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Protein

Catechol O-methyltransferase

Gene

Comt

Organism
Mus musculus (Mouse)
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+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

GO - Biological processi

Keywordsi

Molecular functionMethyltransferase, Transferase
Biological processCatecholamine metabolism, Neurotransmitter degradation
LigandMagnesium, 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-RKiO88587

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 16

Organism-specific databases

MGIiMGI:88470 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 – 265ExtracellularSequence analysisAdd BLAST246

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 Expressed in 313 organ(s), highest expression level in subcutaneous adipose tissue
ExpressionAtlasiO88587 baseline and differential
GenevisibleiO88587 MM

Interactioni

Protein-protein interaction databases

IntActiO88587, 3 interactors
MINTiO88587
STRINGi10090.ENSMUSP00000000335

Chemistry databases

BindingDBiO88587

Structurei

Secondary structure

1265
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO88587
SMRiO88587
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

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

Sequence similaritiesi

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1663 Eukaryota
COG4122 LUCA
GeneTreeiENSGT00390000011316
HOGENOMiHOG000046392
HOVERGENiHBG005376
InParanoidiO88587
KOiK00545
OMAiSRFECTH
OrthoDBiEOG091G0GQK
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

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D3Z227D3Z227_MOUSE
Catechol O-methyltransferase
Comt
171Annotation score:

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

Similar proteinsi

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
MINTiO88587
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
OMAiSRFECTH
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-RKiO88587

Miscellaneous databases

PROiPR:O88587
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000000326 Expressed in 313 organ(s), highest expression level in subcutaneous adipose tissue
ExpressionAtlasiO88587 baseline and differential
GenevisibleiO88587 MM

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_MOUSE
AccessioniPrimary (citable) accession number: O88587
Secondary accession number(s): Q91XH4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: October 3, 2012
Last modified: November 7, 2018
This is version 159 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. 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

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