UniProtKB - Q8WZ04 (TOMT_HUMAN)
Protein
Transmembrane O-methyltransferase
Gene
LRTOMT
Organism
Homo sapiens (Human)
Status
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
- EC:2.1.1.6By similarity
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 137 | S-adenosyl-L-methioninePROSITE-ProRule annotation | 1 | |
Binding sitei | 145 | S-adenosyl-L-methioninePROSITE-ProRule annotation | 1 | |
Binding sitei | 163 | S-adenosyl-L-methioninePROSITE-ProRule annotation | 1 | |
Binding sitei | 193 | S-adenosyl-L-methionine; via amide nitrogenPROSITE-ProRule annotation | 1 |
GO - Molecular functioni
- catechol O-methyltransferase activity Source: UniProtKB
- L-dopa O-methyltransferase activity Source: UniProtKB-EC
- O-methyltransferase activity Source: GO_Central
- orcinol O-methyltransferase activity Source: UniProtKB-EC
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
- methylation Source: UniProtKB-KW
- neurotransmitter catabolic process Source: UniProtKB-KW
- sensory perception of sound Source: UniProtKB
Keywordsi
Molecular function | Methyltransferase, Transferase |
Biological process | Catecholamine metabolism, Hearing, Neurotransmitter degradation |
Ligand | S-adenosyl-L-methionine |
Enzyme and pathway databases
PathwayCommonsi | Q8WZ04 |
Reactomei | R-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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000184154.12 |
HGNCi | HGNC:25033, LRTOMT |
MIMi | 612414, gene |
neXtProti | NX_Q8WZ04 |
Subcellular locationi
Other locations
- Membrane Curated; Single-pass membrane protein Curated
Endoplasmic reticulum
- Endoplasmic reticulum By similarity
Other locations
- Cytoplasm 1 Publication
Note: Localized to the cell body of the cochlear hair cells, but is not present in the stereocilia (PubMed:28504928). Present but not restricted to the apical cistern, Hensen's body and the subsurface cistern (By similarity).By similarity1 Publication
Endoplasmic reticulum
- endoplasmic reticulum Source: UniProtKB-SubCell
Plasma Membrane
- plasma membrane Source: Reactome
Other locations
- integral component of membrane Source: UniProtKB-KW
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transmembranei | 31 – 51 | HelicalSequence analysisAdd BLAST | 21 |
Keywords - Cellular componenti
Cytoplasm, Endoplasmic reticulum, MembranePathology & 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.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_047554 | 16 | L → P in DFNB63; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs891068154Ensembl. | 1 | |
Natural variantiVAR_079506 | 52 | R → W in DFNB63; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1372399805Ensembl. | 1 | |
Natural variantiVAR_054955 | 81 | R → Q in DFNB63. 1 PublicationCorresponds to variant dbSNP:rs137853185EnsemblClinVar. | 1 | |
Natural variantiVAR_054956 | 105 | W → R in DFNB63. 1 PublicationCorresponds to variant dbSNP:rs137853186EnsemblClinVar. | 1 | |
Natural variantiVAR_054957 | 110 | E → K in DFNB63. 1 PublicationCorresponds to variant dbSNP:rs137853187EnsemblClinVar. | 1 | |
Natural variantiVAR_047555 | 158 | R → H in DFNB63; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs758115449Ensembl. | 1 |
Keywords - Diseasei
Deafness, Disease mutation, Non-syndromic deafnessOrganism-specific databases
DisGeNETi | 220074 |
GeneReviewsi | LRTOMT |
MalaCardsi | LRTOMT |
MIMi | 611451, phenotype |
OpenTargetsi | ENSG00000184154 |
Orphaneti | 90636, Autosomal recessive non-syndromic sensorineural deafness type DFNB |
PharmGKBi | PA164722133 |
Miscellaneous databases
Pharosi | Q8WZ04, Tbio |
Polymorphism and mutation databases
BioMutai | LRTOMT |
DMDMi | 226693615 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000354093 | 1 – 291 | Transmembrane O-methyltransferaseAdd BLAST | 291 |
Proteomic databases
PaxDbi | Q8WZ04 |
PeptideAtlasi | Q8WZ04 |
PRIDEi | Q8WZ04 |
ProteomicsDBi | 75203 [Q8WZ04-1] 75204 [Q8WZ04-2] |
PTM databases
PhosphoSitePlusi | Q8WZ04 |
Expressioni
Gene expression databases
Bgeei | ENSG00000184154, Expressed in testis and 140 other tissues |
ExpressionAtlasi | Q8WZ04, baseline and differential |
Genevisiblei | Q8WZ04, HS |
Organism-specific databases
HPAi | ENSG00000184154, Tissue enhanced (fallopian tube, testis) |
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 similarityProtein-protein interaction databases
BioGRIDi | 128624, 2 interactors |
STRINGi | 9606.ENSP00000305742 |
Miscellaneous databases
RNActi | Q8WZ04, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 139 – 140 | S-adenosyl-L-methionine bindingPROSITE-ProRule annotation | 2 |
Sequence similaritiesi
Belongs to the class I-like SAM-binding methyltransferase superfamily. Cation-dependent O-methyltransferase family.PROSITE-ProRule annotation
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG1663, Eukaryota |
HOGENOMi | CLU_050461_5_0_1 |
InParanoidi | Q8WZ04 |
OMAi | EERAYQY |
OrthoDBi | 1274244at2759 |
PhylomeDBi | Q8WZ04 |
TreeFami | TF329140 |
Family and domain databases
InterProi | View protein in InterPro IPR029063, SAM-dependent_MTases IPR002935, SAM_O-MeTrfase IPR033025, TOMT |
PANTHERi | PTHR43836:SF1, PTHR43836:SF1, 1 hit |
Pfami | View protein in Pfam PF01596, Methyltransf_3, 1 hit |
SUPFAMi | SSF53335, SSF53335, 1 hit |
PROSITEi | View protein in PROSITE PS51682, SAM_OMT_I, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q8WZ04-1) [UniParc]FASTAAdd to basket
Also known as: D'
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketQ96E66 | LRC51_HUMAN | Leucine-rich repeat-containing prot... | LRTOMT LRRC51 | 192 | Annotation score: | ||
F5GYI0 | F5GYI0_HUMAN | Leucine-rich repeat-containing prot... | LRTOMT | 103 | Annotation score: | ||
F5H6F7 | F5H6F7_HUMAN | Leucine-rich repeat-containing prot... | LRTOMT | 54 | Annotation score: | ||
F5H6K5 | F5H6K5_HUMAN | Leucine-rich repeat-containing prot... | LRTOMT | 38 | Annotation score: |
Sequence cautioni
The sequence AAL55772 differs from that shown. Reason: Frameshift.Curated
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_047554 | 16 | L → P in DFNB63; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs891068154Ensembl. | 1 | |
Natural variantiVAR_079506 | 52 | R → W in DFNB63; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1372399805Ensembl. | 1 | |
Natural variantiVAR_054955 | 81 | R → Q in DFNB63. 1 PublicationCorresponds to variant dbSNP:rs137853185EnsemblClinVar. | 1 | |
Natural variantiVAR_054956 | 105 | W → R in DFNB63. 1 PublicationCorresponds to variant dbSNP:rs137853186EnsemblClinVar. | 1 | |
Natural variantiVAR_054957 | 110 | E → K in DFNB63. 1 PublicationCorresponds to variant dbSNP:rs137853187EnsemblClinVar. | 1 | |
Natural variantiVAR_047555 | 158 | R → H in DFNB63; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs758115449Ensembl. | 1 | |
Natural variantiVAR_047556 | 208 | R → Q1 PublicationCorresponds to variant dbSNP:rs61741195EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_036898 | 28 – 67 | Missing in isoform 2. 2 PublicationsAdd BLAST | 40 |
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. |
CCDSi | CCDS44668.1 [Q8WZ04-1] |
RefSeqi | NP_001138780.1, NM_001145308.4 [Q8WZ04-1] NP_001138781.1, NM_001145309.3 [Q8WZ04-1] NP_001138782.1, NM_001145310.3 [Q8WZ04-2] |
Genome annotation databases
Ensembli | ENST00000307198; ENSP00000305742; ENSG00000184154 [Q8WZ04-1] ENST00000435085; ENSP00000409789; ENSG00000184154 [Q8WZ04-1] |
GeneIDi | 220074 |
KEGGi | hsa:220074 |
UCSCi | uc010rqw.3, human [Q8WZ04-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Cross-referencesi
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. |
CCDSi | CCDS44668.1 [Q8WZ04-1] |
RefSeqi | NP_001138780.1, NM_001145308.4 [Q8WZ04-1] NP_001138781.1, NM_001145309.3 [Q8WZ04-1] NP_001138782.1, NM_001145310.3 [Q8WZ04-2] |
3D structure databases
SMRi | Q8WZ04 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 128624, 2 interactors |
STRINGi | 9606.ENSP00000305742 |
PTM databases
PhosphoSitePlusi | Q8WZ04 |
Polymorphism and mutation databases
BioMutai | LRTOMT |
DMDMi | 226693615 |
Proteomic databases
PaxDbi | Q8WZ04 |
PeptideAtlasi | Q8WZ04 |
PRIDEi | Q8WZ04 |
ProteomicsDBi | 75203 [Q8WZ04-1] 75204 [Q8WZ04-2] |
Protocols and materials databases
Antibodypediai | 34978, 55 antibodies |
DNASUi | 220074 |
Genome annotation databases
Ensembli | ENST00000307198; ENSP00000305742; ENSG00000184154 [Q8WZ04-1] ENST00000435085; ENSP00000409789; ENSG00000184154 [Q8WZ04-1] |
GeneIDi | 220074 |
KEGGi | hsa:220074 |
UCSCi | uc010rqw.3, human [Q8WZ04-1] |
Organism-specific databases
CTDi | 220074 |
DisGeNETi | 220074 |
EuPathDBi | HostDB:ENSG00000184154.12 |
GeneCardsi | LRTOMT |
GeneReviewsi | LRTOMT |
HGNCi | HGNC:25033, LRTOMT |
HPAi | ENSG00000184154, Tissue enhanced (fallopian tube, testis) |
MalaCardsi | LRTOMT |
MIMi | 611451, phenotype 612414, gene |
neXtProti | NX_Q8WZ04 |
OpenTargetsi | ENSG00000184154 |
Orphaneti | 90636, Autosomal recessive non-syndromic sensorineural deafness type DFNB |
PharmGKBi | PA164722133 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1663, Eukaryota |
HOGENOMi | CLU_050461_5_0_1 |
InParanoidi | Q8WZ04 |
OMAi | EERAYQY |
OrthoDBi | 1274244at2759 |
PhylomeDBi | Q8WZ04 |
TreeFami | TF329140 |
Enzyme and pathway databases
PathwayCommonsi | Q8WZ04 |
Reactomei | R-HSA-379397, Enzymatic degradation of dopamine by COMT |
Miscellaneous databases
BioGRID-ORCSi | 220074, 2 hits in 838 CRISPR screens |
ChiTaRSi | LRTOMT, human |
GenomeRNAii | 220074 |
Pharosi | Q8WZ04, Tbio |
PROi | PR:Q8WZ04 |
RNActi | Q8WZ04, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000184154, Expressed in testis and 140 other tissues |
ExpressionAtlasi | Q8WZ04, baseline and differential |
Genevisiblei | Q8WZ04, HS |
Family and domain databases
InterProi | View protein in InterPro IPR029063, SAM-dependent_MTases IPR002935, SAM_O-MeTrfase IPR033025, TOMT |
PANTHERi | PTHR43836:SF1, PTHR43836:SF1, 1 hit |
Pfami | View protein in Pfam PF01596, Methyltransf_3, 1 hit |
SUPFAMi | SSF53335, SSF53335, 1 hit |
PROSITEi | View protein in PROSITE PS51682, SAM_OMT_I, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | TOMT_HUMAN | |
Accessioni | Q8WZ04Primary (citable) accession number: Q8WZ04 Secondary accession number(s): B7Z816 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 25, 2008 |
Last sequence update: | April 14, 2009 | |
Last modified: | December 2, 2020 | |
This is version 117 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families - Human chromosome 11
Human chromosome 11: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations