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P22734

- COMT_RAT

UniProt

P22734 - COMT_RAT

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Protein

Catechol O-methyltransferase

Gene
Comt
Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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 enzyme

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei85 – 851S-adenosyl-L-methionine; via amide nitrogen
Binding sitei107 – 1071S-adenosyl-L-methionine By similarity
Binding sitei115 – 1151S-adenosyl-L-methionine
Binding sitei133 – 1331S-adenosyl-L-methionine
Binding sitei134 – 1341S-adenosyl-L-methionine; via amide nitrogen By similarity
Binding sitei162 – 1621S-adenosyl-L-methionine; via amide nitrogen By similarity
Metal bindingi184 – 1841Magnesium
Binding sitei184 – 1841S-adenosyl-L-methionine
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: RGD

GO - Biological processi

  1. catecholamine metabolic process Source: RGD
  2. dopamine catabolic process Source: Ensembl
  3. dopamine metabolic process Source: RGD
  4. estrogen metabolic process Source: RGD
  5. female pregnancy Source: RGD
  6. learning Source: RGD
  7. multicellular organismal reproductive process Source: RGD
  8. negative regulation of dopamine metabolic process 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. response to drug Source: RGD
  13. response to lipopolysaccharide Source: RGD
  14. response to organic cyclic compound Source: RGD
  15. response to pain Source: RGD
  16. S-adenosylhomocysteine metabolic process Source: RGD
  17. S-adenosylmethionine metabolic process Source: RGD
Complete GO annotation...

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

Topology

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

GO - Cellular componenti

  1. integral component of membrane Source: UniProtKB-KW
  2. membrane Source: RGD
  3. mitochondrion Source: Ensembl
  4. plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

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.

Miscellaneous databases

EvolutionaryTraceiP22734.

Family & Domainsi

Region

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

Sequence similaritiesi

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. VSP_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

« Hide 'large scale' publications
  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: September 3, 2014
This is version 152 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

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