ID   TOMT_PANTR              Reviewed;         291 AA.
AC   P86243;
DT   05-MAY-2009, integrated into UniProtKB/Swiss-Prot.
DT   05-MAY-2009, sequence version 1.
DT   27-MAR-2024, entry version 62.
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:A1Y9I9};
DE   AltName: Full=Protein LRTOMT2 {ECO:0000303|PubMed:18953341};
GN   Name=TOMT {ECO:0000250|UniProtKB:Q8WZ04};
GN   Synonyms=COMT2 {ECO:0000250|UniProtKB:Q8WZ04}, LRTOMT
GN   {ECO:0000303|PubMed:18953341};
OS   Pan troglodytes (Chimpanzee).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Pan.
OX   NCBI_TaxID=9598;
RN   [1] {ECO:0000305}
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Brain {ECO:0000269|PubMed:18953341};
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=D'
CC       {ECO:0000269|PubMed:18953341};
CC         IsoId=P86243-1; Sequence=Displayed;
CC       Name=2 {ECO:0000269|PubMed:18953341}; Synonyms=E'
CC       {ECO:0000269|PubMed:18953341};
CC         IsoId=P86243-2; Sequence=VSP_037158;
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}.
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DR   EMBL; EU627074; -; NOT_ANNOTATED_CDS; mRNA.
DR   EMBL; EU627075; -; NOT_ANNOTATED_CDS; mRNA.
DR   RefSeq; NP_001186282.1; NM_001199353.1. [P86243-1]
DR   RefSeq; NP_001269004.1; NM_001282075.1. [P86243-2]
DR   RefSeq; XP_016775412.1; XM_016919923.1.
DR   RefSeq; XP_016775414.1; XM_016919925.1.
DR   RefSeq; XP_016775415.1; XM_016919926.1.
DR   AlphaFoldDB; P86243; -.
DR   SMR; P86243; -.
DR   STRING; 9598.ENSPTRP00000075354; -.
DR   Ensembl; ENSPTRT00000107086.1; ENSPTRP00000075354.1; ENSPTRG00000004025.5. [P86243-1]
DR   GeneID; 748243; -.
DR   CTD; 220074; -.
DR   GeneTree; ENSGT00940000161220; -.
DR   InParanoid; P86243; -.
DR   OrthoDB; 4040098at2759; -.
DR   Proteomes; UP000002277; Chromosome 11.
DR   Bgee; ENSPTRG00000004025; Expressed in testis and 21 other cell types or 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:0016020; C:membrane; IEA:UniProtKB-SubCell.
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:0102938; F:orcinol O-methyltransferase activity; IEA:UniProtKB-EC.
DR   GO; GO:0060117; P:auditory receptor cell development; IEA:Ensembl.
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:1904591; P:positive regulation of protein import; IEA:Ensembl.
DR   GO; GO:0007605; P:sensory perception of sound; IEA:UniProtKB-KW.
DR   CDD; cd02440; AdoMet_MTases; 1.
DR   Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 1.
DR   InterPro; IPR029063; SAM-dependent_MTases_sf.
DR   InterPro; IPR002935; SAM_O-MeTrfase.
DR   PANTHER; PTHR43836; CATECHOL O-METHYLTRANSFERASE 1-RELATED; 1.
DR   PANTHER; PTHR43836:SF1; TRANSMEMBRANE O-METHYLTRANSFERASE; 1.
DR   Pfam; PF01596; Methyltransf_3; 1.
DR   SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 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..291
FT                   /note="Transmembrane O-methyltransferase"
FT                   /id="PRO_0000372487"
FT   TRANSMEM        31..51
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         137
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT   BINDING         139..140
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT   BINDING         145
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT   BINDING         163
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT   BINDING         193
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT   VAR_SEQ         28..67
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:18953341"
FT                   /id="VSP_037158"
SQ   SEQUENCE   291 AA;  32124 MW;  171964FA01FA2E67 CRC64;
     MGTPWRKRKG IAGPGLPHLS CALVLQPRAQ VGTMSPAIAL AFLPLVVTLL VRYRHYFRLL
     VRTVLLRSLR DCLSGLRIEE RAFSYVLTHA LPGDPGHILT TLDHWSSCCE YLSHMGPVKG
     QILMRLVEEK APACVLELGT YCGYSTLLIA RALPPGGRLL TVERDPRTAA VAEKLIRLAG
     FDEHMVELIV GSSEDVIPCL RTQYQLSRAD LVLLAHRPRC YLRDLQLLEA HALLPAGATV
     LADHVLFPGA PRFLQYAKSC GRYRCRLHHT GLPDFPAIKD GIAQLTYAGP G
//