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O88587 (COMT_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 124. 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
Synonyms:Comt1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length265 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 By similarity.

Subcellular location

Isoform Soluble: Cytoplasm.

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

Sequence similarities

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

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
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcatechol-containing compound metabolic process

Inferred from mutant phenotype PubMed 19930170. Source: MGI

cellular response to phosphate starvation

Inferred from direct assay PubMed 23863468. Source: MGI

dopamine catabolic process

Inferred from direct assay PubMed 9520487. Source: MGI

dopamine metabolic process

Inferred from direct assay PubMed 23863468. Source: MGI

estrogen metabolic process

Inferred from electronic annotation. Source: Ensembl

female pregnancy

Inferred from electronic annotation. Source: Ensembl

learning

Inferred from electronic annotation. Source: Ensembl

multicellular organismal reproductive process

Inferred from electronic annotation. Source: Ensembl

negative regulation of dopamine metabolic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of smooth muscle cell proliferation

Inferred from electronic annotation. Source: Ensembl

neurotransmitter catabolic process

Inferred from electronic annotation. Source: UniProtKB-KW

positive regulation of homocysteine metabolic process

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

response to lipopolysaccharide

Inferred from electronic annotation. Source: Ensembl

response to organic cyclic compound

Inferred from electronic annotation. Source: Ensembl

response to pain

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentintegral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

mitochondrion

Inferred from direct assay PubMed 18614015. Source: MGI

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functioncatechol O-methyltransferase activity

Inferred from direct assay PubMed 20374420. Source: MGI

magnesium ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative initiation. [Align] [Select]
Isoform Membrane-bound (identifier: O88587-1)

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.
Isoform Soluble (identifier: O88587-2)

Also known as: 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 – 265265Catechol O-methyltransferase
PRO_0000020973

Regions

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

Sites

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

Amino acid modifications

Modified residue2611Phosphoserine Ref.5 Ref.8

Natural variations

Alternative sequence1 – 4343Missing in isoform Soluble.
VSP_018779

Experimental info

Mutagenesis511R → L: Reduces methyltransferase activity against norepinephrine. Ref.6
Sequence conflict1621S → P in AAC33334. Ref.1

Sequences

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

Last modified October 3, 2012. Version 2.
Checksum: E82E9307F6D8A6CF

FASTA26529,486
        10         20         30         40         50         60 
MLLAAVSLGL LLLAFLLLLR HLGWGLVAIG WFEFVQQPVH NLLMGGTKEQ RILRHVQQHA 

        70         80         90        100        110        120 
KPGDPQSVLE AIDTYCSEKE WAMNVGDAKG QIMDAVIREY RPSLVLELGA YCGYSAVRMA 

       130        140        150        160        170        180 
RLLPPGARLL TMEINPDYAA ITQQMLDFAG LQDKVSILIG ASQDLIPQLK KKYDVDTLDM 

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

       250        260 
LEYMKVVDGL EKAVYQGPGS SPVKS 

« Hide

Isoform Soluble (S-COMT) [UniParc].

Checksum: C7D5BB1ADC5B40B2
Show »

FASTA22224,707

References

« Hide 'large scale' references
[1]"Catechol-O-methyltransferase-deficient mice exhibit sexually dimorphic changes in catecholamine levels and behavior."
Gogos J.A., Morgan M., Luine V., Santha M., Ogawa S., Pfaff D., Karayiorgou M.
Proc. Natl. Acad. Sci. U.S.A. 95:9991-9996(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
[3]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[4]"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].
Strain: FVB/N.
Tissue: Liver.
[5]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-261, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[6]"A catechol-O-methyltransferase that is essential for auditory function in mice and humans."
Du X., Schwander M., Moresco E.M.Y., Viviani P., Haller C., Hildebrand M.S., Pak K., Tarantino L., Roberts A., Richardson H., Koob G., Najmabadi H., Ryan A.F., Smith R.J.H., Mueller U., Beutler B.
Proc. Natl. Acad. Sci. U.S.A. 105:14609-14614(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF ARG-51.
[7]"The phagosomal proteome in interferon-gamma-activated macrophages."
Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]"Large scale localization of protein phosphorylation by use of electron capture dissociation mass spectrometry."
Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.
Mol. Cell. Proteomics 8:904-912(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-261, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic fibroblast.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF076156 mRNA. Translation: AAC33334.1.
AK148311 mRNA. Translation: BAE28473.1.
AC133487 Genomic DNA. No translation available.
BC010402 mRNA. Translation: AAH10402.1.
CCDSCCDS28021.1. [O88587-1]
RefSeqNP_001104532.1. NM_001111062.1. [O88587-1]
NP_001104533.1. NM_001111063.1. [O88587-1]
NP_031770.2. NM_007744.3. [O88587-1]
UniGeneMm.100940.

3D structure databases

ProteinModelPortalO88587.
SMRO88587. Positions 47-258.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActO88587. 3 interactions.
MINTMINT-1854931.
STRING10090.ENSMUSP00000111272.

PTM databases

PhosphoSiteO88587.

Proteomic databases

PaxDbO88587.
PRIDEO88587.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000000335; ENSMUSP00000000335; ENSMUSG00000000326. [O88587-1]
ENSMUST00000115609; ENSMUSP00000111272; ENSMUSG00000000326. [O88587-1]
ENSMUST00000165430; ENSMUSP00000130077; ENSMUSG00000000326. [O88587-1]
ENSMUST00000183626; ENSMUSP00000138930; ENSMUSG00000098892. [O88587-1]
ENSMUST00000185030; ENSMUSP00000139196; ENSMUSG00000098892. [O88587-1]
GeneID12846.
KEGGmmu:12846.
UCSCuc007ynu.2. mouse.

Organism-specific databases

CTD1312.
MGIMGI:88470. Comt.

Phylogenomic databases

eggNOGCOG4122.
GeneTreeENSGT00390000011316.
HOGENOMHOG000046392.
HOVERGENHBG005376.
InParanoidO88587.
KOK00545.
OMACTHYSSY.
OrthoDBEOG7PZRZJ.
TreeFamTF329140.

Enzyme and pathway databases

SABIO-RKO88587.

Gene expression databases

ArrayExpressO88587.
GenevestigatorO88587.

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

NextBio282388.
PROO88587.
SOURCESearch...

Entry information

Entry nameCOMT_MOUSE
AccessionPrimary (citable) accession number: O88587
Secondary accession number(s): Q91XH4
Entry history
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: October 3, 2012
Last modified: July 9, 2014
This is version 124 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

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot