TOMT_DANRE
ID TOMT_DANRE Reviewed; 259 AA.
AC A0A193KX02;
DT 25-OCT-2017, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2016, sequence version 1.
DT 03-AUG-2022, entry version 26.
DE RecName: Full=Transmembrane O-methyltransferase homolog {ECO:0000305};
DE EC=2.1.1.6 {ECO:0000250|UniProtKB:P21964};
DE AltName: Full=Protein mercury {ECO:0000303|PubMed:9491988};
GN Name=tomt {ECO:0000303|PubMed:28534737,
GN ECO:0000312|ZFIN:ZDB-GENE-160629-1};
GN Synonyms=mrc {ECO:0000303|PubMed:9491988};
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;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=28534737; DOI=10.7554/elife.28474;
RA Erickson T., Morgan C.P., Olt J., Hardy K., Busch-Nentwich E., Maeda R.,
RA Clemens R., Krey J.F., Nechiporuk A., Barr-Gillespie P.G., Marcotti W.,
RA Nicolson T.;
RT "Integration of Tmc1/2 into the mechanotransduction complex in zebrafish
RT hair cells is regulated by Transmembrane O-methyltransferase (Tomt).";
RL Elife 6:0-0(2017).
RN [2]
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]
RP IDENTIFICATION, AND DISRUPTION PHENOTYPE.
RX PubMed=9491988; DOI=10.1016/s0896-6273(00)80455-9;
RA Nicolson T., Ruesch A., Friedrich R.W., Granato M., Ruppersberg J.P.,
RA Nuesslein-Volhard C.;
RT "Genetic analysis of vertebrate sensory hair cell mechanosensation: the
RT zebrafish circler mutants.";
RL Neuron 20:271-283(1998).
CC -!- FUNCTION: Catalyzes the O-methylation, and thereby the inactivation, of
CC catecholamine neurotransmitters and catechol hormones (By similarity).
CC Required for auditory function. Component of the hair cell's
CC mechanotransduction (MET) machinery. Involved in the assembly of the
CC asymmetric tip-link MET complex. Required for transportation of TMC1
CC and TMC2 proteins into the mechanically sensitive stereocilia of the
CC hair cells. The function in MET is independent of the enzymatic
CC activity (PubMed:28534737). {ECO:0000250|UniProtKB:P21964,
CC ECO:0000269|PubMed:28534737}.
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:0000250|UniProtKB:P21964};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC {ECO:0000269|PubMed:28534737}. Golgi apparatus
CC {ECO:0000269|PubMed:28534737}. Basolateral cell membrane
CC {ECO:0000269|PubMed:28534737}. Note=Enriched in an apical membrane
CC compartment above the nucleus in the hair cells. Not detectable in the
CC hair bundle. May be present at lower levels in the endoplasmic
CC reticulum and the basolateral membrane. {ECO:0000269|PubMed:28534737}.
CC -!- DEVELOPMENTAL STAGE: At 28 hr post-fertilization (hpf), expressed
CC exclusively in the hair cells of the anterior and posterior maculae in
CC the developing ear. At 4 days post-fertilization (dpf), expressed
CC specifically in hair cells of the inner ear and lateral line organ.
CC {ECO:0000269|PubMed:28534737}.
CC -!- DISRUPTION PHENOTYPE: Originally identified in a genetic screen for
CC genes required for hearing and balance. The mercury circler mutant
CC phenotype is characterized by balance defects, an absence of the
CC acoustic startle reflex, failure to inflate the swim bladder, lack of
CC hair cell-dependent calcium responses in the hindbrain, and
CC undetectable microphonic currents. No morphological defects in the
CC sensory hair cell bundles nor epithelium. {ECO:0000269|PubMed:9491988}.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. Cation-dependent O-methyltransferase family.
CC {ECO:0000305}.
CC -!- CAUTION: Despite its name, the zebrafish TOMT protein is not predicted
CC to contain a transmembrane region in contrast to primate orthologs.
CC {ECO:0000305}.
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DR EMBL; KX066099; ANO40802.1; -; mRNA.
DR EMBL; CZQB01095947; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CZQB01095951; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; A0A193KX02; -.
DR SMR; A0A193KX02; -.
DR Ensembl; ENSDART00000190231; ENSDARP00000145949; ENSDARG00000115463.
DR ZFIN; ZDB-GENE-160629-1; tomt.
DR GeneTree; ENSGT00940000161220; -.
DR OrthoDB; 1274244at2759; -.
DR Reactome; R-DRE-379397; Enzymatic degradation of dopamine by COMT.
DR PRO; PR:A0A193KX02; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 15.
DR Bgee; ENSDARG00000115463; Expressed in neuromast hair cell and 6 other tissues.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0016206; F:catechol O-methyltransferase activity; ISS:UniProtKB.
DR GO; GO:0102084; F:L-dopa O-methyltransferase activity; IEA:UniProtKB-EC.
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:0031223; P:auditory behavior; IMP:UniProtKB.
DR GO; GO:0042424; P:catecholamine catabolic process; ISS:UniProtKB.
DR GO; GO:0050974; P:detection of mechanical stimulus involved in sensory perception; IMP:ZFIN.
DR GO; GO:0032502; P:developmental process; IBA:GO_Central.
DR GO; GO:0042417; P:dopamine metabolic process; IBA:GO_Central.
DR GO; GO:0006897; P:endocytosis; IMP:ZFIN.
DR GO; GO:0035315; P:hair cell differentiation; IMP:ZFIN.
DR GO; GO:0060122; P:inner ear receptor cell stereocilium organization; IMP:ZFIN.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0048884; P:neuromast development; IMP:ZFIN.
DR GO; GO:0042135; P:neurotransmitter catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0007605; P:sensory perception of sound; IEA:UniProtKB-KW.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR002935; SAM_O-MeTrfase.
DR InterPro; IPR033025; TOMT.
DR PANTHER; PTHR43836:SF1; PTHR43836:SF1; 1.
DR Pfam; PF01596; Methyltransf_3; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS51682; SAM_OMT_I; 1.
PE 2: Evidence at transcript level;
KW Catecholamine metabolism; Cell membrane; Deafness; Endoplasmic reticulum;
KW Golgi apparatus; Hearing; Membrane; Methyltransferase;
KW Neurotransmitter degradation; Reference proteome; S-adenosyl-L-methionine;
KW Transferase.
FT CHAIN 1..259
FT /note="Transmembrane O-methyltransferase homolog"
FT /id="PRO_0000441917"
FT REGION 1..45
FT /note="Sufficient for localization to the Golgi apparatus"
FT /evidence="ECO:0000269|PubMed:28534737"
FT BINDING 83
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT BINDING 105
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT BINDING 107..108
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT BINDING 113
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT BINDING 131
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT BINDING 161
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
SQ SEQUENCE 259 AA; 29608 MW; EFED3342D025C6D4 CRC64;
MVSPAIALAF LPLLLTLIIR YRYYFVLLYR AVLTRWVRDC LSGISREERA FQYILTHATP
GDSQSILDTF DTWCSKVEFI SNIGPKKGKI LDRLLQENCP ITVLELGTHC GYSTVRMARS
LPIGARIYSV EMDQRNAQVA EKIIRLAGFD DDMVELIQRP SDEVIPRLRE DLGVERLDLV
LMDHWKRCYL PDLHLLEDSG LIGQGSIILA DNVIFPGAPN FLRYARRCGL YEVRVHRATL
EYMRGIPDGM AELTYIGIK
