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Protein

Transmembrane O-methyltransferase

Gene

LRTOMT

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones (By similarity). Required for auditory function (PubMed:18794526). 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 (By similarity).By similarity1 Publication

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.

Catalytic activityi

S-adenosyl-L-methionine + a catechol = S-adenosyl-L-homocysteine + a guaiacol.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei137S-adenosyl-L-methioninePROSITE-ProRule annotation1
Binding sitei145S-adenosyl-L-methioninePROSITE-ProRule annotation1
Binding sitei163S-adenosyl-L-methioninePROSITE-ProRule annotation1
Binding sitei193S-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
  • neurotransmitter catabolic process Source: UniProtKB-KW
  • 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-HSA-379397 Enzymatic degradation of dopamine by COMT

Names & Taxonomyi

Protein namesi
Recommended name:
Transmembrane O-methyltransferaseBy similarity (EC:2.1.1.6By similarity)
Alternative name(s):
Catechol O-methyltransferase 21 Publication
Protein LRTOMT2
Gene namesi
Name:LRTOMT
Synonyms:COMT21 Publication, TOMT
ORF Names:PP7517
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000184154.12
HGNCiHGNC:25033 LRTOMT
MIMi612414 gene
neXtProtiNX_Q8WZ04

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

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei31 – 51HelicalSequence analysisAdd BLAST21

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Membrane

Pathology & Biotechi

Involvement in diseasei

Deafness, autosomal recessive, 63 (DFNB63)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
See also OMIM:611451
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04755416L → P in DFNB63. 1 PublicationCorresponds to variant dbSNP:rs891068154Ensembl.1
Natural variantiVAR_07950652R → W in DFNB63; unknown pathological significance. 1 Publication1
Natural variantiVAR_05495581R → Q in DFNB63. 1 PublicationCorresponds to variant dbSNP:rs137853185Ensembl.1
Natural variantiVAR_054956105W → R in DFNB63. 1 PublicationCorresponds to variant dbSNP:rs137853186Ensembl.1
Natural variantiVAR_054957110E → K in DFNB63. 1 PublicationCorresponds to variant dbSNP:rs137853187Ensembl.1
Natural variantiVAR_047555158R → H in DFNB63. 1 PublicationCorresponds to variant dbSNP:rs758115449Ensembl.1
Natural variantiVAR_047556208R → Q in DFNB63. 1 PublicationCorresponds to variant dbSNP:rs61741195Ensembl.1

Keywords - Diseasei

Deafness, Disease mutation, Non-syndromic deafness

Organism-specific databases

DisGeNETi220074
GeneReviewsiLRTOMT
MalaCardsiLRTOMT
MIMi611451 phenotype
OpenTargetsiENSG00000184154
Orphaneti90636 Autosomal recessive non-syndromic sensorineural deafness type DFNB
PharmGKBiPA164722133

Polymorphism and mutation databases

DMDMi226693615

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003540931 – 291Transmembrane O-methyltransferaseAdd BLAST291

Proteomic databases

PaxDbiQ8WZ04
PeptideAtlasiQ8WZ04
PRIDEiQ8WZ04

PTM databases

PhosphoSitePlusiQ8WZ04

Expressioni

Gene expression databases

BgeeiENSG00000184154
ExpressionAtlasiQ8WZ04 baseline and differential
GenevisibleiQ8WZ04 HS

Interactioni

Subunit structurei

Interacts with LHFPL5, PCDH15, TMC1, TMC2 and TMIE. Interacts directly with TMC1. The interaction of TOMT with TMC1 and TMC2 is required for the transportation of TMC1/2 into the stereocilia of hair cells.By similarity

Protein-protein interaction databases

BioGridi128624, 2 interactors
STRINGi9606.ENSP00000305742

Structurei

3D structure databases

ProteinModelPortaliQ8WZ04
SMRiQ8WZ04
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni139 – 140S-adenosyl-L-methionine bindingPROSITE-ProRule annotation2

Sequence similaritiesi

Belongs to the class I-like SAM-binding methyltransferase superfamily. Cation-dependent O-methyltransferase family.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1663 Eukaryota
COG4122 LUCA
GeneTreeiENSGT00390000011316
HOGENOMiHOG000046392
InParanoidiQ8WZ04
KOiK00545
OMAiFIDHYKP
OrthoDBiEOG091G0GQK
PhylomeDBiQ8WZ04
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

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8WZ04-1) [UniParc]FASTAAdd to basket
Also known as: D'

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MGTPWRKRKG IAGPGLPDLS CALVLQPRAQ VGTMSPAIAL AFLPLVVTLL
60 70 80 90 100
VRYRHYFRLL VRTVLLRSLR DCLSGLRIEE RAFSYVLTHA LPGDPGHILT
110 120 130 140 150
TLDHWSSRCE YLSHMGPVKG QILMRLVEEK APACVLELGT YCGYSTLLIA
160 170 180 190 200
RALPPGGRLL TVERDPRTAA VAEKLIRLAG FDEHMVELIV GSSEDVIPCL
210 220 230 240 250
RTQYQLSRAD LVLLAHRPRC YLRDLQLLEA HALLPAGATV LADHVLFPGA
260 270 280 290
PRFLQYAKSC GRYRCRLHHT GLPDFPAIKD GIAQLTYAGP G
Length:291
Mass (Da):32,155
Last modified:April 14, 2009 - v3
Checksum:iF6108CBEE0FF49E7
GO
Isoform 2 (identifier: Q8WZ04-2) [UniParc]FASTAAdd to basket
Also known as: E'

The sequence of this isoform differs from the canonical sequence as follows:
     28-67: Missing.

Show »
Length:251
Mass (Da):27,548
Checksum:iBB46042216F8830C
GO

Sequence cautioni

The sequence AAL55772 differs from that shown. Reason: Frameshift at position 91.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04755416L → P in DFNB63. 1 PublicationCorresponds to variant dbSNP:rs891068154Ensembl.1
Natural variantiVAR_07950652R → W in DFNB63; unknown pathological significance. 1 Publication1
Natural variantiVAR_05495581R → Q in DFNB63. 1 PublicationCorresponds to variant dbSNP:rs137853185Ensembl.1
Natural variantiVAR_054956105W → R in DFNB63. 1 PublicationCorresponds to variant dbSNP:rs137853186Ensembl.1
Natural variantiVAR_054957110E → K in DFNB63. 1 PublicationCorresponds to variant dbSNP:rs137853187Ensembl.1
Natural variantiVAR_047555158R → H in DFNB63. 1 PublicationCorresponds to variant dbSNP:rs758115449Ensembl.1
Natural variantiVAR_047556208R → Q in DFNB63. 1 PublicationCorresponds to variant dbSNP:rs61741195Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_03689828 – 67Missing in isoform 2. 2 PublicationsAdd BLAST40

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
EU627069 mRNA No translation available.
EU627070 mRNA No translation available.
AF289588 mRNA Translation: AAL55772.1 Frameshift.
AK302772 mRNA Translation: BAH13802.1
AP000812 Genomic DNA No translation available.
CCDSiCCDS44668.1 [Q8WZ04-1]
RefSeqiNP_001138780.1, NM_001145308.4 [Q8WZ04-1]
NP_001138781.1, NM_001145309.3 [Q8WZ04-1]
NP_001138782.1, NM_001145310.3 [Q8WZ04-2]
UniGeneiHs.317243
Hs.667985

Genome annotation databases

EnsembliENST00000307198; ENSP00000305742; ENSG00000184154 [Q8WZ04-1]
ENST00000435085; ENSP00000409789; ENSG00000184154 [Q8WZ04-1]
GeneIDi220074
KEGGihsa:220074
UCSCiuc010rqw.3 human [Q8WZ04-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiTOMT_HUMAN
AccessioniPrimary (citable) accession number: Q8WZ04
Secondary accession number(s): B7Z816
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 25, 2008
Last sequence update: April 14, 2009
Last modified: March 28, 2018
This is version 100 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health