PNMT_MACMU
ID PNMT_MACMU Reviewed; 282 AA.
AC A0A5F8AH41;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 11-DEC-2019, sequence version 1.
DT 03-AUG-2022, entry version 11.
DE RecName: Full=Phenylethanolamine N-methyltransferase;
DE Short=PNMTase;
DE EC=2.1.1.28 {ECO:0000269|PubMed:13863458};
DE AltName: Full=Noradrenaline N-methyltransferase;
GN Name=PNMT;
OS Macaca mulatta (Rhesus macaque).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9544;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=17573;
RX PubMed=17431167; DOI=10.1126/science.1139247;
RA Gibbs R.A., Rogers J., Katze M.G., Bumgarner R., Weinstock G.M.,
RA Mardis E.R., Remington K.A., Strausberg R.L., Venter J.C., Wilson R.K.,
RA Batzer M.A., Bustamante C.D., Eichler E.E., Hahn M.W., Hardison R.C.,
RA Makova K.D., Miller W., Milosavljevic A., Palermo R.E., Siepel A.,
RA Sikela J.M., Attaway T., Bell S., Bernard K.E., Buhay C.J.,
RA Chandrabose M.N., Dao M., Davis C., Delehaunty K.D., Ding Y., Dinh H.H.,
RA Dugan-Rocha S., Fulton L.A., Gabisi R.A., Garner T.T., Godfrey J.,
RA Hawes A.C., Hernandez J., Hines S., Holder M., Hume J., Jhangiani S.N.,
RA Joshi V., Khan Z.M., Kirkness E.F., Cree A., Fowler R.G., Lee S.,
RA Lewis L.R., Li Z., Liu Y.-S., Moore S.M., Muzny D., Nazareth L.V.,
RA Ngo D.N., Okwuonu G.O., Pai G., Parker D., Paul H.A., Pfannkoch C.,
RA Pohl C.S., Rogers Y.-H.C., Ruiz S.J., Sabo A., Santibanez J.,
RA Schneider B.W., Smith S.M., Sodergren E., Svatek A.F., Utterback T.R.,
RA Vattathil S., Warren W., White C.S., Chinwalla A.T., Feng Y., Halpern A.L.,
RA Hillier L.W., Huang X., Minx P., Nelson J.O., Pepin K.H., Qin X.,
RA Sutton G.G., Venter E., Walenz B.P., Wallis J.W., Worley K.C., Yang S.-P.,
RA Jones S.M., Marra M.A., Rocchi M., Schein J.E., Baertsch R., Clarke L.,
RA Csuros M., Glasscock J., Harris R.A., Havlak P., Jackson A.R., Jiang H.,
RA Liu Y., Messina D.N., Shen Y., Song H.X.-Z., Wylie T., Zhang L., Birney E.,
RA Han K., Konkel M.K., Lee J., Smit A.F.A., Ullmer B., Wang H., Xing J.,
RA Burhans R., Cheng Z., Karro J.E., Ma J., Raney B., She X., Cox M.J.,
RA Demuth J.P., Dumas L.J., Han S.-G., Hopkins J., Karimpour-Fard A.,
RA Kim Y.H., Pollack J.R., Vinar T., Addo-Quaye C., Degenhardt J., Denby A.,
RA Hubisz M.J., Indap A., Kosiol C., Lahn B.T., Lawson H.A., Marklein A.,
RA Nielsen R., Vallender E.J., Clark A.G., Ferguson B., Hernandez R.D.,
RA Hirani K., Kehrer-Sawatzki H., Kolb J., Patil S., Pu L.-L., Ren Y.,
RA Smith D.G., Wheeler D.A., Schenck I., Ball E.V., Chen R., Cooper D.N.,
RA Giardine B., Hsu F., Kent W.J., Lesk A., Nelson D.L., O'brien W.E.,
RA Pruefer K., Stenson P.D., Wallace J.C., Ke H., Liu X.-M., Wang P.,
RA Xiang A.P., Yang F., Barber G.P., Haussler D., Karolchik D., Kern A.D.,
RA Kuhn R.M., Smith K.E., Zwieg A.S.;
RT "Evolutionary and biomedical insights from the rhesus macaque genome.";
RL Science 316:222-234(2007).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY
RP REGULATION, TISSUE SPECIFICITY, AND PATHWAY.
RX PubMed=13863458;
RA Axelrod J.;
RT "Purification and properties of phenylethanolamine-N-methyl transferase.";
RL J. Biol. Chem. 237:1657-1660(1962).
CC -!- FUNCTION: Catalyzes the transmethylation of nonepinephrine
CC (noradrenaline) to form epinephrine (adrenaline), using S-adenosyl-L-
CC methionine as the methyl donor (PubMed:13863458). Other substrates
CC include phenylethanolamine, octopamine and normetanephrine
CC (PubMed:13863458). {ECO:0000269|PubMed:13863458}.
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:13863458};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12177;
CC Evidence={ECO:0000305|PubMed:13863458};
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:13863458};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25270;
CC Evidence={ECO:0000305|PubMed:13863458};
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};
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:13863458};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70520;
CC Evidence={ECO:0000305|PubMed:13863458};
CC -!- ACTIVITY REGULATION: Inhibited by p-chloromercuribenaoate.
CC {ECO:0000269|PubMed:13863458}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=5 uM for normetanephrine {ECO:0000269|PubMed:13863458};
CC pH dependence:
CC Optimum pH is 8-9. {ECO:0000269|PubMed:13863458};
CC -!- PATHWAY: Catecholamine biosynthesis; (R)-adrenaline biosynthesis; (R)-
CC adrenaline from (R)-noradrenaline: step 1/1.
CC {ECO:0000269|PubMed:13863458}.
CC -!- TISSUE SPECIFICITY: Expressed in the adrenal medulla.
CC {ECO:0000269|PubMed:13863458}.
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; JSUE03016792; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR STRING; 9544.ENSMMUP00000001796; -.
DR Ensembl; ENSMMUT00000085753; ENSMMUP00000077175; ENSMMUG00000062416.
DR VEuPathDB; HostDB:ENSMMUG00000062416; -.
DR VGNC; VGNC:104642; PNMT.
DR GeneTree; ENSGT00390000011708; -.
DR UniPathway; UPA00749; UER00736.
DR Proteomes; UP000006718; Chromosome 16.
DR Bgee; ENSMMUG00000062416; Expressed in lung and 15 other tissues.
DR GO; GO:0004603; F:phenylethanolamine N-methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0042418; P:epinephrine biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
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; Phosphoprotein;
KW Reference proteome; S-adenosyl-L-methionine; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P11086"
FT CHAIN 2..282
FT /note="Phenylethanolamine N-methyltransferase"
FT /id="PRO_0000455563"
FT BINDING 35
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P11086"
FT BINDING 40
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P11086"
FT BINDING 79..80
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P11086"
FT BINDING 85
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P11086"
FT BINDING 101
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P11086"
FT BINDING 106
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P11086"
FT BINDING 158..159
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P11086"
FT BINDING 181
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P11086"
FT BINDING 219
FT /ligand="octopamine"
FT /ligand_id="ChEBI:CHEBI:58025"
FT /evidence="ECO:0000250|UniProtKB:P11086"
FT BINDING 267
FT /ligand="octopamine"
FT /ligand_id="ChEBI:CHEBI:58025"
FT /evidence="ECO:0000250|UniProtKB:P11086"
SQ SEQUENCE 282 AA; 31013 MW; E8C5777C0EBB679E CRC64;
MSGADRIPAA GAAPDSASGR AAVASAYQRF EPRAYLRNNY APPRGDLCNP NGVGPWKLRC
LAQTFATGEV SGRTLIDIGS GPTVYQLLSA CSHFEDITMT DFLEVNRQEL GRWLREEPGA
FNWSMYSQYA CLIEGKGESW QEKERQLRAR VKRVLPIDVH QPQPLGTGSP APLPADTLVS
AFCLEAVSPD LASFQRALDH ITTLLRPGGH LLLIGALEES WYLAGEARLM VVPVSEEEVR
EALVRSGYEV RDLRTYIMPA HLQTGVDDVK GIFFAWAQKV GL
