TOMT_MACMU
ID TOMT_MACMU Reviewed; 296 AA.
AC B6CZ46; B6CZ47;
DT 05-MAY-2009, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 2.
DT 03-AUG-2022, entry version 50.
DE RecName: Full=Transmembrane O-methyltransferase {ECO:0000250|UniProtKB:A1Y9I9};
DE EC=2.1.1.6 {ECO:0000250|UniProtKB:A1Y9I9};
DE AltName: Full=Catechol O-methyltransferase 2 {ECO:0000250|UniProtKB:Q8WZ04};
DE AltName: Full=Protein LRTOMT2 {ECO:0000303|PubMed:18953341};
GN Name=TOMT {ECO:0000250|UniProtKB:Q8WZ04};
GN Synonyms=COMT2 {ECO:0000250|UniProtKB:Q8WZ04},
GN LRTOMT {ECO:0000303|PubMed:18953341};
OS Macaca mulatta (Rhesus macaque).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9544;
RN [1] {ECO:0000305, ECO:0000312|EMBL:ACF40887.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain {ECO:0000312|EMBL:ACF40887.1};
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: [Isoform 1]: Membrane {ECO:0000255}; Single-pass
CC membrane protein {ECO:0000255}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm
CC {ECO:0000250|UniProtKB:A1Y9I9}. Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:A1Y9I9}. Note=Localized to the cell body of the
CC cochlear hair cells, but is not present in the stereocilia. Present but
CC not restricted to the apical cistern, Hensen's body and the subsurface
CC cistern. {ECO:0000250|UniProtKB:A1Y9I9}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1 {ECO:0000269|PubMed:18953341}; Synonyms=B
CC {ECO:0000269|PubMed:18953341};
CC IsoId=B6CZ46-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:18953341}; Synonyms=C
CC {ECO:0000269|PubMed:18953341};
CC IsoId=B6CZ46-2; Sequence=VSP_053068;
CC -!- MISCELLANEOUS: LRRC51 and TOMT were originally considered as
CC alternative reading frames, LRTOMT1 and LRTOMT2 of the same LRTOMT gene
CC in primates. {ECO:0000303|PubMed:18953341}.
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 -!- SEQUENCE CAUTION:
CC Sequence=ACF40887.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=ACF40888.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; EU627077; ACF40887.1; ALT_FRAME; mRNA.
DR EMBL; EU627078; ACF40888.1; ALT_FRAME; mRNA.
DR RefSeq; NP_001129574.1; NM_001136102.1.
DR AlphaFoldDB; B6CZ46; -.
DR SMR; B6CZ46; -.
DR GeneID; 718286; -.
DR CTD; 220074; -.
DR InParanoid; B6CZ46; -.
DR OrthoDB; 1274244at2759; -.
DR Proteomes; UP000006718; Unplaced.
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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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: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: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 Alternative splicing; Catecholamine metabolism; Cytoplasm; Deafness;
KW Endoplasmic reticulum; Hearing; Membrane; Methyltransferase;
KW Neurotransmitter degradation; Reference proteome; S-adenosyl-L-methionine;
KW Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..296
FT /note="Transmembrane O-methyltransferase"
FT /id="PRO_0000372486"
FT TRANSMEM 36..56
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 142
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT BINDING 144..145
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT BINDING 150
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT BINDING 168
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT BINDING 198
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT VAR_SEQ 11..32
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:18953341"
FT /id="VSP_053068"
SQ SEQUENCE 296 AA; 32666 MW; 9CE89610D5E5EF93 CRC64;
MGTPWRKRKG IAGPGLPNLS CALVLCLSRS QPRTQVGTMS PAIALAFLPL VVTLLVRYRH
YFRLLVGTVL LRSLRDCLSG LRIEERAFSY VLTHALPGDP GHILTTLDHW SSHCEYLSHM
GPVKGQILMR LVEEKAPACV LELGTYCGYS TLLIAQALPP GGRLLTVERD PRTAAVAEKL
IRLAGFDEHM VELIVGSSEE VIPCLRTQYQ LSRADLVLLI HRPRCYLRDL QLLEAHALLP
AGATVLADHV LFPGAPRFLQ YAKSCGRYRC RLYHTGLPDF PAIKDGIAQL TYAGPG
