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P11086

- PNMT_HUMAN

UniProt

P11086 - PNMT_HUMAN

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Protein

Phenylethanolamine N-methyltransferase

Gene

PNMT

Organism
Homo sapiens (Human)
Status
Reviewed - 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 – 269
Helixi27 – 293
Helixi32 – 409
Turni42 – 454
Helixi53 – 6614
Beta strandi73 – 797
Helixi85 – 873
Helixi90 – 934
Beta strandi95 – 1006
Helixi104 – 11411
Helixi124 – 13411
Helixi140 – 15011
Beta strandi151 – 1555
Beta strandi161 – 1633
Beta strandi173 – 18210
Helixi184 – 1874
Helixi191 – 20212
Beta strandi205 – 21814
Beta strandi221 – 2244
Beta strandi227 – 2304
Helixi236 – 24510
Beta strandi248 – 25710
Helixi260 – 2623
Beta strandi265 – 2673
Beta strandi271 – 2799

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
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[»]
ProteinModelPortaliP11086.
SMRiP11086. Positions 14-281.
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-like.
[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:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
Links Updated
J03727 mRNA. Translation: AAA60130.1 .
X52730 Genomic DNA. Translation: CAA36944.1 .
J03280 Genomic DNA. Translation: AAA60131.1 .
BC037246 mRNA. Translation: AAH37246.1 .
CCDSi CCDS11343.1.
PIRi A28171.
RefSeqi NP_002677.1. NM_002686.4.
UniGenei Hs.1892.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1HNN X-ray 2.40 A/B 1-282 [» ]
1N7I X-ray 2.80 A/B 1-282 [» ]
1N7J X-ray 2.70 A/B 1-282 [» ]
1YZ3 X-ray 2.40 A/B 1-282 [» ]
2AN3 X-ray 2.20 A/B 1-282 [» ]
2AN4 X-ray 2.20 A/B 1-282 [» ]
2AN5 X-ray 2.50 A/B 1-282 [» ]
2G70 X-ray 2.40 A/B 1-282 [» ]
2G71 X-ray 2.20 A/B 1-282 [» ]
2G72 X-ray 2.00 A/B 1-282 [» ]
2G8N X-ray 2.15 A/B 1-282 [» ]
2OBF X-ray 2.30 A/B 1-282 [» ]
2ONY X-ray 2.60 A/B 1-282 [» ]
2ONZ X-ray 2.80 A/B 1-282 [» ]
2OPB X-ray 2.80 A/B 1-282 [» ]
3HCA X-ray 2.40 A/B 1-282 [» ]
3HCB X-ray 2.40 A/B 1-282 [» ]
3HCC X-ray 2.30 A/B 1-282 [» ]
3HCD X-ray 2.39 A/B 1-282 [» ]
3HCE X-ray 2.85 A/B 1-282 [» ]
3HCF X-ray 2.70 A/B 1-282 [» ]
3KPJ X-ray 2.50 A/B 1-282 [» ]
3KPU X-ray 2.40 A/B 1-282 [» ]
3KPV X-ray 2.40 A/B 1-282 [» ]
3KPW X-ray 2.40 A/B 1-282 [» ]
3KPY X-ray 2.40 A/B 1-282 [» ]
3KQM X-ray 2.40 A/B 1-282 [» ]
3KQO X-ray 2.40 A/B 1-282 [» ]
3KQP X-ray 2.40 A/B 1-282 [» ]
3KQQ X-ray 2.50 A/B 1-282 [» ]
3KQS X-ray 2.00 A/B 1-282 [» ]
3KQT X-ray 2.40 A/B 1-282 [» ]
3KQV X-ray 2.30 A/B 1-282 [» ]
3KQW X-ray 2.49 A/B 1-282 [» ]
3KQY X-ray 2.20 A/B 1-282 [» ]
3KR0 X-ray 2.60 A/B 1-282 [» ]
3KR1 X-ray 2.30 A/B 1-282 [» ]
3KR2 X-ray 2.30 A/B 1-282 [» ]
4DM3 X-ray 2.40 A/B 1-282 [» ]
4MIK X-ray 1.95 A/B 1-282 [» ]
ProteinModelPortali P11086.
SMRi P11086. Positions 14-281.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 111410. 2 interactions.
STRINGi 9606.ENSP00000269582.

Chemistry

BindingDBi P11086.
ChEMBLi CHEMBL4617.
GuidetoPHARMACOLOGYi 2496.

PTM databases

PhosphoSitei P11086.

Polymorphism databases

DMDMi 130375.

Proteomic databases

PRIDEi P11086.

Protocols and materials databases

DNASUi 5409.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000269582 ; ENSP00000269582 ; ENSG00000141744 .
GeneIDi 5409.
KEGGi hsa:5409.
UCSCi uc002hsi.2. human.

Organism-specific databases

CTDi 5409.
GeneCardsi GC17P037824.
HGNCi HGNC:9160. PNMT.
HPAi CAB017029.
HPA043412.
HPA051005.
MIMi 171190. gene.
neXtProti NX_P11086.
PharmGKBi PA274.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG78422.
GeneTreei ENSGT00390000011708.
HOGENOMi HOG000013229.
HOVERGENi HBG000797.
InParanoidi P11086.
KOi K00553.
OMAi EESWYLA.
PhylomeDBi P11086.
TreeFami TF313114.

Enzyme and pathway databases

UniPathwayi UPA00749 ; UER00736 .
BioCyci MetaCyc:HS06868-MONOMER.
Reactomei REACT_15551. Catecholamine biosynthesis.

Miscellaneous databases

EvolutionaryTracei P11086.
GenomeRNAii 5409.
NextBioi 20943.
PROi P11086.
SOURCEi Search...

Gene expression databases

Bgeei P11086.
CleanExi HS_PNMT.
ExpressionAtlasi P11086. baseline and differential.
Genevestigatori P11086.

Family and domain databases

Gene3Di 3.40.50.150. 1 hit.
InterProi IPR025820. NNMT/PNMT/TEMT_CS.
IPR000940. NNMT_TEMT_trans.
IPR029063. SAM-dependent_MTases-like.
[Graphical view ]
PANTHERi PTHR10867. PTHR10867. 1 hit.
Pfami PF01234. NNMT_PNMT_TEMT. 1 hit.
[Graphical view ]
PIRSFi PIRSF000384. PNMTase. 1 hit.
SUPFAMi SSF53335. SSF53335. 1 hit.
PROSITEi PS01100. NNMT_PNMT_TEMT. 1 hit.
PS51681. SAM_MT_NNMT_PNMT_TEMT. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: October 29, 2014
This is version 146 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