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Protein

Phenylethanolamine N-methyltransferase

Gene

PNMT

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

    Keywordsi

    Molecular functionMethyltransferase, Transferase
    Biological processCatecholamine biosynthesis
    LigandS-adenosyl-L-methionine

    Enzyme and pathway databases

    BioCyciMetaCyc:HS06868-MONOMER
    BRENDAi2.1.1.28 2681
    ReactomeiR-HSA-209905 Catecholamine biosynthesis
    UniPathwayi
    UPA00749;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

    EuPathDBiHostDB:ENSG00000141744.3
    HGNCiHGNC:9160 PNMT
    MIMi171190 gene
    neXtProtiNX_P11086

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    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
    DrugBankiDB08129 (1R)-2-amino-1-[3-(trifluoromethyl)phenyl]ethanol
    DB01752 S-Adenosyl-L-Homocysteine
    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
    ProteomicsDBi52692

    PTM databases

    iPTMnetiP11086
    PhosphoSitePlusiP11086

    Expressioni

    Gene expression databases

    BgeeiENSG00000141744 Expressed in 153 organ(s), highest expression level in right adrenal gland
    CleanExiHS_PNMT
    ExpressionAtlasiP11086 baseline and differential
    GenevisibleiP11086 HS

    Organism-specific databases

    HPAiCAB017029
    HPA043412
    HPA051005

    Interactioni

    Protein-protein interaction databases

    BioGridi111410, 3 interactors
    IntActiP11086, 4 interactors
    STRINGi9606.ENSP00000269582

    Chemistry databases

    BindingDBiP11086

    Structurei

    Secondary structure

    1282
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    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
    OMAiSACAHFE
    OrthoDBiEOG091G0EF7
    PhylomeDBiP11086
    TreeFamiTF313114

    Family and domain databases

    InterProiView protein in InterPro
    IPR025820 NNMT/PNMT/TEMT_CS
    IPR000940 NNMT_TEMT_trans
    IPR029063 SAM-dependent_MTases
    PANTHERiPTHR10867 PTHR10867, 1 hit
    PfamiView protein in Pfam
    PF01234 NNMT_PNMT_TEMT, 1 hit
    PIRSFiPIRSF000384 PNMTase, 1 hit
    SUPFAMiSSF53335 SSF53335, 1 hit
    PROSITEiView protein in PROSITE
    PS01100 NNMT_PNMT_TEMT, 1 hit
    PS51681 SAM_MT_NNMT_PNMT_TEMT, 1 hit

    Sequence (1+)i

    Sequence statusi: Complete.

    This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

    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

    Computationally mapped potential isoform sequencesi

    There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    A8MT87A8MT87_HUMAN
    Phenylethanolamine N-methyltransfer...
    PNMT
    184Annotation score:
    J3QRI3J3QRI3_HUMAN
    Phenylethanolamine N-methyltransfer...
    PNMT
    137Annotation score:

    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 → S1 PublicationCorresponds to variant dbSNP:rs11569781Ensembl.1
    Natural variantiVAR_03682998T → A Lower activity levels than wild-type. 1 PublicationCorresponds to variant dbSNP:rs36060376Ensembl.1
    Natural variantiVAR_036830112R → C1 PublicationCorresponds to variant dbSNP:rs34530498Ensembl.1
    Natural variantiVAR_036831175A → T1 PublicationCorresponds to variant dbSNP:rs34341496Ensembl.1
    Natural variantiVAR_037611188S → C. Corresponds to variant dbSNP:rs5639Ensembl.1
    Natural variantiVAR_037612211L → H. Corresponds to variant dbSNP:rs5640Ensembl.1
    Natural variantiVAR_037613217L → Q. Corresponds to variant dbSNP:rs5641Ensembl.1
    Natural variantiVAR_037614254R → H. Corresponds to variant dbSNP:rs5642Ensembl.1
    Natural variantiVAR_024547276W → R. Corresponds to variant dbSNP:rs5643Ensembl.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

    Similar proteinsi

    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, 4 interactors
    STRINGi9606.ENSP00000269582

    Chemistry databases

    BindingDBiP11086
    ChEMBLiCHEMBL4617
    DrugBankiDB08129 (1R)-2-amino-1-[3-(trifluoromethyl)phenyl]ethanol
    DB01752 S-Adenosyl-L-Homocysteine
    GuidetoPHARMACOLOGYi2496

    PTM databases

    iPTMnetiP11086
    PhosphoSitePlusiP11086

    Polymorphism and mutation databases

    DMDMi130375

    Proteomic databases

    PaxDbiP11086
    PeptideAtlasiP11086
    PRIDEiP11086
    ProteomicsDBi52692

    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
    EuPathDBiHostDB:ENSG00000141744.3
    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
    OMAiSACAHFE
    OrthoDBiEOG091G0EF7
    PhylomeDBiP11086
    TreeFamiTF313114

    Enzyme and pathway databases

    UniPathwayi
    UPA00749;UER00736

    BioCyciMetaCyc:HS06868-MONOMER
    BRENDAi2.1.1.28 2681
    ReactomeiR-HSA-209905 Catecholamine biosynthesis

    Miscellaneous databases

    EvolutionaryTraceiP11086
    GenomeRNAii5409
    PROiPR:P11086
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000141744 Expressed in 153 organ(s), highest expression level in right adrenal gland
    CleanExiHS_PNMT
    ExpressionAtlasiP11086 baseline and differential
    GenevisibleiP11086 HS

    Family and domain databases

    InterProiView protein in InterPro
    IPR025820 NNMT/PNMT/TEMT_CS
    IPR000940 NNMT_TEMT_trans
    IPR029063 SAM-dependent_MTases
    PANTHERiPTHR10867 PTHR10867, 1 hit
    PfamiView protein in Pfam
    PF01234 NNMT_PNMT_TEMT, 1 hit
    PIRSFiPIRSF000384 PNMTase, 1 hit
    SUPFAMiSSF53335 SSF53335, 1 hit
    PROSITEiView protein in PROSITE
    PS01100 NNMT_PNMT_TEMT, 1 hit
    PS51681 SAM_MT_NNMT_PNMT_TEMT, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiPNMT_HUMAN
    AccessioniPrimary (citable) accession number: P11086
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1989
    Last sequence update: July 1, 1989
    Last modified: September 12, 2018
    This is version 172 of the entry and version 1 of the sequence. See 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 entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    2. SIMILARITY comments
      Index of protein domains and families
    3. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    4. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    5. Human chromosome 17
      Human chromosome 17: entries, gene names and cross-references to MIM
    6. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    7. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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