[1]	NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE INITIATION. TISSUE=Liver; PubMed=8280056 [NCBI, ExPASy, EBI, Israel, Japan] Tenhunen J., Ulmanen I.; "Production of rat soluble and membrane-bound catechol O-methyltransferase forms from bifunctional mRNAs."; Biochem. J. 296:595-600(1993).
[2]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). TISSUE=Heart; DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan] The MGC Project Team; "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."; Genome Res. 14:2121-2127(2004).
[3]	NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 11-264. DOI=10.1016/0378-1119(90)90231-F; PubMed=2227437 [NCBI, ExPASy, EBI, Israel, Japan] Salminen M., Lundstroem K., Tilgmann C., Savolainen R., Kalkkinen N., Ulmanen I.; "Molecular cloning and characterization of rat liver catechol-O-methyltransferase."; Gene 93:241-247(1990).
[4]	NUCLEOTIDE SEQUENCE [MRNA] OF 1-10, AND CHARACTERIZATION OF THE TWO FORMS. PubMed=1765063 [NCBI, ExPASy, EBI, Israel, Japan] Ulmanen I., Lundstroem K.; "Cell-free synthesis of rat and human catechol O-methyltransferase. Insertion of the membrane-bound form into microsomal membranes in vitro."; Eur. J. Biochem. 202:1013-1020(1991).
[5]	PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-260, AND MASS SPECTROMETRY. TISSUE=Liver; DOI=10.1021/pr0503073; PubMed=16396499 [NCBI, ExPASy, EBI, Israel, Japan] Moser K., White F.M.; "Phosphoproteomic analysis of rat liver by high capacity IMAC and LC-MS/MS."; J. Proteome Res. 5:98-104(2006).
[6]	X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 44-264. DOI=10.1038/368354a0; PubMed=8127373 [NCBI, ExPASy, EBI, Israel, Japan] Vidgren J., Svensson L.A., Liljas A.; "Crystal structure of catechol O-methyltransferase."; Nature 368:354-358(1994).
[7]	X-RAY CRYSTALLOGRAPHY (2.63 ANGSTROMS) OF 44-264 IN COMPLEX WITH SUBSTRATE ANALOG. PubMed=10785817 [NCBI, ExPASy, EBI, Israel, Japan] Masjost B., Ballmer P., Borroni E., Zuercher G., Winkler F.K., Jakob-Roetne R., Diederich F.; "Structure-based design, synthesis, and in vitro evaluation of bisubstrate inhibitors for catechol O-methyltransferase (COMT)."; Chemistry 6:971-982(2000).
[8]	X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 44-264 IN COMPLEX WITH S-ADENOSYL-L-METHIONINE AND SUBSTRATE ANALOG. DOI=10.1124/mol.62.4.795; PubMed=12237326 [NCBI, ExPASy, EBI, Israel, Japan] Bonifacio M.J., Archer M., Rodrigues M.L., Matias P.M., Learmonth D.A., Carrondo M.A., Soares-da-Silva P.; "Kinetics and crystal structure of catechol-O-methyltransferase complex with co-substrate and a novel inhibitor with potential therapeutic application."; Mol. Pharmacol. 62:795-805(2002).
[9]	X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 44-264 IN COMPLEX WITH SUBSTRATE ANALOG, AND BIOPHYSICOCHEMICAL PROPERTIES. DOI=10.1124/mol.106.023119; PubMed=16618795 [NCBI, ExPASy, EBI, Israel, Japan] Palma P.N., Rodrigues M.L., Archer M., Bonifacio M.J., Loureiro A.I., Learmonth D.A., Carrondo M.A., Soares-da-Silva P.; "Comparative study of ortho- and meta-nitrated inhibitors of catechol-O-methyltransferase: interactions with the active site and regioselectivity of O-methylation."; Mol. Pharmacol. 70:143-153(2006).

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.
BIOPHYSICOCHEMICAL PROPERTIES:

Kinetic parameters: K_M=30 µM for S-adenosyl-L-methionine;
V_max=377 nmol/h/mg enzyme;
SUBCELLULAR LOCATION: Isoform 2: Cytoplasm.
SUBCELLULAR LOCATION: Isoform 1: Cell membrane; Single-pass type II membrane protein; Extracellular side.

ALTERNATIVE PRODUCTS: 2 named isoforms [FASTA] produced by alternative initiation.

Name	1
Synonyms	Membrane-bound, MB-COMT
Isoform ID	P22734-1
This is the isoform sequence displayed in this entry.

Name	2
Synonyms	Soluble, S-COMT
Isoform ID	P22734-2
Features which should be applied to build the isoform sequence: VSP_018780.

PTM: The N-terminus is blocked.
SIMILARITY: Belongs to the methyltransferase superfamily. Catechol-O-methyltransferase family.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

Z12651; CAA78276.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
M60754; AAA40882.1; ALT_INIT; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC081850; AAH81850.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
M60753; AAA40881.1; ALT_INIT; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

S22090; S22090.

NP_036663.1; -.

3D structure databases

PDB

1H1D; X-ray; 2.00 A; A=44-264.	[ExPASy / RCSB / EBI]
1JR4; X-ray; 2.63 A; A=44-264.	[ExPASy / RCSB / EBI]
1VID; X-ray; 2.00 A; A=44-264.	[ExPASy / RCSB / EBI]
2CL5; X-ray; 1.60 A; A/B=44-264.	[ExPASy / RCSB / EBI]

Detailed list of linked structures.

PDBsum

1H1D; -.
1JR4; -.
1VID; -.
2CL5; -.

ModBase

P22734.

PTM databases

PhosphoSite

P22734; -.

Organism-specific databases

RGD

2379; Comt.

Gene expression databases

ArrayExpress

P22734; -.

GermOnline

ENSRNOG00000001889; Rattus norvegicus.

Ontologies

GO:0005737;	Cellular component: cytoplasm (inferred from electronic annotation from UniProtKB-KW).
GO:0016021;	Cellular component: integral to membrane (inferred from electronic annotation from UniProtKB-KW).
GO:0005886;	Cellular component: plasma membrane (inferred from electronic annotation from UniProtKB-KW).
GO:0016206;	Molecular function: catechol O-methyltransferase activity (inferred from electronic annotation from EC).
GO:0000287;	Molecular function: magnesium ion binding (inferred from electronic annotation from UniProtKB-KW).
GO:0042135;	Biological process: neurotransmitter catabolic process (inferred from electronic annotation from UniProtKB-KW).
QuickGo view.

Family and domain databases

InterPro

IPR017128; Catechol_O-MeTrfase_euk.
IPR002935; O-MeTrfase_3.
Graphical view of domain structure.

PANTHER

PTHR10509; Methyltransf_3; 1.

Pfam

PF01596; Methyltransf_3; 1.
Pfam graphical view of domain structure.

PIRSF

PIRSF037177; Catechol_O-mtfrase_euk; 1.

ProtoNet

P22734.

Genome annotation databases

Ensembl

ENSRNOG00000001889; Rattus norvegicus. [Contig view]

GeneID

24267; -.

KEGG

rno:24267; -.

Phylogenomic databases

HOVERGEN

P22734; -.

Other

LinkHub

P22734; -.

NextBio

602825; -.

UniRef

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

3D-structure; Alternative initiation; Catecholamine metabolism; Cell membrane; Cytoplasm; Magnesium; Membrane; Metal-binding; Methyltransferase; Neurotransmitter degradation; Phosphoprotein; S-adenosyl-L-methionine; Signal-anchor; Transferase; Transmembrane.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 264`	`264`	`Catechol O-methyltransferase.`	`PRO_0000020975`
`TRANSMEM`	`3 19`	`17`	`Signal-anchor for type II membrane protein (Potential).`
`REGION`	`160 163`	`4`	`S-adenosyl-L-methionine binding.`
`METAL`	`184 184`		`Magnesium.`
`METAL`	`212 212`		`Magnesium.`
`METAL`	`213 213`		`Magnesium.`
`BINDING`	`85 85`		`S-adenosyl-L-methionine; via amide nitrogen.`
`BINDING`	`115 115`		`S-adenosyl-L-methionine.`
`BINDING`	`133 133`		`S-adenosyl-L-methionine.`
`BINDING`	`184 184`		`S-adenosyl-L-methionine.`
`BINDING`	`187 187`		`Substrate.`
`BINDING`	`213 213`		`Substrate.`
`BINDING`	`242 242`		`Substrate.`
`MOD_RES`	`260 260`		`Phosphoserine.`
`VAR_SEQ`	`1 43`		`Missing (in isoform 2).`	`VSP_018780`
`HELIX`	`48 59`	`12`
`HELIX`	`65 78`	`14`
`HELIX`	`86 100`	`15`
`STRAND`	`103 108`	`6`
`HELIX`	`114 120`	`7`
`STRAND`	`128 133`	`6`
`HELIX`	`136 149`	`14`
`TURN`	`152 154`	`3`
`STRAND`	`155 160`	`6`
`HELIX`	`162 165`	`4`
`HELIX`	`166 168`	`3`
`HELIX`	`169 173`	`5`
`STRAND`	`179 183`	`5`
`HELIX`	`187 189`	`3`
`HELIX`	`190 199`	`10`
`STRAND`	`208 212`	`5`
`HELIX`	`214 218`	`5`
`HELIX`	`220 228`	`9`
`STRAND`	`232 240`	`9`
`STRAND`	`244 255`	`12`

Sequence information

Length: 264 AA [This is the length of the unprocessed precursor]

Molecular weight: 29597 Da [This is the MW of the unprocessed precursor]

CRC64: F535DFF49C062854 [This is a checksum on the sequence]

        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

P22734 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools