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Protein

Catechol O-methyltransferase

Gene

Comt

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

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

  • catechol O-methyltransferase activity Source: RGD
  • magnesium ion binding Source: InterPro

GO - Biological processi

  • cellular response to phosphate starvation Source: Ensembl
  • developmental process Source: RGD
  • dopamine catabolic process Source: Ensembl
  • estrogen metabolic process Source: RGD
  • female pregnancy Source: RGD
  • learning Source: RGD
  • multicellular organismal reproductive process Source: RGD
  • negative regulation of dopamine metabolic process Source: RGD
  • negative regulation of renal sodium excretion Source: RGD
  • negative regulation of smooth muscle cell proliferation Source: RGD
  • neurotransmitter catabolic process Source: UniProtKB-KW
  • positive regulation of homocysteine metabolic process Source: RGD
  • regulation of sensory perception of pain Source: RGD
  • response to drug Source: RGD
  • response to lipopolysaccharide Source: RGD
  • response to organic cyclic compound Source: RGD
  • response to pain Source: RGD
  • S-adenosylhomocysteine metabolic process Source: RGD
  • S-adenosylmethionine metabolic process Source: RGD
  • short-term memory 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.
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-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
Proteomesi
  • UP000002494 Componenti: Chromosome 11

Organism-specific databases

RGDi2379. Comt.

Subcellular locationi

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

GO - Cellular componenti

  • axon Source: RGD
  • cell body Source: RGD
  • cytosol Source: RGD
  • dendrite Source: RGD
  • dendritic spine Source: RGD
  • extracellular exosome Source: Ensembl
  • integral component of membrane Source: UniProtKB-KW
  • membrane Source: RGD
  • mitochondrion Source: Ensembl
  • postsynaptic membrane Source: RGD
Complete GO annotation...

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.
ExpressionAtlasiP22734. baseline and differential.
GenevisibleiP22734. RN.

Interactioni

Protein-protein interaction databases

MINTiMINT-4567724.
STRINGi10116.ENSRNOP00000043148.

Chemistry databases

BindingDBiP22734.

Structurei

Secondary structure

1264
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi48 – 59Combined sources12
Helixi65 – 79Combined sources15
Helixi82 – 84Combined sources3
Helixi87 – 100Combined sources14
Beta strandi103 – 108Combined sources6
Beta strandi111 – 113Combined sources3
Helixi114 – 120Combined sources7
Beta strandi128 – 134Combined sources7
Helixi136 – 149Combined sources14
Helixi152 – 154Combined sources3
Beta strandi155 – 160Combined sources6
Helixi162 – 165Combined sources4
Helixi166 – 168Combined sources3
Helixi169 – 172Combined sources4
Beta strandi179 – 183Combined sources5
Helixi187 – 189Combined sources3
Helixi190 – 199Combined sources10
Beta strandi208 – 212Combined sources5
Helixi214 – 218Combined sources5
Helixi220 – 228Combined sources9
Beta strandi232 – 241Combined sources10
Turni242 – 245Combined sources4
Beta strandi246 – 255Combined sources10

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[»]
ProteinModelPortaliP22734.
SMRiP22734.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP22734.

Family & Domainsi

Region

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

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

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

Family and domain databases

Gene3Di3.40.50.150. 1 hit.
InterProiIPR017128. Catechol_O-MeTrfase_euk.
IPR002935. O-MeTrfase_3.
IPR029063. SAM-dependent_MTases.
[Graphical view]
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. 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

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[»]
ProteinModelPortaliP22734.
SMRiP22734.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

MINTiMINT-4567724.
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.
OMAiGDEKGCI.
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-RKP22734.

Miscellaneous databases

EvolutionaryTraceiP22734.
PROiP22734.

Gene expression databases

BgeeiENSRNOG00000001889.
ExpressionAtlasiP22734. baseline and differential.
GenevisibleiP22734. RN.

Family and domain databases

Gene3Di3.40.50.150. 1 hit.
InterProiIPR017128. Catechol_O-MeTrfase_euk.
IPR002935. O-MeTrfase_3.
IPR029063. SAM-dependent_MTases.
[Graphical view]
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]
ProtoNetiSearch...

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: November 30, 2016
This is version 172 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

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.