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UniProtKB - P9WNF9 (ETHA_MYCTU)

Entry version 36 (07 Oct 2020)
Sequence version 1 (16 Apr 2014)
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Protein

FAD-containing monooxygenase EthA

Gene

ethA

Organism
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Monooxygenase able to convert a wide range of ketones to the corresponding esters or lactones via a Baeyer-Villiger oxidation reaction. Can act on long-chain aliphatic ketones (2-hexanone to 2-dodecanone) and on aromatic ketones (phenylacetone and benzylacetone). Is also able to catalyze enantioselective sulfoxidation of methyl-p-tolylsulfide. In vivo, likely functions as a BVMO, but the exact nature of the physiological substrate(s) remains to be established.1 Publication
Is responsible for the activation of several thiocarbamide-containing pro-drugs into cytotoxic species. Thus, catalyzes the oxidation of the antitubercular pro-drug ethionamide (ETH) to the corresponding sulfoxide, which is further oxidized by EthA to 2-ethyl-4-amidopyridine, presumably via the unstable doubly oxidized sulfinic acid intermediate; the final metabolite 2-ethyl-4-amidopyridine has no antitubercular activity, so the cytotoxic species is a metabolite intermediate formed by EthA. Also oxidizes thiacetazone (TAC), thiobenzamide, and isothionicotinamide and therefore is probably responsible, as suggested by the observation of crossover resistance, for the oxidative activation of these other thioamide antitubercular drugs.4 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the 'Function' section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori

FAD2 PublicationsNote: Binds 1 FAD per subunit.2 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

Activity can be increased by one order of magnitude by adding bovine serum albumin in vitro. This result suggests that the enzyme is activated in vivo by protein-protein or interactions with other cellular components.1 Publication

<p>This subsection of the 'Function' section describes biophysical and chemical properties, such as maximal absorption, kinetic parameters, pH dependence, redox potentials and temperature dependence.<p><a href='/help/biophysicochemical_properties' target='_top'>More...</a></p>Kineticsi

kcat is 0.027 sec(-1) with ethionamide as substrate. kcat is 0.017 sec(-1) with phenylacetone as substrate. kcat is 0.021 sec(-1) with benzylacetone as substrate. kcat is 0.023 sec(-1) with 2-dodecanone as substrate.1 Publication
  1. KM=194 µM for ethionamide1 Publication
  2. KM=340 µM for ethionamide1 Publication
  3. KM=10 µM for NADPH1 Publication
  4. KM=61 µM for phenylacetone1 Publication
  5. KM=520 µM for benzylacetone1 Publication
  6. KM=200 µM for 2-dodecanone1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei15FADBy similarity1
    Binding sitei36FADBy similarity1
    Binding sitei56FADBy similarity1
    Binding sitei104FAD; via amide nitrogen and carbonyl oxygenBy similarity1
    <p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections ('Function', 'PTM / Processing', 'Pathology and Biotech') according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei292Transition state stabilizerBy similarity1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi44 – 47FADBy similarity4
    Nucleotide bindingi54 – 56NADPBy similarity3
    Nucleotide bindingi183 – 189NADPBy similarity7
    Nucleotide bindingi207 – 208NADPBy similarity2

    <p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

    Complete GO annotation on QuickGO ...

    GO - Biological processi

    Complete GO annotation on QuickGO ...

    <p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

    Molecular functionMonooxygenase, Oxidoreductase
    LigandFAD, Flavoprotein, NADP

    Enzyme and pathway databases

    BioCyc Collection of Pathway/Genome Databases

    More...    BioCyci    		MetaCyc:G185E-8152-MONOMER

    SABIO-RK: Biochemical Reaction Kinetics Database

    More...    SABIO-RKi    		P9WNF9

    <p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

    <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
    Recommended name:
    FAD-containing monooxygenase EthA1 Publication (EC:1.14.13.-1 Publication)
    Alternative name(s):
    Baeyer-Villiger monooxygenase EtaA1 Publication
    Short name:
    BVMO1 Publication
    Prodrug activator EtaA1 Publication
    <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
    Name:ethA1 Publication
    Synonyms:etaA2 Publications
    Ordered Locus Names:Rv3854c
    <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiMycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
    <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri83332 [NCBI]
    <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiBacteria › Actinobacteria › Corynebacteriales › Mycobacteriaceae › Mycobacterium › Mycobacterium tuberculosis complex ›
    <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
    • UP000001584 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome

    Organism-specific databases

    Mycobacterium tuberculosis strain H37Rv genome database

    More...    TubercuListi    		Rv3854c

    <p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation on QuickGO ...

    Keywords - Cellular componenti

    Cell membrane, Membrane

    <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

    <p>This subsection of the 'Pathology and Biotech' section describes the in vivo effects caused by ablation of the gene (or one or more transcripts) coding for the protein described in the entry. This includes gene knockout and knockdown, provided experiments have been performed in the context of a whole organism or a specific tissue, and not at the single-cell level.<p><a href='/help/disruption_phenotype' target='_top'>More...</a></p>Disruption phenotypei

    Inactivation of this gene leads to a strong resistance to ETH.1 Publication

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi84Y → C: ETH-resistant. 1 Publication1

    <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

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00003985811 – 489FAD-containing monooxygenase EthAAdd BLAST489

    Proteomic databases

    PaxDb, a database of protein abundance averages across all three domains of life

    More...    PaxDbi    		P9WNF9

    <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

    <p>This subsection of the 'Expression' section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductioni

    Repressed by the transcriptional regulator EthR.1 Publication

    <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

    <p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

    Exists as a mixture of relatively large homooligomers ranging from 200 to 600 kDa.

    1 Publication

    Protein-protein interaction databases

    STRING: functional protein association networks

    More...    STRINGi    		83332.Rv3854c

    <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

    SWISS-MODEL Repository - a database of annotated 3D protein structure models

    More...    SMRi    		P9WNF9

    Database of comparative protein structure models

    More...    ModBasei    		Search...

    <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

    <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

    Belongs to the FAD-binding monooxygenase family.Curated

    Phylogenomic databases

    evolutionary genealogy of genes: Non-supervised Orthologous Groups

    More...    eggNOGi    		COG2072, Bacteria

    KEGG Orthology (KO)

    More...    KOi    		K10215

    Identification of Orthologs from Complete Genome Data

    More...    OMAi    		ASWTLKC

    Database for complete collections of gene phylogenies

    More...    PhylomeDBi    		P9WNF9

    Family and domain databases

    Gene3D Structural and Functional Annotation of Protein Families

    More...    Gene3Di    		3.50.50.60, 3 hits

    Integrated resource of protein families, domains and functional sites

    More...    InterProi    		View protein in InterPro
    IPR036188, FAD/NAD-bd_sf
    IPR020946, Flavin_mOase-like

    Pfam protein domain database

    More...    Pfami    		View protein in Pfam
    PF00743, FMO-like, 1 hit

    Superfamily database of structural and functional annotation

    More...    SUPFAMi    		SSF51905, SSF51905, 1 hit

    <p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequencei

    <p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

    P9WNF9-1 [UniParc]FASTAAdd to basket
    « Hide
            10         20         30         40         50
    MTEHLDVVIV GAGISGVSAA WHLQDRCPTK SYAILEKRES MGGTWDLFRY 
            60         70         80         90        100
    PGIRSDSDMY TLGFRFRPWT GRQAIADGKP ILEYVKSTAA MYGIDRHIRF 
           110        120        130        140        150
    HHKVISADWS TAENRWTVHI QSHGTLSALT CEFLFLCSGY YNYDEGYSPR 
           160        170        180        190        200
    FAGSEDFVGP IIHPQHWPED LDYDAKNIVV IGSGATAVTL VPALADSGAK 
           210        220        230        240        250
    HVTMLQRSPT YIVSQPDRDG IAEKLNRWLP ETMAYTAVRW KNVLRQAAVY 
           260        270        280        290        300
    SACQKWPRRM RKMFLSLIQR QLPEGYDVRK HFGPHYNPWD QRLCLVPNGD 
           310        320        330        340        350
    LFRAIRHGKV EVVTDTIERF TATGIRLNSG RELPADIIIT ATGLNLQLFG 
           360        370        380        390        400
    GATATIDGQQ VDITTTMAYK GMMLSGIPNM AYTVGYTNAS WTLKADLVSE 
           410        420        430        440        450
    FVCRLLNYMD DNGFDTVVVE RPGSDVEERP FMEFTPGYVL RSLDELPKQG 
           460        470        480 
    SRTPWRLNQN YLRDIRLIRR GKIDDEGLRF AKRPAPVGV
    Length:489
    Mass (Da):55,326
    Last modified:April 16, 2014 - v1
    <p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i844611B7E831180D
    GO

    Sequence databases

    Select the link destinations:

    EMBL nucleotide sequence database

    More...    EMBLi

    GenBank nucleotide sequence database

    More...    GenBanki

    DNA Data Bank of Japan; a nucleotide sequence database

    More...    DDBJi
    Links Updated
    		AL123456 Genomic DNA Translation: CCP46683.1

    Protein sequence database of the Protein Information Resource

    More...    PIRi    		C70655

    NCBI Reference Sequences

    More...    RefSeqi    		NP_218371.1, NC_000962.3
    WP_003899731.1, NZ_NVQJ01000057.1

    Genome annotation databases

    Ensembl bacterial and archaeal genome annotation project

    More...    EnsemblBacteriai    		CCP46683; CCP46683; Rv3854c

    Database of genes from NCBI RefSeq genomes

    More...    GeneIDi    		23489854
    886175

    KEGG: Kyoto Encyclopedia of Genes and Genomes

    More...    KEGGi    		mtu:Rv3854c
    mtv:RVBD_3854c

    <p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

    <p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    		AL123456 Genomic DNA Translation: CCP46683.1
    PIRiC70655
    RefSeqiNP_218371.1, NC_000962.3
    WP_003899731.1, NZ_NVQJ01000057.1

    3D structure databases

    SMRiP9WNF9
    ModBaseiSearch...

    Protein-protein interaction databases

    STRINGi83332.Rv3854c

    Proteomic databases

    PaxDbiP9WNF9

    Genome annotation databases

    EnsemblBacteriaiCCP46683; CCP46683; Rv3854c
    GeneIDi23489854
    886175
    KEGGimtu:Rv3854c
    mtv:RVBD_3854c

    Organism-specific databases

    TubercuListiRv3854c

    Phylogenomic databases

    eggNOGiCOG2072, Bacteria
    KOiK10215
    OMAiASWTLKC
    PhylomeDBiP9WNF9

    Enzyme and pathway databases

    BioCyciMetaCyc:G185E-8152-MONOMER
    SABIO-RKiP9WNF9

    Family and domain databases

    Gene3Di3.50.50.60, 3 hits
    InterProiView protein in InterPro
    IPR036188, FAD/NAD-bd_sf
    IPR020946, Flavin_mOase-like
    PfamiView protein in Pfam
    PF00743, FMO-like, 1 hit
    SUPFAMiSSF51905, SSF51905, 1 hit

    ProtoNet; Automatic hierarchical classification of proteins

    More...    ProtoNeti    		Search...

    MobiDB: a database of protein disorder and mobility annotations

    More...    MobiDBi    		Search...

    <p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

    <p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiETHA_MYCTU
    <p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P9WNF9
    Secondary accession number(s): L0TDR6, P96223, Q7D4Q8
    <p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 16, 2014
    Last sequence update: April 16, 2014
    Last modified: October 7, 2020
    This is version 36 of the entry and version 1 of the sequence. See complete history.
    <p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    <p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

    Keywords - Technical termi

    Reference proteome

    Documents

    1. Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh
      Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh: entries and gene names
    2. SIMILARITY comments
      Index of protein domains and families
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