Reviewed, UniProtKB/Swiss-Prot P22734 (COMT_RAT)

Names and origin

Protein names

Recommended name:
    Catechol O-methyltransferase
    EC=2.1.1.6

Gene names

Name:

Comt

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	264 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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 methyltransferase superfamily. Catechol-O-methyltransferase family.
biophysicochemical properties	Kinetic parameters: KM=30 µM for S-adenosyl-L-methionine Vmax=377 nmol/h/mg enzyme

Ontologies

Keywords
Biological process	Catecholamine metabolism Neurotransmitter degradation
Cellular component	Cell membrane Cytoplasm Membrane
Coding sequence diversity	Alternative initiation
Domain	Signal-anchor Transmembrane
Ligand	Magnesium Metal-binding S-adenosyl-L-methionine
Molecular function	Methyltransferase Transferase
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	S-adenosylhomocysteine metabolic process Traceable author statement. Source: RGD S-adenosylmethionine metabolic process Traceable author statement. Source: RGD estrogen metabolic process Inferred from mutant phenotype. Source: RGD female pregnancy Inferred from mutant phenotype. Source: RGD learning Inferred from mutant phenotype. Source: RGD negative regulation of dopamine metabolic process Inferred from mutant phenotype. Source: RGD negative regulation of smooth muscle cell proliferation Inferred from mutant phenotype. Source: RGD neurotransmitter catabolic process Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of homocysteine metabolic process Inferred from mutant phenotype. Source: RGD reproductive process in a multicellular organism Inferred from mutant phenotype. Source: RGD response to drug Inferred from expression pattern. Source: RGD response to lipopolysaccharide Inferred from expression pattern. Source: RGD response to organic cyclic substance Inferred from expression pattern. Source: RGD response to pain Inferred from mutant phenotype. Source: RGD
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW membrane fraction Inferred from direct assay. Source: RGD plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell soluble fraction Inferred from direct assay. Source: RGD
Molecular function	catechol O-methyltransferase activity Inferred from direct assay. Source: RGD magnesium ion binding Traceable author statement. 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 264

264

Catechol O-methyltransferase

PRO_0000020975

Regions

Transmembrane

3 – 19

17

Signal-anchor for type II membrane protein Potential

Region

160 – 163

4

S-adenosyl-L-methionine binding

Sites

Metal binding

184

1

Magnesium

Metal binding

212

1

Magnesium

Metal binding

213

1

Magnesium

Binding site

85

1

S-adenosyl-L-methionine; via amide nitrogen

Binding site

115

1

S-adenosyl-L-methionine

Binding site

133

1

S-adenosyl-L-methionine

Binding site

184

1

S-adenosyl-L-methionine

Binding site

187

1

Substrate

Binding site

213

1

Substrate

Binding site

242

1

Substrate

Amino acid modifications

Modified residue

260

1

Phosphoserine Ref.5

Natural variations

Alternative sequence

1 – 43

43

Missing in isoform 2.

VSP_018780

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

264

Helix Strand Turn

Details...

Helix

48 – 59

12

Helix

65 – 78

14

Helix

86 – 100

15

Beta strand

103 – 108

6

Helix

114 – 120

7

Beta strand

128 – 133

6

Helix

136 – 149

14

Turn

152 – 154

3

Beta strand

155 – 160

6

Helix

162 – 165

4

Helix

166 – 168

3

Helix

169 – 173

5

Beta strand

179 – 183

5

Helix

187 – 189

3

Helix

190 – 199

10

Beta strand

208 – 212

5

Helix

214 – 218

5

Helix

220 – 228

9

Beta strand

232 – 240

9

Beta strand

244 – 255

12

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Membrane-bound) (MB-COMT) [UniParc]. Last modified May 1, 1992. Version 2. Checksum: F535DFF49C062854	FASTA	264	29,597
	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
	Isoform 2 (Soluble) (S-COMT). Checksum: C797794F205FA41D	FASTA	221	24,747
	10 20 30 40 50 60 MGDTKEQRIL RYVQQNAKPG DPQSVLEAID TYCTQKEWAM NVGDAKGQIM DAVIREYSPS 70 80 90 100 110 120 LVLELGAYCG YSAVRMARLL QPGARLLTME MNPDYAAITQ QMLNFAGLQD KVTILNGASQ 130 140 150 160 170 180 DLIPQLKKKY DVDTLDMVFL DHWKDRYLPD TLLLEKCGLL RKGTVLLADN VIVPGTPDFL 190 200 210 220 AYVRGSSSFE CTHYSSYLEY MKVVDGLEKA IYQGPSSPDK S

References

	« Hide 'large scale' referencesShow '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: 8280056] [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: 15489334] [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: 2227437] [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: 1765063] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-10, CHARACTERIZATION OF THE TWO FORMS.
[5]	"Phosphoproteomic analysis of rat liver by high capacity IMAC and LC-MS/MS." Moser K., White F.M. J. Proteome Res. 5:98-104(2006) [PubMed: 16396499] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-260, MASS SPECTROMETRY. Tissue: Liver.
[6]	"Crystal structure of catechol O-methyltransferase." Vidgren J., Svensson L.A., Liljas A. Nature 368:354-358(1994) [PubMed: 8127373] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 44-264.
[7]	"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: 10785817] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.63 ANGSTROMS) OF 44-264 IN COMPLEX WITH SUBSTRATE ANALOG.
[8]	"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: 12237326] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 44-264 IN COMPLEX WITH S-ADENOSYL-L-METHIONINE AND SUBSTRATE ANALOG.
[9]	"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: 16618795] [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

EMBLGenBankDDBJ

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.

IPI

IPI00210280.
IPI00760117.

PIR

S22090.

RefSeq

NP_036663.1.

UniGene

Rn.220

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1H1D	X-ray	2.00	A	44-264	[»]
1JR4	X-ray	2.63	A	44-264	[»]
1VID	X-ray	2.00	A	44-264	[»]
2CL5	X-ray	1.60	A/B	44-264	[»]
2ZLB	X-ray	2.20	A	44-264	[»]
2ZTH	X-ray	2.60	A	44-264	[»]
2ZVJ	X-ray	2.30	A	44-264	[»]

ModBase

Search...

PTM databases

PhosphoSite

P22734.

Proteomic databases

PRIDE

P22734.

Genome annotation databases

Ensembl

ENSRNOG00000001889. Rattus norvegicus. [Contig view]

GeneID

24267.

KEGG

rno:24267.

Organism-specific databases

RGD

2379. Comt.

Phylogenomic databases

HOVERGEN

P22734.

OMA

P22734. VVDGLEK.

Enzyme and pathway databases

BRENDA

2.1.1.6. 248.

Gene expression databases

ArrayExpress

P22734.

GermOnline

ENSRNOG00000001889. Rattus norvegicus.

Family and domain databases

InterPro

IPR017128. Catechol_O-MeTrfase_euk.
IPR002935. O-MeTrfase_3.
[Graphical view]

PANTHER

PTHR10509. Methyltransf_3. 1 hit.

Pfam

PF01596. Methyltransf_3. 1 hit.
[Graphical view]

PIRSF

PIRSF037177. Catechol_O-mtfrase_euk. 1 hit.

ProtoNet

Search...

Other Resources

NextBio

602825.

Entry information

Entry name

COMT_RAT

Accession

Primary (citable) accession number: P22734

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1991
Last sequence update:	May 1, 1992
Last modified:	June 16, 2009
This is version 101 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)