Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Transmembrane O-methyltransferase

Gene

LRTOMT

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.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:2.1.1.6)
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.

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, Membrane

Pathology & Biotechi

Involvement in diseasei

Deafness, autosomal recessive, 63 (DFNB63)2 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 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.

Expressioni

Gene expression databases

BgeeiENSG00000184154.
ExpressionAtlasiQ8WZ04. baseline and differential.
GenevisibleiQ8WZ04. HS.

Interactioni

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.
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 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: September 27, 2017
This is version 96 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

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families