P40261 · NNMT_HUMAN

  • Protein
    Nicotinamide N-methyltransferase
  • Gene
    NNMT
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

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).

Miscellaneous

Prominently expressed in the stroma of high-grade serous carcinomas (PubMed:31043742).
In tumorigenesis, regulates the epigenetic reprograming of cancer cells associated with increased cell migration and metastasis (PubMed:23455543, PubMed:31043742).

Catalytic activity

Activity regulation

Inactivated by deimination on Arg-132.

Kinetics

KM SUBSTRATE pH TEMPERATURE[C] NOTES EVIDENCE
0.43 mMnicotinamide7.537
0.105 mMnicotinamide8.637
1.8 μMS-adenosyl-L-methionine7.537
5 μMS-adenosyl-L-methionine8.637

Pathway

Cofactor metabolism.
Amino-acid degradation.

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site20S-adenosyl-L-methionine (UniProtKB | ChEBI)
Binding site25S-adenosyl-L-methionine (UniProtKB | ChEBI)
Binding site63S-adenosyl-L-methionine (UniProtKB | ChEBI)
Binding site69S-adenosyl-L-methionine (UniProtKB | ChEBI)
Binding site85S-adenosyl-L-methionine (UniProtKB | ChEBI)
Binding site90S-adenosyl-L-methionine (UniProtKB | ChEBI)
Binding site142-143S-adenosyl-L-methionine (UniProtKB | ChEBI)
Binding site163S-adenosyl-L-methionine (UniProtKB | ChEBI)
Binding site197nicotinamide (UniProtKB | ChEBI)
Binding site213nicotinamide (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentcytosol
Molecular Functionnicotinamide N-methyltransferase activity
Molecular Functionpyridine N-methyltransferase activity
Biological Processanimal organ regeneration
Biological Processmethylation
Biological ProcessNAD biosynthesis via nicotinamide riboside salvage pathway
Biological Processnicotinamide metabolic process
Biological Processpositive regulation of gluconeogenesis
Biological Processpositive regulation of protein deacetylation
Biological Processresponse to organonitrogen compound
Biological Processresponse to xenobiotic stimulus

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Nicotinamide N-methyltransferase
  • EC number

Gene names

    • Name
      NNMT

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    P40261

Proteomes

Organism-specific databases

Subcellular Location

Keywords

Disease & Variants

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis18Has no effect on N-methyltransferase activity.
Mutagenesis20Loss of N-methyltransferase activity.
Mutagenesis20Decreases N-methyltransferase activity.
Mutagenesis132Loss of N-methyltransferase activity like its citrullinated counterpart.
Mutagenesis181Has no effect on N-methyltransferase activity.
Mutagenesis197Loss of N-methyltransferase activity.
Mutagenesis201Has no effect on N-methyltransferase activity.
Mutagenesis213Has no effect on N-methyltransferase activity.

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 420 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Organism-specific databases

Miscellaneous

Chemistry

Genetic variation databases

PTM/Processing

Features

Showing features for chain, modified residue (large scale data), modified residue.

TypeIDPosition(s)SourceDescription
ChainPRO_00001597061-264UniProtNicotinamide N-methyltransferase
Modified residue (large scale data)11PRIDEPhosphotyrosine
Modified residue18UniProtCitrulline; alternate
Modified residue39UniProtN6-acetyllysine
Modified residue (large scale data)108PRIDEPhosphoserine
Modified residue132UniProtCitrulline; alternate
Modified residue181UniProtCitrulline; alternate

Post-translational modification

Deiminated by PADI1 and PADI2.

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Predominantly expressed in the liver. A lower expression is seen in the kidney, lung, skeletal muscle, placenta and heart. Not detected in the brain or pancreas.

Gene expression databases

Organism-specific databases

Interaction

Subunit

Monomer.

Protein-protein interaction databases

Chemistry

Miscellaneous

Family & Domains

Sequence similarities

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    264
  • Mass (Da)
    29,574
  • Last updated
    1995-02-01 v1
  • Checksum
    280B12748F4488AC
MESGFTSKDTYLSHFNPRDYLEKYYKFGSRHSAESQILKHLLKNLFKIFCLDGVKGDLLIDIGSGPTIYQLLSACESFKEIVVTDYSDQNLQELEKWLKKEPEAFDWSPVVTYVCDLEGNRVKGPEKEEKLRQAVKQVLKCDVTQSQPLGAVPLPPADCVLSTLCLDAACPDLPTYCRALRNLGSLLKPGGFLVIMDALKSSYYMIGEQKFSSLPLGREAVEAAVKEAGYTIEWFEVISQSYSSTMANNEGLFSLVARKLSRPL

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
U08021
EMBL· GenBank· DDBJ
AAA19904.1
EMBL· GenBank· DDBJ
mRNA
U20971
EMBL· GenBank· DDBJ
AAA93158.1
EMBL· GenBank· DDBJ
Genomic DNA
U20970
EMBL· GenBank· DDBJ
AAA93158.1
EMBL· GenBank· DDBJ
Genomic DNA
BC000234
EMBL· GenBank· DDBJ
AAH00234.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

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