PNMT_MOUSE
ID PNMT_MOUSE Reviewed; 295 AA.
AC P40935;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Phenylethanolamine N-methyltransferase;
DE Short=PNMTase;
DE EC=2.1.1.28 {ECO:0000269|PubMed:17698731};
DE AltName: Full=Noradrenaline N-methyltransferase;
GN Name=Pnmt;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY.
RX PubMed=8000434; DOI=10.1007/bf01976770;
RA Quaife C.J., Hoyle G.W., Froelick G.J., Findley S.D., Baetge E.E.,
RA Behringer R.R., Hammang J.P., Brinster R.L., Palmiter R.D.;
RT "Visualization and ablation of phenylethanolamine N-methyltransferase
RT producing cells in transgenic mice.";
RL Transgenic Res. 3:388-400(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY.
RC STRAIN=DBA/2J;
RX PubMed=1320721; DOI=10.1016/0169-328x(92)90214-v;
RA Morita S., Kobayashi K., Hidaka H., Nagatsu T.;
RT "Organization and complete nucleotide sequence of the gene encoding mouse
RT phenylethanolamine N-methyltransferase.";
RL Brain Res. Mol. Brain Res. 13:313-319(1992).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND
RP PATHWAY.
RX PubMed=17698731; DOI=10.1161/circulationaha.107.696005;
RA Bao X., Lu C.M., Liu F., Gu Y., Dalton N.D., Zhu B.Q., Foster E., Chen J.,
RA Karliner J.S., Ross J. Jr., Simpson P.C., Ziegler M.G.;
RT "Epinephrine is required for normal cardiovascular responses to stress in
RT the phenylethanolamine N-methyltransferase knockout mouse.";
RL Circulation 116:1024-1031(2007).
CC -!- FUNCTION: Catalyzes the transmethylation of nonepinephrine
CC (noradrenaline) to form epinephrine (adrenaline), using S-adenosyl-L-
CC methionine as the methyl donor (PubMed:17698731). Other substrates
CC include phenylethanolamine, octopamine and normetanephrine (By
CC similarity). {ECO:0000250|UniProtKB:P11086,
CC ECO:0000269|PubMed:17698731}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=phenylethanolamine + S-adenosyl-L-methionine = H(+) + N-
CC methylphenylethanolamine + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:12176, ChEBI:CHEBI:15378, ChEBI:CHEBI:57741,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:57946, ChEBI:CHEBI:59789; EC=2.1.1.28;
CC Evidence={ECO:0000250|UniProtKB:P11086};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12177;
CC Evidence={ECO:0000250|UniProtKB:P11086};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-noradrenaline + S-adenosyl-L-methionine = (R)-adrenaline +
CC H(+) + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:25269,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:71406, ChEBI:CHEBI:72587; EC=2.1.1.28;
CC Evidence={ECO:0000269|PubMed:17698731};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25270;
CC Evidence={ECO:0000305|PubMed:17698731};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-normetanephrine + S-adenosyl-L-methionine = H(+) + N-
CC methyl-(R)-normetanephrine + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:70683, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:189645, ChEBI:CHEBI:189646;
CC Evidence={ECO:0000250|UniProtKB:P10937};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70684;
CC Evidence={ECO:0000250|UniProtKB:P10937};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-octopamine + S-adenosyl-L-methionine = (R)-synephrine +
CC H(+) + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:70519,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:63694, ChEBI:CHEBI:141486;
CC Evidence={ECO:0000250|UniProtKB:P10937};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70520;
CC Evidence={ECO:0000250|UniProtKB:P10937};
CC -!- PATHWAY: Catecholamine biosynthesis; (R)-adrenaline biosynthesis; (R)-
CC adrenaline from (R)-noradrenaline: step 1/1.
CC {ECO:0000269|PubMed:17698731}.
CC -!- TISSUE SPECIFICITY: Brain (pons and medulla oblongata), adrenal gland,
CC retina and heart. {ECO:0000269|PubMed:1320721,
CC ECO:0000269|PubMed:17698731, ECO:0000269|PubMed:8000434}.
CC -!- DISRUPTION PHENOTYPE: In knockout (KO) mice, resting cardiovascular
CC function, including blood pressure (BP), heart rate and cardiac output
CC is the same as that in wild-type mice (PubMed:17698731). Significant
CC difference, however, is observed in the BP response to exercise
CC (PubMed:17698731). The relative diastolic wall thickness and the ratio
CC of left ventricular posterior wall thickness (LVPW) to left ventricular
CC internal dimension (LVID) are significantly increased in KO mice
CC (PubMed:17698731). {ECO:0000269|PubMed:17698731}.
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; L12687; AAA68934.1; -; Genomic_DNA.
DR CCDS; CCDS25347.1; -.
DR RefSeq; NP_032916.1; NM_008890.1.
DR AlphaFoldDB; P40935; -.
DR SMR; P40935; -.
DR STRING; 10090.ENSMUSP00000035549; -.
DR ChEMBL; CHEMBL4874; -.
DR iPTMnet; P40935; -.
DR PhosphoSitePlus; P40935; -.
DR PaxDb; P40935; -.
DR PRIDE; P40935; -.
DR ProteomicsDB; 289638; -.
DR Antibodypedia; 28325; 535 antibodies from 32 providers.
DR DNASU; 18948; -.
DR Ensembl; ENSMUST00000041301; ENSMUSP00000035549; ENSMUSG00000038216.
DR GeneID; 18948; -.
DR KEGG; mmu:18948; -.
DR UCSC; uc007lgg.1; mouse.
DR CTD; 5409; -.
DR MGI; MGI:97724; Pnmt.
DR VEuPathDB; HostDB:ENSMUSG00000038216; -.
DR eggNOG; ENOG502QT44; Eukaryota.
DR GeneTree; ENSGT00390000011708; -.
DR HOGENOM; CLU_082526_2_0_1; -.
DR InParanoid; P40935; -.
DR OMA; IDVHCSQ; -.
DR OrthoDB; 1054662at2759; -.
DR PhylomeDB; P40935; -.
DR TreeFam; TF313114; -.
DR BRENDA; 2.1.1.28; 3474.
DR Reactome; R-MMU-209905; Catecholamine biosynthesis.
DR UniPathway; UPA00749; UER00736.
DR BioGRID-ORCS; 18948; 5 hits in 73 CRISPR screens.
DR PRO; PR:P40935; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; P40935; protein.
DR Bgee; ENSMUSG00000038216; Expressed in adrenal gland and 31 other tissues.
DR ExpressionAtlas; P40935; baseline and differential.
DR Genevisible; P40935; MM.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0043204; C:perikaryon; ISO:MGI.
DR GO; GO:0043195; C:terminal bouton; ISO:MGI.
DR GO; GO:0043196; C:varicosity; ISO:MGI.
DR GO; GO:0008170; F:N-methyltransferase activity; IBA:GO_Central.
DR GO; GO:0004603; F:phenylethanolamine N-methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0042418; P:epinephrine biosynthetic process; ISO:MGI.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0042415; P:norepinephrine metabolic process; ISO:MGI.
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 1: Evidence at protein level;
KW Catecholamine biosynthesis; Methyltransferase; Reference proteome; Repeat;
KW S-adenosyl-L-methionine; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P11086"
FT CHAIN 2..295
FT /note="Phenylethanolamine N-methyltransferase"
FT /id="PRO_0000159710"
FT REPEAT 4..10
FT /note="1"
FT REPEAT 14..20
FT /note="2"
FT REGION 1..26
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 4..20
FT /note="2 X 7 AA repeats of G-S-D-[LP]-K-H-A"
FT BINDING 46
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P11086"
FT BINDING 51
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P11086"
FT BINDING 90..91
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P11086"
FT BINDING 96
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P11086"
FT BINDING 112
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P11086"
FT BINDING 117
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P11086"
FT BINDING 169..170
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P11086"
FT BINDING 192
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P11086"
FT BINDING 230
FT /ligand="octopamine"
FT /ligand_id="ChEBI:CHEBI:58025"
FT /evidence="ECO:0000250|UniProtKB:P11086"
FT BINDING 278
FT /ligand="octopamine"
FT /ligand_id="ChEBI:CHEBI:58025"
FT /evidence="ECO:0000250|UniProtKB:P11086"
SQ SEQUENCE 295 AA; 32544 MW; ED392D6D2244069A CRC64;
MNGGSDLKHA TGSGSDPKHA AEMDPDSDAG QVAVALAYQR FEPRAYLRNN YAPPRGDLSN
PDGVGPWKLR CMAQVFATGE VSGRVLIDIG SGPTIYQLLS ACAHFEDITM TDFLEVNRQE
LGLWLREEPG AFDWSVYSQH ACLIEDKGES WQEKERQLRA RVKRVLPIDV HKPQPLGTPS
LVPLPADALV SAFCLEAVSP DLTSFQRALH HITTLLRPGG HLLLIGALEE SWYLAGEARL
SVVPVSEEEV REALVLGGYE VRELRTYIMP AHLCTGVDDV KGIFFAWAQK MEVQV
