Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Catechol O-methyltransferase

Gene

Comt

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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

Mg2+Note: Binds 1 Mg2+ ion per subunit.

Kineticsi

  1. KM=30 µM for S-adenosyl-L-methionine1 Publication
  1. Vmax=377 nmol/h/mg enzyme1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei85S-adenosyl-L-methionine; via amide nitrogenPROSITE-ProRule annotation1 Publication1
Binding sitei107S-adenosyl-L-methioninePROSITE-ProRule annotation1
Binding sitei115S-adenosyl-L-methioninePROSITE-ProRule annotation1 Publication1
Binding sitei133S-adenosyl-L-methioninePROSITE-ProRule annotation1 Publication1
Binding sitei134S-adenosyl-L-methionine; via amide nitrogenPROSITE-ProRule annotation1
Binding sitei162S-adenosyl-L-methionine; via amide nitrogenPROSITE-ProRule annotation1
Metal bindingi184Magnesium1
Binding sitei184S-adenosyl-L-methioninePROSITE-ProRule annotation1 Publication1
Binding sitei187Substrate1
Metal bindingi212Magnesium1
Metal bindingi213Magnesium1
Binding sitei213Substrate1
Binding sitei242Substrate1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionMethyltransferase, Transferase
Biological processCatecholamine metabolism, Neurotransmitter degradation
LigandMagnesium, Metal-binding, S-adenosyl-L-methionine

Enzyme and pathway databases

BioCyciMetaCyc:MONOMER-15100
BRENDAi2.1.1.6 5301
ReactomeiR-RNO-156581 Methylation
R-RNO-379397 Enzymatic degradation of dopamine by COMT
R-RNO-379398 Enzymatic degradation of Dopamine by monoamine oxidase
SABIO-RKiP22734

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 11

Organism-specific databases

RGDi2379 Comt

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

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 2CytoplasmicSequence analysis2
Transmembranei3 – 19Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST17
Topological domaini20 – 264ExtracellularSequence analysisAdd BLAST245

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL2372
GuidetoPHARMACOLOGYi2472

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000209751 – 264Catechol O-methyltransferaseAdd BLAST264

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei259PhosphoserineCombined sources1
Modified residuei260PhosphoserineCombined sources1
Modified residuei264PhosphoserineCombined sources1

Post-translational modificationi

The N-terminus is blocked.

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP22734
PRIDEiP22734

PTM databases

iPTMnetiP22734
PhosphoSitePlusiP22734

Expressioni

Gene expression databases

BgeeiENSRNOG00000001889 Expressed in 10 organ(s), highest expression level in liver
ExpressionAtlasiP22734 baseline and differential
GenevisibleiP22734 RN

Interactioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000043148

Chemistry databases

BindingDBiP22734

Structurei

Secondary structure

1264
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP22734
SMRiP22734
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP22734

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni160 – 163S-adenosyl-L-methionine binding4

Sequence similaritiesi

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1663 Eukaryota
COG4122 LUCA
GeneTreeiENSGT00390000011316
HOGENOMiHOG000046392
HOVERGENiHBG005376
InParanoidiP22734
KOiK00545
OMAiSRFECTH
OrthoDBiEOG091G0GQK
PhylomeDBiP22734
TreeFamiTF329140

Family and domain databases

InterProiView protein in InterPro
IPR017128 Catechol_O-MeTrfase_euk
IPR002935 O-MeTrfase_3
IPR029063 SAM-dependent_MTases
PfamiView protein in Pfam
PF01596 Methyltransf_3, 1 hit
PIRSFiPIRSF037177 Catechol_O-mtfrase_euk, 1 hit
SUPFAMiSSF53335 SSF53335, 1 hit
PROSITEiView protein in PROSITE
PS51682 SAM_OMT_I, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative initiation. AlignAdd to basket
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
        10         20         30         40         50
MPLAAVSLGL LLLALLLLLR HLGWGLVTIF WFEYVLQPVH NLIMGDTKEQ
60 70 80 90 100
RILRYVQQNA KPGDPQSVLE AIDTYCTQKE WAMNVGDAKG QIMDAVIREY
110 120 130 140 150
SPSLVLELGA YCGYSAVRMA RLLQPGARLL TMEMNPDYAA ITQQMLNFAG
160 170 180 190 200
LQDKVTILNG ASQDLIPQLK KKYDVDTLDM VFLDHWKDRY LPDTLLLEKC
210 220 230 240 250
GLLRKGTVLL ADNVIVPGTP DFLAYVRGSS SFECTHYSSY LEYMKVVDGL
260
EKAIYQGPSS PDKS
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 differs from that shown. Reason: Erroneous initiation.Curated
The sequence AAA40882 differs from that shown. Reason: Erroneous initiation.Curated

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0187801 – 43Missing in isoform 2. CuratedAdd BLAST43

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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]
UniGeneiRn.220

Genome annotation databases

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

Keywords - Coding sequence diversityi

Alternative initiation

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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]
UniGeneiRn.220

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
5FHQX-ray1.63A46-258[»]
5FHRX-ray1.63A/B46-258[»]
5K01X-ray1.38A46-258[»]
5K03X-ray1.81A46-259[»]
5K05X-ray2.14A/B46-259[»]
5K09X-ray2.70A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X45-260[»]
5K0BX-ray2.36A/B/C/D/E/F/G/H45-261[»]
5K0CX-ray1.95A/B45-259[»]
5K0EX-ray2.30A45-259[»]
5K0FX-ray1.81A/B45-263[»]
5K0GX-ray1.89A/B45-264[»]
5K0JX-ray1.94A/B45-264[»]
5K0LX-ray2.02A/B/C/D45-263[»]
5K0NX-ray1.99A/B/C/D45-264[»]
5LQAX-ray1.20A46-258[»]
5LQCX-ray1.90A44-264[»]
5LQJX-ray2.41A/B/C/D44-264[»]
5LQKX-ray2.24A44-264[»]
5LQNX-ray1.72A44-264[»]
5LQRX-ray1.50A44-264[»]
5LQUX-ray1.80A/B44-264[»]
5LR6X-ray2.30A/B/C/D44-264[»]
5P8WX-ray2.03A/B/C44-264[»]
5P8XX-ray1.31A44-264[»]
5P8YX-ray1.42A44-264[»]
5P8ZX-ray1.42A44-264[»]
5P90X-ray1.24A44-264[»]
5P91X-ray1.20A44-264[»]
5P92X-ray1.61A44-264[»]
5P93X-ray1.24A44-264[»]
5P94X-ray1.20A44-264[»]
5P95X-ray1.30A44-264[»]
5P96X-ray1.40A44-264[»]
5P97X-ray1.30A44-264[»]
5P98X-ray1.20A44-264[»]
5P99X-ray1.20A44-264[»]
5P9AX-ray1.91A44-264[»]
5P9BX-ray1.45A44-264[»]
5P9CX-ray1.70A44-264[»]
5P9DX-ray1.42A44-264[»]
5P9EX-ray1.50A44-264[»]
5P9NX-ray1.17A44-264[»]
5P9OX-ray1.10A44-264[»]
5P9PX-ray1.12A44-264[»]
5P9QX-ray1.63A44-264[»]
5P9RX-ray1.70A/B44-264[»]
5P9SX-ray2.30A44-264[»]
5P9TX-ray1.24A44-264[»]
5P9UX-ray1.42A44-264[»]
5P9VX-ray1.04A44-264[»]
5P9WX-ray1.43A44-264[»]
5P9XX-ray1.12A44-264[»]
5P9YX-ray1.20A44-264[»]
5P9ZX-ray1.60A44-264[»]
5PA0X-ray1.26A44-264[»]
5PA1X-ray1.24A44-264[»]
5PA2X-ray1.12A44-264[»]
5PA3X-ray1.60A44-264[»]
5PA4X-ray1.99A44-264[»]
5PA5X-ray1.63A44-264[»]
5PA6X-ray1.29A44-264[»]
5PA7X-ray2.12A/B44-264[»]
ProteinModelPortaliP22734
SMRiP22734
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000043148

Chemistry databases

BindingDBiP22734
ChEMBLiCHEMBL2372
GuidetoPHARMACOLOGYi2472

PTM databases

iPTMnetiP22734
PhosphoSitePlusiP22734

Proteomic databases

PaxDbiP22734
PRIDEiP22734

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi1312
RGDi2379 Comt

Phylogenomic databases

eggNOGiKOG1663 Eukaryota
COG4122 LUCA
GeneTreeiENSGT00390000011316
HOGENOMiHOG000046392
HOVERGENiHBG005376
InParanoidiP22734
KOiK00545
OMAiSRFECTH
OrthoDBiEOG091G0GQK
PhylomeDBiP22734
TreeFamiTF329140

Enzyme and pathway databases

BioCyciMetaCyc:MONOMER-15100
BRENDAi2.1.1.6 5301
ReactomeiR-RNO-156581 Methylation
R-RNO-379397 Enzymatic degradation of dopamine by COMT
R-RNO-379398 Enzymatic degradation of Dopamine by monoamine oxidase
SABIO-RKiP22734

Miscellaneous databases

EvolutionaryTraceiP22734
PROiPR:P22734

Gene expression databases

BgeeiENSRNOG00000001889 Expressed in 10 organ(s), highest expression level in liver
ExpressionAtlasiP22734 baseline and differential
GenevisibleiP22734 RN

Family and domain databases

InterProiView protein in InterPro
IPR017128 Catechol_O-MeTrfase_euk
IPR002935 O-MeTrfase_3
IPR029063 SAM-dependent_MTases
PfamiView protein in Pfam
PF01596 Methyltransf_3, 1 hit
PIRSFiPIRSF037177 Catechol_O-mtfrase_euk, 1 hit
SUPFAMiSSF53335 SSF53335, 1 hit
PROSITEiView protein in PROSITE
PS51682 SAM_OMT_I, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCOMT_RAT
AccessioniPrimary (citable) accession number: P22734
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: May 1, 1992
Last modified: November 7, 2018
This is version 186 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again