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Protein

Phenylethanolamine N-methyltransferase

Gene

PNMT

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Converts noradrenaline to adrenaline.

Catalytic activityi

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

Kineticsi

  1. KM=99 µM for phenylethanolamine1 Publication
  2. KM=3.4 µM for S-adenosyl-L-methionine1 Publication

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei35 – 351S-adenosyl-L-methionine
Binding sitei40 – 401S-adenosyl-L-methionine
Binding sitei85 – 851S-adenosyl-L-methionine
Binding sitei101 – 1011S-adenosyl-L-methionine
Binding sitei106 – 1061S-adenosyl-L-methionine
Binding sitei181 – 1811S-adenosyl-L-methionine; via carbonyl oxygen
Binding sitei219 – 2191Substrate

GO - Molecular functioni

  1. phenylethanolamine N-methyltransferase activity Source: ProtInc

GO - Biological processi

  1. catecholamine biosynthetic process Source: Reactome
  2. cellular nitrogen compound metabolic process Source: Reactome
  3. epinephrine biosynthetic process Source: UniProtKB-UniPathway
  4. small molecule metabolic process Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Methyltransferase, Transferase

Keywords - Biological processi

Catecholamine biosynthesis

Keywords - Ligandi

S-adenosyl-L-methionine

Enzyme and pathway databases

BioCyciMetaCyc:HS06868-MONOMER.
ReactomeiREACT_15551. Catecholamine biosynthesis.
UniPathwayiUPA00749; UER00736.

Names & Taxonomyi

Protein namesi
Recommended name:
Phenylethanolamine N-methyltransferase (EC:2.1.1.28)
Short name:
PNMTase
Alternative name(s):
Noradrenaline N-methyltransferase
Gene namesi
Name:PNMT
Synonyms:PENT
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 17

Organism-specific databases

HGNCiHGNC:9160. PNMT.

Subcellular locationi

GO - Cellular componenti

  1. cytosol Source: Reactome
Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi35 – 351Y → F: Strongly increases KM for substrate and S-adenosyl-L-methionine. 1 Publication
Mutagenesisi185 – 1851E → A or Q: Strongly reduced enzyme activity. Increases affinity for S-adenosyl-L-methionine. 1 Publication
Mutagenesisi185 – 1851E → D: Strongly reduced enzyme activity. Decreases affinity for substrate and S-adenosyl-L-methionine 3-fold. 1 Publication
Mutagenesisi219 – 2191E → A: Reduced enzyme activity. Decreases affinity for substrate 6-fold. Decreases affinity for S-adenosyl-L-methionine 2-fold. 1 Publication
Mutagenesisi267 – 2671D → A or N: Strongly reduced enzyme activity. Decreases affinity for substrate 200-fold. Decreases affinity for S-adenosyl-L-methionine 3-fold. 1 Publication

Organism-specific databases

PharmGKBiPA274.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 282282Phenylethanolamine N-methyltransferasePRO_0000159709Add
BLAST

Proteomic databases

PRIDEiP11086.

PTM databases

PhosphoSiteiP11086.

Expressioni

Gene expression databases

BgeeiP11086.
CleanExiHS_PNMT.
ExpressionAtlasiP11086. baseline and differential.
GenevestigatoriP11086.

Organism-specific databases

HPAiCAB017029.
HPA043412.
HPA051005.

Interactioni

Protein-protein interaction databases

BioGridi111410. 2 interactions.
STRINGi9606.ENSP00000269582.

Structurei

Secondary structure

1
282
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi18 – 269Combined sources
Helixi27 – 293Combined sources
Helixi32 – 409Combined sources
Turni42 – 454Combined sources
Helixi53 – 6614Combined sources
Beta strandi73 – 797Combined sources
Helixi85 – 873Combined sources
Helixi90 – 923Combined sources
Beta strandi95 – 1006Combined sources
Helixi104 – 11411Combined sources
Helixi124 – 13411Combined sources
Helixi140 – 15011Combined sources
Beta strandi151 – 1555Combined sources
Beta strandi161 – 1633Combined sources
Beta strandi173 – 18210Combined sources
Turni184 – 1863Combined sources
Helixi191 – 20212Combined sources
Beta strandi205 – 21814Combined sources
Beta strandi221 – 2244Combined sources
Beta strandi227 – 2304Combined sources
Helixi236 – 24611Combined sources
Beta strandi248 – 25710Combined sources
Helixi260 – 2623Combined sources
Beta strandi265 – 2673Combined sources
Beta strandi271 – 2799Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
4MIKX-ray1.95A/B1-282[»]
4MQ4X-ray2.20A/B1-282[»]
ProteinModelPortaliP11086.
SMRiP11086. Positions 16-280.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP11086.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni79 – 802S-adenosyl-L-methionine binding
Regioni158 – 1592S-adenosyl-L-methionine binding

Sequence similaritiesi

Phylogenomic databases

eggNOGiNOG78422.
GeneTreeiENSGT00390000011708.
HOGENOMiHOG000013229.
HOVERGENiHBG000797.
InParanoidiP11086.
KOiK00553.
OMAiEESWYLA.
PhylomeDBiP11086.
TreeFamiTF313114.

Family and domain databases

Gene3Di3.40.50.150. 1 hit.
InterProiIPR025820. NNMT/PNMT/TEMT_CS.
IPR000940. NNMT_TEMT_trans.
IPR029063. SAM-dependent_MTases.
[Graphical view]
PANTHERiPTHR10867. PTHR10867. 1 hit.
PfamiPF01234. NNMT_PNMT_TEMT. 1 hit.
[Graphical view]
PIRSFiPIRSF000384. PNMTase. 1 hit.
SUPFAMiSSF53335. SSF53335. 1 hit.
PROSITEiPS01100. NNMT_PNMT_TEMT. 1 hit.
PS51681. SAM_MT_NNMT_PNMT_TEMT. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P11086-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSGADRSPNA GAAPDSAPGQ AAVASAYQRF EPRAYLRNNY APPRGDLCNP
60 70 80 90 100
NGVGPWKLRC LAQTFATGEV SGRTLIDIGS GPTVYQLLSA CSHFEDITMT
110 120 130 140 150
DFLEVNRQEL GRWLQEEPGA FNWSMYSQHA CLIEGKGECW QDKERQLRAR
160 170 180 190 200
VKRVLPIDVH QPQPLGAGSP APLPADALVS AFCLEAVSPD LASFQRALDH
210 220 230 240 250
ITTLLRPGGH LLLIGALEES WYLAGEARLT VVPVSEEEVR EALVRSGYKV
260 270 280
RDLRTYIMPA HLQTGVDDVK GVFFAWAQKV GL
Length:282
Mass (Da):30,855
Last modified:July 1, 1989 - v1
Checksum:i56F3A9981D9ABF4C
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti169 – 1702SP → AQ in AAA60131 (PubMed:2835776).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti9 – 91N → S.1 Publication
Corresponds to variant rs11569781 [ dbSNP | Ensembl ].
VAR_029351
Natural varianti98 – 981T → A Lower activity levels than wild-type. 1 Publication
Corresponds to variant rs36060376 [ dbSNP | Ensembl ].
VAR_036829
Natural varianti112 – 1121R → C.1 Publication
Corresponds to variant rs34530498 [ dbSNP | Ensembl ].
VAR_036830
Natural varianti175 – 1751A → T.1 Publication
Corresponds to variant rs34341496 [ dbSNP | Ensembl ].
VAR_036831
Natural varianti188 – 1881S → C.
Corresponds to variant rs5639 [ dbSNP | Ensembl ].
VAR_037611
Natural varianti211 – 2111L → H.
Corresponds to variant rs5640 [ dbSNP | Ensembl ].
VAR_037612
Natural varianti217 – 2171L → Q.
Corresponds to variant rs5641 [ dbSNP | Ensembl ].
VAR_037613
Natural varianti254 – 2541R → H.
Corresponds to variant rs5642 [ dbSNP | Ensembl ].
VAR_037614
Natural varianti276 – 2761W → R.
Corresponds to variant rs5643 [ dbSNP | Ensembl ].
VAR_024547

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J03727 mRNA. Translation: AAA60130.1.
X52730 Genomic DNA. Translation: CAA36944.1.
J03280 Genomic DNA. Translation: AAA60131.1.
BC037246 mRNA. Translation: AAH37246.1.
CCDSiCCDS11343.1.
PIRiA28171.
RefSeqiNP_002677.1. NM_002686.4.
UniGeneiHs.1892.

Genome annotation databases

EnsembliENST00000269582; ENSP00000269582; ENSG00000141744.
GeneIDi5409.
KEGGihsa:5409.
UCSCiuc002hsi.2. human.

Polymorphism databases

DMDMi130375.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J03727 mRNA. Translation: AAA60130.1.
X52730 Genomic DNA. Translation: CAA36944.1.
J03280 Genomic DNA. Translation: AAA60131.1.
BC037246 mRNA. Translation: AAH37246.1.
CCDSiCCDS11343.1.
PIRiA28171.
RefSeqiNP_002677.1. NM_002686.4.
UniGeneiHs.1892.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
4MIKX-ray1.95A/B1-282[»]
4MQ4X-ray2.20A/B1-282[»]
ProteinModelPortaliP11086.
SMRiP11086. Positions 16-280.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111410. 2 interactions.
STRINGi9606.ENSP00000269582.

Chemistry

BindingDBiP11086.
ChEMBLiCHEMBL4617.
GuidetoPHARMACOLOGYi2496.

PTM databases

PhosphoSiteiP11086.

Polymorphism databases

DMDMi130375.

Proteomic databases

PRIDEiP11086.

Protocols and materials databases

DNASUi5409.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000269582; ENSP00000269582; ENSG00000141744.
GeneIDi5409.
KEGGihsa:5409.
UCSCiuc002hsi.2. human.

Organism-specific databases

CTDi5409.
GeneCardsiGC17P037824.
HGNCiHGNC:9160. PNMT.
HPAiCAB017029.
HPA043412.
HPA051005.
MIMi171190. gene.
neXtProtiNX_P11086.
PharmGKBiPA274.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG78422.
GeneTreeiENSGT00390000011708.
HOGENOMiHOG000013229.
HOVERGENiHBG000797.
InParanoidiP11086.
KOiK00553.
OMAiEESWYLA.
PhylomeDBiP11086.
TreeFamiTF313114.

Enzyme and pathway databases

UniPathwayiUPA00749; UER00736.
BioCyciMetaCyc:HS06868-MONOMER.
ReactomeiREACT_15551. Catecholamine biosynthesis.

Miscellaneous databases

EvolutionaryTraceiP11086.
GenomeRNAii5409.
NextBioi20943.
PROiP11086.
SOURCEiSearch...

Gene expression databases

BgeeiP11086.
CleanExiHS_PNMT.
ExpressionAtlasiP11086. baseline and differential.
GenevestigatoriP11086.

Family and domain databases

Gene3Di3.40.50.150. 1 hit.
InterProiIPR025820. NNMT/PNMT/TEMT_CS.
IPR000940. NNMT_TEMT_trans.
IPR029063. SAM-dependent_MTases.
[Graphical view]
PANTHERiPTHR10867. PTHR10867. 1 hit.
PfamiPF01234. NNMT_PNMT_TEMT. 1 hit.
[Graphical view]
PIRSFiPIRSF000384. PNMTase. 1 hit.
SUPFAMiSSF53335. SSF53335. 1 hit.
PROSITEiPS01100. NNMT_PNMT_TEMT. 1 hit.
PS51681. SAM_MT_NNMT_PNMT_TEMT. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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.

Entry informationi

Entry nameiPNMT_HUMAN
AccessioniPrimary (citable) accession number: P11086
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: March 4, 2015
This is version 150 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.