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Protein

Catechol O-methyltransferase

Gene

COMT

Organism
Homo sapiens (Human)
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.1 Publication

Catalytic activityi

S-adenosyl-L-methionine + a catechol = S-adenosyl-L-homocysteine + a guaiacol.2 Publications

Cofactori

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei92S-adenosyl-L-methionine; via amide nitrogenPROSITE-ProRule annotation1 Publication1
Binding sitei114S-adenosyl-L-methioninePROSITE-ProRule annotation1
Binding sitei122S-adenosyl-L-methioninePROSITE-ProRule annotation1 Publication1
Binding sitei140S-adenosyl-L-methioninePROSITE-ProRule annotation1 Publication1
Binding sitei141S-adenosyl-L-methionine; via amide nitrogenPROSITE-ProRule annotation1
Binding sitei169S-adenosyl-L-methionine; via amide nitrogenPROSITE-ProRule annotation1
Metal bindingi191Magnesium1 Publication1
Binding sitei191S-adenosyl-L-methioninePROSITE-ProRule annotation1 Publication1
Binding sitei194Substrate1
Metal bindingi219Magnesium1 Publication1
Metal bindingi220Magnesium1 Publication1
Binding sitei220Substrate1
Binding sitei249Substrate1

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:HS01791-MONOMER
BRENDAi2.1.1.6 2681
ReactomeiR-HSA-156581 Methylation
R-HSA-379397 Enzymatic degradation of dopamine by COMT
R-HSA-379398 Enzymatic degradation of Dopamine by monoamine oxidase
SIGNORiP21964

Chemistry databases

SwissLipidsiSLP:000001714 [P21964-2]

Names & Taxonomyi

Protein namesi
Recommended name:
Catechol O-methyltransferase (EC:2.1.1.62 Publications)
Gene namesi
Name:COMT
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

EuPathDBiHostDB:ENSG00000093010.11
HGNCiHGNC:2228 COMT
MIMi116790 gene+phenotype
neXtProtiNX_P21964

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 – 6CytoplasmicSequence analysis6
Transmembranei7 – 26Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST20
Topological domaini27 – 271ExtracellularSequence analysisAdd BLAST245

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Involvement in diseasei

Schizophrenia (SCZD)1 Publication
Disease susceptibility may be associated with variations affecting the gene represented in this entry.
Disease descriptionA complex, multifactorial psychotic disorder or group of disorders characterized by disturbances in the form and content of thought (e.g. delusions, hallucinations), in mood (e.g. inappropriate affect), in sense of self and relationship to the external world (e.g. loss of ego boundaries, withdrawal), and in behavior (e.g bizarre or apparently purposeless behavior). Although it affects emotions, it is distinguished from mood disorders in which such disturbances are primary. Similarly, there may be mild impairment of cognitive function, and it is distinguished from the dementias in which disturbed cognitive function is considered primary. Some patients manifest schizophrenic as well as bipolar disorder symptoms and are often given the diagnosis of schizoaffective disorder.
See also OMIM:181500

Keywords - Diseasei

Schizophrenia

Organism-specific databases

DisGeNETi1312
MalaCardsiCOMT
MIMi103780 phenotype
116790 gene+phenotype
181500 phenotype
OpenTargetsiENSG00000093010
Orphaneti567 22q11.2 deletion syndrome
240863 Cisplatin toxicity
284121 Toxicity or absent response to clozapine
PharmGKBiPA117

Chemistry databases

ChEMBLiCHEMBL2023
DrugBankiDB02342 2-Methoxyestradiol
DB03336 BIA
DB00286 Conjugated Equine Estrogens
DB00255 Diethylstilbestrol
DB00841 Dobutamine
DB00988 Dopamine
DB00494 Entacapone
DB00968 Methyldopa
DB01141 Micafungin
DB04820 Nialamide
DB00118 S-Adenosylmethionine
DB01420 Testosterone Propionate
DB00323 Tolcapone
GuidetoPHARMACOLOGYi2472

Polymorphism and mutation databases

BioMutaiCOMT
DMDMi116907

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000209711 – 271Catechol O-methyltransferaseAdd BLAST271

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei267PhosphoserineBy similarity1

Post-translational modificationi

The N-terminus is blocked.

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP21964
MaxQBiP21964
PaxDbiP21964
PeptideAtlasiP21964
PRIDEiP21964
ProteomicsDBi53945
53946 [P21964-2]
TopDownProteomicsiP21964-1 [P21964-1]
P21964-2 [P21964-2]

2D gel databases

REPRODUCTION-2DPAGEiIPI00375513

PTM databases

iPTMnetiP21964
PhosphoSitePlusiP21964
SwissPalmiP21964

Expressioni

Tissue specificityi

Brain, liver, placenta, lymphocytes and erythrocytes.

Gene expression databases

BgeeiENSG00000093010 Expressed in 234 organ(s), highest expression level in liver
CleanExiHS_COMT
ExpressionAtlasiP21964 baseline and differential
GenevisibleiP21964 HS

Organism-specific databases

HPAiCAB011233
HPA001169

Interactioni

Binary interactionsi

Protein-protein interaction databases

BioGridi107707, 44 interactors
IntActiP21964, 69 interactors
MINTiP21964
STRINGi9606.ENSP00000354511

Chemistry databases

BindingDBiP21964

Structurei

Secondary structure

1271
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP21964
SMRiP21964
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP21964

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni167 – 170S-adenosyl-L-methionine binding4

Sequence similaritiesi

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1663 Eukaryota
COG4122 LUCA
GeneTreeiENSGT00390000011316
HOGENOMiHOG000046392
HOVERGENiHBG005376
InParanoidiP21964
KOiK00545
OMAiSRFECTH
OrthoDBiEOG091G0GQK
PhylomeDBiP21964
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 4 potential isoforms that are computationally mapped.Show allAlign All

Isoform Membrane-bound (identifier: P21964-1) [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
MPEAPPLLLA AVLLGLVLLV VLLLLLRHWG WGLCLIGWNE FILQPIHNLL
60 70 80 90 100
MGDTKEQRIL NHVLQHAEPG NAQSVLEAID TYCEQKEWAM NVGDKKGKIV
110 120 130 140 150
DAVIQEHQPS VLLELGAYCG YSAVRMARLL SPGARLITIE INPDCAAITQ
160 170 180 190 200
RMVDFAGVKD KVTLVVGASQ DIIPQLKKKY DVDTLDMVFL DHWKDRYLPD
210 220 230 240 250
TLLLEECGLL RKGTVLLADN VICPGAPDFL AHVRGSSCFE CTHYQSFLEY
260 270
REVVDGLEKA IYKGPGSEAG P
Length:271
Mass (Da):30,037
Last modified:May 1, 1992 - v2
Checksum:iD2547A1C399AC758
GO
Isoform Soluble (identifier: P21964-2) [UniParc]FASTAAdd to basket
Also known as: S-COMT

The sequence of this isoform differs from the canonical sequence as follows:
     1-50: Missing.

Show »
Length:221
Mass (Da):24,449
Checksum:iF17399A01E493B63
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E7EMS6E7EMS6_HUMAN
Catechol O-methyltransferase
COMT
223Annotation score:
E7EUU8E7EUU8_HUMAN
Catechol O-methyltransferase
COMT
235Annotation score:
F8WBW9F8WBW9_HUMAN
Catechol O-methyltransferase
COMT
199Annotation score:
H7BZ45H7BZ45_HUMAN
Catechol O-methyltransferase
COMT
152Annotation score:

Sequence cautioni

The sequence AAH00419 differs from that shown. Reason: Erroneous termination at position 85. Translated as Gln.Curated
The sequence AAH05867 differs from that shown. Reason: Erroneous termination at position 85. Translated as Gln.Curated
The sequence ACI46037 differs from that shown. Reason: Erroneous termination at position 85. Translated as Gln.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti245Q → N AA sequence (PubMed:1993083).Curated1

Mass spectrometryi

Molecular mass is 24352±2 Da from positions 52 - 271. Determined by ESI. 1 Publication

Polymorphismi

Two alleles, COMT*1 or COMT*H with Val-158 and COMT*2 or COMT*L with Met-158 are responsible for a three to four-fold difference in enzymatic activity.3 Publications
Low enzyme activity alleles are associated with genetic susceptibility to alcoholism [MIMi:103780].1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01392534C → S2 PublicationsCorresponds to variant dbSNP:rs6270Ensembl.1
Natural variantiVAR_01392672A → S Correlated with reduced enzyme activity; associated with increased risk for schizophrenia. 3 PublicationsCorresponds to variant dbSNP:rs6267EnsemblClinVar.1
Natural variantiVAR_020274102A → T. Corresponds to variant dbSNP:rs5031015Ensembl.1
Natural variantiVAR_020275146A → V. Corresponds to variant dbSNP:rs4986871Ensembl.1
Natural variantiVAR_005139158V → M in allele COMT*2; associated with low enzyme activity and thermolability; may increase the tendency to develop high blood pressure and abdominal obesity. 6 PublicationsCorresponds to variant dbSNP:rs4680EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0187781 – 50Missing in isoform Soluble. CuratedAdd BLAST50

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M65212 mRNA Translation: AAA68927.1
M65213 mRNA Translation: AAA68928.1
M58525 mRNA Translation: AAA68929.1
Z26491 Genomic DNA Translation: CAA81263.1
FJ224345 mRNA Translation: ACI46037.1 Different termination.
AK290440 mRNA Translation: BAF83129.1
CR456422 mRNA Translation: CAG30308.1
CR456997 mRNA Translation: CAG33278.1
AY341246 Genomic DNA Translation: AAP88929.1
AC000080 Genomic DNA No translation available.
AC000090 Genomic DNA No translation available.
AC005663 Genomic DNA No translation available.
CH471176 Genomic DNA Translation: EAX03010.1
BC000419 mRNA Translation: AAH00419.2 Different termination.
BC005867 mRNA Translation: AAH05867.1 Different termination.
BC011935 mRNA Translation: AAH11935.1
BC100018 mRNA Translation: AAI00019.1
CCDSiCCDS13770.1 [P21964-1]
CCDS46663.1 [P21964-2]
PIRiI37256 A38459
RefSeqiNP_000745.1, NM_000754.3 [P21964-1]
NP_001128633.1, NM_001135161.1 [P21964-1]
NP_001128634.1, NM_001135162.1 [P21964-1]
NP_009294.1, NM_007310.2 [P21964-2]
XP_016884083.1, XM_017028594.1
XP_016884084.1, XM_017028595.1 [P21964-1]
UniGeneiHs.370408
Hs.693979
Hs.713616
Hs.738526

Genome annotation databases

EnsembliENST00000361682; ENSP00000354511; ENSG00000093010 [P21964-1]
ENST00000403710; ENSP00000385917; ENSG00000093010 [P21964-1]
ENST00000406520; ENSP00000385150; ENSG00000093010 [P21964-1]
ENST00000407537; ENSP00000384654; ENSG00000093010 [P21964-1]
ENST00000449653; ENSP00000416778; ENSG00000093010 [P21964-2]
GeneIDi1312
KEGGihsa:1312
UCSCiuc002zqu.4 human [P21964-1]

Keywords - Coding sequence diversityi

Alternative initiation, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

NIEHS-SNPs
Wikipedia

Catechol-O-methyl transferase entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M65212 mRNA Translation: AAA68927.1
M65213 mRNA Translation: AAA68928.1
M58525 mRNA Translation: AAA68929.1
Z26491 Genomic DNA Translation: CAA81263.1
FJ224345 mRNA Translation: ACI46037.1 Different termination.
AK290440 mRNA Translation: BAF83129.1
CR456422 mRNA Translation: CAG30308.1
CR456997 mRNA Translation: CAG33278.1
AY341246 Genomic DNA Translation: AAP88929.1
AC000080 Genomic DNA No translation available.
AC000090 Genomic DNA No translation available.
AC005663 Genomic DNA No translation available.
CH471176 Genomic DNA Translation: EAX03010.1
BC000419 mRNA Translation: AAH00419.2 Different termination.
BC005867 mRNA Translation: AAH05867.1 Different termination.
BC011935 mRNA Translation: AAH11935.1
BC100018 mRNA Translation: AAI00019.1
CCDSiCCDS13770.1 [P21964-1]
CCDS46663.1 [P21964-2]
PIRiI37256 A38459
RefSeqiNP_000745.1, NM_000754.3 [P21964-1]
NP_001128633.1, NM_001135161.1 [P21964-1]
NP_001128634.1, NM_001135162.1 [P21964-1]
NP_009294.1, NM_007310.2 [P21964-2]
XP_016884083.1, XM_017028594.1
XP_016884084.1, XM_017028595.1 [P21964-1]
UniGeneiHs.370408
Hs.693979
Hs.713616
Hs.738526

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3A7EX-ray2.80A51-264[»]
3BWMX-ray1.98A52-265[»]
3BWYX-ray1.30A52-265[»]
4PYIX-ray1.35A51-271[»]
4PYJX-ray1.90A51-271[»]
4PYKX-ray2.22A51-271[»]
4XUCX-ray1.80A48-265[»]
4XUDX-ray2.40A48-265[»]
4XUEX-ray2.30A/B52-265[»]
5LSAX-ray1.50A51-271[»]
ProteinModelPortaliP21964
SMRiP21964
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107707, 44 interactors
IntActiP21964, 69 interactors
MINTiP21964
STRINGi9606.ENSP00000354511

Chemistry databases

BindingDBiP21964
ChEMBLiCHEMBL2023
DrugBankiDB02342 2-Methoxyestradiol
DB03336 BIA
DB00286 Conjugated Equine Estrogens
DB00255 Diethylstilbestrol
DB00841 Dobutamine
DB00988 Dopamine
DB00494 Entacapone
DB00968 Methyldopa
DB01141 Micafungin
DB04820 Nialamide
DB00118 S-Adenosylmethionine
DB01420 Testosterone Propionate
DB00323 Tolcapone
GuidetoPHARMACOLOGYi2472
SwissLipidsiSLP:000001714 [P21964-2]

PTM databases

iPTMnetiP21964
PhosphoSitePlusiP21964
SwissPalmiP21964

Polymorphism and mutation databases

BioMutaiCOMT
DMDMi116907

2D gel databases

REPRODUCTION-2DPAGEiIPI00375513

Proteomic databases

EPDiP21964
MaxQBiP21964
PaxDbiP21964
PeptideAtlasiP21964
PRIDEiP21964
ProteomicsDBi53945
53946 [P21964-2]
TopDownProteomicsiP21964-1 [P21964-1]
P21964-2 [P21964-2]

Protocols and materials databases

DNASUi1312
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000361682; ENSP00000354511; ENSG00000093010 [P21964-1]
ENST00000403710; ENSP00000385917; ENSG00000093010 [P21964-1]
ENST00000406520; ENSP00000385150; ENSG00000093010 [P21964-1]
ENST00000407537; ENSP00000384654; ENSG00000093010 [P21964-1]
ENST00000449653; ENSP00000416778; ENSG00000093010 [P21964-2]
GeneIDi1312
KEGGihsa:1312
UCSCiuc002zqu.4 human [P21964-1]

Organism-specific databases

CTDi1312
DisGeNETi1312
EuPathDBiHostDB:ENSG00000093010.11
GeneCardsiCOMT
HGNCiHGNC:2228 COMT
HPAiCAB011233
HPA001169
MalaCardsiCOMT
MIMi103780 phenotype
116790 gene+phenotype
181500 phenotype
neXtProtiNX_P21964
OpenTargetsiENSG00000093010
Orphaneti567 22q11.2 deletion syndrome
240863 Cisplatin toxicity
284121 Toxicity or absent response to clozapine
PharmGKBiPA117
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1663 Eukaryota
COG4122 LUCA
GeneTreeiENSGT00390000011316
HOGENOMiHOG000046392
HOVERGENiHBG005376
InParanoidiP21964
KOiK00545
OMAiSRFECTH
OrthoDBiEOG091G0GQK
PhylomeDBiP21964
TreeFamiTF329140

Enzyme and pathway databases

BioCyciMetaCyc:HS01791-MONOMER
BRENDAi2.1.1.6 2681
ReactomeiR-HSA-156581 Methylation
R-HSA-379397 Enzymatic degradation of dopamine by COMT
R-HSA-379398 Enzymatic degradation of Dopamine by monoamine oxidase
SIGNORiP21964

Miscellaneous databases

ChiTaRSiCOMT human
EvolutionaryTraceiP21964
GeneWikiiCatechol-O-methyl_transferase
GenomeRNAii1312
PROiPR:P21964
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000093010 Expressed in 234 organ(s), highest expression level in liver
CleanExiHS_COMT
ExpressionAtlasiP21964 baseline and differential
GenevisibleiP21964 HS

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_HUMAN
AccessioniPrimary (citable) accession number: P21964
Secondary accession number(s): A8MPV9
, Q6IB07, Q6ICE6, Q9BWC7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: May 1, 1992
Last modified: November 7, 2018
This is version 211 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  6. 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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