ID NNMT_PIG Reviewed; 264 AA. AC Q06AV1; DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot. DT 31-OCT-2006, sequence version 1. DT 02-SEP-2026, entry version 87. DE RecName: Full=Nicotinamide N-methyltransferase; DE EC=2.1.1.1 {ECO:0000250|UniProtKB:O55239, ECO:0000250|UniProtKB:P40261}; GN Name=NNMT; OS Sus scrofa (Pig). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus. OX NCBI_TaxID=9823; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Liu G.Y.; RL Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Catalyzes the N-methylation of nicotinamide using the CC universal methyl donor S-adenosyl-L-methionine to form N1- CC methylnicotinamide and S-adenosyl-L-homocysteine, a predominant CC nicotinamide/vitamin B3 clearance pathway (By similarity). Plays a CC central role in regulating cellular methylation potential, by consuming CC S-adenosyl-L-methionine and limiting its availability for other CC methyltransferases (By similarity). Actively mediates genome-wide CC epigenetic and transcriptional changes through hypomethylation of CC repressive chromatin marks, such as H3K27me3 (By similarity). In a CC developmental context, contributes to low levels of the repressive CC histone marks that characterize pluripotent embryonic stem cell pre- CC implantation state (By similarity). Acts as a metabolic regulator CC primarily on white adipose tissue energy expenditure as well as hepatic CC gluconeogenesis and cholesterol biosynthesis (By similarity). In white CC adipocytes, regulates polyamine flux by consuming S-adenosyl-L- CC methionine which provides for propylamine group in polyamine CC biosynthesis, whereas by consuming nicotinamide controls NAD(+) levels CC through the salvage pathway (By similarity). Via its product N1- CC methylnicotinamide regulates protein acetylation in hepatocytes, by CC repressing the ubiquitination and increasing the stability of SIRT1 CC deacetylase (By similarity). Can also N-methylate other pyridines CC structurally related to nicotinamide and play a role in xenobiotic CC detoxification (By similarity). {ECO:0000250|UniProtKB:O55239, CC ECO:0000250|UniProtKB:P40261}. CC -!- CATALYTIC ACTIVITY: CC Reaction=nicotinamide + S-adenosyl-L-methionine = 1-methylnicotinamide CC + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:23884, ChEBI:CHEBI:16797, CC ChEBI:CHEBI:17154, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789; EC=2.1.1.1; CC Evidence={ECO:0000250|UniProtKB:O55239, CC ECO:0000250|UniProtKB:P40261}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23885; CC Evidence={ECO:0000250|UniProtKB:O55239, CC ECO:0000250|UniProtKB:P40261}; CC -!- PATHWAY: Cofactor metabolism. {ECO:0000250|UniProtKB:P40261}. CC -!- PATHWAY: Amino-acid degradation. {ECO:0000250|UniProtKB:P40261}. CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:P40261}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. CC -!- PTM: Deiminated by PADI1 and PADI2. {ECO:0000250|UniProtKB:P40261}. CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase CC superfamily. NNMT/PNMT/TEMT family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; DQ917624; ABI97169.1; -; mRNA. DR RefSeq; NP_001116618.1; NM_001123146.1. DR AlphaFoldDB; Q06AV1; -. DR SMR; Q06AV1; -. DR FunCoup; Q06AV1; 44. DR STRING; 9823.ENSSSCP00000015979; -. DR PaxDb; 9823-ENSSSCP00000015979; -. DR PeptideAtlas; Q06AV1; -. DR Ensembl; ENSSSCT00055020637.1; ENSSSCP00055016316.1; ENSSSCG00055010549.1. DR Ensembl; ENSSSCT00065048879.1; ENSSSCP00065021128.1; ENSSSCG00065035867.1. DR GeneID; 100144485; -. DR KEGG; ssc:100144485; -. DR CTD; 4837; -. DR eggNOG; KOG4564; Eukaryota. DR HOGENOM; CLU_141713_1_0_1; -. DR InParanoid; Q06AV1; -. DR OrthoDB; 10050085at2759; -. DR Proteomes; UP000008227; Unplaced. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0008112; F:nicotinamide N-methyltransferase activity; ISS:UniProtKB. DR GO; GO:0006769; P:nicotinamide metabolic process; ISS:UniProtKB. DR GO; GO:0045722; P:positive regulation of gluconeogenesis; ISS:UniProtKB. DR GO; GO:0090312; P:positive regulation of protein deacetylation; ISS:UniProtKB. DR CDD; cd02440; AdoMet_MTases; 1. DR FunFam; 3.40.50.150:FF:000065; Phenylethanolamine N-methyltransferase; 1. DR Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 1. DR InterPro; IPR025820; NNMT/PNMT/TEMT_CS. DR InterPro; IPR000940; NNMT_TEMT_trans. DR InterPro; IPR053384; SAM-dep_methyltransferase. DR InterPro; IPR029063; SAM-dependent_MTases_sf. DR NCBIfam; NF041360; GntF_guanitoxin; 1. DR PANTHER; PTHR10867:SF32; NICOTINAMIDE N-METHYLTRANSFERASE; 1. DR PANTHER; PTHR10867; NNMT/PNMT/TEMT FAMILY MEMBER; 1. DR Pfam; PF01234; NNMT_PNMT_TEMT; 1. DR PIRSF; PIRSF000384; PNMTase; 1. DR SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 1. DR PROSITE; PS01100; NNMT_PNMT_TEMT; 1. DR PROSITE; PS51681; SAM_MT_NNMT_PNMT_TEMT; 1. PE 2: Evidence at transcript level; KW Citrullination; Cytoplasm; Methyltransferase; Reference proteome; KW S-adenosyl-L-methionine; Transferase. FT CHAIN 1..264 FT /note="Nicotinamide N-methyltransferase" FT /id="PRO_0000262881" FT BINDING 20 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000250|UniProtKB:P40261" FT BINDING 25 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000250|UniProtKB:P40261" FT BINDING 63 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000250|UniProtKB:P40261" FT BINDING 69 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000250|UniProtKB:P40261" FT BINDING 85 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000250|UniProtKB:P40261" FT BINDING 90 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000250|UniProtKB:P40261" FT BINDING 142..143 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000250|UniProtKB:P40261" FT BINDING 163 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000250|UniProtKB:P40261" FT BINDING 197 FT /ligand="nicotinamide" FT /ligand_id="ChEBI:CHEBI:17154" FT /evidence="ECO:0000250|UniProtKB:P40261" FT BINDING 213 FT /ligand="nicotinamide" FT /ligand_id="ChEBI:CHEBI:17154" FT /evidence="ECO:0000250|UniProtKB:P40261" FT MOD_RES 132 FT /note="Citrulline; alternate" FT /evidence="ECO:0000250|UniProtKB:P40261" SQ SEQUENCE 264 AA; 29479 MW; A9EC0A3A152E2BB4 CRC64; MESGFTSKDA YLSHFNPQDY LEKYYNFGAK HSAEDQILRH LLKILFKIFC LDGVKGDLLI DIGSGPTIYQ LLSACESFKE IIATDYTDQN LQELEKWLKK EPGAFDWSPV VTYVCELEGN RVKGTEKEEK LRRAVKRVLK CDVTQSWPLG AVPLPPADCL LSTLCLHAAC PDLPTYRTAL GNLRSLLKPG GFLVLVDALK SSYYMIGEQR FSSLCLGQEA VEAAVREAGY TIEHFEVISQ SYSSTMANNE GLFSLVGRKL SPCV //