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Q8WZ04 (TOMT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 70. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Transmembrane O-methyltransferase

EC=2.1.1.6
Alternative name(s):
Catechol O-methyltransferase 2
Protein LRTOMT2
Gene names
Name:LRTOMT
Synonyms:COMT2, TOMT
ORF Names:PP7517
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length291 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones By similarity. Required for auditory function. Ref.5 UniProtKB P21964

Catalytic activity

S-adenosyl-L-methionine + a catechol = S-adenosyl-L-homocysteine + a guaiacol. UniProtKB P21964

Subcellular location

Isoform 1: Membrane; Single-pass membrane protein Potential.

Isoform 2: Cytoplasm By similarity.

Involvement in disease

Deafness, autosomal recessive, 63 (DFNB63) [MIM:611451]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.5

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.

Sequence similarities

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

Sequence caution

The sequence AAL55772.1 differs from that shown. Reason: Frameshift at position 91.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8WZ04-1)

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.
Isoform 2 (identifier: Q8WZ04-2)

Also known as: E';

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 291291Transmembrane O-methyltransferase
PRO_0000354093

Regions

Transmembrane31 – 5121Helical; Potential
Region139 – 1402S-adenosyl-L-methionine binding By similarity

Sites

Binding site1371S-adenosyl-L-methionine By similarity
Binding site1451S-adenosyl-L-methionine By similarity
Binding site1631S-adenosyl-L-methionine By similarity
Binding site1931S-adenosyl-L-methionine; via amide nitrogen By similarity

Natural variations

Alternative sequence28 – 6740Missing in isoform 2.
VSP_036898
Natural variant161L → P in DFNB63. Ref.5
VAR_047554
Natural variant811R → Q in DFNB63. Ref.1
VAR_054955
Natural variant1051W → R in DFNB63. Ref.1
VAR_054956
Natural variant1101E → K in DFNB63. Ref.1
VAR_054957
Natural variant1581R → H in DFNB63. Ref.5
VAR_047555
Natural variant2081R → Q in DFNB63. Ref.5
Corresponds to variant rs61741195 [ dbSNP | Ensembl ].
VAR_047556

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (D') [UniParc].

Last modified April 14, 2009. Version 3.
Checksum: F6108CBEE0FF49E7

FASTA29132,155
        10         20         30         40         50         60 
MGTPWRKRKG IAGPGLPDLS CALVLQPRAQ VGTMSPAIAL AFLPLVVTLL VRYRHYFRLL 

        70         80         90        100        110        120 
VRTVLLRSLR DCLSGLRIEE RAFSYVLTHA LPGDPGHILT TLDHWSSRCE YLSHMGPVKG 

       130        140        150        160        170        180 
QILMRLVEEK APACVLELGT YCGYSTLLIA RALPPGGRLL TVERDPRTAA VAEKLIRLAG 

       190        200        210        220        230        240 
FDEHMVELIV GSSEDVIPCL RTQYQLSRAD LVLLAHRPRC YLRDLQLLEA HALLPAGATV 

       250        260        270        280        290 
LADHVLFPGA PRFLQYAKSC GRYRCRLHHT GLPDFPAIKD GIAQLTYAGP G 

« Hide

Isoform 2 (E') [UniParc].

Checksum: BB46042216F8830C
Show »

FASTA25127,548

References

« Hide 'large scale' references
[1]"Mutations of LRTOMT, a fusion gene with alternative reading frames, cause nonsyndromic deafness in humans."
Ahmed Z.M., Masmoudi S., Kalay E., Belyantseva I.A., Mosrati M.A., Collin R.W.J., Riazuddin S., Hmani-Aifa M., Venselaar H., Kawar M.N., Tlili A., van der Zwaag B., Khan S.Y., Ayadi L., Riazuddin S.A., Morell R.J., Griffith A.J., Charfedine I. expand/collapse author list , Caylan R., Oostrik J., Karaguzel A., Ghorbel A., Riazuddin S., Friedman T.B., Ayadi H., Kremer H.
Nat. Genet. 40:1335-1340(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANTS DFNB63 GLN-81; ARG-105 AND LYS-110.
Tissue: Brain.
[2]"Large-scale cDNA transfection screening for genes related to cancer development and progression."
Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X., Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X. expand/collapse author list , Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.
Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Testis.
[4]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"A catechol-O-methyltransferase that is essential for auditory function in mice and humans."
Du X., Schwander M., Moresco E.M.Y., Viviani P., Haller C., Hildebrand M.S., Pak K., Tarantino L., Roberts A., Richardson H., Koob G., Najmabadi H., Ryan A.F., Smith R.J.H., Mueller U., Beutler B.
Proc. Natl. Acad. Sci. U.S.A. 105:14609-14614(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION, FUNCTION, VARIANTS DFNB63 PRO-16; HIS-158 AND GLN-208.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001138780.1. NM_001145308.4.
NP_001138781.1. NM_001145309.3.
NP_001138782.1. NM_001145310.3.
UniGeneHs.317243.
Hs.667985.

3D structure databases

ProteinModelPortalQ8WZ04.
SMRQ8WZ04. Positions 79-290.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid128624. 1 interaction.
STRING9606.ENSP00000409403.

Polymorphism databases

DMDM226693615.

Proteomic databases

PRIDEQ8WZ04.

Protocols and materials databases

DNASU220074.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000307198; ENSP00000305742; ENSG00000184154. [Q8WZ04-1]
ENST00000419228; ENSP00000392233; ENSG00000184154. [Q8WZ04-2]
ENST00000435085; ENSP00000409789; ENSG00000184154. [Q8WZ04-1]
GeneID220074.
KEGGhsa:220074.
UCSCuc001ors.4. human. [Q8WZ04-2]
uc010rqv.2. human. [Q8WZ04-1]

Organism-specific databases

CTD220074.
GeneCardsGC11P071792.
HGNCHGNC:25033. LRTOMT.
MIM611451. phenotype.
612414. gene.
neXtProtNX_Q8WZ04.
Orphanet90636. Autosomal recessive nonsyndromic sensorineural deafness type DFNB.
PharmGKBPA164722133.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG4122.
HOGENOMHOG000046392.
OMAIPCLRTQ.
PhylomeDBQ8WZ04.
TreeFamTF329140.

Gene expression databases

ArrayExpressQ8WZ04.
BgeeQ8WZ04.
GenevestigatorQ8WZ04.

Family and domain databases

InterProIPR025782. Catechol_O-MeTrfase.
IPR002935. O-MeTrfase_3.
[Graphical view]
PANTHERPTHR10509. PTHR10509. 1 hit.
PfamPF01596. Methyltransf_3. 1 hit.
[Graphical view]
PROSITEPS51682. SAM_OMT_I. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSLRTOMT. human.
GenomeRNAi220074.
NextBio90973.
PROQ8WZ04.
SOURCESearch...

Entry information

Entry nameTOMT_HUMAN
AccessionPrimary (citable) accession number: Q8WZ04
Secondary accession number(s): B7Z816
Entry history
Integrated into UniProtKB/Swiss-Prot: November 25, 2008
Last sequence update: April 14, 2009
Last modified: April 16, 2014
This is version 70 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM