O88587 (COMT_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Catechol O-methyltransferase
EC=2.1.1.6

Gene names

Name:	Comt
Synonyms:	Comt1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	265 AA.
Sequence status	Complete.
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 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 methyltransferase superfamily. Catechol-O-methyltransferase family.

Ontologies

Keywords
Biological process	Catecholamine metabolism Neurotransmitter degradation
Cellular component	Cell membrane Cytoplasm Membrane
Coding sequence diversity	Alternative initiation
Domain	Signal-anchor Transmembrane Transmembrane helix
Ligand	Magnesium Metal-binding S-adenosyl-L-methionine
Molecular function	Methyltransferase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	catecholamine metabolic process Inferred from electronic annotation. Source: UniProtKB-KW dopamine catabolic process Inferred from direct assay PubMed 9520487. Source: MGI estrogen metabolic process Inferred from electronic annotation. Source: Compara female pregnancy Inferred from electronic annotation. Source: Compara learning Inferred from electronic annotation. Source: Compara multicellular organismal reproductive process Inferred from electronic annotation. Source: Compara negative regulation of dopamine metabolic process Inferred from electronic annotation. Source: Compara negative regulation of smooth muscle cell proliferation Inferred from electronic annotation. Source: Compara neurotransmitter catabolic process Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of homocysteine metabolic process Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara response to lipopolysaccharide Inferred from electronic annotation. Source: Compara response to organic cyclic compound Inferred from electronic annotation. Source: Compara response to pain Inferred from electronic annotation. Source: Compara
Cellular_component	integral to 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_function	catechol 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 265	265	Catechol O-methyltransferase		PRO_0000020973
Regions
	Transmembrane	3 – 19	17	Helical; Signal-anchor for type II membrane protein; Potential
	Region	160 – 163	4	S-adenosyl-L-methionine binding By similarity
Sites
	Metal binding	184	1	Magnesium By similarity
	Metal binding	212	1	Magnesium By similarity
	Metal binding	213	1	Magnesium By similarity
	Binding site	85	1	S-adenosyl-L-methionine; via amide nitrogen By similarity
	Binding site	115	1	S-adenosyl-L-methionine By similarity
	Binding site	133	1	S-adenosyl-L-methionine By similarity
	Binding site	184	1	S-adenosyl-L-methionine By similarity
	Binding site	187	1	Substrate By similarity
	Binding site	213	1	Substrate By similarity
	Binding site	242	1	Substrate By similarity
Amino acid modifications
	Modified residue	261	1	Phosphoserine Ref.5 Ref.7
Natural variations
	Alternative sequence	1 – 43	43	Missing in isoform Soluble.		VSP_018779
Experimental info
	Mutagenesis	51	1	R → L: Reduces methyltransferase activity against norepinephrine. Ref.6
	Sequence conflict	162	1	S → P in AAC33334. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform Membrane-bound (MB-COMT) [UniParc]. Last modified October 3, 2012. Version 2. Checksum: E82E9307F6D8A6CF	FASTA	265	29,486
	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
	Isoform Soluble (S-COMT) [UniParc]. Checksum: C7D5BB1ADC5B40B2	FASTA	222	24,707
	10 20 30 40 50 60 MGGTKEQRIL RHVQQHAKPG DPQSVLEAID TYCSEKEWAM NVGDAKGQIM DAVIREYRPS 70 80 90 100 110 120 LVLELGAYCG YSAVRMARLL PPGARLLTME INPDYAAITQ QMLDFAGLQD KVSILIGASQ 130 140 150 160 170 180 DLIPQLKKKY DVDTLDMVFL DHWKDRYLPD TLLLEECGLL RKGTVLLADN VIVPGTPDFL 190 200 210 220 AYVRGSSSFE CTHYSSYLEY MKVVDGLEKA VYQGPGSSPV KS

References

	« Hide 'large scale' referencesShow '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. , 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. , 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, MASS SPECTROMETRY. 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]	"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, MASS SPECTROMETRY. 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.
IPI	IPI00132076. IPI00759876.
RefSeq	NP_001104532.1. NM_001111062.1. NP_001104533.1. NM_001111063.1. NP_031770.2. NM_007744.3.
UniGene	Mm.100940.
3D structure databases
ProteinModelPortal	O88587.
SMR	O88587. Positions 47-258.
ModBase	Search...
Protein-protein interaction databases
STRING	10090.ENSMUSP00000111272.
PTM databases
PhosphoSite	O88587.
Proteomic databases
PaxDb	O88587.
PRIDE	O88587.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000000335; ENSMUSP00000000335; ENSMUSG00000000326. ENSMUST00000115609; ENSMUSP00000111272; ENSMUSG00000000326. ENSMUST00000165430; ENSMUSP00000130077; ENSMUSG00000000326.
GeneID	12846.
KEGG	mmu:12846.
Organism-specific databases
CTD	1312.
MGI	MGI:88470. Comt.
Phylogenomic databases
eggNOG	COG4122.
GeneTree	ENSGT00390000011316.
HOGENOM	HOG000046392.
HOVERGEN	HBG005376.
InParanoid	O88587.
KO	K00545.
OMA	ICPGAPD.
OrthoDB	EOG4G1MH8.
Gene expression databases
Genevestigator	O88587.
GermOnline	ENSMUSG00000000326. Mus musculus.
Family and domain databases
InterPro	IPR025782. Catechol_O-MeTrfase. IPR017128. Catechol_O-MeTrfase_euk. IPR002935. O-MeTrfase_3. [Graphical view]
PANTHER	PTHR10509. PTHR10509. 1 hit.
Pfam	PF01596. Methyltransf_3. 1 hit. [Graphical view]
PIRSF	PIRSF037177. Catechol_O-mtfrase_euk. 1 hit.
ProtoNet	Search...
Other
NextBio	282388.
SOURCE	Search...

Entry information

Entry name

COMT_MOUSE

Accession

Primary (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:	May 1, 2013
This is version 112 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program