1712-1722. 2023 Jun 2. PMID: 37159428.