NNMT_PIG
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 03-AUG-2022, entry version 72.
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}.
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DR EMBL; DQ917624; ABI97169.1; -; mRNA.
DR RefSeq; NP_001116618.1; NM_001123146.1.
DR AlphaFoldDB; Q06AV1; -.
DR SMR; Q06AV1; -.
DR STRING; 9823.ENSSSCP00000015979; -.
DR PaxDb; Q06AV1; -.
DR PeptideAtlas; Q06AV1; -.
DR PRIDE; Q06AV1; -.
DR Ensembl; ENSSSCT00055020637; ENSSSCP00055016316; ENSSSCG00055010549.
DR Ensembl; ENSSSCT00065048879; ENSSSCP00065021128; ENSSSCG00065035867.
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; 1054662at2759; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0008112; F:nicotinamide N-methyltransferase activity; ISS:UniProtKB.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
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 Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR025820; NNMT/PNMT/TEMT_CS.
DR InterPro; IPR000940; NNMT_TEMT_trans.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR PANTHER; PTHR10867; PTHR10867; 1.
DR Pfam; PF01234; NNMT_PNMT_TEMT; 1.
DR PIRSF; PIRSF000384; PNMTase; 1.
DR SUPFAM; SSF53335; SSF53335; 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
