Q8WZ04 (TOMT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	291 AA.
Sequence status	Complete.
Protein existence	Evidence 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 methyltransferase superfamily. Catechol-O-methyltransferase family.
Sequence caution	The sequence AAL55772.1 differs from that shown. Reason: Frameshift at position 91.

Ontologies

Keywords
Biological process	Catecholamine metabolism Hearing Neurotransmitter degradation
Cellular component	Cytoplasm Membrane
Coding sequence diversity	Alternative splicing
Disease	Deafness Disease mutation Non-syndromic deafness
Domain	Transmembrane Transmembrane helix
Molecular function	Methyltransferase Transferase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	auditory receptor cell development Inferred from sequence or structural similarity Ref.5. Source: UniProtKB catecholamine catabolic process Inferred from sequence or structural similarity Ref.5. Source: UniProtKB neurotransmitter catabolic process Inferred from electronic annotation. Source: UniProtKB-KW sensory perception of sound Inferred from sequence or structural similarity Ref.5. Source: UniProtKB
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	catechol O-methyltransferase activity Inferred from sequence or structural similarity Ref.5. Source: UniProtKB
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 291	291	Transmembrane O-methyltransferase		PRO_0000354093
Regions
	Transmembrane	31 – 51	21	Helical; Potential
Natural variations
	Alternative sequence	28 – 67	40	Missing in isoform 2.		VSP_036898
	Natural variant	16	1	L → P in DFNB63. Ref.5		VAR_047554
	Natural variant	81	1	R → Q in DFNB63. Ref.1		VAR_054955
	Natural variant	105	1	W → R in DFNB63. Ref.1		VAR_054956
	Natural variant	110	1	E → K in DFNB63. Ref.1		VAR_054957
	Natural variant	158	1	R → H in DFNB63. Ref.5		VAR_047555
	Natural variant	208	1	R → Q in DFNB63. Ref.5		VAR_047556

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (D') [UniParc]. Last modified April 14, 2009. Version 3. Checksum: F6108CBEE0FF49E7	FASTA	291	32,155
	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
	Isoform 2 (E') [UniParc]. Checksum: BB46042216F8830C	FASTA	251	27,548
	10 20 30 40 50 60 MGTPWRKRKG IAGPGLPDLS CALVLQPSLR DCLSGLRIEE RAFSYVLTHA LPGDPGHILT 70 80 90 100 110 120 TLDHWSSRCE YLSHMGPVKG QILMRLVEEK APACVLELGT YCGYSTLLIA RALPPGGRLL 130 140 150 160 170 180 TVERDPRTAA VAEKLIRLAG FDEHMVELIV GSSEDVIPCL RTQYQLSRAD LVLLAHRPRC 190 200 210 220 230 240 YLRDLQLLEA HALLPAGATV LADHVLFPGA PRFLQYAKSC GRYRCRLHHT GLPDFPAIKD 250 GIAQLTYAGP G

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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. , 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.
IPI	IPI00103767. IPI00922926.
RefSeq	NP_001138780.1. NM_001145308.4. NP_001138781.1. NM_001145309.3. NP_001138782.1. NM_001145310.3.
UniGene	Hs.317243.
3D structure databases
ProteinModelPortal	Q8WZ04.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000409403.
Polymorphism databases
DMDM	226693615.
Proteomic databases
PRIDE	Q8WZ04.
Protocols and materials databases
DNASU	220074.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000307198; ENSP00000305742; ENSG00000184154. ENST00000419228; ENSP00000392233; ENSG00000184154. ENST00000435085; ENSP00000409789; ENSG00000184154.
GeneID	220074.
KEGG	hsa:220074.
UCSC	uc001ors.4. human. uc010rqv.2. human.
Organism-specific databases
CTD	220074.
GeneCards	GC11P071792.
HGNC	HGNC:25033. LRTOMT.
MIM	611451. phenotype. 612414. gene.
neXtProt	NX_Q8WZ04.
PharmGKB	PA164722133.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG4122.
HOGENOM	HOG000046392.
OMA	KSCGRYR.
Gene expression databases
ArrayExpress	Q8WZ04.
Bgee	Q8WZ04.
Genevestigator	Q8WZ04.
Family and domain databases
InterPro	IPR025782. Catechol_O-MeTrfase. IPR002935. O-MeTrfase_3. [Graphical view]
PANTHER	PTHR10509. PTHR10509. 1 hit.
Pfam	PF01596. Methyltransf_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	LRTOMT. human.
GenomeRNAi	220074.
NextBio	90973.
SOURCE	Search...

Entry information

Entry name

TOMT_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 61 of the entry and version 3 of the sequence. [Complete history]

Entry status

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.