PNMT_BOVIN
ID PNMT_BOVIN Reviewed; 283 AA.
AC P10938;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1990, sequence version 2.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=Phenylethanolamine N-methyltransferase;
DE Short=PNMTase;
DE EC=2.1.1.28 {ECO:0000269|PubMed:5412063};
DE AltName: Full=Noradrenaline N-methyltransferase;
GN Name=PNMT;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2874553; DOI=10.1073/pnas.83.15.5454;
RA Baetge E.E., Suh Y.H., Joh T.H.;
RT "Complete nucleotide and deduced amino acid sequence of bovine
RT phenylethanolamine N-methyltransferase: partial amino acid homology with
RT rat tyrosine hydroxylase.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:5454-5458(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3379652; DOI=10.1002/jnr.490190313;
RA Batter D.K., D'Mello S.R., Turzai L.M., Hughes H.B. III, Gioio A.E.,
RA Kaplan B.B.;
RT "The complete nucleotide sequence and structure of the gene encoding bovine
RT phenylethanolamine N-methyltransferase.";
RL J. Neurosci. Res. 19:367-376(1988).
RN [3]
RP PARTIAL PROTEIN SEQUENCE.
RX PubMed=3379653; DOI=10.1002/jnr.490190314;
RA Weisberg E.P., Batter D.K., Brown W.E., Kaplan B.B.;
RT "Purification and partial amino acid sequence of bovine adrenal
RT phenylethanolamine N-methyltransferase: a comparison of nucleic acid and
RT protein sequence data.";
RL J. Neurosci. Res. 19:377-382(1988).
RN [4]
RP PARTIAL PROTEIN SEQUENCE, AND PTM.
RX PubMed=2363805;
RA Wong D.L., Yoo Y.S., Lau K., Schilling J.W.;
RT "Primary structure of bovine adrenal phenylethanolamine N-
RT methyltransferase.";
RL Neuropsychopharmacology 3:175-180(1990).
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, ACTIVITY
RP REGULATION, AND PATHWAY.
RX PubMed=5412063; DOI=10.1016/s0021-9258(18)63396-4;
RA Connett R.J., Kirshner N.;
RT "Purification and properties of bovine phenylethanolamine N-
RT methyltransferase.";
RL J. Biol. Chem. 245:329-334(1970).
CC -!- FUNCTION: Catalyzes the transmethylation of nonepinephrine
CC (noradrenaline) to form epinephrine (adrenaline), using S-adenosyl-L-
CC methionine as the methyl donor (PubMed:5412063). Other substrates
CC include phenylethanolamine and octopamine (By similarity). Also
CC methylates normetanephrine (PubMed:13863458, PubMed:5412063).
CC {ECO:0000250|UniProtKB:P11086, ECO:0000269|PubMed:13863458,
CC ECO:0000269|PubMed:5412063}.
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:5412063};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25270;
CC Evidence={ECO:0000269|PubMed:5412063};
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:5412063};
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:0000250|UniProtKB:P10937};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70520;
CC Evidence={ECO:0000250|UniProtKB:P10937};
CC -!- ACTIVITY REGULATION: Inhibited by p-hydroxymercuribenzoate and p-
CC chloromercuriphenylsulfonate. {ECO:0000269|PubMed:5412063}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.9. {ECO:0000269|PubMed:5412063};
CC -!- PATHWAY: Catecholamine biosynthesis; (R)-adrenaline biosynthesis; (R)-
CC adrenaline from (R)-noradrenaline: step 1/1.
CC {ECO:0000269|PubMed:5412063}.
CC -!- TISSUE SPECIFICITY: Expressed in the adrenal medulla.
CC {ECO:0000269|PubMed:13863458}.
CC -!- PTM: The N-terminus is blocked. {ECO:0000269|PubMed:2363805}.
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; M36706; AAA30716.1; -; Genomic_DNA.
DR EMBL; M14318; AAA30715.1; -; mRNA.
DR PIR; A24313; A24313.
DR PIR; I45962; I45962.
DR AlphaFoldDB; P10938; -.
DR SMR; P10938; -.
DR STRING; 9913.ENSBTAP00000055240; -.
DR BindingDB; P10938; -.
DR ChEMBL; CHEMBL2331; -.
DR PaxDb; P10938; -.
DR eggNOG; ENOG502QT44; Eukaryota.
DR InParanoid; P10938; -.
DR UniPathway; UPA00749; UER00736.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
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; 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; Direct protein sequencing; Methyltransferase;
KW Phosphoprotein; Reference proteome; S-adenosyl-L-methionine; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P11086"
FT CHAIN 2..283
FT /note="Phenylethanolamine N-methyltransferase"
FT /id="PRO_0000159708"
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"
FT MOD_RES 7
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11086"
FT CONFLICT 246..248
FT /note="TAT -> SAM (in Ref. 1; AAA30715)"
FT /evidence="ECO:0000305"
FT CONFLICT 255..276
FT /note="RTPMPAHLQTGVDDVKGIFFTR -> LHLHHACPPSDRCRRCQGHLLHL
FT (in Ref. 1; AAA30715)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 283 AA; 30918 MW; AE8B4C53E6C987E5 CRC64;
MSGTDRSQAA GAVPDSDPGL AAVSSAYQRF EPRAYLRNNY APPRGDLSCP DGVGPWKLRC
LAQTFATGEV SGRTLIDIGS GPTIYQLLSA CAHFEDITMT DFLEVNRQEL RLWLREEPGA
FDWSVYSQHV CLIEGKGESW QEKECQLRAR VKRILPIDVH RPQPLGAGGL APLPADALVS
AFCLEAVSPD LASFQRALDH ITTLLRPGGH LLLIGALEES WYLAGEARLA VVPVREEEVR
EALVRTATRC GICARTPMPA HLQTGVDDVK GIFFTRAQKK VGV
