PNMT_RAT
ID PNMT_RAT Reviewed; 285 AA.
AC P10937;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 3.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=Phenylethanolamine N-methyltransferase;
DE Short=PNMTase;
DE EC=2.1.1.28 {ECO:0000269|PubMed:683413};
DE AltName: Full=Noradrenaline N-methyltransferase;
GN Name=Pnmt;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Sprague-Dawley;
RX PubMed=7931317; DOI=10.1046/j.1471-4159.1994.63051603.x;
RA Suh Y.H., Chun Y.S., Lee I.S., Kim S.S., Choi W., Chong Y.H., Hong L.,
RA Kim S.H., Park C.W., Kim C.G.;
RT "Complete nucleotide sequence and tissue-specific expression of the rat
RT phenylethanolamine N-methyltransferase gene.";
RL J. Neurochem. 63:1603-1608(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Wistar; TISSUE=Spleen;
RX PubMed=7558218; DOI=10.1161/01.hyp.26.4.595;
RA Koike G., Jacob H.J., Krieger J.E., Szpirer C., Hoehe M.R., Horiuchi M.,
RA Dzau V.J.;
RT "Investigation of the phenylethanolamine N-methyltransferase gene as a
RT candidate gene for hypertension.";
RL Hypertension 26:595-601(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 16-285.
RC TISSUE=Adrenal gland;
RX PubMed=2575695; DOI=10.1016/0169-328x(89)90050-8;
RA Weisberg E.P., Baruchin A., Stachowiak M.K., Stricker E.M., Zigmond M.J.,
RA Kaplan B.B.;
RT "Isolation of a rat adrenal cDNA clone encoding phenylethanolamine N-
RT methyltransferase and cold-induced alterations in adrenal PNMT mRNA and
RT protein.";
RL Brain Res. Mol. Brain Res. 6:159-166(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 26-285.
RC STRAIN=Sprague-Dawley;
RX PubMed=2928117; DOI=10.1093/nar/17.5.2125;
RA Mezey E.;
RT "Cloning of the rat adrenal medullary phenylethanolamine-N-
RT methyltransferase.";
RL Nucleic Acids Res. 17:2125-2125(1989).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND TISSUE SPECIFICITY.
RX PubMed=13863458;
RA Axelrod J.;
RT "Purification and properties of phenylethanolamine-N-methyl transferase.";
RL J. Biol. Chem. 237:1657-1660(1962).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE
RP SPECIFICITY, AND ACTIVITY REGULATION.
RX PubMed=683413; DOI=10.1007/bf00964357;
RA Diaz Borges J.M., Urbina M., Drujan B.D.;
RT "Some properties of phenylethanolamine-N-methyltransferase of rat brain.";
RL Neurochem. Res. 3:15-26(1978).
CC -!- FUNCTION: Catalyzes the transmethylation of nonepinephrine
CC (noradrenaline) to form epinephrine (adrenaline), using S-adenosyl-L-
CC methionine as the methyl donor (By similarity). Other substrates
CC include phenylethanolamine, octopamine and normetanephrine
CC (PubMed:13863458, PubMed:683413). {ECO:0000250|UniProtKB:P11086,
CC ECO:0000269|PubMed:13863458, ECO:0000269|PubMed:683413}.
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:0000269|PubMed:683413};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12177;
CC Evidence={ECO:0000305|PubMed:683413};
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:0000250|UniProtKB:P11086};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25270;
CC Evidence={ECO:0000250|UniProtKB:P11086};
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:0000269|PubMed:13863458, ECO:0000269|PubMed:683413};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70684;
CC Evidence={ECO:0000305|PubMed:13863458};
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:0000269|PubMed:683413};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70520;
CC Evidence={ECO:0000305|PubMed:683413};
CC -!- ACTIVITY REGULATION: Inhibited by 3-methyl-l,2,3,4-
CC tetrahydro[1]benzothieno[3,2-c]pyridine hydrochloride.
CC {ECO:0000269|PubMed:683413}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=288 uM for normetanephrine (enzyme found in the brain)
CC {ECO:0000269|PubMed:683413};
CC KM=272 uM for normetanephrine (enzyme found in the adrenal gland)
CC {ECO:0000269|PubMed:683413};
CC KM=1.9 uM for S-adenosyl-L-methionine (enzyme found in the brain)
CC {ECO:0000269|PubMed:683413};
CC KM=2.9 uM for S-adenosyl-L-methionine (enzyme found in the adrenal
CC gland) {ECO:0000269|PubMed:683413};
CC pH dependence:
CC Optimum pH is 7.9 in phosphate buffer. {ECO:0000269|PubMed:683413};
CC -!- PATHWAY: Catecholamine biosynthesis; (R)-adrenaline biosynthesis; (R)-
CC adrenaline from (R)-noradrenaline: step 1/1.
CC {ECO:0000250|UniProtKB:P11086}.
CC -!- TISSUE SPECIFICITY: Expressed in the adrenal medulla and brain.
CC {ECO:0000269|PubMed:13863458, ECO:0000269|PubMed:683413}.
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; X75333; CAA53082.1; -; Genomic_DNA.
DR EMBL; U11694; AAA91779.1; -; Genomic_DNA.
DR EMBL; U11275; AAA91779.1; JOINED; Genomic_DNA.
DR EMBL; X14211; CAA32428.1; -; mRNA.
DR PIR; S38567; S38567.
DR RefSeq; NP_113714.1; NM_031526.1.
DR AlphaFoldDB; P10937; -.
DR SMR; P10937; -.
DR STRING; 10116.ENSRNOP00000067392; -.
DR PaxDb; P10937; -.
DR PRIDE; P10937; -.
DR GeneID; 24661; -.
DR KEGG; rno:24661; -.
DR CTD; 5409; -.
DR RGD; 3361; Pnmt.
DR eggNOG; ENOG502QT44; Eukaryota.
DR InParanoid; P10937; -.
DR OrthoDB; 1054662at2759; -.
DR PhylomeDB; P10937; -.
DR Reactome; R-RNO-209905; Catecholamine biosynthesis.
DR UniPathway; UPA00749; UER00736.
DR PRO; PR:P10937; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0030424; C:axon; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0043204; C:perikaryon; IDA:RGD.
DR GO; GO:0043195; C:terminal bouton; IDA:RGD.
DR GO; GO:0043196; C:varicosity; IDA:RGD.
DR GO; GO:0008168; F:methyltransferase activity; TAS:RGD.
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:0008757; F:S-adenosylmethionine-dependent methyltransferase activity; TAS:RGD.
DR GO; GO:0016740; F:transferase activity; TAS:RGD.
DR GO; GO:0030325; P:adrenal gland development; IEP:RGD.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEP:RGD.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; IEP:RGD.
DR GO; GO:0071375; P:cellular response to peptide hormone stimulus; IEP:RGD.
DR GO; GO:0042418; P:epinephrine biosynthetic process; IDA:RGD.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0042415; P:norepinephrine metabolic process; IDA:RGD.
DR GO; GO:0014823; P:response to activity; IEP:RGD.
DR GO; GO:0009409; P:response to cold; IEP:RGD.
DR GO; GO:0031960; P:response to corticosteroid; IEP:RGD.
DR GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR GO; GO:0045472; P:response to ether; IEP:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0035902; P:response to immobilization stress; IEP:RGD.
DR GO; GO:0032868; P:response to insulin; IEP:RGD.
DR GO; GO:0035900; P:response to isolation stress; IEP:RGD.
DR GO; GO:0043434; P:response to peptide hormone; IEP:RGD.
DR GO; GO:0009414; P:response to water deprivation; IEP:RGD.
DR GO; GO:0046498; P:S-adenosylhomocysteine metabolic process; TAS:RGD.
DR GO; GO:0046500; P:S-adenosylmethionine metabolic process; TAS:RGD.
DR GO; GO:0050909; P:sensory perception of taste; IEP:RGD.
DR GO; GO:0035176; P:social behavior; IEP:RGD.
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;
KW S-adenosyl-L-methionine; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P11086"
FT CHAIN 2..285
FT /note="Phenylethanolamine N-methyltransferase"
FT /id="PRO_0000159711"
FT BINDING 36
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P11086"
FT BINDING 41
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P11086"
FT BINDING 80..81
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P11086"
FT BINDING 86
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P11086"
FT BINDING 102
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P11086"
FT BINDING 107
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P11086"
FT BINDING 159..160
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P11086"
FT BINDING 182
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P11086"
FT BINDING 220
FT /ligand="octopamine"
FT /ligand_id="ChEBI:CHEBI:58025"
FT /evidence="ECO:0000250|UniProtKB:P11086"
FT BINDING 268
FT /ligand="octopamine"
FT /ligand_id="ChEBI:CHEBI:58025"
FT /evidence="ECO:0000250|UniProtKB:P11086"
FT CONFLICT 16..17
FT /note="DS -> LA (in Ref. 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 52
FT /note="D -> H (in Ref. 4; CAA32428)"
FT /evidence="ECO:0000305"
FT CONFLICT 204
FT /note="T -> A (in Ref. 4; CAA32428)"
FT /evidence="ECO:0000305"
FT CONFLICT 211
FT /note="N -> H (in Ref. 2 and 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 214
FT /note="F -> L (in Ref. 2 and 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 285
FT /note="V -> A (in Ref. 2; AAA91779)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 285 AA; 31670 MW; 28A239A5411AD2F6 CRC64;
MDRGSDPKHT AGMDSDSDPG QAEVALAYQR FEPRAYLRNN YAPPRGDLSN PDGVGPWKLR
CMAQVFATGE VSGQVLIDIG SGPTIYQLLS ACAHFEDITM TDFLEVNRQE LGLWLREEPG
AFDWSVYSQH VCLIEDKGES WQEKERQLRA RVKRVLPIDV HKPQPLGASG LAPLPADALV
SAFCLEAVSP DLPSFRQALY HITTLLRPGG NLLFIGALEE SWYLAGEARL SVVPVSEEEV
REALVCSGYE VRDLRTYIMP AHLRTGVDDV KGIFFAWAQK IEVQV
