TOMT_RAT
ID TOMT_RAT Reviewed; 258 AA.
AC B6CZ62;
DT 05-MAY-2009, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 1.
DT 03-AUG-2022, entry version 75.
DE RecName: Full=Transmembrane O-methyltransferase homolog {ECO:0000312|RGD:1561509};
DE EC=2.1.1.6 {ECO:0000250|UniProtKB:A1Y9I9};
DE AltName: Full=Catechol O-methyltransferase 2 {ECO:0000250|UniProtKB:A1Y9I9};
GN Name=Tomt {ECO:0000312|RGD:1561509};
GN Synonyms=Comt2 {ECO:0000250|UniProtKB:A1Y9I9};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1] {ECO:0000312|EMBL:ACF40903.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley {ECO:0000312|EMBL:ACF40903.1};
RC TISSUE=Brain {ECO:0000312|EMBL:ACF40903.1};
RX PubMed=18953341; DOI=10.1038/ng.245;
RA Ahmed Z.M., Masmoudi S., Kalay E., Belyantseva I.A., Mosrati M.A.,
RA Collin R.W.J., Riazuddin S., Hmani-Aifa M., Venselaar H., Kawar M.N.,
RA Tlili A., van der Zwaag B., Khan S.Y., Ayadi L., Riazuddin S.A.,
RA Morell R.J., Griffith A.J., Charfedine I., Caylan R., Oostrik J.,
RA Karaguzel A., Ghorbel A., Riazuddin S., Friedman T.B., Ayadi H., Kremer H.;
RT "Mutations of LRTOMT, a fusion gene with alternative reading frames, cause
RT nonsyndromic deafness in humans.";
RL Nat. Genet. 40:1335-1340(2008).
CC -!- FUNCTION: Catalyzes the O-methylation, and thereby the inactivation, of
CC catecholamine neurotransmitters and catechol hormones (By similarity).
CC Required for auditory function (By similarity). Component of the
CC cochlear hair cell's mechanotransduction (MET) machinery. Involved in
CC the assembly of the asymmetric tip-link MET complex. Required for
CC transportation of TMC1 and TMC2 proteins into the mechanically
CC sensitive stereocilia of the hair cells. The function in MET is
CC independent of the enzymatic activity (By similarity).
CC {ECO:0000250|UniProtKB:A1Y9I9, ECO:0000250|UniProtKB:Q8WZ04}.
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:A1Y9I9};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17878;
CC Evidence={ECO:0000250|UniProtKB:A1Y9I9};
CC -!- SUBUNIT: Interacts with LHFPL5, PCDH15, TMC1, TMC2 and TMIE. Interacts
CC directly with TMC1. The interaction of TOMT with TMC1 and TMC2 is
CC required for the transportation of TMC1/2 into the stereocilia of hair
CC cells. {ECO:0000250|UniProtKB:A1Y9I9}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:A1Y9I9}.
CC Endoplasmic reticulum {ECO:0000250|UniProtKB:A1Y9I9}. Note=Localized to
CC the cell body of the cochlear hair cells, but is not present in the
CC stereocilia. Present but not restricted to the apical cistern, Hensen's
CC body and the subsurface cistern. {ECO:0000250|UniProtKB:A1Y9I9}.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. Cation-dependent O-methyltransferase family.
CC {ECO:0000255|PROSITE-ProRule:PRU01019}.
CC -!- CAUTION: Despite its name, the rat TOMT protein does not contain a
CC transmembrane region in contrast to primate orthologs. {ECO:0000305}.
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DR EMBL; EU627093; ACF40903.1; -; mRNA.
DR RefSeq; NP_001132966.1; NM_001139494.1.
DR RefSeq; XP_017444679.1; XM_017589190.1.
DR RefSeq; XP_017444680.1; XM_017589191.1.
DR AlphaFoldDB; B6CZ62; -.
DR SMR; B6CZ62; -.
DR STRING; 10116.ENSRNOP00000036144; -.
DR PhosphoSitePlus; B6CZ62; -.
DR PaxDb; B6CZ62; -.
DR PRIDE; B6CZ62; -.
DR Ensembl; ENSRNOT00000039564; ENSRNOP00000036144; ENSRNOG00000023434.
DR GeneID; 308868; -.
DR KEGG; rno:308868; -.
DR CTD; 220074; -.
DR RGD; 1561509; Tomt.
DR eggNOG; KOG1663; Eukaryota.
DR GeneTree; ENSGT00940000161220; -.
DR HOGENOM; CLU_050461_5_0_1; -.
DR InParanoid; B6CZ62; -.
DR OMA; YVLTHST; -.
DR OrthoDB; 1274244at2759; -.
DR PhylomeDB; B6CZ62; -.
DR TreeFam; TF329140; -.
DR Reactome; R-RNO-379397; Enzymatic degradation of dopamine by COMT.
DR PRO; PR:B6CZ62; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000023434; Expressed in thymus and 17 other tissues.
DR GO; GO:0045177; C:apical part of cell; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS: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:0060117; P:auditory receptor cell development; ISO:RGD.
DR GO; GO:0042424; P:catecholamine catabolic process; ISS:UniProtKB.
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 GO; GO:1904591; P:positive regulation of protein import; ISO:RGD.
DR GO; GO:0007605; P:sensory perception of sound; ISO:RGD.
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; Cytoplasm; Deafness; Endoplasmic reticulum;
KW Hearing; Methyltransferase; Neurotransmitter degradation;
KW Reference proteome; S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..258
FT /note="Transmembrane O-methyltransferase homolog"
FT /id="PRO_0000372489"
FT BINDING 104
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT BINDING 106..107
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT BINDING 112
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT BINDING 130
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT BINDING 160
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
SQ SEQUENCE 258 AA; 28864 MW; AF1EFE98697A0B42 CRC64;
MSPAIALAFL PLVVTLLVRY RHHFRLLVRT VLLRSFRDCL SGLRIEERAF SYVITHALPG
DPGHILTTLD HWSSCCEYLS HMGPIKGQIL MRLVEEKAPA CVLELGTHCG YSTLLIARAL
PPGSRLLTVE RDSRTAAVAE KVIRLAGFDE QMVELIAGSS EEVIPRLRAQ HQLNRADLVL
LAHRPRYYLR DLQLLEAHAL LPHGATVLAD HVLFPGAPRF LQYTKSCGRY RCRLHHTSLP
DFPAIKDGIA QLTYTGPG
