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P22734 (COMT_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 151. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Catechol O-methyltransferase

EC=2.1.1.6
Gene names
Name:Comt
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length264 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 activity

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

Cofactor

Binds 1 magnesium ion per subunit.

Subcellular location

Isoform 2: Cytoplasm.

Isoform 1: Cell membrane; Single-pass type II membrane protein; Extracellular side.

Post-translational modification

The N-terminus is blocked.

Sequence similarities

Belongs to the class I-like SAM-binding methyltransferase superfamily. Cation-dependent O-methyltransferase family.

Biophysicochemical properties

Kinetic parameters:

KM=30 µM for S-adenosyl-L-methionine Ref.8

Vmax=377 nmol/h/mg enzyme

Sequence caution

The sequence AAA40881.1 differs from that shown. Reason: Erroneous initiation.

The sequence AAA40882.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processCatecholamine metabolism
Neurotransmitter degradation
   Cellular componentCell membrane
Cytoplasm
Membrane
   Coding sequence diversityAlternative initiation
   DomainSignal-anchor
Transmembrane
Transmembrane helix
   LigandMagnesium
Metal-binding
S-adenosyl-L-methionine
   Molecular functionMethyltransferase
Transferase
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processS-adenosylhomocysteine metabolic process

Traceable author statement PubMed 12584150. Source: RGD

S-adenosylmethionine metabolic process

Traceable author statement PubMed 12584150. Source: RGD

catecholamine metabolic process

Traceable author statement PubMed 12584150. Source: RGD

dopamine catabolic process

Inferred from electronic annotation. Source: Ensembl

dopamine metabolic process

Traceable author statement PubMed 12584150. Source: RGD

estrogen metabolic process

Inferred from mutant phenotype PubMed 11071850. Source: RGD

female pregnancy

Inferred from mutant phenotype PubMed 18042640. Source: RGD

learning

Inferred from mutant phenotype PubMed 15190105. Source: RGD

multicellular organismal reproductive process

Inferred from mutant phenotype PubMed 17699737. Source: RGD

negative regulation of dopamine metabolic process

Inferred from mutant phenotype PubMed 15190105. Source: RGD

negative regulation of smooth muscle cell proliferation

Inferred from mutant phenotype PubMed 11071850. Source: RGD

neurotransmitter catabolic process

Inferred from electronic annotation. Source: UniProtKB-KW

positive regulation of homocysteine metabolic process

Inferred from mutant phenotype PubMed 15779086. Source: RGD

response to drug

Inferred from expression pattern PubMed 17868501. Source: RGD

response to lipopolysaccharide

Inferred from expression pattern PubMed 17573159. Source: RGD

response to organic cyclic compound

Inferred from expression pattern PubMed 15964593. Source: RGD

response to pain

Inferred from mutant phenotype PubMed 17084978. Source: RGD

   Cellular_componentintegral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

membrane

Inferred from direct assay PubMed 14714585. Source: RGD

mitochondrion

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functioncatechol O-methyltransferase activity

Inferred from direct assay PubMed 12584150. Source: RGD

magnesium ion binding

Traceable author statement PubMed 12584150. Source: RGD

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative initiation. [Align] [Select]
Isoform 1 (identifier: P22734-1)

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.
Isoform 2 (identifier: P22734-2)

Also known as: Soluble; S-COMT;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 264264Catechol O-methyltransferase
PRO_0000020975

Regions

Transmembrane3 – 1917Helical; Signal-anchor for type II membrane protein; Potential
Region160 – 1634S-adenosyl-L-methionine binding

Sites

Metal binding1841Magnesium
Metal binding2121Magnesium
Metal binding2131Magnesium
Binding site851S-adenosyl-L-methionine; via amide nitrogen
Binding site1071S-adenosyl-L-methionine By similarity
Binding site1151S-adenosyl-L-methionine
Binding site1331S-adenosyl-L-methionine
Binding site1341S-adenosyl-L-methionine; via amide nitrogen By similarity
Binding site1621S-adenosyl-L-methionine; via amide nitrogen By similarity
Binding site1841S-adenosyl-L-methionine
Binding site1871Substrate
Binding site2131Substrate
Binding site2421Substrate

Natural variations

Alternative sequence1 – 4343Missing in isoform 2.
VSP_018780

Secondary structure

........................................ 264
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Membrane-bound) (MB-COMT) [UniParc].

Last modified May 1, 1992. Version 2.
Checksum: F535DFF49C062854

FASTA26429,597
        10         20         30         40         50         60 
MPLAAVSLGL LLLALLLLLR HLGWGLVTIF WFEYVLQPVH NLIMGDTKEQ RILRYVQQNA 

        70         80         90        100        110        120 
KPGDPQSVLE AIDTYCTQKE WAMNVGDAKG QIMDAVIREY SPSLVLELGA YCGYSAVRMA 

       130        140        150        160        170        180 
RLLQPGARLL TMEMNPDYAA ITQQMLNFAG LQDKVTILNG ASQDLIPQLK KKYDVDTLDM 

       190        200        210        220        230        240 
VFLDHWKDRY LPDTLLLEKC GLLRKGTVLL ADNVIVPGTP DFLAYVRGSS SFECTHYSSY 

       250        260 
LEYMKVVDGL EKAIYQGPSS PDKS 

« Hide

Isoform 2 (Soluble) (S-COMT) [UniParc].

Checksum: C797794F205FA41D
Show »

FASTA22124,747

References

« Hide 'large scale' references
[1]"Production of rat soluble and membrane-bound catechol O-methyltransferase forms from bifunctional mRNAs."
Tenhunen J., Ulmanen I.
Biochem. J. 296:595-600(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE INITIATION.
Tissue: Liver.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Heart.
[3]"Molecular cloning and characterization of rat liver catechol-O-methyltransferase."
Salminen M., Lundstroem K., Tilgmann C., Savolainen R., Kalkkinen N., Ulmanen I.
Gene 93:241-247(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 11-264.
[4]"Cell-free synthesis of rat and human catechol O-methyltransferase. Insertion of the membrane-bound form into microsomal membranes in vitro."
Ulmanen I., Lundstroem K.
Eur. J. Biochem. 202:1013-1020(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-10, CHARACTERIZATION OF THE TWO FORMS.
[5]"Crystal structure of catechol O-methyltransferase."
Vidgren J., Svensson L.A., Liljas A.
Nature 368:354-358(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 44-264.
[6]"Structure-based design, synthesis, and in vitro evaluation of bisubstrate inhibitors for catechol O-methyltransferase (COMT)."
Masjost B., Ballmer P., Borroni E., Zuercher G., Winkler F.K., Jakob-Roetne R., Diederich F.
Chemistry 6:971-982(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.63 ANGSTROMS) OF 44-264 IN COMPLEX WITH SUBSTRATE ANALOG.
[7]"Kinetics and crystal structure of catechol-O-methyltransferase complex with co-substrate and a novel inhibitor with potential therapeutic application."
Bonifacio M.J., Archer M., Rodrigues M.L., Matias P.M., Learmonth D.A., Carrondo M.A., Soares-da-Silva P.
Mol. Pharmacol. 62:795-805(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 44-264 IN COMPLEX WITH S-ADENOSYL-L-METHIONINE AND SUBSTRATE ANALOG.
[8]"Comparative study of ortho- and meta-nitrated inhibitors of catechol-O-methyltransferase: interactions with the active site and regioselectivity of O-methylation."
Palma P.N., Rodrigues M.L., Archer M., Bonifacio M.J., Loureiro A.I., Learmonth D.A., Carrondo M.A., Soares-da-Silva P.
Mol. Pharmacol. 70:143-153(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 44-264 IN COMPLEX WITH SUBSTRATE ANALOG, BIOPHYSICOCHEMICAL PROPERTIES.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRS22090.
RefSeqNP_036663.1. NM_012531.2. [P22734-1]
XP_006248665.1. XM_006248603.1.
UniGeneRn.220.

3D structure databases

PDBe
RCSB-PDB
PDBj
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[»]
ProteinModelPortalP22734.
SMRP22734. Positions 45-258.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

MINTMINT-4567724.
STRING10116.ENSRNOP00000043148.

Chemistry

BindingDBP22734.
ChEMBLCHEMBL2372.

PTM databases

PhosphoSiteP22734.

Proteomic databases

PaxDbP22734.
PRIDEP22734.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000050269; ENSRNOP00000043148; ENSRNOG00000001889. [P22734-1]
GeneID24267.
KEGGrno:24267.

Organism-specific databases

CTD1312.
RGD2379. Comt.

Phylogenomic databases

eggNOGCOG4122.
GeneTreeENSGT00390000011316.
HOGENOMHOG000046392.
HOVERGENHBG005376.
InParanoidP22734.
KOK00545.
OMACTHYSSY.
OrthoDBEOG7PZRZJ.
PhylomeDBP22734.
TreeFamTF329140.

Enzyme and pathway databases

BioCycMetaCyc:MONOMER-15100.
SABIO-RKP22734.

Gene expression databases

ArrayExpressP22734.
GenevestigatorP22734.

Family and domain databases

Gene3D3.40.50.150. 1 hit.
InterProIPR025782. Catechol_O-MeTrfase.
IPR017128. Catechol_O-MeTrfase_euk.
IPR002935. O-MeTrfase_3.
IPR029063. SAM-dependent_MTases-like.
[Graphical view]
PANTHERPTHR10509. PTHR10509. 1 hit.
PfamPF01596. Methyltransf_3. 1 hit.
[Graphical view]
PIRSFPIRSF037177. Catechol_O-mtfrase_euk. 1 hit.
SUPFAMSSF53335. SSF53335. 1 hit.
PROSITEPS51682. SAM_OMT_I. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP22734.
NextBio602825.
PROP22734.

Entry information

Entry nameCOMT_RAT
AccessionPrimary (citable) accession number: P22734
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: May 1, 1992
Last modified: June 11, 2014
This is version 151 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references