LRTOMT

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 key	Position(s)	DescriptionActions	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
Inferred from sequence or structural similarityⁱ
- 18794526
L-dopa O-methyltransferase activity Source: UniProtKB-EC
orcinol O-methyltransferase activity Source: UniProtKB-EC

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

auditory receptor cell development
Source: UniProtKB
Inferred from sequence or structural similarityⁱ
- 18794526
catecholamine catabolic process
Source: UniProtKB
Inferred from sequence or structural similarityⁱ
- 18794526
developmental process
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
dopamine metabolic process
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
neurotransmitter catabolic process Source: UniProtKB-KW
sensory perception of sound
Source: UniProtKB
Inferred from sequence or structural similarityⁱ
- 18794526

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Methyltransferase, Transferase
Biological process	Catecholamine metabolism, Hearing, Neurotransmitter degradation
Ligand	S-adenosyl-L-methionine

Enzyme and pathway databases

Reactomeⁱ	R-HSA-379397 Enzymatic degradation of dopamine by COMT

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	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 11

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000184154.12
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:25033 LRTOMT
MIMⁱ	612414 gene
neXtProtⁱ	NX_Q8WZ04

Topology

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Transmembraneⁱ	31 – 51	HelicalSequence analysisAdd BLAST		21

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.

Keywords - Diseaseⁱ

Deafness, Disease mutation, Non-syndromic deafness

Organism-specific databases

DisGeNET More...DisGeNETⁱ	220074
GeneReviewsⁱ	LRTOMT
MalaCards human disease database More...MalaCardsⁱ	LRTOMT
MIMⁱ	611451 phenotype
Open Targets More...OpenTargetsⁱ	ENSG00000184154
Orphanetⁱ	90636 Autosomal recessive non-syndromic sensorineural deafness type DFNB
PharmGKBⁱ	PA164722133

Polymorphism and mutation databases

DMDMⁱ	226693615

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
PeptideAtlas More...PeptideAtlasⁱ	Q8WZ04
PRIDEⁱ	Q8WZ04
ProteomicsDBⁱ	75203 75204 [Q8WZ04-2]

PTM databases

PhosphoSitePlusⁱ	Q8WZ04

PhosphoSitePlusⁱ

Q8WZ04

Expressionⁱ

Gene expression databases

Bgeeⁱ	ENSG00000184154 Expressed in 122 organ(s), highest expression level in testis
ExpressionAtlasⁱ	Q8WZ04 baseline and differential
Genevisibleⁱ	Q8WZ04 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

BioGridⁱ	128624, 2 interactors
STRINGⁱ	9606.ENSP00000305742

Structureⁱ

3D structure databases

ProteinModelPortalⁱ	Q8WZ04
SMRⁱ	Q8WZ04
ModBaseⁱ	Search...
MobiDBⁱ	Search...

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 helix

Phylogenomic databases

eggNOGⁱ	KOG1663 Eukaryota COG4122 LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00390000011316
HOGENOMⁱ	HOG000046392
InParanoidⁱ	Q8WZ04
KEGG Orthology (KO) More...KOⁱ	K00545
OMAⁱ	FIDHYKP
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G0GQK
PhylomeDBⁱ	Q8WZ04
TreeFamⁱ	TF329140

Family and domain databases

InterProⁱ	View protein in InterPro IPR002935 O-MeTrfase_3 IPR029063 SAM-dependent_MTases IPR033025 TOMT
PANTHERⁱ	PTHR43836:SF1 PTHR43836:SF1, 1 hit
Pfam protein domain database More...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

Sequences (2+)ⁱ

Sequence statusⁱ: Complete.

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

This entry has 2 described isoforms and 6 potential isoforms that are computationally mapped.Show all Align All

Isoform 1 (identifier: Q8WZ04-1) [UniParc]FASTA Add 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]FASTA Add to basket

Also known as: E'

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

« Hide

        10         20         30         40         50
MGTPWRKRKG IAGPGLPDLS CALVLQPSLR DCLSGLRIEE RAFSYVLTHA 
        60         70         80         90        100
LPGDPGHILT TLDHWSSRCE YLSHMGPVKG QILMRLVEEK APACVLELGT 
       110        120        130        140        150
YCGYSTLLIA RALPPGGRLL TVERDPRTAA VAEKLIRLAG FDEHMVELIV 
       160        170        180        190        200
GSSEDVIPCL RTQYQLSRAD LVLLAHRPRC YLRDLQLLEA HALLPAGATV 
       210        220        230        240        250
LADHVLFPGA PRFLQYAKSC GRYRCRLHHT GLPDFPAIKD GIAQLTYAGP 

G

Show »

Length:251

Mass (Da):27,548

Checksum:ⁱBB46042216F8830C

GO

Computationally mapped potential isoform sequencesⁱ

There are 6 potential isoforms mapped to this entry.BLAST Align Show all Add to basket

Entry	Entry name	Protein names	Gene names	Length	Annotation

Q96E66	LRC51_HUMAN	Leucine-rich repeat-containing prot... Leucine-rich repeat-containing protein 51 (Protein LRTOMT1)	LRTOMT LRRC51	192	Annotation score:
F5GYI0	F5GYI0_HUMAN	Leucine-rich repeat-containing prot... Leucine-rich repeat-containing protein 51	LRTOMT	103	Annotation score:
F5H614	F5H614_HUMAN	Leucine-rich repeat-containing prot... Leucine-rich repeat-containing protein 51	LRTOMT	65	Annotation score:
F5H6F7	F5H6F7_HUMAN	cDNA, FLJ79541, highly similar to L... cDNA, FLJ79541, highly similar to Leucine-rich repeat-containing protein 51	LRTOMT	54	Annotation score:
F5H6K5	F5H6K5_HUMAN	Leucine-rich repeat-containing prot... Leucine-rich repeat-containing protein 51	LRTOMT	38	Annotation score:
F5H0M6	F5H0M6_HUMAN	Leucine-rich repeat-containing prot... Leucine-rich repeat-containing protein 51	LRTOMT	92	Annotation score:

Sequence cautionⁱ

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

Natural variant

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_047554	16	L → P in DFNB63. 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. 1 PublicationCorresponds to variant dbSNP:rs758115449Ensembl.	1
Natural variantⁱVAR_047556	208	R → Q in DFNB63. 1 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.
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS44668.1 [Q8WZ04-1]
NCBI Reference Sequences More...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]
UniGeneⁱ	Hs.317243 Hs.667985

Genome annotation databases

Ensemblⁱ	ENST00000307198; ENSP00000305742; ENSG00000184154 [Q8WZ04-1] ENST00000435085; ENSP00000409789; ENSG00000184154 [Q8WZ04-1]
GeneIDⁱ	220074
KEGGⁱ	hsa:220074
UCSC genome browser More...UCSCⁱ	uc010rqw.3 human [Q8WZ04-1]

Keywords - Coding sequence diversityⁱ

Alternative splicing

Similar proteinsⁱ

90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
Q8WZ04	Transmembrane O-methyltransferase		PANTR		291	UniRef90_Q8WZ04
Uncharacterized protein		PANPA		291
Uncharacterized protein		MACFA		291
Uncharacterized protein		SAIBB		290
LRTOMT isoform D'		PAPAN		258
+6
Q8WZ04-2	Transmembrane O-methyltransferase homolog		RAT		258	UniRef90_Q8WZ04-2
Uncharacterized protein		NOMLE		291
Uncharacterized protein		CALJA		290
Uncharacterized protein		PROCO		288
UPI0004541FDE		CRIGR		261
+2

Protein	Similar proteins		Species	Score	Length	Source
Q8WZ04	Transmembrane O-methyltransferase		PANTR		291	UniRef50_Q8WZ04
Transmembrane O-methyltransferase		MACMU		296
Uncharacterized protein		MACFA		291
Uncharacterized protein		PANPA		291
Uncharacterized protein		SAIBB		290
+58
Q8WZ04-2	Transmembrane O-methyltransferase homolog		MOUSE		258	UniRef50_A1Y9I9
Transmembrane O-methyltransferase homolog		DANRE		259
Transmembrane O-methyltransferase homolog		RAT		258
Transmembrane O-methyltransferase		PROCO		274
Transmembrane O-methyltransferase		MYOBR		293
+161

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]
UniGeneⁱ	Hs.317243 Hs.667985

3D structure databases

ProteinModelPortalⁱ	Q8WZ04
SMRⁱ	Q8WZ04
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	128624, 2 interactors
STRINGⁱ	9606.ENSP00000305742

PTM databases

PhosphoSitePlusⁱ	Q8WZ04

PhosphoSitePlusⁱ

Q8WZ04

Polymorphism and mutation databases

DMDMⁱ	226693615

DMDMⁱ

226693615

Proteomic databases

PaxDbⁱ	Q8WZ04
PeptideAtlasⁱ	Q8WZ04
PRIDEⁱ	Q8WZ04
ProteomicsDBⁱ	75203 75204 [Q8WZ04-2]

Protocols and materials databases

The DNASU plasmid repository More...DNASUⁱ	220074
Structural Biology Knowledgebase	Search...

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
MalaCardsⁱ	LRTOMT
MIMⁱ	611451 phenotype 612414 gene
neXtProtⁱ	NX_Q8WZ04
OpenTargetsⁱ	ENSG00000184154
Orphanetⁱ	90636 Autosomal recessive non-syndromic sensorineural deafness type DFNB
PharmGKBⁱ	PA164722133
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	KOG1663 Eukaryota COG4122 LUCA
GeneTreeⁱ	ENSGT00390000011316
HOGENOMⁱ	HOG000046392
InParanoidⁱ	Q8WZ04
KOⁱ	K00545
OMAⁱ	FIDHYKP
OrthoDBⁱ	EOG091G0GQK
PhylomeDBⁱ	Q8WZ04
TreeFamⁱ	TF329140

Enzyme and pathway databases

Reactomeⁱ	R-HSA-379397 Enzymatic degradation of dopamine by COMT

Reactomeⁱ

R-HSA-379397 Enzymatic degradation of dopamine by COMT

Miscellaneous databases

ChiTaRSⁱ	LRTOMT human
GenomeRNAiⁱ	220074
Protein Ontology More...PROⁱ	PR:Q8WZ04
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000184154 Expressed in 122 organ(s), highest expression level in testis
ExpressionAtlasⁱ	Q8WZ04 baseline and differential
Genevisibleⁱ	Q8WZ04 HS

Family and domain databases

InterProⁱ	View protein in InterPro IPR002935 O-MeTrfase_3 IPR029063 SAM-dependent_MTases 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...

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:	November 7, 2018
	This is version 105 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

Complete proteome, Reference proteome

Documents

SIMILARITY comments
Index of protein domains and families
Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations
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
Human chromosome 11
Human chromosome 11: entries, gene names and cross-references to MIM

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UniProtKB - Q8WZ04 (TOMT_HUMAN)

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Transmembrane O-methyltransferase

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Plasma Membrane

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Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Keywords - Diseasei

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<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Proteomic databases

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<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

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<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

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<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Keywords - Domaini

Phylogenomic databases

Family and domain databases

<p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

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Keywords - Coding sequence diversityi

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

Keywords - Diseaseⁱ

PTM / Processingⁱ

Expressionⁱ

Interactionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Domainⁱ

Sequence cautionⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ