COMTA_DANRE
ID COMTA_DANRE Reviewed; 256 AA.
AC F4ZGF2; F1QFV7; Q4V8T4;
DT 18-JUL-2018, integrated into UniProtKB/Swiss-Prot.
DT 28-JUN-2011, sequence version 1.
DT 03-AUG-2022, entry version 57.
DE RecName: Full=Catechol O-methyltransferase A {ECO:0000303|PubMed:28844929};
DE EC=2.1.1.6 {ECO:0000255|PROSITE-ProRule:PRU01019, ECO:0000269|PubMed:21371608};
DE Flags: Precursor;
GN Name=comta {ECO:0000303|PubMed:28844929};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955 {ECO:0000312|Proteomes:UP000000437};
RN [1] {ECO:0000312|EMBL:ADM47479.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=21371608; DOI=10.1016/j.aquatox.2010.12.016;
RA Alazizi A., Liu M.Y., Williams F.E., Kurogi K., Sakakibara Y., Suiko M.,
RA Liu M.C.;
RT "Identification, characterization, and ontogenic study of a catechol O-
RT methyltransferase from zebrafish.";
RL Aquat. Toxicol. 102:18-23(2011).
RN [2] {ECO:0000312|Proteomes:UP000000437}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [3] {ECO:0000312|EMBL:AAH97207.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Larva {ECO:0000312|EMBL:AAH97207.1};
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000305}
RP TISSUE SPECIFICITY.
RX PubMed=28844929; DOI=10.1016/j.bcp.2017.08.017;
RA Semenova S., Rozov S., Panula P.;
RT "Distribution, properties, and inhibitor sensitivity of zebrafish catechol-
RT O-methyl transferases (COMT).";
RL Biochem. Pharmacol. 145:147-157(2017).
CC -!- FUNCTION: Catalyzes the O-methylation, and thereby the inactivation, of
CC catecholamine neurotransmitters and catechol hormones. Shows highest
CC activity towards catecholestrogens and dobutamine. Also has lower
CC activity towards L-DOPA, dopamine and epinephrine. Active towards the
CC xenobiotic compounds methyl-DOPA, carbidopa, isoproterenol, and
CC apomorphine. {ECO:0000269|PubMed:21371608}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a catechol + S-adenosyl-L-methionine = a guaiacol + H(+) + S-
CC adenosyl-L-homocysteine; Xref=Rhea:RHEA:17877, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:33566, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:134251; EC=2.1.1.6;
CC Evidence={ECO:0000269|PubMed:21371608};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|PIRSR:PIRSR037177-3};
CC Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000255|PIRSR:PIRSR037177-3};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.5-10.5. Active from pH 5.5-11.5.
CC {ECO:0000269|PubMed:21371608};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=F4ZGF2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=F4ZGF2-2; Sequence=VSP_059648, VSP_059649;
CC -!- TISSUE SPECIFICITY: Widely expressed (PubMed:28844929). Has higher
CC expression in females compared to males (PubMed:21371608). Strongly
CC expressed in liver and diencephalon (PubMed:28844929). Expressed at
CC lower levels in hindbrain, spinal cord, eye, telencephalon, spleen,
CC gut, gill and muscle (PubMed:28844929). Detected in ovary and testis
CC (PubMed:28844929). In eye, detected in all layers of the retina with
CC highest expression in the inner nuclear layer (PubMed:28844929). In
CC gut, expressed in the lamina propria but has little or no expression in
CC gut epithelium (PubMed:28844929). In brain, has strongest expression
CC near the midline of the telencephalon, in the periventricular gray zone
CC of the optic tectum, in the preglomerular nucleus, and near the walls
CC of the diencephalic ventricle (PubMed:28844929).
CC {ECO:0000269|PubMed:21371608, ECO:0000269|PubMed:28844929}.
CC -!- DEVELOPMENTAL STAGE: Highly expressed in unfertilized eggs. Has low
CC expression during embryogenesis. Expression then increases after
CC hatching (48 hours post-fertilization), reaching maximum levels at 3
CC weeks of age. {ECO:0000269|PubMed:21371608}.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. Cation-dependent O-methyltransferase family.
CC {ECO:0000255|PROSITE-ProRule:PRU01019}.
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DR EMBL; HM997189; ADM47479.1; -; mRNA.
DR EMBL; CR457452; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC097207; AAH97207.1; -; mRNA.
DR RefSeq; NP_001025328.2; NM_001030157.2. [F4ZGF2-1]
DR RefSeq; XP_005166768.1; XM_005166711.3. [F4ZGF2-1]
DR AlphaFoldDB; F4ZGF2; -.
DR SMR; F4ZGF2; -.
DR STRING; 7955.ENSDARP00000119183; -.
DR Ensembl; ENSDART00000014939; ENSDARP00000024187; ENSDARG00000015337. [F4ZGF2-2]
DR Ensembl; ENSDART00000186684; ENSDARP00000156115; ENSDARG00000015337. [F4ZGF2-1]
DR GeneID; 561372; -.
DR KEGG; dre:561372; -.
DR CTD; 561372; -.
DR ZFIN; ZDB-GENE-050913-117; comta.
DR GeneTree; ENSGT00940000155317; -.
DR HOGENOM; CLU_050461_5_1_1; -.
DR OrthoDB; 1274244at2759; -.
DR Reactome; R-DRE-156581; Methylation.
DR Reactome; R-DRE-379397; Enzymatic degradation of dopamine by COMT.
DR Reactome; R-DRE-379398; Enzymatic degradation of Dopamine by monoamine oxidase.
DR PRO; PR:F4ZGF2; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 8.
DR Bgee; ENSDARG00000015337; Expressed in liver and 29 other tissues.
DR ExpressionAtlas; F4ZGF2; baseline.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016206; F:catechol O-methyltransferase activity; IDA:ZFIN.
DR GO; GO:0102084; F:L-dopa O-methyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0008171; F:O-methyltransferase activity; IBA:GO_Central.
DR GO; GO:0102938; F:orcinol O-methyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0042424; P:catecholamine catabolic process; IBA:GO_Central.
DR GO; GO:0032502; P:developmental process; IBA:GO_Central.
DR GO; GO:0042417; P:dopamine metabolic process; IBA:GO_Central.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0042135; P:neurotransmitter catabolic process; IEA:UniProtKB-KW.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR017128; Catechol_O-MeTrfase_euk.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR002935; SAM_O-MeTrfase.
DR Pfam; PF01596; Methyltransf_3; 1.
DR PIRSF; PIRSF037177; Catechol_O-mtfrase_euk; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS51682; SAM_OMT_I; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Catecholamine metabolism; Glycoprotein; Magnesium;
KW Metal-binding; Methyltransferase; Neurotransmitter degradation;
KW Reference proteome; S-adenosyl-L-methionine; Secreted; Signal; Transferase.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..256
FT /note="Catechol O-methyltransferase A"
FT /evidence="ECO:0000255"
FT /id="PRO_0000444753"
FT BINDING 84
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PIRSR:PIRSR037177-1"
FT BINDING 114
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PIRSR:PIRSR037177-1"
FT BINDING 132
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PIRSR:PIRSR037177-1"
FT BINDING 183
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|PIRSR:PIRSR037177-3"
FT BINDING 183
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PIRSR:PIRSR037177-1"
FT BINDING 186
FT /ligand="substrate"
FT /evidence="ECO:0000255|PIRSR:PIRSR037177-2"
FT BINDING 211
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|PIRSR:PIRSR037177-3"
FT BINDING 212
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|PIRSR:PIRSR037177-3"
FT BINDING 212
FT /ligand="substrate"
FT /evidence="ECO:0000255|PIRSR:PIRSR037177-2"
FT BINDING 241
FT /ligand="substrate"
FT /evidence="ECO:0000255|PIRSR:PIRSR037177-2"
FT CARBOHYD 58
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT VAR_SEQ 137..143
FT /note="YAAIARQ -> RAVVEEI (in isoform 2)"
FT /id="VSP_059648"
FT VAR_SEQ 144..256
FT /note="Missing (in isoform 2)"
FT /id="VSP_059649"
FT CONFLICT 24
FT /note="G -> D (in Ref. 3; AAH97207)"
FT /evidence="ECO:0000305"
FT CONFLICT 40
FT /note="N -> D (in Ref. 3; AAH97207)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 256 AA; 28719 MW; 64E9FA6F842D2075 CRC64;
MLWVVLAVVV VLASVLVLLR QSSGLLALLW HDVVHQRLLN FFTGLSRPQR ILKAVQKNAT
KGNPESVIAA IDHYCRHSEW AMNVGDEKGL ILDSVVTEVN PSTALELGTY CGYSTVRIAR
LLSPGTKLIT LEFNPDYAAI ARQIIAYAGL QDKVILVEGP SGDLIPKMKQ QHGIKSFDFV
FLDHWKDRYV PDTKLLEECG LLRKGSVLLA DNVICPGTPE YLKYVRNDPR YESRYFKSNL
EYTKVEDGLE KSVFLG
