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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: (R)-adrenaline biosynthesis

    This protein is involved in step 1 of the subpathway that synthesizes (R)-adrenaline from (R)-noradrenaline.
    Proteins known to be involved in this subpathway in this organism are:
    1. Phenylethanolamine N-methyltransferase (PNMT)
    This subpathway is part of the pathway (R)-adrenaline biosynthesis, which is itself part of Catecholamine biosynthesis.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes (R)-adrenaline from (R)-noradrenaline, the pathway (R)-adrenaline biosynthesis and in Catecholamine biosynthesis.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei35S-adenosyl-L-methionine1
    Binding sitei40S-adenosyl-L-methionine1
    Binding sitei85S-adenosyl-L-methionine1
    Binding sitei101S-adenosyl-L-methionine1
    Binding sitei106S-adenosyl-L-methionine1
    Binding sitei181S-adenosyl-L-methionine; via carbonyl oxygen1
    Binding sitei219Substrate1

    GO - Molecular functioni

    GO - Biological processi

    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.
    ZFISH:HS06868-MONOMER.
    BRENDAi2.1.1.28. 2681.
    ReactomeiR-HSA-209905. 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
    Proteomesi
    • UP000005640 Componenti: Chromosome 17

    Organism-specific databases

    HGNCiHGNC:9160. PNMT.

    Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation...

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi35Y → F: Strongly increases KM for substrate and S-adenosyl-L-methionine. 1 Publication1
    Mutagenesisi185E → A or Q: Strongly reduced enzyme activity. Increases affinity for S-adenosyl-L-methionine. 1 Publication1
    Mutagenesisi185E → D: Strongly reduced enzyme activity. Decreases affinity for substrate and S-adenosyl-L-methionine 3-fold. 1 Publication1
    Mutagenesisi219E → A: Reduced enzyme activity. Decreases affinity for substrate 6-fold. Decreases affinity for S-adenosyl-L-methionine 2-fold. 1 Publication1
    Mutagenesisi267D → A or N: Strongly reduced enzyme activity. Decreases affinity for substrate 200-fold. Decreases affinity for S-adenosyl-L-methionine 3-fold. 1 Publication1

    Organism-specific databases

    DisGeNETi5409.
    OpenTargetsiENSG00000141744.
    PharmGKBiPA274.

    Chemistry databases

    ChEMBLiCHEMBL4617.
    GuidetoPHARMACOLOGYi2496.

    Polymorphism and mutation databases

    DMDMi130375.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00001597091 – 282Phenylethanolamine N-methyltransferaseAdd BLAST282

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei7PhosphoserineCombined sources1

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PaxDbiP11086.
    PeptideAtlasiP11086.
    PRIDEiP11086.

    PTM databases

    iPTMnetiP11086.
    PhosphoSitePlusiP11086.

    Expressioni

    Gene expression databases

    BgeeiENSG00000141744.
    CleanExiHS_PNMT.
    ExpressionAtlasiP11086. baseline and differential.
    GenevisibleiP11086. HS.

    Organism-specific databases

    HPAiCAB017029.
    HPA043412.
    HPA051005.

    Interactioni

    Protein-protein interaction databases

    BioGridi111410. 3 interactors.
    IntActiP11086. 3 interactors.
    STRINGi9606.ENSP00000269582.

    Chemistry databases

    BindingDBiP11086.

    Structurei

    Secondary structure

    1282
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi17 – 25Combined sources9
    Helixi27 – 29Combined sources3
    Helixi32 – 40Combined sources9
    Turni42 – 45Combined sources4
    Helixi53 – 66Combined sources14
    Beta strandi73 – 79Combined sources7
    Helixi85 – 87Combined sources3
    Helixi90 – 92Combined sources3
    Beta strandi95 – 100Combined sources6
    Helixi104 – 114Combined sources11
    Helixi124 – 134Combined sources11
    Helixi140 – 150Combined sources11
    Beta strandi151 – 155Combined sources5
    Beta strandi161 – 163Combined sources3
    Beta strandi173 – 182Combined sources10
    Turni184 – 186Combined sources3
    Helixi191 – 202Combined sources12
    Beta strandi205 – 218Combined sources14
    Beta strandi221 – 224Combined sources4
    Beta strandi227 – 230Combined sources4
    Helixi236 – 246Combined sources11
    Beta strandi248 – 257Combined sources10
    Helixi260 – 262Combined sources3
    Beta strandi265 – 267Combined sources3
    Beta strandi271 – 279Combined sources9

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB 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.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP11086.

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni79 – 80S-adenosyl-L-methionine binding2
    Regioni158 – 159S-adenosyl-L-methionine binding2

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiENOG410IJGY. Eukaryota.
    ENOG4111F9R. LUCA.
    GeneTreeiENSGT00390000011708.
    HOGENOMiHOG000013229.
    HOVERGENiHBG000797.
    InParanoidiP11086.
    KOiK00553.
    OMAiFAWAQKK.
    OrthoDBiEOG091G0EF7.
    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)DescriptionActionsGraphical viewLength
    Sequence conflicti169 – 170SP → AQ in AAA60131 (PubMed:2835776).Curated2

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_0293519N → S.1 PublicationCorresponds to variant rs11569781dbSNPEnsembl.1
    Natural variantiVAR_03682998T → A Lower activity levels than wild-type. 1 PublicationCorresponds to variant rs36060376dbSNPEnsembl.1
    Natural variantiVAR_036830112R → C.1 PublicationCorresponds to variant rs34530498dbSNPEnsembl.1
    Natural variantiVAR_036831175A → T.1 PublicationCorresponds to variant rs34341496dbSNPEnsembl.1
    Natural variantiVAR_037611188S → C.Corresponds to variant rs5639dbSNPEnsembl.1
    Natural variantiVAR_037612211L → H.Corresponds to variant rs5640dbSNPEnsembl.1
    Natural variantiVAR_037613217L → Q.Corresponds to variant rs5641dbSNPEnsembl.1
    Natural variantiVAR_037614254R → H.Corresponds to variant rs5642dbSNPEnsembl.1
    Natural variantiVAR_024547276W → R.Corresponds to variant rs5643dbSNPEnsembl.1

    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.3. human.

    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
    PDB 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.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi111410. 3 interactors.
    IntActiP11086. 3 interactors.
    STRINGi9606.ENSP00000269582.

    Chemistry databases

    BindingDBiP11086.
    ChEMBLiCHEMBL4617.
    GuidetoPHARMACOLOGYi2496.

    PTM databases

    iPTMnetiP11086.
    PhosphoSitePlusiP11086.

    Polymorphism and mutation databases

    DMDMi130375.

    Proteomic databases

    PaxDbiP11086.
    PeptideAtlasiP11086.
    PRIDEiP11086.

    Protocols and materials databases

    DNASUi5409.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000269582; ENSP00000269582; ENSG00000141744.
    GeneIDi5409.
    KEGGihsa:5409.
    UCSCiuc002hsi.3. human.

    Organism-specific databases

    CTDi5409.
    DisGeNETi5409.
    GeneCardsiPNMT.
    HGNCiHGNC:9160. PNMT.
    HPAiCAB017029.
    HPA043412.
    HPA051005.
    MIMi171190. gene.
    neXtProtiNX_P11086.
    OpenTargetsiENSG00000141744.
    PharmGKBiPA274.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiENOG410IJGY. Eukaryota.
    ENOG4111F9R. LUCA.
    GeneTreeiENSGT00390000011708.
    HOGENOMiHOG000013229.
    HOVERGENiHBG000797.
    InParanoidiP11086.
    KOiK00553.
    OMAiFAWAQKK.
    OrthoDBiEOG091G0EF7.
    PhylomeDBiP11086.
    TreeFamiTF313114.

    Enzyme and pathway databases

    UniPathwayiUPA00749; UER00736.
    BioCyciMetaCyc:HS06868-MONOMER.
    ZFISH:HS06868-MONOMER.
    BRENDAi2.1.1.28. 2681.
    ReactomeiR-HSA-209905. Catecholamine biosynthesis.

    Miscellaneous databases

    EvolutionaryTraceiP11086.
    GenomeRNAii5409.
    PROiP11086.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000141744.
    CleanExiHS_PNMT.
    ExpressionAtlasiP11086. baseline and differential.
    GenevisibleiP11086. HS.

    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...

    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: November 30, 2016
    This is version 165 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

    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 one 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.