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P22734

- COMT_RAT

UniProt

P22734 - COMT_RAT

Protein

Catechol O-methyltransferase

Gene

Comt

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 153 (01 Oct 2014)
      Sequence version 2 (01 May 1992)
      Previous versions | rss
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    Functioni

    Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like L-DOPA, alpha-methyl DOPA and isoproterenol.

    Catalytic activityi

    S-adenosyl-L-methionine + a catechol = S-adenosyl-L-homocysteine + a guaiacol.

    Cofactori

    Binds 1 magnesium ion per subunit.

    Kineticsi

    1. KM=30 µM for S-adenosyl-L-methionine1 Publication

    Vmax=377 nmol/h/mg enzyme1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei85 – 851S-adenosyl-L-methionine; via amide nitrogen1 PublicationPROSITE-ProRule annotation
    Binding sitei107 – 1071S-adenosyl-L-methioninePROSITE-ProRule annotation
    Binding sitei115 – 1151S-adenosyl-L-methionine1 PublicationPROSITE-ProRule annotation
    Binding sitei133 – 1331S-adenosyl-L-methionine1 PublicationPROSITE-ProRule annotation
    Binding sitei134 – 1341S-adenosyl-L-methionine; via amide nitrogenPROSITE-ProRule annotation
    Binding sitei162 – 1621S-adenosyl-L-methionine; via amide nitrogenPROSITE-ProRule annotation
    Metal bindingi184 – 1841Magnesium
    Binding sitei184 – 1841S-adenosyl-L-methionine1 PublicationPROSITE-ProRule annotation
    Binding sitei187 – 1871Substrate
    Metal bindingi212 – 2121Magnesium
    Metal bindingi213 – 2131Magnesium
    Binding sitei213 – 2131Substrate
    Binding sitei242 – 2421Substrate

    GO - Molecular functioni

    1. catechol O-methyltransferase activity Source: RGD
    2. magnesium ion binding Source: InterPro

    GO - Biological processi

    1. developmental process Source: RGD
    2. dopamine catabolic process Source: Ensembl
    3. estrogen metabolic process Source: RGD
    4. female pregnancy Source: RGD
    5. learning Source: RGD
    6. multicellular organismal reproductive process Source: RGD
    7. negative regulation of dopamine metabolic process Source: RGD
    8. negative regulation of renal sodium excretion Source: RGD
    9. negative regulation of smooth muscle cell proliferation Source: RGD
    10. neurotransmitter catabolic process Source: UniProtKB-KW
    11. positive regulation of homocysteine metabolic process Source: RGD
    12. regulation of sensory perception of pain Source: RGD
    13. response to drug Source: RGD
    14. response to lipopolysaccharide Source: RGD
    15. response to organic cyclic compound Source: RGD
    16. response to pain Source: RGD
    17. S-adenosylhomocysteine metabolic process Source: RGD
    18. S-adenosylmethionine metabolic process Source: RGD
    19. short-term memory Source: RGD

    Keywords - Molecular functioni

    Methyltransferase, Transferase

    Keywords - Biological processi

    Catecholamine metabolism, Neurotransmitter degradation

    Keywords - Ligandi

    Magnesium, Metal-binding, S-adenosyl-L-methionine

    Enzyme and pathway databases

    BioCyciMetaCyc:MONOMER-15100.
    SABIO-RKP22734.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Catechol O-methyltransferase (EC:2.1.1.6)
    Gene namesi
    Name:Comt
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Chromosome 11

    Organism-specific databases

    RGDi2379. Comt.

    Subcellular locationi

    GO - Cellular componenti

    1. axon Source: RGD
    2. cell body Source: RGD
    3. cytosol Source: RGD
    4. dendrite Source: RGD
    5. dendritic spine Source: RGD
    6. integral component of membrane Source: UniProtKB-KW
    7. membrane Source: RGD
    8. mitochondrion Source: Ensembl
    9. postsynaptic membrane Source: RGD

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 264264Catechol O-methyltransferasePRO_0000020975Add
    BLAST

    Post-translational modificationi

    The N-terminus is blocked.

    Proteomic databases

    PaxDbiP22734.
    PRIDEiP22734.

    PTM databases

    PhosphoSiteiP22734.

    Expressioni

    Gene expression databases

    ArrayExpressiP22734.
    GenevestigatoriP22734.

    Interactioni

    Protein-protein interaction databases

    MINTiMINT-4567724.
    STRINGi10116.ENSRNOP00000043148.

    Structurei

    Secondary structure

    1
    264
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi48 – 5912
    Helixi65 – 7915
    Helixi82 – 843
    Helixi87 – 10014
    Beta strandi103 – 1086
    Beta strandi111 – 1133
    Helixi114 – 1207
    Beta strandi128 – 1347
    Helixi136 – 14914
    Helixi152 – 1543
    Beta strandi155 – 1606
    Helixi162 – 1654
    Helixi166 – 1683
    Helixi169 – 1724
    Beta strandi179 – 1835
    Helixi187 – 1893
    Helixi190 – 19910
    Beta strandi208 – 2125
    Helixi214 – 2185
    Helixi220 – 2289
    Beta strandi232 – 24110
    Turni242 – 2454
    Beta strandi246 – 25510

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1H1DX-ray2.00A44-264[»]
    1JR4X-ray2.63A44-264[»]
    1VIDX-ray2.00A44-264[»]
    2CL5X-ray1.60A/B44-264[»]
    2ZLBX-ray2.20A44-264[»]
    2ZTHX-ray2.60A44-264[»]
    2ZVJX-ray2.30A44-264[»]
    3A7DX-ray2.40A44-264[»]
    3HVHX-ray1.30A44-264[»]
    3HVIX-ray1.20A44-264[»]
    3HVJX-ray1.79A/B44-264[»]
    3HVKX-ray1.30A44-264[»]
    3NW9X-ray1.65A44-264[»]
    3NWBX-ray1.30A44-264[»]
    3NWEX-ray1.50A44-264[»]
    3OE4X-ray1.49A44-264[»]
    3OE5X-ray1.52A44-264[»]
    3OZRX-ray1.73A44-264[»]
    3OZSX-ray1.44A44-264[»]
    3OZTX-ray1.48A44-264[»]
    3R6TX-ray1.20A44-264[»]
    3S68X-ray1.85A44-264[»]
    3U81X-ray1.13A44-264[»]
    4P7GX-ray2.58A/B/C/D44-264[»]
    4P7JX-ray1.45A44-264[»]
    4P7KX-ray1.22A44-264[»]
    4PYLX-ray2.20A44-264[»]
    4PYMX-ray1.19A44-264[»]
    4PYNX-ray1.20A44-264[»]
    4PYOX-ray2.10A/B44-264[»]
    4PYQX-ray1.39A/B44-264[»]
    ProteinModelPortaliP22734.
    SMRiP22734. Positions 45-258.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP22734.

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei3 – 1917Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni160 – 1634S-adenosyl-L-methionine binding

    Sequence similaritiesi

    Belongs to the class I-like SAM-binding methyltransferase superfamily. Cation-dependent O-methyltransferase family.PROSITE-ProRule annotation

    Keywords - Domaini

    Signal-anchor, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG4122.
    GeneTreeiENSGT00390000011316.
    HOGENOMiHOG000046392.
    HOVERGENiHBG005376.
    InParanoidiP22734.
    KOiK00545.
    OMAiCTHYSSY.
    OrthoDBiEOG7PZRZJ.
    PhylomeDBiP22734.
    TreeFamiTF329140.

    Family and domain databases

    Gene3Di3.40.50.150. 1 hit.
    InterProiIPR025782. Catechol_O-MeTrfase.
    IPR017128. Catechol_O-MeTrfase_euk.
    IPR002935. O-MeTrfase_3.
    IPR029063. SAM-dependent_MTases-like.
    [Graphical view]
    PANTHERiPTHR10509. PTHR10509. 1 hit.
    PfamiPF01596. Methyltransf_3. 1 hit.
    [Graphical view]
    PIRSFiPIRSF037177. Catechol_O-mtfrase_euk. 1 hit.
    SUPFAMiSSF53335. SSF53335. 1 hit.
    PROSITEiPS51682. SAM_OMT_I. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative initiation. Align

    Isoform 1 (identifier: P22734-1) [UniParc]FASTAAdd to Basket

    Also known as: Membrane-bound, MB-COMT

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MPLAAVSLGL LLLALLLLLR HLGWGLVTIF WFEYVLQPVH NLIMGDTKEQ    50
    RILRYVQQNA KPGDPQSVLE AIDTYCTQKE WAMNVGDAKG QIMDAVIREY 100
    SPSLVLELGA YCGYSAVRMA RLLQPGARLL TMEMNPDYAA ITQQMLNFAG 150
    LQDKVTILNG ASQDLIPQLK KKYDVDTLDM VFLDHWKDRY LPDTLLLEKC 200
    GLLRKGTVLL ADNVIVPGTP DFLAYVRGSS SFECTHYSSY LEYMKVVDGL 250
    EKAIYQGPSS PDKS 264
    Length:264
    Mass (Da):29,597
    Last modified:May 1, 1992 - v2
    Checksum:iF535DFF49C062854
    GO
    Isoform 2 (identifier: P22734-2) [UniParc]FASTAAdd to Basket

    Also known as: Soluble, S-COMT

    The sequence of this isoform differs from the canonical sequence as follows:
         1-43: Missing.

    Show »
    Length:221
    Mass (Da):24,747
    Checksum:iC797794F205FA41D
    GO

    Sequence cautioni

    The sequence AAA40881.1 differs from that shown. Reason: Erroneous initiation.
    The sequence AAA40882.1 differs from that shown. Reason: Erroneous initiation.

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 4343Missing in isoform 2. CuratedVSP_018780Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Z12651 Genomic DNA. Translation: CAA78276.1.
    M60754 Genomic DNA. Translation: AAA40882.1. Different initiation.
    BC081850 mRNA. Translation: AAH81850.1.
    M60753 mRNA. Translation: AAA40881.1. Different initiation.
    PIRiS22090.
    RefSeqiNP_036663.1. NM_012531.2. [P22734-1]
    XP_006248665.1. XM_006248603.1.
    UniGeneiRn.220.

    Genome annotation databases

    EnsembliENSRNOT00000050269; ENSRNOP00000043148; ENSRNOG00000001889. [P22734-1]
    GeneIDi24267.
    KEGGirno:24267.

    Keywords - Coding sequence diversityi

    Alternative initiation

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Z12651 Genomic DNA. Translation: CAA78276.1 .
    M60754 Genomic DNA. Translation: AAA40882.1 . Different initiation.
    BC081850 mRNA. Translation: AAH81850.1 .
    M60753 mRNA. Translation: AAA40881.1 . Different initiation.
    PIRi S22090.
    RefSeqi NP_036663.1. NM_012531.2. [P22734-1 ]
    XP_006248665.1. XM_006248603.1.
    UniGenei Rn.220.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1H1D X-ray 2.00 A 44-264 [» ]
    1JR4 X-ray 2.63 A 44-264 [» ]
    1VID X-ray 2.00 A 44-264 [» ]
    2CL5 X-ray 1.60 A/B 44-264 [» ]
    2ZLB X-ray 2.20 A 44-264 [» ]
    2ZTH X-ray 2.60 A 44-264 [» ]
    2ZVJ X-ray 2.30 A 44-264 [» ]
    3A7D X-ray 2.40 A 44-264 [» ]
    3HVH X-ray 1.30 A 44-264 [» ]
    3HVI X-ray 1.20 A 44-264 [» ]
    3HVJ X-ray 1.79 A/B 44-264 [» ]
    3HVK X-ray 1.30 A 44-264 [» ]
    3NW9 X-ray 1.65 A 44-264 [» ]
    3NWB X-ray 1.30 A 44-264 [» ]
    3NWE X-ray 1.50 A 44-264 [» ]
    3OE4 X-ray 1.49 A 44-264 [» ]
    3OE5 X-ray 1.52 A 44-264 [» ]
    3OZR X-ray 1.73 A 44-264 [» ]
    3OZS X-ray 1.44 A 44-264 [» ]
    3OZT X-ray 1.48 A 44-264 [» ]
    3R6T X-ray 1.20 A 44-264 [» ]
    3S68 X-ray 1.85 A 44-264 [» ]
    3U81 X-ray 1.13 A 44-264 [» ]
    4P7G X-ray 2.58 A/B/C/D 44-264 [» ]
    4P7J X-ray 1.45 A 44-264 [» ]
    4P7K X-ray 1.22 A 44-264 [» ]
    4PYL X-ray 2.20 A 44-264 [» ]
    4PYM X-ray 1.19 A 44-264 [» ]
    4PYN X-ray 1.20 A 44-264 [» ]
    4PYO X-ray 2.10 A/B 44-264 [» ]
    4PYQ X-ray 1.39 A/B 44-264 [» ]
    ProteinModelPortali P22734.
    SMRi P22734. Positions 45-258.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    MINTi MINT-4567724.
    STRINGi 10116.ENSRNOP00000043148.

    Chemistry

    BindingDBi P22734.
    ChEMBLi CHEMBL2372.

    PTM databases

    PhosphoSitei P22734.

    Proteomic databases

    PaxDbi P22734.
    PRIDEi P22734.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSRNOT00000050269 ; ENSRNOP00000043148 ; ENSRNOG00000001889 . [P22734-1 ]
    GeneIDi 24267.
    KEGGi rno:24267.

    Organism-specific databases

    CTDi 1312.
    RGDi 2379. Comt.

    Phylogenomic databases

    eggNOGi COG4122.
    GeneTreei ENSGT00390000011316.
    HOGENOMi HOG000046392.
    HOVERGENi HBG005376.
    InParanoidi P22734.
    KOi K00545.
    OMAi CTHYSSY.
    OrthoDBi EOG7PZRZJ.
    PhylomeDBi P22734.
    TreeFami TF329140.

    Enzyme and pathway databases

    BioCyci MetaCyc:MONOMER-15100.
    SABIO-RK P22734.

    Miscellaneous databases

    EvolutionaryTracei P22734.
    NextBioi 602825.
    PROi P22734.

    Gene expression databases

    ArrayExpressi P22734.
    Genevestigatori P22734.

    Family and domain databases

    Gene3Di 3.40.50.150. 1 hit.
    InterProi IPR025782. Catechol_O-MeTrfase.
    IPR017128. Catechol_O-MeTrfase_euk.
    IPR002935. O-MeTrfase_3.
    IPR029063. SAM-dependent_MTases-like.
    [Graphical view ]
    PANTHERi PTHR10509. PTHR10509. 1 hit.
    Pfami PF01596. Methyltransf_3. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF037177. Catechol_O-mtfrase_euk. 1 hit.
    SUPFAMi SSF53335. SSF53335. 1 hit.
    PROSITEi PS51682. SAM_OMT_I. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Production of rat soluble and membrane-bound catechol O-methyltransferase forms from bifunctional mRNAs."
      Tenhunen J., Ulmanen I.
      Biochem. J. 296:595-600(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE INITIATION.
      Tissue: Liver.
    2. "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] (ISOFORM 1).
      Tissue: Heart.
    3. "Molecular cloning and characterization of rat liver catechol-O-methyltransferase."
      Salminen M., Lundstroem K., Tilgmann C., Savolainen R., Kalkkinen N., Ulmanen I.
      Gene 93:241-247(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 11-264.
    4. "Cell-free synthesis of rat and human catechol O-methyltransferase. Insertion of the membrane-bound form into microsomal membranes in vitro."
      Ulmanen I., Lundstroem K.
      Eur. J. Biochem. 202:1013-1020(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-10, CHARACTERIZATION OF THE TWO FORMS.
    5. "Crystal structure of catechol O-methyltransferase."
      Vidgren J., Svensson L.A., Liljas A.
      Nature 368:354-358(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 44-264.
    6. "Structure-based design, synthesis, and in vitro evaluation of bisubstrate inhibitors for catechol O-methyltransferase (COMT)."
      Masjost B., Ballmer P., Borroni E., Zuercher G., Winkler F.K., Jakob-Roetne R., Diederich F.
      Chemistry 6:971-982(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.63 ANGSTROMS) OF 44-264 IN COMPLEX WITH SUBSTRATE ANALOG.
    7. "Kinetics and crystal structure of catechol-O-methyltransferase complex with co-substrate and a novel inhibitor with potential therapeutic application."
      Bonifacio M.J., Archer M., Rodrigues M.L., Matias P.M., Learmonth D.A., Carrondo M.A., Soares-da-Silva P.
      Mol. Pharmacol. 62:795-805(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 44-264 IN COMPLEX WITH S-ADENOSYL-L-METHIONINE AND SUBSTRATE ANALOG.
    8. "Comparative study of ortho- and meta-nitrated inhibitors of catechol-O-methyltransferase: interactions with the active site and regioselectivity of O-methylation."
      Palma P.N., Rodrigues M.L., Archer M., Bonifacio M.J., Loureiro A.I., Learmonth D.A., Carrondo M.A., Soares-da-Silva P.
      Mol. Pharmacol. 70:143-153(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 44-264 IN COMPLEX WITH SUBSTRATE ANALOG, BIOPHYSICOCHEMICAL PROPERTIES.

    Entry informationi

    Entry nameiCOMT_RAT
    AccessioniPrimary (citable) accession number: P22734
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1991
    Last sequence update: May 1, 1992
    Last modified: October 1, 2014
    This is version 153 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3