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P11086 (PNMT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 143. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Phenylethanolamine N-methyltransferase

Short name=PNMTase
EC=2.1.1.28
Alternative name(s):
Noradrenaline N-methyltransferase
Gene names
Name:PNMT
Synonyms:PENT
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length282 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Converts noradrenaline to adrenaline.

Catalytic activity

S-adenosyl-L-methionine + phenylethanolamine = S-adenosyl-L-homocysteine + N-methylphenylethanolamine.

Pathway

Catecholamine biosynthesis; (R)-adrenaline biosynthesis; (R)-adrenaline from (R)-noradrenaline: step 1/1.

Sequence similarities

Belongs to the class I-like SAM-binding methyltransferase superfamily. NNMT/PNMT/TEMT family.

Biophysicochemical properties

Kinetic parameters:

KM=99 µM for phenylethanolamine Ref.6

KM=3.4 µM for S-adenosyl-L-methionine

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 282282Phenylethanolamine N-methyltransferase
PRO_0000159709

Regions

Region79 – 802S-adenosyl-L-methionine binding
Region158 – 1592S-adenosyl-L-methionine binding

Sites

Binding site351S-adenosyl-L-methionine
Binding site401S-adenosyl-L-methionine
Binding site851S-adenosyl-L-methionine
Binding site1011S-adenosyl-L-methionine
Binding site1061S-adenosyl-L-methionine
Binding site1811S-adenosyl-L-methionine; via carbonyl oxygen
Binding site2191Substrate

Natural variations

Natural variant91N → S. Ref.9
Corresponds to variant rs11569781 [ dbSNP | Ensembl ].
VAR_029351
Natural variant981T → A Lower activity levels than wild-type. Ref.9
Corresponds to variant rs36060376 [ dbSNP | Ensembl ].
VAR_036829
Natural variant1121R → C. Ref.9
Corresponds to variant rs34530498 [ dbSNP | Ensembl ].
VAR_036830
Natural variant1751A → T. Ref.9
Corresponds to variant rs34341496 [ dbSNP | Ensembl ].
VAR_036831
Natural variant1881S → C.
Corresponds to variant rs5639 [ dbSNP | Ensembl ].
VAR_037611
Natural variant2111L → H.
Corresponds to variant rs5640 [ dbSNP | Ensembl ].
VAR_037612
Natural variant2171L → Q.
Corresponds to variant rs5641 [ dbSNP | Ensembl ].
VAR_037613
Natural variant2541R → H.
Corresponds to variant rs5642 [ dbSNP | Ensembl ].
VAR_037614
Natural variant2761W → R.
Corresponds to variant rs5643 [ dbSNP | Ensembl ].
VAR_024547

Experimental info

Mutagenesis351Y → F: Strongly increases KM for substrate and S-adenosyl-L-methionine. Ref.6
Mutagenesis1851E → A or Q: Strongly reduced enzyme activity. Increases affinity for S-adenosyl-L-methionine. Ref.6
Mutagenesis1851E → D: Strongly reduced enzyme activity. Decreases affinity for substrate and S-adenosyl-L-methionine 3-fold. Ref.6
Mutagenesis2191E → A: Reduced enzyme activity. Decreases affinity for substrate 6-fold. Decreases affinity for S-adenosyl-L-methionine 2-fold. Ref.6
Mutagenesis2671D → A or N: Strongly reduced enzyme activity. Decreases affinity for substrate 200-fold. Decreases affinity for S-adenosyl-L-methionine 3-fold. Ref.6
Sequence conflict169 – 1702SP → AQ in AAA60131. Ref.3

Secondary structure

................................................. 282
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P11086 [UniParc].

Last modified July 1, 1989. Version 1.
Checksum: 56F3A9981D9ABF4C

FASTA28230,855
        10         20         30         40         50         60 
MSGADRSPNA GAAPDSAPGQ AAVASAYQRF EPRAYLRNNY APPRGDLCNP NGVGPWKLRC 

        70         80         90        100        110        120 
LAQTFATGEV SGRTLIDIGS GPTVYQLLSA CSHFEDITMT DFLEVNRQEL GRWLQEEPGA 

       130        140        150        160        170        180 
FNWSMYSQHA CLIEGKGECW QDKERQLRAR VKRVLPIDVH QPQPLGAGSP APLPADALVS 

       190        200        210        220        230        240 
AFCLEAVSPD LASFQRALDH ITTLLRPGGH LLLIGALEES WYLAGEARLT VVPVSEEEVR 

       250        260        270        280 
EALVRSGYKV RDLRTYIMPA HLQTGVDDVK GVFFAWAQKV GL 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning of cDNA and chromosomal assignment of the gene for human phenylethanolamine N-methyltransferase, the enzyme for epinephrine biosynthesis."
Kaneda N., Ichinose H., Kobayashi K., Oka K., Kishi F., Nakazawa A., Kurosawa Y., Fujita K., Nagatsu T.
J. Biol. Chem. 263:7672-7677(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Structure of human phenylethanolamine N-methyltransferase gene: existence of two types of mRNA with different transcription initiation sites."
Sasaoka T., Kaneda N., Kurosawa Y., Fujita K., Nagatsu T.
Neurochem. Int. 15:555-565(1989)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Placenta.
[3]"Transgenic mice express the human phenylethanolamine N-methyltransferase gene in adrenal medulla and retina."
Baetge E.E., Behringer R.R., Messing A., Brinster R.L., Palmiter R.D.
Proc. Natl. Acad. Sci. U.S.A. 85:3648-3652(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain, Lung and Testis.
[5]"Getting the adrenaline going: crystal structure of the adrenaline-synthesizing enzyme PNMT."
Martin J.L., Begun J., McLeish M.J., Caine J.M., Grunewald G.L.
Structure 9:977-985(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH S-ADENOSYL-L-HOMOCYSTEINE AND SYNTHETIC INHIBITOR.
[6]"Mode of binding of methyl acceptor substrates to the adrenaline-synthesizing enzyme phenylethanolamine N-methyltransferase: implications for catalysis."
Gee C.L., Tyndall J.D.A., Grunewald G.L., Wu Q., McLeish M.J., Martin J.L.
Biochemistry 44:16875-16885(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEXES WITH SUBSTRATE ANALOGS AND S-ADENOSYL-L-HOMOCYSTEINE, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF TYR-35; GLU-185; GLU-219 AND ASP-267.
[7]"Comparison of the binding of 3-fluoromethyl-7-sulfonyl-1,2,3,4-tetrahydroisoquinolines with their isosteric sulfonamides to the active site of phenylethanolamine N-methyltransferase."
Grunewald G.L., Seim M.R., Regier R.C., Martin J.L., Gee C.L., Drinkwater N., Criscione K.R.
J. Med. Chem. 49:5424-5433(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) IN COMPLEX WITH SYNTHETIC INHIBITOR.
[8]"Enzyme adaptation to inhibitor binding: a cryptic binding site in phenylethanolamine N-methyltransferase."
Gee C.L., Drinkwater N., Tyndall J.D.A., Grunewald G.L., Wu Q., McLeish M.J., Martin J.L.
J. Med. Chem. 50:4845-4853(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEXES WITH SYNTHETIC INHIBITOR.
[9]"Human phenylethanolamine N-methyltransferase pharmacogenomics: gene re-sequencing and functional genomics."
Ji Y., Salavaggione O.E., Wang L., Adjei A.A., Eckloff B., Wieben E.D., Weinshilboum R.M.
J. Neurochem. 95:1766-1776(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SER-9; ALA-98; CYS-112 AND THR-175, CHARACTERIZATION OF VARIANT ALA-98.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J03727 mRNA. Translation: AAA60130.1.
X52730 Genomic DNA. Translation: CAA36944.1.
J03280 Genomic DNA. Translation: AAA60131.1.
BC037246 mRNA. Translation: AAH37246.1.
CCDSCCDS11343.1.
PIRA28171.
RefSeqNP_002677.1. NM_002686.4.
UniGeneHs.1892.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1HNNX-ray2.40A/B1-282[»]
1N7IX-ray2.80A/B1-282[»]
1N7JX-ray2.70A/B1-282[»]
1YZ3X-ray2.40A/B1-282[»]
2AN3X-ray2.20A/B1-282[»]
2AN4X-ray2.20A/B1-282[»]
2AN5X-ray2.50A/B1-282[»]
2G70X-ray2.40A/B1-282[»]
2G71X-ray2.20A/B1-282[»]
2G72X-ray2.00A/B1-282[»]
2G8NX-ray2.15A/B1-282[»]
2OBFX-ray2.30A/B1-282[»]
2ONYX-ray2.60A/B1-282[»]
2ONZX-ray2.80A/B1-282[»]
2OPBX-ray2.80A/B1-282[»]
3HCAX-ray2.40A/B1-282[»]
3HCBX-ray2.40A/B1-282[»]
3HCCX-ray2.30A/B1-282[»]
3HCDX-ray2.39A/B1-282[»]
3HCEX-ray2.85A/B1-282[»]
3HCFX-ray2.70A/B1-282[»]
3KPJX-ray2.50A/B1-282[»]
3KPUX-ray2.40A/B1-282[»]
3KPVX-ray2.40A/B1-282[»]
3KPWX-ray2.40A/B1-282[»]
3KPYX-ray2.40A/B1-282[»]
3KQMX-ray2.40A/B1-282[»]
3KQOX-ray2.40A/B1-282[»]
3KQPX-ray2.40A/B1-282[»]
3KQQX-ray2.50A/B1-282[»]
3KQSX-ray2.00A/B1-282[»]
3KQTX-ray2.40A/B1-282[»]
3KQVX-ray2.30A/B1-282[»]
3KQWX-ray2.49A/B1-282[»]
3KQYX-ray2.20A/B1-282[»]
3KR0X-ray2.60A/B1-282[»]
3KR1X-ray2.30A/B1-282[»]
3KR2X-ray2.30A/B1-282[»]
4DM3X-ray2.40A/B1-282[»]
ProteinModelPortalP11086.
SMRP11086. Positions 14-281.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111410. 2 interactions.
STRING9606.ENSP00000269582.

Chemistry

BindingDBP11086.
ChEMBLCHEMBL4617.
GuidetoPHARMACOLOGY2496.

PTM databases

PhosphoSiteP11086.

Polymorphism databases

DMDM130375.

Proteomic databases

PRIDEP11086.

Protocols and materials databases

DNASU5409.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000269582; ENSP00000269582; ENSG00000141744.
GeneID5409.
KEGGhsa:5409.
UCSCuc002hsi.2. human.

Organism-specific databases

CTD5409.
GeneCardsGC17P037824.
HGNCHGNC:9160. PNMT.
HPACAB017029.
HPA043412.
HPA051005.
MIM171190. gene.
neXtProtNX_P11086.
PharmGKBPA274.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG78422.
HOGENOMHOG000013229.
HOVERGENHBG000797.
InParanoidP11086.
KOK00553.
OMAEESWYLA.
PhylomeDBP11086.
TreeFamTF313114.

Enzyme and pathway databases

BioCycMetaCyc:HS06868-MONOMER.
ReactomeREACT_111217. Metabolism.
UniPathwayUPA00749; UER00736.

Gene expression databases

ArrayExpressP11086.
BgeeP11086.
CleanExHS_PNMT.
GenevestigatorP11086.

Family and domain databases

Gene3D3.40.50.150. 1 hit.
InterProIPR025820. NNMT/PNMT/TEMT_CS.
IPR000940. NNMT_TEMT_trans.
IPR029063. SAM-dependent_MTases-like.
[Graphical view]
PANTHERPTHR10867. PTHR10867. 1 hit.
PfamPF01234. NNMT_PNMT_TEMT. 1 hit.
[Graphical view]
PIRSFPIRSF000384. PNMTase. 1 hit.
SUPFAMSSF53335. SSF53335. 1 hit.
PROSITEPS01100. NNMT_PNMT_TEMT. 1 hit.
PS51681. SAM_MT_NNMT_PNMT_TEMT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP11086.
GenomeRNAi5409.
NextBio20943.
PROP11086.
SOURCESearch...

Entry information

Entry namePNMT_HUMAN
AccessionPrimary (citable) accession number: P11086
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: July 9, 2014
This is version 143 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM