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Protein

Catechol O-methyltransferase

Gene

Comt

Organism
Mus musculus (Mouse)
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+By similarityNote: Binds 1 Mg2+ ion per subunit.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei85S-adenosyl-L-methionine; via amide nitrogenPROSITE-ProRule annotation1
Binding sitei107S-adenosyl-L-methioninePROSITE-ProRule annotation1
Binding sitei115S-adenosyl-L-methioninePROSITE-ProRule annotation1
Binding sitei133S-adenosyl-L-methioninePROSITE-ProRule annotation1
Binding sitei134S-adenosyl-L-methionine; via amide nitrogenPROSITE-ProRule annotation1
Binding sitei162S-adenosyl-L-methionine; via amide nitrogenPROSITE-ProRule annotation1
Metal bindingi184MagnesiumBy similarity1
Binding sitei184S-adenosyl-L-methioninePROSITE-ProRule annotation1
Binding sitei187SubstrateBy similarity1
Metal bindingi212MagnesiumBy similarity1
Metal bindingi213MagnesiumBy similarity1
Binding sitei213SubstrateBy similarity1
Binding sitei242SubstrateBy similarity1

GO - Molecular functioni

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

GO - Biological processi

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

ReactomeiR-MMU-156581. Methylation.
R-MMU-379397. Enzymatic degradation of dopamine by COMT.
R-MMU-379398. Enzymatic degradation of Dopamine by monoamine oxidase.
SABIO-RKO88587.

Names & Taxonomyi

Protein namesi
Recommended name:
Catechol O-methyltransferase (EC:2.1.1.6)
Gene namesi
Name:Comt
Synonyms:Comt1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 16

Organism-specific databases

MGIiMGI:88470. 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 – 265ExtracellularSequence analysisAdd BLAST246

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi51R → L: Reduces methyltransferase activity against norepinephrine. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL3286068.
GuidetoPHARMACOLOGYi2472.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000209731 – 265Catechol O-methyltransferaseAdd BLAST265

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei260PhosphoserineBy similarity1
Modified residuei261PhosphoserineCombined sources1
Modified residuei265PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiO88587.
PeptideAtlasiO88587.
PRIDEiO88587.

PTM databases

iPTMnetiO88587.
PhosphoSitePlusiO88587.
SwissPalmiO88587.

Expressioni

Gene expression databases

BgeeiENSMUSG00000000326.
ExpressionAtlasiO88587. baseline and differential.
GenevisibleiO88587. MM.

Interactioni

Protein-protein interaction databases

IntActiO88587. 3 interactors.
MINTiMINT-1854931.
STRINGi10090.ENSMUSP00000000335.

Chemistry databases

BindingDBiO88587.

Structurei

Secondary structure

1265
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi48 – 59Combined sources12
Helixi65 – 78Combined sources14
Beta strandi81 – 83Combined sources3
Helixi85 – 88Combined sources4
Helixi90 – 100Combined sources11
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 – 173Combined sources5
Beta strandi178 – 183Combined sources6
Helixi187 – 189Combined sources3
Helixi190 – 199Combined sources10
Beta strandi203 – 212Combined sources10
Helixi220 – 228Combined sources9
Beta strandi232 – 239Combined sources8
Beta strandi243 – 245Combined sources3
Beta strandi247 – 255Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4P58X-ray2.06A47-258[»]
4P7FX-ray1.37A44-265[»]
ProteinModelPortaliO88587.
SMRiO88587.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni160 – 163S-adenosyl-L-methionine bindingPROSITE-ProRule annotation4

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.
InParanoidiO88587.
KOiK00545.
OMAiGDEKGCI.
OrthoDBiEOG091G0GQK.
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 Membrane-bound (identifier: O88587-1) [UniParc]FASTAAdd to basket
Also known as: 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
MLLAAVSLGL LLLAFLLLLR HLGWGLVAIG WFEFVQQPVH NLLMGGTKEQ
60 70 80 90 100
RILRHVQQHA KPGDPQSVLE AIDTYCSEKE WAMNVGDAKG QIMDAVIREY
110 120 130 140 150
RPSLVLELGA YCGYSAVRMA RLLPPGARLL TMEINPDYAA ITQQMLDFAG
160 170 180 190 200
LQDKVSILIG ASQDLIPQLK KKYDVDTLDM VFLDHWKDRY LPDTLLLEEC
210 220 230 240 250
GLLRKGTVLL ADNVIVPGTP DFLAYVRGSS SFECTHYSSY LEYMKVVDGL
260
EKAVYQGPGS SPVKS
Length:265
Mass (Da):29,486
Last modified:October 3, 2012 - v2
Checksum:iE82E9307F6D8A6CF
GO
Isoform Soluble (identifier: O88587-2) [UniParc]FASTAAdd to basket
Also known as: S-COMT

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

Show »
Length:222
Mass (Da):24,707
Checksum:iC7D5BB1ADC5B40B2
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti162S → P in AAC33334 (PubMed:9707588).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0187791 – 43Missing in isoform Soluble. CuratedAdd BLAST43

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF076156 mRNA. Translation: AAC33334.1.
AK148311 mRNA. Translation: BAE28473.1.
AC133487 Genomic DNA. No translation available.
BC010402 mRNA. Translation: AAH10402.1.
CCDSiCCDS28021.1. [O88587-1]
RefSeqiNP_001104532.1. NM_001111062.1. [O88587-1]
NP_001104533.1. NM_001111063.1. [O88587-1]
NP_031770.2. NM_007744.3. [O88587-1]
UniGeneiMm.100940.

Genome annotation databases

EnsembliENSMUST00000000335; ENSMUSP00000000335; ENSMUSG00000000326. [O88587-1]
ENSMUST00000115609; ENSMUSP00000111272; ENSMUSG00000000326. [O88587-1]
ENSMUST00000165430; ENSMUSP00000130077; ENSMUSG00000000326. [O88587-1]
ENSMUST00000183626; ENSMUSP00000138930; ENSMUSG00000098892. [O88587-1]
ENSMUST00000185030; ENSMUSP00000139196; ENSMUSG00000098892. [O88587-1]
ENSMUST00000195169; ENSMUSP00000141683; ENSMUSG00000098892. [O88587-1]
GeneIDi12846.
KEGGimmu:12846.
UCSCiuc007ynu.2. mouse. [O88587-1]

Keywords - Coding sequence diversityi

Alternative initiation

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF076156 mRNA. Translation: AAC33334.1.
AK148311 mRNA. Translation: BAE28473.1.
AC133487 Genomic DNA. No translation available.
BC010402 mRNA. Translation: AAH10402.1.
CCDSiCCDS28021.1. [O88587-1]
RefSeqiNP_001104532.1. NM_001111062.1. [O88587-1]
NP_001104533.1. NM_001111063.1. [O88587-1]
NP_031770.2. NM_007744.3. [O88587-1]
UniGeneiMm.100940.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4P58X-ray2.06A47-258[»]
4P7FX-ray1.37A44-265[»]
ProteinModelPortaliO88587.
SMRiO88587.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiO88587. 3 interactors.
MINTiMINT-1854931.
STRINGi10090.ENSMUSP00000000335.

Chemistry databases

BindingDBiO88587.
ChEMBLiCHEMBL3286068.
GuidetoPHARMACOLOGYi2472.

PTM databases

iPTMnetiO88587.
PhosphoSitePlusiO88587.
SwissPalmiO88587.

Proteomic databases

PaxDbiO88587.
PeptideAtlasiO88587.
PRIDEiO88587.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000000335; ENSMUSP00000000335; ENSMUSG00000000326. [O88587-1]
ENSMUST00000115609; ENSMUSP00000111272; ENSMUSG00000000326. [O88587-1]
ENSMUST00000165430; ENSMUSP00000130077; ENSMUSG00000000326. [O88587-1]
ENSMUST00000183626; ENSMUSP00000138930; ENSMUSG00000098892. [O88587-1]
ENSMUST00000185030; ENSMUSP00000139196; ENSMUSG00000098892. [O88587-1]
ENSMUST00000195169; ENSMUSP00000141683; ENSMUSG00000098892. [O88587-1]
GeneIDi12846.
KEGGimmu:12846.
UCSCiuc007ynu.2. mouse. [O88587-1]

Organism-specific databases

CTDi1312.
MGIiMGI:88470. Comt.

Phylogenomic databases

eggNOGiKOG1663. Eukaryota.
COG4122. LUCA.
GeneTreeiENSGT00390000011316.
HOGENOMiHOG000046392.
HOVERGENiHBG005376.
InParanoidiO88587.
KOiK00545.
OMAiGDEKGCI.
OrthoDBiEOG091G0GQK.
TreeFamiTF329140.

Enzyme and pathway databases

ReactomeiR-MMU-156581. Methylation.
R-MMU-379397. Enzymatic degradation of dopamine by COMT.
R-MMU-379398. Enzymatic degradation of Dopamine by monoamine oxidase.
SABIO-RKO88587.

Miscellaneous databases

PROiO88587.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000000326.
ExpressionAtlasiO88587. baseline and differential.
GenevisibleiO88587. MM.

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_MOUSE
AccessioniPrimary (citable) accession number: O88587
Secondary accession number(s): Q91XH4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: October 3, 2012
Last modified: November 2, 2016
This is version 148 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. 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.