UniProtKB - P40261 (NNMT_HUMAN)
Nicotinamide N-methyltransferase
NNMT
Functioni
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).
By similarity6 PublicationsMiscellaneous
Catalytic activityi
- nicotinamide + S-adenosyl-L-methionine = 1-methylnicotinamide + S-adenosyl-L-homocysteine3 PublicationsEC:2.1.1.13 PublicationsThis reaction proceeds in the forward3 Publications direction.
Activity regulationi
Kineticsi
- KM=0.43 mM for nicotinamide (at pH 7.5 and 37 degrees Celsius)1 Publication
- KM=0.105 mM for nicotinamide (at pH 8.6 and 37 degrees Celsius)1 Publication
- KM=1.8 µM for S-adenosyl-L-methionine (at pH 7.5 and 37 degrees Celsius)1 Publication
- KM=5 µM for S-adenosyl-L-methionine (at pH 8.6 and 37 degrees Celsius)1 Publication
: Cofactor metabolism Pathwayi
This protein is involved in Cofactor metabolism.2 PublicationsView all proteins of this organism that are known to be involved in Cofactor metabolism.
Pathwayi: Amino-acid degradation
This protein is involved in Amino-acid degradation.2 PublicationsView all proteins of this organism that are known to be involved in Amino-acid degradation.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 20 | S-adenosyl-L-methionine2 Publications | 1 | |
Binding sitei | 25 | S-adenosyl-L-methionine2 Publications | 1 | |
Binding sitei | 63 | S-adenosyl-L-methionine; via carbonyl oxygen2 Publications | 1 | |
Binding sitei | 69 | S-adenosyl-L-methionine2 Publications | 1 | |
Binding sitei | 85 | S-adenosyl-L-methionine2 Publications | 1 | |
Binding sitei | 90 | S-adenosyl-L-methionine2 Publications | 1 | |
Binding sitei | 163 | S-adenosyl-L-methionine; via carbonyl oxygen2 Publications | 1 | |
Binding sitei | 197 | Nicotinamide1 Publication | 1 | |
Binding sitei | 213 | Nicotinamide1 Publication | 1 |
GO - Molecular functioni
- nicotinamide N-methyltransferase activity Source: UniProtKB
- N-methyltransferase activity Source: GO_Central
- pyridine N-methyltransferase activity Source: Reactome
GO - Biological processi
- animal organ regeneration Source: Ensembl
- methylation Source: Reactome
- NAD biosynthesis via nicotinamide riboside salvage pathway Source: Reactome
- nicotinamide metabolic process Source: UniProtKB
- positive regulation of gluconeogenesis Source: UniProtKB
- positive regulation of protein deacetylation Source: UniProtKB
- regulation of histone H3-K4 methylation Source: Ensembl
- regulation of histone methylation Source: UniProtKB
- regulation of polyamine biosynthetic process Source: Ensembl
- response to organonitrogen compound Source: Ensembl
- response to xenobiotic stimulus Source: Ensembl
Keywordsi
Molecular function | Methyltransferase, Transferase |
Ligand | S-adenosyl-L-methionine |
Enzyme and pathway databases
BRENDAi | 2.1.1.1, 2681 |
PathwayCommonsi | P40261 |
Reactomei | R-HSA-156581, Methylation R-HSA-197264, Nicotinamide salvaging R-HSA-2408508, Metabolism of ingested SeMet, Sec, MeSec into H2Se |
SignaLinki | P40261 |
Names & Taxonomyi
Protein namesi | |
Gene namesi | Name:NNMT1 Publication |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:7861, NNMT |
MIMi | 600008, gene |
neXtProti | NX_P40261 |
VEuPathDBi | HostDB:ENSG00000166741 |
Subcellular locationi
Cytoplasm and Cytosol
Cytosol
- cytosol Source: GO_Central
Keywords - Cellular componenti
CytoplasmPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 18 | R → K: Has no effect on N-methyltransferase activity. 1 Publication | 1 | |
Mutagenesisi | 20 | Y → A: Loss of N-methyltransferase activity. 2 Publications | 1 | |
Mutagenesisi | 20 | Y → F: Decreases N-methyltransferase activity. 1 Publication | 1 | |
Mutagenesisi | 132 | R → K: Loss of N-methyltransferase activity like its citrullinated counterpart. 1 Publication | 1 | |
Mutagenesisi | 181 | R → K: Has no effect on N-methyltransferase activity. 1 Publication | 1 | |
Mutagenesisi | 197 | D → A: Loss of N-methyltransferase activity. 1 Publication | 1 | |
Mutagenesisi | 201 | S → A: Has no effect on N-methyltransferase activity. 1 Publication | 1 | |
Mutagenesisi | 213 | S → A: Has no effect on N-methyltransferase activity. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 4837 |
OpenTargetsi | ENSG00000166741 |
PharmGKBi | PA251 |
Miscellaneous databases
Pharosi | P40261, Tchem |
Chemistry databases
ChEMBLi | CHEMBL2346486 |
DrugBanki | DB00627, Niacin |
DrugCentrali | P40261 |
Genetic variation databases
BioMutai | NNMT |
DMDMi | 730163 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000159706 | 1 – 264 | Nicotinamide N-methyltransferaseAdd BLAST | 264 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 18 | Citrulline; alternate1 Publication | 1 | |
Modified residuei | 39 | N6-acetyllysineCombined sources | 1 | |
Modified residuei | 132 | Citrulline; alternate1 Publication | 1 | |
Modified residuei | 181 | Citrulline; alternate1 Publication | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, CitrullinationProteomic databases
EPDi | P40261 |
jPOSTi | P40261 |
MassIVEi | P40261 |
PaxDbi | P40261 |
PeptideAtlasi | P40261 |
PRIDEi | P40261 |
ProteomicsDBi | 55358 |
TopDownProteomicsi | P40261 |
PTM databases
GlyGeni | P40261, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | P40261 |
MetOSitei | P40261 |
PhosphoSitePlusi | P40261 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000166741, Expressed in right lobe of liver and 210 other tissues |
ExpressionAtlasi | P40261, baseline and differential |
Genevisiblei | P40261, HS |
Organism-specific databases
HPAi | ENSG00000166741, Tissue enhanced (liver) |
Interactioni
Subunit structurei
Monomer.
1 PublicationProtein-protein interaction databases
BioGRIDi | 110900, 8 interactors |
IntActi | P40261, 3 interactors |
MINTi | P40261 |
STRINGi | 9606.ENSP00000441434 |
Chemistry databases
BindingDBi | P40261 |
Miscellaneous databases
RNActi | P40261, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | P40261 |
SMRi | P40261 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P40261 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 142 – 143 | S-adenosyl-L-methionine binding2 Publications | 2 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG4564, Eukaryota |
GeneTreei | ENSGT00390000011708 |
HOGENOMi | CLU_082526_1_1_1 |
InParanoidi | P40261 |
OMAi | YNFGSRH |
OrthoDBi | 1054662at2759 |
PhylomeDBi | P40261 |
TreeFami | TF313114 |
Family and domain databases
Gene3Di | 3.40.50.150, 1 hit |
InterProi | View protein in InterPro IPR025820, NNMT/PNMT/TEMT_CS IPR000940, NNMT_TEMT_trans IPR029063, SAM-dependent_MTases |
PANTHERi | PTHR10867, PTHR10867, 1 hit |
Pfami | View protein in Pfam PF01234, NNMT_PNMT_TEMT, 1 hit |
PIRSFi | PIRSF000384, PNMTase, 1 hit |
SUPFAMi | SSF53335, SSF53335, 1 hit |
PROSITEi | View protein in PROSITE PS01100, NNMT_PNMT_TEMT, 1 hit PS51681, SAM_MT_NNMT_PNMT_TEMT, 1 hit |
i Sequence
Sequence statusi: Complete.
10 20 30 40 50
MESGFTSKDT YLSHFNPRDY LEKYYKFGSR HSAESQILKH LLKNLFKIFC
60 70 80 90 100
LDGVKGDLLI DIGSGPTIYQ LLSACESFKE IVVTDYSDQN LQELEKWLKK
110 120 130 140 150
EPEAFDWSPV VTYVCDLEGN RVKGPEKEEK LRQAVKQVLK CDVTQSQPLG
160 170 180 190 200
AVPLPPADCV LSTLCLDAAC PDLPTYCRAL RNLGSLLKPG GFLVIMDALK
210 220 230 240 250
SSYYMIGEQK FSSLPLGREA VEAAVKEAGY TIEWFEVISQ SYSSTMANNE
260
GLFSLVARKL SRPL
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U08021 mRNA Translation: AAA19904.1 U20971, U20970 Genomic DNA Translation: AAA93158.1 BC000234 mRNA Translation: AAH00234.1 |
CCDSi | CCDS8368.1 |
PIRi | A54060 |
RefSeqi | NP_006160.1, NM_006169.2 |
Genome annotation databases
Ensembli | ENST00000299964.4; ENSP00000299964.3; ENSG00000166741.8 ENST00000535401.5; ENSP00000441434.1; ENSG00000166741.8 |
GeneIDi | 4837 |
KEGGi | hsa:4837 |
MANE-Selecti | ENST00000299964.4; ENSP00000299964.3; NM_006169.3; NP_006160.1 |
Similar proteinsi
Cross-referencesi
Web resourcesi
Atlas of Genetics and Cytogenetics in Oncology and Haematology |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U08021 mRNA Translation: AAA19904.1 U20971, U20970 Genomic DNA Translation: AAA93158.1 BC000234 mRNA Translation: AAH00234.1 |
CCDSi | CCDS8368.1 |
PIRi | A54060 |
RefSeqi | NP_006160.1, NM_006169.2 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2IIP | X-ray | 2.05 | A/B/C/D | 1-264 | [»] | |
3ROD | X-ray | 2.72 | A/B/C/D | 1-264 | [»] | |
5YJF | X-ray | 2.49 | A/B/C/D | 1-264 | [»] | |
6B1A | X-ray | 2.30 | A/B/C/D | 1-264 | [»] | |
6CHH | X-ray | 2.30 | A/B/C/D | 1-264 | [»] | |
6ORR | X-ray | 2.25 | A/B/C/D | 1-264 | [»] | |
6PVE | X-ray | 2.30 | A/B/C/D | 1-264 | [»] | |
6PVS | X-ray | 2.58 | A/B/C/D | 1-264 | [»] | |
7BKG | X-ray | 2.33 | A/B/C/D | 1-264 | [»] | |
7BLE | X-ray | 2.81 | A/B/C/D | 1-264 | [»] | |
7EGU | X-ray | 1.90 | A | 3-260 | [»] | |
7EHZ | X-ray | 2.50 | A | 3-260 | [»] | |
7NBJ | X-ray | 2.27 | A/B/C/D | 1-264 | [»] | |
7NBM | X-ray | 2.69 | A/B/C/D | 1-264 | [»] | |
7NBQ | X-ray | 2.48 | A/B/C/D | 1-264 | [»] | |
AlphaFoldDBi | P40261 | |||||
SMRi | P40261 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 110900, 8 interactors |
IntActi | P40261, 3 interactors |
MINTi | P40261 |
STRINGi | 9606.ENSP00000441434 |
Chemistry databases
BindingDBi | P40261 |
ChEMBLi | CHEMBL2346486 |
DrugBanki | DB00627, Niacin |
DrugCentrali | P40261 |
PTM databases
GlyGeni | P40261, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | P40261 |
MetOSitei | P40261 |
PhosphoSitePlusi | P40261 |
Genetic variation databases
BioMutai | NNMT |
DMDMi | 730163 |
Proteomic databases
EPDi | P40261 |
jPOSTi | P40261 |
MassIVEi | P40261 |
PaxDbi | P40261 |
PeptideAtlasi | P40261 |
PRIDEi | P40261 |
ProteomicsDBi | 55358 |
TopDownProteomicsi | P40261 |
Protocols and materials databases
Antibodypediai | 18379, 486 antibodies from 34 providers |
DNASUi | 4837 |
Genome annotation databases
Ensembli | ENST00000299964.4; ENSP00000299964.3; ENSG00000166741.8 ENST00000535401.5; ENSP00000441434.1; ENSG00000166741.8 |
GeneIDi | 4837 |
KEGGi | hsa:4837 |
MANE-Selecti | ENST00000299964.4; ENSP00000299964.3; NM_006169.3; NP_006160.1 |
Organism-specific databases
CTDi | 4837 |
DisGeNETi | 4837 |
GeneCardsi | NNMT |
HGNCi | HGNC:7861, NNMT |
HPAi | ENSG00000166741, Tissue enhanced (liver) |
MIMi | 600008, gene |
neXtProti | NX_P40261 |
OpenTargetsi | ENSG00000166741 |
PharmGKBi | PA251 |
VEuPathDBi | HostDB:ENSG00000166741 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4564, Eukaryota |
GeneTreei | ENSGT00390000011708 |
HOGENOMi | CLU_082526_1_1_1 |
InParanoidi | P40261 |
OMAi | YNFGSRH |
OrthoDBi | 1054662at2759 |
PhylomeDBi | P40261 |
TreeFami | TF313114 |
Enzyme and pathway databases
BRENDAi | 2.1.1.1, 2681 |
PathwayCommonsi | P40261 |
Reactomei | R-HSA-156581, Methylation R-HSA-197264, Nicotinamide salvaging R-HSA-2408508, Metabolism of ingested SeMet, Sec, MeSec into H2Se |
SignaLinki | P40261 |
Miscellaneous databases
BioGRID-ORCSi | 4837, 6 hits in 1075 CRISPR screens |
ChiTaRSi | NNMT, human |
EvolutionaryTracei | P40261 |
GeneWikii | NNMT |
GenomeRNAii | 4837 |
Pharosi | P40261, Tchem |
PROi | PR:P40261 |
RNActi | P40261, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000166741, Expressed in right lobe of liver and 210 other tissues |
ExpressionAtlasi | P40261, baseline and differential |
Genevisiblei | P40261, HS |
Family and domain databases
Gene3Di | 3.40.50.150, 1 hit |
InterProi | View protein in InterPro IPR025820, NNMT/PNMT/TEMT_CS IPR000940, NNMT_TEMT_trans IPR029063, SAM-dependent_MTases |
PANTHERi | PTHR10867, PTHR10867, 1 hit |
Pfami | View protein in Pfam PF01234, NNMT_PNMT_TEMT, 1 hit |
PIRSFi | PIRSF000384, PNMTase, 1 hit |
SUPFAMi | SSF53335, SSF53335, 1 hit |
PROSITEi | View protein in PROSITE PS01100, NNMT_PNMT_TEMT, 1 hit PS51681, SAM_MT_NNMT_PNMT_TEMT, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | NNMT_HUMAN | |
Accessioni | P40261Primary (citable) accession number: P40261 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 1, 1995 |
Last sequence update: | February 1, 1995 | |
Last modified: | May 25, 2022 | |
This is version 175 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 11
Human chromosome 11: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families