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Protein

Catechol O-methyltransferase

Gene

Comt

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.

Catalytic activityi

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

Cofactori

Mg2+By similarityNote: Binds 1 Mg2+ ion per subunit.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei85 – 851S-adenosyl-L-methionine; via amide nitrogenPROSITE-ProRule annotation
Binding sitei107 – 1071S-adenosyl-L-methioninePROSITE-ProRule annotation
Binding sitei115 – 1151S-adenosyl-L-methioninePROSITE-ProRule annotation
Binding sitei133 – 1331S-adenosyl-L-methioninePROSITE-ProRule annotation
Binding sitei134 – 1341S-adenosyl-L-methionine; via amide nitrogenPROSITE-ProRule annotation
Binding sitei162 – 1621S-adenosyl-L-methionine; via amide nitrogenPROSITE-ProRule annotation
Metal bindingi184 – 1841MagnesiumBy similarity
Binding sitei184 – 1841S-adenosyl-L-methioninePROSITE-ProRule annotation
Binding sitei187 – 1871SubstrateBy similarity
Metal bindingi212 – 2121MagnesiumBy similarity
Metal bindingi213 – 2131MagnesiumBy similarity
Binding sitei213 – 2131SubstrateBy similarity
Binding sitei242 – 2421SubstrateBy similarity

GO - Molecular functioni

  • catechol O-methyltransferase activity Source: MGI
  • magnesium ion binding Source: InterPro

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Methyltransferase, Transferase

Keywords - Biological processi

Catecholamine metabolism, Neurotransmitter degradation

Keywords - Ligandi

Magnesium, Metal-binding, S-adenosyl-L-methionine

Enzyme and pathway databases

ReactomeiREACT_283123. Methylation.
REACT_292468. Enzymatic degradation of Dopamine by monoamine oxidase.
REACT_329048. Enzymatic degradation of dopamine by COMT.
SABIO-RKO88587.

Names & Taxonomyi

Protein namesi
Recommended name:
Catechol O-methyltransferase (EC:2.1.1.6)
Gene namesi
Name:Comt
Synonyms:Comt1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componentsi: Chromosome 16, Unplaced

Organism-specific databases

MGIiMGI:88470. Comt.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 22CytoplasmicSequence Analysis
Transmembranei3 – 1917Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
BLAST
Topological domaini20 – 265246ExtracellularSequence AnalysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi51 – 511R → L: Reduces methyltransferase activity against norepinephrine. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 265265Catechol O-methyltransferasePRO_0000020973Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei261 – 2611Phosphoserine2 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiO88587.
PaxDbiO88587.
PRIDEiO88587.

PTM databases

PhosphoSiteiO88587.

Expressioni

Gene expression databases

ExpressionAtlasiO88587. baseline and differential.
GenevestigatoriO88587.

Interactioni

Protein-protein interaction databases

IntActiO88587. 3 interactions.
MINTiMINT-1854931.
STRINGi10090.ENSMUSP00000111272.

Structurei

Secondary structure

1
265
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi48 – 5912Combined sources
Helixi65 – 7814Combined sources
Beta strandi81 – 833Combined sources
Helixi85 – 884Combined sources
Helixi90 – 10011Combined sources
Beta strandi103 – 1086Combined sources
Beta strandi111 – 1133Combined sources
Helixi114 – 1207Combined sources
Beta strandi128 – 1347Combined sources
Helixi136 – 14914Combined sources
Helixi152 – 1543Combined sources
Beta strandi155 – 1606Combined sources
Helixi162 – 1654Combined sources
Helixi166 – 1683Combined sources
Helixi169 – 1735Combined sources
Beta strandi178 – 1836Combined sources
Helixi187 – 1893Combined sources
Helixi190 – 19910Combined sources
Beta strandi203 – 21210Combined sources
Helixi220 – 2289Combined sources
Beta strandi232 – 2398Combined sources
Beta strandi243 – 2453Combined sources
Beta strandi247 – 2559Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4P58X-ray2.06A47-258[»]
4P7FX-ray1.37A44-265[»]
ProteinModelPortaliO88587.
SMRiO88587. Positions 46-258.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni160 – 1634S-adenosyl-L-methionine bindingPROSITE-ProRule annotation

Sequence similaritiesi

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

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG4122.
GeneTreeiENSGT00390000011316.
HOGENOMiHOG000046392.
HOVERGENiHBG005376.
InParanoidiO88587.
KOiK00545.
OMAiCTHYSSY.
OrthoDBiEOG7PZRZJ.
TreeFamiTF329140.

Family and domain databases

Gene3Di3.40.50.150. 1 hit.
InterProiIPR017128. Catechol_O-MeTrfase_euk.
IPR002935. O-MeTrfase_3.
IPR029063. SAM-dependent_MTases.
[Graphical view]
PANTHERiPTHR10509. PTHR10509. 1 hit.
PfamiPF01596. Methyltransf_3. 1 hit.
[Graphical view]
PIRSFiPIRSF037177. Catechol_O-mtfrase_euk. 1 hit.
SUPFAMiSSF53335. SSF53335. 1 hit.
PROSITEiPS51682. SAM_OMT_I. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative initiation. AlignAdd to basket

Isoform Membrane-bound (identifier: O88587-1) [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
MLLAAVSLGL LLLAFLLLLR HLGWGLVAIG WFEFVQQPVH NLLMGGTKEQ
60 70 80 90 100
RILRHVQQHA KPGDPQSVLE AIDTYCSEKE WAMNVGDAKG QIMDAVIREY
110 120 130 140 150
RPSLVLELGA YCGYSAVRMA RLLPPGARLL TMEINPDYAA ITQQMLDFAG
160 170 180 190 200
LQDKVSILIG ASQDLIPQLK KKYDVDTLDM VFLDHWKDRY LPDTLLLEEC
210 220 230 240 250
GLLRKGTVLL ADNVIVPGTP DFLAYVRGSS SFECTHYSSY LEYMKVVDGL
260
EKAVYQGPGS SPVKS
Length:265
Mass (Da):29,486
Last modified:October 3, 2012 - v2
Checksum:iE82E9307F6D8A6CF
GO
Isoform Soluble (identifier: O88587-2) [UniParc]FASTAAdd to basket

Also known as: S-COMT

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

Show »
Length:222
Mass (Da):24,707
Checksum:iC7D5BB1ADC5B40B2
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti162 – 1621S → P in AAC33334 (PubMed:9707588).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 4343Missing in isoform Soluble. CuratedVSP_018779Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF076156 mRNA. Translation: AAC33334.1.
AK148311 mRNA. Translation: BAE28473.1.
AC133487 Genomic DNA. No translation available.
BC010402 mRNA. Translation: AAH10402.1.
CCDSiCCDS28021.1. [O88587-1]
RefSeqiNP_001104532.1. NM_001111062.1. [O88587-1]
NP_001104533.1. NM_001111063.1. [O88587-1]
NP_031770.2. NM_007744.3. [O88587-1]
UniGeneiMm.100940.

Genome annotation databases

EnsembliENSMUST00000000335; ENSMUSP00000000335; ENSMUSG00000000326. [O88587-1]
ENSMUST00000115609; ENSMUSP00000111272; ENSMUSG00000000326. [O88587-1]
ENSMUST00000165430; ENSMUSP00000130077; ENSMUSG00000000326. [O88587-1]
ENSMUST00000183626; ENSMUSP00000138930; ENSMUSG00000098892. [O88587-1]
ENSMUST00000185030; ENSMUSP00000139196; ENSMUSG00000098892. [O88587-1]
ENSMUST00000195169; ENSMUSP00000141683; ENSMUSG00000098892. [O88587-1]
GeneIDi12846.
KEGGimmu:12846.
UCSCiuc007ynu.2. mouse.

Keywords - Coding sequence diversityi

Alternative initiation

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF076156 mRNA. Translation: AAC33334.1.
AK148311 mRNA. Translation: BAE28473.1.
AC133487 Genomic DNA. No translation available.
BC010402 mRNA. Translation: AAH10402.1.
CCDSiCCDS28021.1. [O88587-1]
RefSeqiNP_001104532.1. NM_001111062.1. [O88587-1]
NP_001104533.1. NM_001111063.1. [O88587-1]
NP_031770.2. NM_007744.3. [O88587-1]
UniGeneiMm.100940.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4P58X-ray2.06A47-258[»]
4P7FX-ray1.37A44-265[»]
ProteinModelPortaliO88587.
SMRiO88587. Positions 46-258.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiO88587. 3 interactions.
MINTiMINT-1854931.
STRINGi10090.ENSMUSP00000111272.

Chemistry

ChEMBLiCHEMBL3286068.

PTM databases

PhosphoSiteiO88587.

Proteomic databases

MaxQBiO88587.
PaxDbiO88587.
PRIDEiO88587.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000000335; ENSMUSP00000000335; ENSMUSG00000000326. [O88587-1]
ENSMUST00000115609; ENSMUSP00000111272; ENSMUSG00000000326. [O88587-1]
ENSMUST00000165430; ENSMUSP00000130077; ENSMUSG00000000326. [O88587-1]
ENSMUST00000183626; ENSMUSP00000138930; ENSMUSG00000098892. [O88587-1]
ENSMUST00000185030; ENSMUSP00000139196; ENSMUSG00000098892. [O88587-1]
ENSMUST00000195169; ENSMUSP00000141683; ENSMUSG00000098892. [O88587-1]
GeneIDi12846.
KEGGimmu:12846.
UCSCiuc007ynu.2. mouse.

Organism-specific databases

CTDi1312.
MGIiMGI:88470. Comt.

Phylogenomic databases

eggNOGiCOG4122.
GeneTreeiENSGT00390000011316.
HOGENOMiHOG000046392.
HOVERGENiHBG005376.
InParanoidiO88587.
KOiK00545.
OMAiCTHYSSY.
OrthoDBiEOG7PZRZJ.
TreeFamiTF329140.

Enzyme and pathway databases

ReactomeiREACT_283123. Methylation.
REACT_292468. Enzymatic degradation of Dopamine by monoamine oxidase.
REACT_329048. Enzymatic degradation of dopamine by COMT.
SABIO-RKO88587.

Miscellaneous databases

NextBioi282388.
PROiO88587.
SOURCEiSearch...

Gene expression databases

ExpressionAtlasiO88587. baseline and differential.
GenevestigatoriO88587.

Family and domain databases

Gene3Di3.40.50.150. 1 hit.
InterProiIPR017128. Catechol_O-MeTrfase_euk.
IPR002935. O-MeTrfase_3.
IPR029063. SAM-dependent_MTases.
[Graphical view]
PANTHERiPTHR10509. PTHR10509. 1 hit.
PfamiPF01596. Methyltransf_3. 1 hit.
[Graphical view]
PIRSFiPIRSF037177. Catechol_O-mtfrase_euk. 1 hit.
SUPFAMiSSF53335. SSF53335. 1 hit.
PROSITEiPS51682. SAM_OMT_I. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-261, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  6. 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.

Entry informationi

Entry nameiCOMT_MOUSE
AccessioniPrimary (citable) accession number: O88587
Secondary accession number(s): Q91XH4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: October 3, 2012
Last modified: May 27, 2015
This is version 133 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.