PNMT_HUMAN
ID PNMT_HUMAN Reviewed; 282 AA.
AC P11086;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 195.
DE RecName: Full=Phenylethanolamine N-methyltransferase;
DE Short=PNMTase;
DE EC=2.1.1.28 {ECO:0000269|PubMed:16363801, ECO:0000269|PubMed:20496117, ECO:0000269|PubMed:8812853};
DE AltName: Full=Noradrenaline N-methyltransferase;
GN Name=PNMT; Synonyms=PENT;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3372503; DOI=10.1016/s0021-9258(18)68551-5;
RA Kaneda N., Ichinose H., Kobayashi K., Oka K., Kishi F., Nakazawa A.,
RA Kurosawa Y., Fujita K., Nagatsu T.;
RT "Molecular cloning of cDNA and chromosomal assignment of the gene for human
RT phenylethanolamine N-methyltransferase, the enzyme for epinephrine
RT biosynthesis.";
RL J. Biol. Chem. 263:7672-7677(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Placenta;
RA Sasaoka T., Kaneda N., Kurosawa Y., Fujita K., Nagatsu T.;
RT "Structure of human phenylethanolamine N-methyltransferase gene: existence
RT of two types of mRNA with different transcription initiation sites.";
RL Neurochem. Int. 15:555-565(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2835776; DOI=10.1073/pnas.85.10.3648;
RA Baetge E.E., Behringer R.R., Messing A., Brinster R.L., Palmiter R.D.;
RT "Transgenic mice express the human phenylethanolamine N-methyltransferase
RT gene in adrenal medulla and retina.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:3648-3652(1988).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 2-11, CLEAVAGE OF INITIATOR
RP METHIONINE, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP MASS SPECTROMETRY, AND ACTIVITY REGULATION.
RX PubMed=8812853; DOI=10.1006/prep.1996.0088;
RA Caine J.M., Macreadie I.G., Grunewald G.L., McLeish M.J.;
RT "Recombinant human phenylethanolamine N-methyltransferase: overproduction
RT in Escherichia coli, purification, and characterization.";
RL Protein Expr. Purif. 8:160-166(1996).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Lung, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND PATHWAY.
RX PubMed=20496117; DOI=10.1007/s10059-010-0074-3;
RA Kang D.I., Lee J.Y., Kim W., Jeong K.W., Shin S., Yang J., Park E.,
RA Chae Y.K., Kim Y.;
RT "Discovery of novel human phenylethanolamine N-methyltransferase (hPNMT)
RT inhibitors using 3D pharmacophore-based in silico, biophysical screening
RT and enzymatic activity assays.";
RL Mol. Cells 29:595-602(2010).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-7, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH
RP S-ADENOSYL-L-HOMOCYSTEINE AND SYNTHETIC INHIBITOR.
RX PubMed=11591352; DOI=10.1016/s0969-2126(01)00662-1;
RA Martin J.L., Begun J., McLeish M.J., Caine J.M., Grunewald G.L.;
RT "Getting the adrenaline going: crystal structure of the adrenaline-
RT synthesizing enzyme PNMT.";
RL Structure 9:977-985(2001).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEXES WITH SUBSTRATE ANALOGS
RP AND S-ADENOSYL-L-HOMOCYSTEINE, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS
RP OF TYR-35; GLU-185; GLU-219 AND ASP-267, FUNCTION, CATALYTIC ACTIVITY,
RP S-ADENOSYL-L-METHIONINE-BINDING SITES, AND OCTOPAMINE-BINDING SITES.
RX PubMed=16363801; DOI=10.1021/bi051636b;
RA Gee C.L., Tyndall J.D.A., Grunewald G.L., Wu Q., McLeish M.J., Martin J.L.;
RT "Mode of binding of methyl acceptor substrates to the adrenaline-
RT synthesizing enzyme phenylethanolamine N-methyltransferase: implications
RT for catalysis.";
RL Biochemistry 44:16875-16885(2005).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) IN COMPLEX WITH SYNTHETIC INHIBITOR.
RX PubMed=16942016; DOI=10.1021/jm060466d;
RA Grunewald G.L., Seim M.R., Regier R.C., Martin J.L., Gee C.L.,
RA Drinkwater N., Criscione K.R.;
RT "Comparison of the binding of 3-fluoromethyl-7-sulfonyl-1,2,3,4-
RT tetrahydroisoquinolines with their isosteric sulfonamides to the active
RT site of phenylethanolamine N-methyltransferase.";
RL J. Med. Chem. 49:5424-5433(2006).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEXES WITH SYNTHETIC
RP INHIBITOR, AND S-ADENOSYL-L-METHIONINE-BINDING SITES.
RX PubMed=17845018; DOI=10.1021/jm0703385;
RA Gee C.L., Drinkwater N., Tyndall J.D.A., Grunewald G.L., Wu Q.,
RA McLeish M.J., Martin J.L.;
RT "Enzyme adaptation to inhibitor binding: a cryptic binding site in
RT phenylethanolamine N-methyltransferase.";
RL J. Med. Chem. 50:4845-4853(2007).
RN [13]
RP VARIANTS SER-9; ALA-98; CYS-112 AND THR-175, CHARACTERIZATION OF VARIANTS
RP SER-9; ALA-98; CYS-112 AND THR-175, FUNCTION, CATALYTIC ACTIVITY, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=16277617; DOI=10.1111/j.1471-4159.2005.03453.x;
RA Ji Y., Salavaggione O.E., Wang L., Adjei A.A., Eckloff B., Wieben E.D.,
RA Weinshilboum R.M.;
RT "Human phenylethanolamine N-methyltransferase pharmacogenomics: gene re-
RT sequencing and functional genomics.";
RL J. Neurochem. 95:1766-1776(2005).
CC -!- FUNCTION: Catalyzes the transmethylation of nonepinephrine
CC (noradrenaline) to form epinephrine (adrenaline), using S-adenosyl-L-
CC methionine as the methyl donor (PubMed:20496117). Other substrates
CC include phenylethanolamine and octopamine (PubMed:8812853,
CC PubMed:16363801, PubMed:16277617). Also methylates normetanephrine (By
CC similarity). {ECO:0000250|UniProtKB:P10937,
CC ECO:0000269|PubMed:16277617, ECO:0000269|PubMed:16363801,
CC ECO:0000269|PubMed:20496117, ECO:0000269|PubMed:8812853}.
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:16363801, ECO:0000269|PubMed:8812853};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12177;
CC Evidence={ECO:0000305|PubMed:16363801};
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:20496117};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25270;
CC Evidence={ECO:0000305|PubMed:20496117};
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:P10938};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70684;
CC Evidence={ECO:0000250|UniProtKB:P10938};
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:16277617, ECO:0000269|PubMed:16363801};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70520;
CC Evidence={ECO:0000305|PubMed:16363801};
CC -!- ACTIVITY REGULATION: Inhibited by methyl methanethiosulfonate,
CC phenylglyoxal, tetranitromethane and diethyl pyrocarbonate
CC (PubMed:8812853). Inhibited by 4-oxo-1,4-dihydro-quinoline-3,7-
CC dicarboxylic acid, 4-(benzo[d][1,3]dioxol-5-ylamino)-4-oxobutanoic acid
CC and 1,4-diaminonaphthalene-2,6-disulfonic acid (PubMed:20496117).
CC {ECO:0000269|PubMed:20496117, ECO:0000269|PubMed:8812853}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=99 uM for phenylethanolamine {ECO:0000269|PubMed:16363801};
CC KM=3.4 uM for S-adenosyl-L-methionine {ECO:0000269|PubMed:16363801};
CC KM=5.3 uM for octopamine {ECO:0000269|PubMed:16363801};
CC KM=23.5 uM for octopamine {ECO:0000269|PubMed:16277617};
CC KM=6.2 uM for S-adenosyl-L-methionine {ECO:0000269|PubMed:16277617};
CC KM=130 uM for phenylethanolamine {ECO:0000269|PubMed:8812853};
CC KM=16 uM for S-adenosyl-L-methionine {ECO:0000269|PubMed:8812853};
CC Vmax=195 pmol/min/mg enzyme for phenylethanolamine
CC {ECO:0000269|PubMed:8812853};
CC -!- PATHWAY: Catecholamine biosynthesis; (R)-adrenaline biosynthesis; (R)-
CC adrenaline from (R)-noradrenaline: step 1/1.
CC {ECO:0000269|PubMed:20496117}.
CC -!- INTERACTION:
CC P11086; Q9P2G9-2: KLHL8; NbExp=3; IntAct=EBI-11305767, EBI-11959635;
CC P11086; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-11305767, EBI-739832;
CC -!- MASS SPECTROMETRY: Mass=30721; Mass_error=3.0; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:8812853};
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; J03727; AAA60130.1; -; mRNA.
DR EMBL; X52730; CAA36944.1; -; Genomic_DNA.
DR EMBL; J03280; AAA60131.1; -; Genomic_DNA.
DR EMBL; AC087491; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC037246; AAH37246.1; -; mRNA.
DR CCDS; CCDS11343.1; -.
DR PIR; A28171; A28171.
DR RefSeq; NP_002677.1; NM_002686.4.
DR PDB; 1HNN; X-ray; 2.40 A; A/B=1-282.
DR PDB; 1N7I; X-ray; 2.80 A; A/B=1-282.
DR PDB; 1N7J; X-ray; 2.70 A; A/B=1-282.
DR PDB; 1YZ3; X-ray; 2.40 A; A/B=1-282.
DR PDB; 2AN3; X-ray; 2.20 A; A/B=1-282.
DR PDB; 2AN4; X-ray; 2.20 A; A/B=1-282.
DR PDB; 2AN5; X-ray; 2.50 A; A/B=1-282.
DR PDB; 2G70; X-ray; 2.40 A; A/B=1-282.
DR PDB; 2G71; X-ray; 2.20 A; A/B=1-282.
DR PDB; 2G72; X-ray; 2.00 A; A/B=1-282.
DR PDB; 2G8N; X-ray; 2.15 A; A/B=1-282.
DR PDB; 2OBF; X-ray; 2.30 A; A/B=1-282.
DR PDB; 2ONY; X-ray; 2.60 A; A/B=1-282.
DR PDB; 2ONZ; X-ray; 2.80 A; A/B=1-282.
DR PDB; 2OPB; X-ray; 2.80 A; A/B=1-282.
DR PDB; 3HCA; X-ray; 2.40 A; A/B=1-282.
DR PDB; 3HCB; X-ray; 2.40 A; A/B=1-282.
DR PDB; 3HCC; X-ray; 2.30 A; A/B=1-282.
DR PDB; 3HCD; X-ray; 2.39 A; A/B=1-282.
DR PDB; 3HCE; X-ray; 2.85 A; A/B=1-282.
DR PDB; 3HCF; X-ray; 2.70 A; A/B=1-282.
DR PDB; 3KPJ; X-ray; 2.50 A; A/B=1-282.
DR PDB; 3KPU; X-ray; 2.40 A; A/B=1-282.
DR PDB; 3KPV; X-ray; 2.40 A; A/B=1-282.
DR PDB; 3KPW; X-ray; 2.40 A; A/B=1-282.
DR PDB; 3KPY; X-ray; 2.40 A; A/B=1-282.
DR PDB; 3KQM; X-ray; 2.40 A; A/B=1-282.
DR PDB; 3KQO; X-ray; 2.40 A; A/B=1-282.
DR PDB; 3KQP; X-ray; 2.40 A; A/B=1-282.
DR PDB; 3KQQ; X-ray; 2.50 A; A/B=1-282.
DR PDB; 3KQS; X-ray; 2.00 A; A/B=1-282.
DR PDB; 3KQT; X-ray; 2.40 A; A/B=1-282.
DR PDB; 3KQV; X-ray; 2.30 A; A/B=1-282.
DR PDB; 3KQW; X-ray; 2.49 A; A/B=1-282.
DR PDB; 3KQY; X-ray; 2.20 A; A/B=1-282.
DR PDB; 3KR0; X-ray; 2.60 A; A/B=1-282.
DR PDB; 3KR1; X-ray; 2.30 A; A/B=1-282.
DR PDB; 3KR2; X-ray; 2.30 A; A/B=1-282.
DR PDB; 4DM3; X-ray; 2.40 A; A/B=1-282.
DR PDB; 4MIK; X-ray; 1.95 A; A/B=1-282.
DR PDB; 4MQ4; X-ray; 2.20 A; A/B=1-282.
DR PDB; 6WS1; X-ray; 2.76 A; A/B=1-282.
DR PDBsum; 1HNN; -.
DR PDBsum; 1N7I; -.
DR PDBsum; 1N7J; -.
DR PDBsum; 1YZ3; -.
DR PDBsum; 2AN3; -.
DR PDBsum; 2AN4; -.
DR PDBsum; 2AN5; -.
DR PDBsum; 2G70; -.
DR PDBsum; 2G71; -.
DR PDBsum; 2G72; -.
DR PDBsum; 2G8N; -.
DR PDBsum; 2OBF; -.
DR PDBsum; 2ONY; -.
DR PDBsum; 2ONZ; -.
DR PDBsum; 2OPB; -.
DR PDBsum; 3HCA; -.
DR PDBsum; 3HCB; -.
DR PDBsum; 3HCC; -.
DR PDBsum; 3HCD; -.
DR PDBsum; 3HCE; -.
DR PDBsum; 3HCF; -.
DR PDBsum; 3KPJ; -.
DR PDBsum; 3KPU; -.
DR PDBsum; 3KPV; -.
DR PDBsum; 3KPW; -.
DR PDBsum; 3KPY; -.
DR PDBsum; 3KQM; -.
DR PDBsum; 3KQO; -.
DR PDBsum; 3KQP; -.
DR PDBsum; 3KQQ; -.
DR PDBsum; 3KQS; -.
DR PDBsum; 3KQT; -.
DR PDBsum; 3KQV; -.
DR PDBsum; 3KQW; -.
DR PDBsum; 3KQY; -.
DR PDBsum; 3KR0; -.
DR PDBsum; 3KR1; -.
DR PDBsum; 3KR2; -.
DR PDBsum; 4DM3; -.
DR PDBsum; 4MIK; -.
DR PDBsum; 4MQ4; -.
DR PDBsum; 6WS1; -.
DR AlphaFoldDB; P11086; -.
DR PCDDB; P11086; -.
DR SMR; P11086; -.
DR BioGRID; 111410; 15.
DR IntAct; P11086; 5.
DR STRING; 9606.ENSP00000269582; -.
DR BindingDB; P11086; -.
DR ChEMBL; CHEMBL4617; -.
DR DrugBank; DB08129; (1R)-2-amino-1-[3-(trifluoromethyl)phenyl]ethanol.
DR DrugBank; DB08128; (1S,4R,9S)-5-(trifluoromethyl)-1,2,3,4-tetrahydro-1,4-methanonaphthalen-9-amine.
DR DrugBank; DB07739; (3R)-3-(FLUOROMETHYL)-7-(THIOMORPHOLIN-4-YLSULFONYL)-1,2,3,4-TETRAHYDROISOQUINOLINE.
DR DrugBank; DB07798; (3R)-3-(FLUOROMETHYL)-N-(3,3,3-TRIFLUOROPROPYL)-1,2,3,4-TETRAHYDROISOQUINOLINE-7-SULFONAMIDE.
DR DrugBank; DB07747; (3R)-N-(4-CHLOROPHENYL)-3-(HYDROXYMETHYL)-1,2,3,4-TETRAHYDROISOQUINOLINE-7-SULFONAMIDE.
DR DrugBank; DB03468; 1,2,3,4-Tetrahydro-Isoquinoline-7-Sulfonic Acid Amide.
DR DrugBank; DB08550; 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
DR DrugBank; DB03824; 7-Iodo-1,2,3,4-Tetrahydro-Isoquinoline.
DR DrugBank; DB04273; 8,9-Dichloro-2,3,4,5-Tetrahydro-1h-Benzo[C]Azepine.
DR DrugBank; DB07906; [(3R)-7-NITRO-1,2,3,4-TETRAHYDROISOQUINOLIN-3-YL]METHANOL.
DR DrugBank; DB07597; CIS-(1R,2S)-2-AMINO-1,2,3,4-TETRAHYDRONAPHTHALEN-1-OL.
DR DrugBank; DB09571; Levmetamfetamine.
DR DrugBank; DB00968; Methyldopa.
DR DrugBank; DB08631; N-(4-CHLOROPHENYL)-1,2,3,4-TETRAHYDROISOQUINOLINE-7-SULFONAMIDE.
DR DrugBank; DB01752; S-adenosyl-L-homocysteine.
DR DrugBank; DB08654; TRANS-(1S,2S)-2-AMINO-1,2,3,4-TETRAHYDRONAPHTHALEN-1-OL.
DR DrugCentral; P11086; -.
DR GuidetoPHARMACOLOGY; 2496; -.
DR iPTMnet; P11086; -.
DR PhosphoSitePlus; P11086; -.
DR BioMuta; PNMT; -.
DR DMDM; 130375; -.
DR CPTAC; CPTAC-150; -.
DR CPTAC; CPTAC-151; -.
DR MassIVE; P11086; -.
DR PaxDb; P11086; -.
DR PeptideAtlas; P11086; -.
DR PRIDE; P11086; -.
DR ProteomicsDB; 52692; -.
DR Antibodypedia; 28325; 535 antibodies from 32 providers.
DR CPTC; P11086; 3 antibodies.
DR DNASU; 5409; -.
DR Ensembl; ENST00000269582.3; ENSP00000269582.2; ENSG00000141744.4.
DR GeneID; 5409; -.
DR KEGG; hsa:5409; -.
DR MANE-Select; ENST00000269582.3; ENSP00000269582.2; NM_002686.4; NP_002677.1.
DR UCSC; uc002hsi.3; human.
DR CTD; 5409; -.
DR DisGeNET; 5409; -.
DR GeneCards; PNMT; -.
DR HGNC; HGNC:9160; PNMT.
DR HPA; ENSG00000141744; Tissue enriched (adrenal).
DR MIM; 171190; gene.
DR neXtProt; NX_P11086; -.
DR OpenTargets; ENSG00000141744; -.
DR Orphanet; 243761; NON RARE IN EUROPE: Essential hypertension.
DR PharmGKB; PA274; -.
DR VEuPathDB; HostDB:ENSG00000141744; -.
DR eggNOG; ENOG502QT44; Eukaryota.
DR GeneTree; ENSGT00390000011708; -.
DR HOGENOM; CLU_082526_2_0_1; -.
DR InParanoid; P11086; -.
DR OMA; IDVHCSQ; -.
DR OrthoDB; 1054662at2759; -.
DR PhylomeDB; P11086; -.
DR TreeFam; TF313114; -.
DR BioCyc; MetaCyc:HS06868-MON; -.
DR BRENDA; 2.1.1.28; 2681.
DR PathwayCommons; P11086; -.
DR Reactome; R-HSA-209905; Catecholamine biosynthesis.
DR SignaLink; P11086; -.
DR SIGNOR; P11086; -.
DR UniPathway; UPA00749; UER00736.
DR BioGRID-ORCS; 5409; 15 hits in 1077 CRISPR screens.
DR EvolutionaryTrace; P11086; -.
DR GenomeRNAi; 5409; -.
DR Pharos; P11086; Tchem.
DR PRO; PR:P11086; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P11086; protein.
DR Bgee; ENSG00000141744; Expressed in nucleus accumbens and 122 other tissues.
DR ExpressionAtlas; P11086; baseline and differential.
DR Genevisible; P11086; HS.
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:0042423; P:catecholamine biosynthetic process; TAS:Reactome.
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 3D-structure; Catecholamine biosynthesis; Direct protein sequencing;
KW Methyltransferase; Phosphoprotein; Reference proteome;
KW S-adenosyl-L-methionine; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:8812853"
FT CHAIN 2..282
FT /note="Phenylethanolamine N-methyltransferase"
FT /id="PRO_0000159709"
FT BINDING 35
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:16363801,
FT ECO:0000269|PubMed:17845018, ECO:0007744|PDB:2AN4,
FT ECO:0007744|PDB:2G70, ECO:0007744|PDB:2G72"
FT BINDING 40
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:16363801,
FT ECO:0000269|PubMed:17845018, ECO:0007744|PDB:2AN4,
FT ECO:0007744|PDB:2G70, ECO:0007744|PDB:2G72"
FT BINDING 79..80
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:17845018,
FT ECO:0007744|PDB:2G70, ECO:0007744|PDB:2G72"
FT BINDING 85
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:16363801,
FT ECO:0000269|PubMed:17845018, ECO:0007744|PDB:2AN4,
FT ECO:0007744|PDB:2G70, ECO:0007744|PDB:2G72"
FT BINDING 101
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:16363801,
FT ECO:0000269|PubMed:17845018, ECO:0007744|PDB:2AN4,
FT ECO:0007744|PDB:2G70, ECO:0007744|PDB:2G72"
FT BINDING 106
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:16363801,
FT ECO:0000269|PubMed:17845018, ECO:0007744|PDB:2AN4,
FT ECO:0007744|PDB:2G70, ECO:0007744|PDB:2G72"
FT BINDING 158..159
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:17845018,
FT ECO:0007744|PDB:2G70, ECO:0007744|PDB:2G72"
FT BINDING 181
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:16363801,
FT ECO:0000269|PubMed:17845018, ECO:0007744|PDB:2AN4,
FT ECO:0007744|PDB:2G70, ECO:0007744|PDB:2G72"
FT BINDING 219
FT /ligand="octopamine"
FT /ligand_id="ChEBI:CHEBI:58025"
FT /evidence="ECO:0000269|PubMed:16363801,
FT ECO:0007744|PDB:2AN4"
FT BINDING 267
FT /ligand="octopamine"
FT /ligand_id="ChEBI:CHEBI:58025"
FT /evidence="ECO:0000269|PubMed:16363801,
FT ECO:0007744|PDB:2AN4"
FT MOD_RES 7
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 9
FT /note="N -> S (slight increase in protein expression and
FT enzyme activity with octopamine as substrate;
FT dbSNP:rs11569781)"
FT /evidence="ECO:0000269|PubMed:16277617"
FT /id="VAR_029351"
FT VARIANT 98
FT /note="T -> A (significant decrease in protein expression
FT and enzyme activity with octopamine as substrate;
FT dbSNP:rs36060376)"
FT /evidence="ECO:0000269|PubMed:16277617"
FT /id="VAR_036829"
FT VARIANT 112
FT /note="R -> C (no significant effect on protein expression
FT and enzyme activity with octopamine as substrate;
FT dbSNP:rs34530498)"
FT /evidence="ECO:0000269|PubMed:16277617"
FT /id="VAR_036830"
FT VARIANT 175
FT /note="A -> T (no significant effect on protein expression
FT and enzyme activity with octopamine as substrate;
FT dbSNP:rs34341496)"
FT /evidence="ECO:0000269|PubMed:16277617"
FT /id="VAR_036831"
FT VARIANT 188
FT /note="S -> C (in dbSNP:rs5639)"
FT /id="VAR_037611"
FT VARIANT 211
FT /note="L -> H (in dbSNP:rs5640)"
FT /id="VAR_037612"
FT VARIANT 217
FT /note="L -> Q (in dbSNP:rs5641)"
FT /id="VAR_037613"
FT VARIANT 254
FT /note="R -> H (in dbSNP:rs5642)"
FT /id="VAR_037614"
FT VARIANT 276
FT /note="W -> R (in dbSNP:rs5643)"
FT /id="VAR_024547"
FT MUTAGEN 35
FT /note="Y->F: Strongly increases KM for phenylethanolamine
FT and S-adenosyl-L-methionine."
FT /evidence="ECO:0000269|PubMed:16363801"
FT MUTAGEN 185
FT /note="E->A,Q: Strongly reduced enzyme activity towards
FT phenylethanolamine. Increases affinity for S-adenosyl-L-
FT methionine."
FT /evidence="ECO:0000269|PubMed:16363801"
FT MUTAGEN 185
FT /note="E->D: Strongly reduced enzyme activity towards
FT phenylethanolamine. Decreases affinity for
FT phenylethanolamine and S-adenosyl-L-methionine 3-fold."
FT /evidence="ECO:0000269|PubMed:16363801"
FT MUTAGEN 219
FT /note="E->A: Reduced enzyme activity towards
FT phenylethanolamine. Decreases affinity for
FT phenylethanolamine 6-fold. Decreases affinity for S-
FT adenosyl-L-methionine 2-fold."
FT /evidence="ECO:0000269|PubMed:16363801"
FT MUTAGEN 267
FT /note="D->A,N: Strongly reduced enzyme activity towards
FT phenylethanolamine. Decreases affinity for
FT phenylethanolamine 200-fold. Decreases affinity for S-
FT adenosyl-L-methionine 3-fold."
FT /evidence="ECO:0000269|PubMed:16363801"
FT CONFLICT 169..170
FT /note="SP -> AQ (in Ref. 3; AAA60131)"
FT /evidence="ECO:0000305"
FT HELIX 17..25
FT /evidence="ECO:0007829|PDB:4MIK"
FT HELIX 27..29
FT /evidence="ECO:0007829|PDB:4MIK"
FT HELIX 32..40
FT /evidence="ECO:0007829|PDB:4MIK"
FT TURN 42..45
FT /evidence="ECO:0007829|PDB:4MIK"
FT HELIX 53..66
FT /evidence="ECO:0007829|PDB:4MIK"
FT STRAND 73..79
FT /evidence="ECO:0007829|PDB:4MIK"
FT HELIX 85..87
FT /evidence="ECO:0007829|PDB:4MIK"
FT HELIX 90..92
FT /evidence="ECO:0007829|PDB:4MIK"
FT STRAND 95..100
FT /evidence="ECO:0007829|PDB:4MIK"
FT HELIX 104..114
FT /evidence="ECO:0007829|PDB:4MIK"
FT HELIX 124..134
FT /evidence="ECO:0007829|PDB:4MIK"
FT HELIX 140..150
FT /evidence="ECO:0007829|PDB:4MIK"
FT STRAND 151..155
FT /evidence="ECO:0007829|PDB:4MIK"
FT STRAND 161..163
FT /evidence="ECO:0007829|PDB:4MIK"
FT STRAND 173..182
FT /evidence="ECO:0007829|PDB:4MIK"
FT TURN 184..186
FT /evidence="ECO:0007829|PDB:4MIK"
FT HELIX 191..202
FT /evidence="ECO:0007829|PDB:4MIK"
FT STRAND 205..218
FT /evidence="ECO:0007829|PDB:4MIK"
FT STRAND 221..224
FT /evidence="ECO:0007829|PDB:4MIK"
FT STRAND 227..230
FT /evidence="ECO:0007829|PDB:4MIK"
FT HELIX 236..246
FT /evidence="ECO:0007829|PDB:4MIK"
FT STRAND 248..257
FT /evidence="ECO:0007829|PDB:4MIK"
FT HELIX 260..262
FT /evidence="ECO:0007829|PDB:4MIK"
FT STRAND 265..267
FT /evidence="ECO:0007829|PDB:4MIK"
FT STRAND 271..279
FT /evidence="ECO:0007829|PDB:4MIK"
SQ SEQUENCE 282 AA; 30855 MW; 56F3A9981D9ABF4C CRC64;
MSGADRSPNA GAAPDSAPGQ AAVASAYQRF EPRAYLRNNY APPRGDLCNP NGVGPWKLRC
LAQTFATGEV SGRTLIDIGS GPTVYQLLSA CSHFEDITMT DFLEVNRQEL GRWLQEEPGA
FNWSMYSQHA CLIEGKGECW QDKERQLRAR VKRVLPIDVH QPQPLGAGSP APLPADALVS
AFCLEAVSPD LASFQRALDH ITTLLRPGGH LLLIGALEES WYLAGEARLT VVPVSEEEVR
EALVRSGYKV RDLRTYIMPA HLQTGVDDVK GVFFAWAQKV GL
