TOMT_PROCO
ID TOMT_PROCO Reviewed; 274 AA.
AC B6CZ56; B6CZ57;
DT 05-MAY-2009, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 2.
DT 03-AUG-2022, entry version 41.
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 Propithecus coquereli (Coquerel's sifaka) (Propithecus verreauxi
OS coquereli).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Strepsirrhini; Lemuriformes;
OC Indriidae; Propithecus.
OX NCBI_TaxID=379532;
RN [1] {ECO:0000305, ECO:0000312|EMBL:ACF40897.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain {ECO:0000312|EMBL:ACF40897.1};
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=C
CC {ECO:0000269|PubMed:18953341};
CC IsoId=B6CZ56-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:18953341}; Synonyms=D
CC {ECO:0000269|PubMed:18953341};
CC IsoId=B6CZ56-2; Sequence=VSP_053069;
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=ACF40897.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; EU627087; ACF40897.1; ALT_FRAME; mRNA.
DR EMBL; EU627088; ACF40898.1; -; mRNA.
DR AlphaFoldDB; B6CZ56; -.
DR SMR; B6CZ56; -.
DR Proteomes; UP000233160; Whole Genome Shotgun Assembly.
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:0102938; F:orcinol O-methyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0042424; P:catecholamine catabolic process; ISS:UniProtKB.
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..274
FT /note="Transmembrane O-methyltransferase"
FT /id="PRO_0000372488"
FT TRANSMEM 14..34
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 120
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT BINDING 122..123
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT BINDING 128
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT BINDING 146
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT BINDING 176
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT VAR_SEQ 12..102
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:18953341"
FT /id="VSP_053069"
SQ SEQUENCE 274 AA; 30432 MW; 12B1949D04FC4107 CRC64;
MGTPWRKRKG ITQVGTMSPA IALAFLPLVV TLLVRYRHYF RLLVGTVLLR SLRDCLSGLR
IEERAFSYVL THALPGDPGH ILTTLDHWSS HCEYLSHMGP VKGQILMRLV EEKAPACVLE
LGTYCGYSTL LIAQALPPGG RLLTVERDPR TAAVAEKLIR LAGFDEHMVE LIVGSSEEVI
PCLRTQYQLS RADLVLLIHR PRCYLRDLQL LEAHALLPAG ATVLADHVLF PGAPRFLQYA
KSCGRYRCRL YHTGLPDFPA IKDGIAQLTY AGPG
