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Protein

Transmembrane O-methyltransferase homolog

Gene

Tomt

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones (PubMed:18794526). Required for auditory function (PubMed:18794526, PubMed:28504928). Component of the cochlear hair cell's mechanotransduction (MET) machinery. Involved in the assembly of the asymmetric tip-link MET complex. Required for transportation of TMC1 and TMC2 proteins into the mechanically sensitive stereocilia of the hair cells. The function in MET is independent of the enzymatic activity (PubMed:28504928).2 Publications

Miscellaneous

In primates, this protein is produced by a bicistronic gene which also produces the LRRC51 protein from an overlapping reading frame. In rodents, these proteins are produced by 2 separate adjacent genes which together are orthologous to the single primate gene.

Caution

Despite its name, the murine TOMT protein does not contain a transmembrane region in contrast to primate orthologs.Curated

Catalytic activityi

S-adenosyl-L-methionine + a catechol = S-adenosyl-L-homocysteine + a guaiacol.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei104S-adenosyl-L-methioninePROSITE-ProRule annotation1
Binding sitei112S-adenosyl-L-methioninePROSITE-ProRule annotation1
Binding sitei130S-adenosyl-L-methioninePROSITE-ProRule annotation1
Binding sitei160S-adenosyl-L-methionine; via amide nitrogenPROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

  • auditory receptor cell development Source: UniProtKB
  • catecholamine catabolic process Source: UniProtKB
  • developmental process Source: GO_Central
  • dopamine metabolic process Source: GO_Central
  • neurotransmitter catabolic process Source: UniProtKB-KW
  • positive regulation of protein import Source: UniProtKB
  • sensory perception of sound Source: UniProtKB

Keywordsi

Molecular functionMethyltransferase, Transferase
Biological processCatecholamine metabolism, Hearing, Neurotransmitter degradation
LigandS-adenosyl-L-methionine

Enzyme and pathway databases

ReactomeiR-MMU-379397 Enzymatic degradation of dopamine by COMT
SABIO-RKiA1Y9I9

Names & Taxonomyi

Protein namesi
Recommended name:
Transmembrane O-methyltransferase homologCurated (EC:2.1.1.61 Publication)
Short name:
mTOMT1 Publication
Alternative name(s):
Catechol O-methyltransferase 21 Publication
Protein LRTOMT2
Gene namesi
Name:Tomt
Synonyms:Comt21 Publication
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:3769724 Tomt

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum

Pathology & Biotechi

Disruption phenotypei

Absence of auditory brain stem response (ABR) to click stimuli demonstrates that the mice are profoundly deaf. Normal hair bundle morphology as at postnatal day (P) 5 the sensory epithelia are patterned into three rows of outer hair cells (OHCs) and one row of inner hair cells (IHCs). The bundles of OHCs appear similar in size to those of wild-type mice and form a normal staircase pattern. Hair cells are maintained in the presence of gentamicin, an aminoglycoside antibiotic that enters hair cells through their transduction channels and normally causes hair cell death. No difference in the expression or localization of tip link proteins CDH23 and PCDH15 or ATP2B2, MYO7A, ESPN and WHRN proteins at P5-P8 in hair bundles of hair cells. Normal localization of LHFPL5 and TMIE in OHCs, but TMC1 and TMC2 are absent from the hair bundles of OHCs.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi22 – 25Missing : Absence of auditory brain stem response (ABR) to click stimuli demonstrates that the mice are profoundly deaf. Distortion product otoacoustic emissions (DPOAEs) are absent at 4 weeks of age at all frequencies tested. Normal hair bundle morphology as at postnatal day (P) 5 the sensory epithelia are patterned into three rows of outer hair cells (OHCs) and one row of inner hair cells (IHCs). The bundles of OHCs appear similar in size to those of wild-type mice and form a normal staircase pattern. 1 Publication4
Mutagenesisi48R → L in add; reduces methyltransferase activity; causes hyperkinesis, circling, head-tossing, aggression, progressive degeneration of the organ of Corti, hair cell defects and profound deafness. Distortion product otoacoustic emissions (DPOAEs) are absent at 4 weeks of age at all frequencies tested. At postnatal day (P) 5 the sensory epithelia are patterned into three rows of outer hair cells (OHCs) and one row of inner hair cells (IHCs) with no obvious structural abnormalities. The bundles of OHCs appear similar in size to those of wild-type mice and form a normal staircase pattern. The hair bundles of OHCs have a slightly more rounded morphology, especially in basal regions of the cochlea. The morphology of IHCs is not significantly altered. Hair cells are maintained in the presence of gentamicin, an aminoglycoside antibiotic that enters hair cells through their transduction channels and normally causes hair cell death. Mechanotransduction currents are very small in P4 hair cells and completely absent in P7 hair cells. Membrane potential, outward-evoked currents and nonlinear capacitance are normal in OHCs. No difference in the expression or localization of tip link proteins CDH23 and PCDH15 or ATP2B2, MYO7A, ESPN and WHRN proteins at P5-P8 in hair bundles of hair cells. No difference in the number of tip links in IHCs and OHCs at P7-P8. No difference in the levels of catecholamines, including norepinephrine, homovanillic acid (HVA) and norepinephrine, or serotonin levels in the inner ear. Loss of reverse polarity currents. 2 Publications1
Mutagenesisi108Y → A: Is able to rescue the mechanotransduction defect of L-48. 1 Publication1
Mutagenesisi183H → A: Enhanced interaction with TMC1. 1 Publication1

Keywords - Diseasei

Deafness

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003540941 – 258Transmembrane O-methyltransferase homologAdd BLAST258

Proteomic databases

PaxDbiA1Y9I9
PRIDEiA1Y9I9

PTM databases

iPTMnetiA1Y9I9
PhosphoSitePlusiA1Y9I9

Expressioni

Tissue specificityi

Widely expressed with high levels in outer and inner hair cells of the cochlea and vestibule.2 Publications

Developmental stagei

Not detected in the embryo at E12.5. At E14.5, expressed in the developing inner ear. At E16.5, expressed in the utricle and saccule. At E18.5, expressed specifically in the region of the sensory cells of the cochlea, utricle, saccule and crista ampullaris.1 Publication

Gene expression databases

BgeeiENSMUSG00000078630 Expressed in 19 organ(s), highest expression level in embryo

Interactioni

Subunit structurei

Interacts with LHFPL5, PCDH15, TMC1, TMC2 and TMIE (PubMed:28504928). The interaction of TOMT with TMC1 and TMC2 is required for the transportation of TMC1/2 into the stereocilia of hair cells (PubMed:28504928, PubMed:28534737). Interacts directly with TMC1 (PubMed:28534737).2 Publications

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000102582

Structurei

3D structure databases

ProteinModelPortaliA1Y9I9
SMRiA1Y9I9
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni106 – 107S-adenosyl-L-methionine bindingPROSITE-ProRule annotation2

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1663 Eukaryota
COG4122 LUCA
GeneTreeiENSGT00390000011316
HOGENOMiHOG000046392
InParanoidiA1Y9I9
KOiK00545
OMAiFIDHYKP
OrthoDBiEOG091G0GQK
PhylomeDBiA1Y9I9
TreeFamiTF329140

Family and domain databases

InterProiView protein in InterPro
IPR002935 O-MeTrfase_3
IPR029063 SAM-dependent_MTases
IPR033025 TOMT
PANTHERiPTHR43836:SF1 PTHR43836:SF1, 1 hit
PfamiView protein in Pfam
PF01596 Methyltransf_3, 1 hit
SUPFAMiSSF53335 SSF53335, 1 hit
PROSITEiView protein in PROSITE
PS51682 SAM_OMT_I, 1 hit

Sequencei

Sequence statusi: Complete.

A1Y9I9-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MSPAIALAFL PLVVTLLVRY RHHFRLLVRT VLLRGFRDCL SGLRIEERAF
60 70 80 90 100
SYVLTHALPG DPGHILTTLD HWSSCCEYLS HMGPVKGQIL MRLVEEKAPA
110 120 130 140 150
CVLELGTYCG YSTLLIARAL PPGSRLLTVE RDSRTAAVAE KVIRLAGFDE
160 170 180 190 200
QMVELIAGSS EEVIPRLRAQ HQLNRADLVL LAHRPRYYLR DLQLLEAHAL
210 220 230 240 250
LPHGATVLAD HVLFPGAPRF LQYTKSCGRY RCRLHHTSLP DFPAIKDGIA

QLTYTGPG
Length:258
Mass (Da):28,846
Last modified:February 6, 2007 - v1
Checksum:i393954F017C67E0C
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
EU627091 mRNA Translation: ACF40901.1
DQ854743 mRNA Translation: ABI37014.1
CCDSiCCDS40044.1
RefSeqiNP_001075148.1, NM_001081679.1
NP_001269017.1, NM_001282088.1
XP_017167892.1, XM_017312403.1
UniGeneiMm.475469

Genome annotation databases

EnsembliENSMUST00000106969; ENSMUSP00000102582; ENSMUSG00000078630
ENSMUST00000106970; ENSMUSP00000102583; ENSMUSG00000078630
GeneIDi791260
KEGGimmu:791260
UCSCiuc009ipu.1 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
EU627091 mRNA Translation: ACF40901.1
DQ854743 mRNA Translation: ABI37014.1
CCDSiCCDS40044.1
RefSeqiNP_001075148.1, NM_001081679.1
NP_001269017.1, NM_001282088.1
XP_017167892.1, XM_017312403.1
UniGeneiMm.475469

3D structure databases

ProteinModelPortaliA1Y9I9
SMRiA1Y9I9
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000102582

PTM databases

iPTMnetiA1Y9I9
PhosphoSitePlusiA1Y9I9

Proteomic databases

PaxDbiA1Y9I9
PRIDEiA1Y9I9

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000106969; ENSMUSP00000102582; ENSMUSG00000078630
ENSMUST00000106970; ENSMUSP00000102583; ENSMUSG00000078630
GeneIDi791260
KEGGimmu:791260
UCSCiuc009ipu.1 mouse

Organism-specific databases

CTDi791260
MGIiMGI:3769724 Tomt

Phylogenomic databases

eggNOGiKOG1663 Eukaryota
COG4122 LUCA
GeneTreeiENSGT00390000011316
HOGENOMiHOG000046392
InParanoidiA1Y9I9
KOiK00545
OMAiFIDHYKP
OrthoDBiEOG091G0GQK
PhylomeDBiA1Y9I9
TreeFamiTF329140

Enzyme and pathway databases

ReactomeiR-MMU-379397 Enzymatic degradation of dopamine by COMT
SABIO-RKiA1Y9I9

Miscellaneous databases

PROiPR:A1Y9I9
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000078630 Expressed in 19 organ(s), highest expression level in embryo

Family and domain databases

InterProiView protein in InterPro
IPR002935 O-MeTrfase_3
IPR029063 SAM-dependent_MTases
IPR033025 TOMT
PANTHERiPTHR43836:SF1 PTHR43836:SF1, 1 hit
PfamiView protein in Pfam
PF01596 Methyltransf_3, 1 hit
SUPFAMiSSF53335 SSF53335, 1 hit
PROSITEiView protein in PROSITE
PS51682 SAM_OMT_I, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTOMT_MOUSE
AccessioniPrimary (citable) accession number: A1Y9I9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 16, 2008
Last sequence update: February 6, 2007
Last modified: November 7, 2018
This is version 82 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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