TB Genome Annotation Portal

Rv0006 (gyrA)

Amino Acid Sequence

MTDTTLPPDDSLDRIEPVDIEQEMQRSYIDYAMSVIVGRALPEVRDGLKPVHRRVLYAMFDSGFRPDRSHAKSARSVAETMGNYHPHGDASIYDSLVRMA
QPWSLRYPLVDGQGNFGSPGNDPPAAMRYTEARLTPLAMEMLREIDEETVDFIPNYDGRVQEPTVLPSRFPNLLANGSGGIAVGMATNIPPHNLRELADA
VFWALENHDADEEETLAAVMGRVKGPDFPTAGLIVGSQGTADAYKTGRGSIRMRGVVEVEEDSRGRTSLVITELPYQVNHDNFITSIAEQVRDGKLAGIS
NIEDQSSDRVGLRIVIEIKRDAVAKVVINNLYKHTQLQTSFGANMLAIVDGVPRTLRLDQLIRYYVDHQLDVIVRRTTYRLRKANERAHILRGLVKALDA
LDEVIALIRASETVDIARAGLIELLDIDEIQAQAILDMQLRRLAALERQRIIDDLAKIEAEIADLEDILAKPERQRGIVRDELAEIVDRHGDDRRTRIIA
ADGDVSDEDLIAREDVVVTITETGYAKRTKTDLYRSQKRGGKGVQGAGLKQDDIVAHFFVCSTHDLILFFTTQGRVYRAKAYDLPEASRTARGQHVANLL
AFQPEERIAQVIQIRGYTDAPYLVLATRNGLVKKSKLTDFDSNRSGGIVAVNLRDNDELVGAVLCSAGDDLLLVSANGQSIRFSATDEALRPMGRATSGV
QGMRFNIDDRLLSLNVVREGTYLLVATSGGYAKRTAIEEYPVQGRGGKGVLTVMYDRRRGRLVGALIVDDDSELYAVTSGGGVIRTAARQVRKAGRQTKG
VRLMNLGEGDTLLAIARNAEESGDDNAVDANGADQTGN
(Nucleotide sequence available on KEGG)

Additional Information




Analysis of Positive Selection in Clinical Isolates *new*

Moldova (2,057)global set (5,195)
under significant positive selection?YESYES
omega peak height (95%CI lower bound)6.72 (3.25)3.06 (1.02)
codons under selection70, 71, 72, 73, 74, 88, 89, 90, 91, 92, 93, 94, 9594
omega plots
genetic variants*linklink
statistics at each codonlinklink
* example format for variants: "D27 (GAC): D27H (CAC,11)" means "Asp27 (native codon GAC) mutated to His (codon CAC) in 11 isolates"


ESSENTIALITY

MtbTnDB - interactive tool for exploring a database of published TnSeq datasets for Mtb

TnSeqCorr - genes with correlated TnSeq profiles across ~100 conditions

Rv0006/gyrA, gene len: 2516 bp, num TA sites: 46
conditiondatasetcallmediummethodnotes
in-vitroDeJesus 2017 mBioessential7H9HMMfully saturated, 14 TnSeq libraries combined
in-vitroSassetti 2003 Mol Microno data 7H9TRASHessential if hybridization ratio<0.2
in-vivo (mice)Sassetti 2003 PNASno data BL6 miceTRASHessential if hybridization ratio<0.4, min over 4 timepoints (1-8 weeks)
in-vitro (glycerol)Griffin 2011 PPathuncertainM9 minimal+glycerolGumbel2 replicates; Padj<0.05
in-vitro (cholesterol)Griffin 2011 PPathuncertainM9 minimal+cholesterolGumbel3 replicates; Padj<0.05
differentially essential in cholesterol Griffin 2011 PPathNO (LFC=-0.91)cholesterol vs glycerolresampling-SRYES if Padj<0.05, else not significant; LFC<0 means less insertions/more essential in cholesterol
in-vitroSmith 2022 eLifeessential7H9HMM6 replicates (raw data in Subramaniam 2017, PMID 31752678)
in-vivo (mice)Smith 2022 eLifeessentialBL6 miceHMM6 replicates (raw data in Subramaniam 2017, PMID 31752678)
differentially essential in miceSmith 2022 eLifeNO (LFC=-0.048)in-vivo vs in-vitroZINBYES if Padj<0.05, else not significant; LFC<0 means less insertions/more essential in mice
in-vitro (minimal)Minato 2019 mSysessentialminimal mediumHMM
in-vitro (YM rich medium)Minato 2019 mSysessentialYM rich mediumHMM7H9 supplemented with ~20 metabolites (amino acids, cofactors)
differentially essential in YM rich mediumMinato 2019 mSysNO (LFC=0.0)YM rich vs minimal mediumresampling

TnSeq Data No data currently available.
  • No TnSeq data currently available for this Target.
RNASeq Data No data currently available.
  • No RNA-Seq data currently available for this Target.
Metabolomic Profiles No data currently available.
  • No Metabolomic data currently available for this Target.
Proteomic Data No data currently available.
  • No Proteomic data currently available for this Target.

Regulatory Relationships from Systems Biology
  • BioCyc

    Gene interactions based on ChIPSeq and Transcription Factor Over-Expression (TFOE) (Systems Biology)

    NOTE: Green edges represent the connected genes being classified as differentially essential as a result of the middle gene being knocked out. These interactions are inferred based on RNASeq.

    Interactions based on ChIPSeq data

    • Binds To:

      • No bindings to other targets were found.
    • Bound By:

    Interactions based on ChIPSeq data (Minch et al. 2014)

    Interactions based on TFOE data (Rustad et al. 2014)

    • Upregulates:

      • Does not upregulate other genes.
    • Upregulated by:

      • Not upregulated by other genes.
    • Downregulates:

      • Does not downregulate other genes.
    • Downregulated by:



    TBCAP

    Tubculosis Community Annotation Project (
    Slayden et al., 2013)

    Rv0006 (gyrA)

    PropertyValueCreatorEvidencePMIDComment
    InteractionInhibition Rv3361cvashishtrvIDAStructural Analysis
    authors,SS. Hegde,MW. Vetting,SL. Roderick,LA. Mitchenall,A. Maxwell,HE. Takiff,JS. Blanchard A fluoroquinolone resistance protein from Mycobacterium tuberculosis that mimics DNA. Science 2005
    InteractionInhibition Rv3361cvashishtrvIDAStructural Analysis
    A. Mrens, S. Matrat et al. The pentapeptide Repeat Proteins MtMfpA and QnrB4 Exhibit Opposite Effects on DNA Gyrase Catalytic Reactions and on the Ternary Gyrase-DNA-Quinolone Complex. J. Bacteriol. 2008
    InteractionInhibition Rv3361cvashishtrvIDASpectrophotometric
    authors,SS. Hegde,MW. Vetting,SL. Roderick,LA. Mitchenall,A. Maxwell,HE. Takiff,JS. Blanchard A fluoroquinolone resistance protein from Mycobacterium tuberculosis that mimics DNA. Science 2005
    InteractionInhibition Rv3361cvashishtrvIDASpectrophotometric
    A. Mrens, S. Matrat et al. The pentapeptide Repeat Proteins MtMfpA and QnrB4 Exhibit Opposite Effects on DNA Gyrase Catalytic Reactions and on the Ternary Gyrase-DNA-Quinolone Complex. J. Bacteriol. 2008
    InteractionInhibition Rv3361cshahanup86IDASpectrophotometric
    A. Mrens, S. Matrat et al. The pentapeptide Repeat Proteins MtMfpA and QnrB4 Exhibit Opposite Effects on DNA Gyrase Catalytic Reactions and on the Ternary Gyrase-DNA-Quinolone Complex. J. Bacteriol. 2008
    InteractionInhibition Rv3361cshahanup86IDAStructural Analysis
    authors,SS. Hegde,MW. Vetting,SL. Roderick,LA. Mitchenall,A. Maxwell,HE. Takiff,JS. Blanchard A fluoroquinolone resistance protein from Mycobacterium tuberculosis that mimics DNA. Science 2005
    InteractionInhibition Rv3361cshahanup86IDAStructural Analysis
    A. Mrens, S. Matrat et al. The pentapeptide Repeat Proteins MtMfpA and QnrB4 Exhibit Opposite Effects on DNA Gyrase Catalytic Reactions and on the Ternary Gyrase-DNA-Quinolone Complex. J. Bacteriol. 2008
    InteractionInhibition Rv3361cvashishtrvIDAStructural Analysis
    authors,SS. Hegde,MW. Vetting,SL. Roderick,LA. Mitchenall,A. Maxwell,HE. Takiff,JS. Blanchard A fluoroquinolone resistance protein from Mycobacterium tuberculosis that mimics DNA. Science 2005
    InteractionInhibition Rv3361cvashishtrvIDAStructural Analysis
    A. Mrens, S. Matrat et al. The pentapeptide Repeat Proteins MtMfpA and QnrB4 Exhibit Opposite Effects on DNA Gyrase Catalytic Reactions and on the Ternary Gyrase-DNA-Quinolone Complex. J. Bacteriol. 2008
    InteractionInhibition Rv3361cshahanup86IDASpectrophotometric
    authors,SS. Hegde,MW. Vetting,SL. Roderick,LA. Mitchenall,A. Maxwell,HE. Takiff,JS. Blanchard A fluoroquinolone resistance protein from Mycobacterium tuberculosis that mimics DNA. Science 2005
    InteractionInhibition Rv3361cshahanup86IDAStructural Analysis
    A. Mrens, S. Matrat et al. The pentapeptide Repeat Proteins MtMfpA and QnrB4 Exhibit Opposite Effects on DNA Gyrase Catalytic Reactions and on the Ternary Gyrase-DNA-Quinolone Complex. J. Bacteriol. 2008
    InteractionInhibition Rv3361cvashishtrvIDASpectrophotometric
    authors,SS. Hegde,MW. Vetting,SL. Roderick,LA. Mitchenall,A. Maxwell,HE. Takiff,JS. Blanchard A fluoroquinolone resistance protein from Mycobacterium tuberculosis that mimics DNA. Science 2005
    InteractionInhibition Rv3361cvashishtrvIDASpectrophotometric
    A. Mrens, S. Matrat et al. The pentapeptide Repeat Proteins MtMfpA and QnrB4 Exhibit Opposite Effects on DNA Gyrase Catalytic Reactions and on the Ternary Gyrase-DNA-Quinolone Complex. J. Bacteriol. 2008
    InteractionInhibition Rv3361cshahanup86IDASpectrophotometric
    authors,SS. Hegde,MW. Vetting,SL. Roderick,LA. Mitchenall,A. Maxwell,HE. Takiff,JS. Blanchard A fluoroquinolone resistance protein from Mycobacterium tuberculosis that mimics DNA. Science 2005
    InteractionInhibition Rv3361cshahanup86IDASpectrophotometric
    A. Mrens, S. Matrat et al. The pentapeptide Repeat Proteins MtMfpA and QnrB4 Exhibit Opposite Effects on DNA Gyrase Catalytic Reactions and on the Ternary Gyrase-DNA-Quinolone Complex. J. Bacteriol. 2008
    InteractionInhibition Rv3361cshahanup86IDAStructural Analysis
    authors,SS. Hegde,MW. Vetting,SL. Roderick,LA. Mitchenall,A. Maxwell,HE. Takiff,JS. Blanchard A fluoroquinolone resistance protein from Mycobacterium tuberculosis that mimics DNA. Science 2005
    InteractionInhibitedBy Rv1338shahanup86IDAAffinity purification (Physical interaction)
    S. Sengupta, M. Shah et al. Glutamate racemase from Mycobacterium tuberculosis inhibits DNA gyrase by affecting its DNA-binding. Nucleic Acids Res. 2006
    CitationMonoclonal antibodies to mycobacterial DNA gyrase A inhibit DNA supercoiling activity. UH. Manjunatha, S. Mahadevan et al. Eur. J. Biochem. 2001vmevada102IPI11277926Affinity purification (Physical interaction)
    InteractionPhysicalInteraction Rv0005vmevada102IPIAffinity purification (Physical interaction)
    UH. Manjunatha, S. Mahadevan et al. Monoclonal antibodies to mycobacterial DNA gyrase A inhibit DNA supercoiling activity. Eur. J. Biochem. 2001
    CitationCorrelation between quinolone susceptibility patterns and sequences in the A and B subunits of DNA gyrase in mycobacteria. I. Guillemin, V. Jarlier et al. Antimicrob. Agents Chemother. 1998vmevada102IPI9687411Affinity purification (Physical interaction)
    InteractionPhysicalInteraction Rv0005vmevada102IPIAffinity purification (Physical interaction)
    I. Guillemin, V. Jarlier et al. Correlation between quinolone susceptibility patterns and sequences in the A and B subunits of DNA gyrase in mycobacteria. Antimicrob. Agents Chemother. 1998
    InteractionPhysicalInteraction Rv0007gaat3sRCA
    authors,M. Strong,D. Eisenberg The protein network as a tool for finding novel drug targets. Prog Drug Res 2007
    InteractionPhysicalInteraction Rv0005vmevada102IPIAffinity purification (Physical interaction)
    S. Niemann, D. Harmsen et al. Differentiation of clinical Mycobacterium tuberculosis complex isolates by gyrB DNA sequence polymorphism analysis. J. Clin. Microbiol. 2000
    InteractionPhysicalInteraction Rv0005vmevada102IPIAffinity purification (Physical interaction)
    X. Yin & Z. Yu Mutation Characterization of gyrA and gyrB Genes in Levofloxacin-resistant Mycobacterium tuberculosis Clinical Isolates from Guangdong Province in China. The Journal of infection 2010
    InteractionPhysicalInteraction Rv0005vmevada102IPIAffinity purification (Physical interaction)
    A. Aubry, XS. Pan et al. Mycobacterium tuberculosis DNA gyrase: interaction with quinolones and correlation with antimycobacterial drug activity. Antimicrob. Agents Chemother. 2004
    InteractionPhysicalInteraction Rv0005vmevada102IPIAffinity purification (Physical interaction)
    Y. Onodera, M. Tanaka et al. Inhibitory activity of quinolones against DNA gyrase of Mycobacterium tuberculosis. J. Antimicrob. Chemother. 2001
    CitationInhibitory activity of quinolones against DNA gyrase of Mycobacterium tuberculosis. Y. Onodera, M. Tanaka et al. J. Antimicrob. Chemother. 2001vmevada102IPI11266418Affinity purification (Physical interaction)
    InteractionPhysicalInteraction Rv0005vmevada102IPIAffinity purification (Physical interaction)
    Y. Onodera, M. Tanaka et al. Inhibitory activity of quinolones against DNA gyrase of Mycobacterium tuberculosis. J. Antimicrob. Chemother. 2001
    InteractionPhysicalInteraction Rv0005vmevada102IPIAffinity purification (Physical interaction)
    authors,G. Fu,J. Wu,W. Liu,D. Zhu,Y. Hu,J. Deng,XE. Zhang,L. Bi,DC. Wang Crystal structure of DNA gyrase B' domain sheds lights on the mechanism for T-segment navigation. Nucleic Acids Res. 2009
    InteractionPhysicalInteraction Rv0005vmevada102IPIAffinity purification (Physical interaction)
    I. Guillemin, V. Jarlier et al. Correlation between quinolone susceptibility patterns and sequences in the A and B subunits of DNA gyrase in mycobacteria. Antimicrob. Agents Chemother. 1998
    InteractionPhysicalInteraction Rv0005vmevada102IPIAffinity purification (Physical interaction)
    KS. Goh, M. Fabre et al. Study of the gyrB gene polymorphism as a tool to differentiate among Mycobacterium tuberculosis complex subspecies further underlines the older evolutionary age of 'Mycobacterium canettii'. Mol. Cell. Probes null
    InteractionPhysicalInteraction Rv0005vmevada102IPIAffinity purification (Physical interaction)
    HE. Takiff, L. Salazar et al. Cloning and nucleotide sequence of Mycobacterium tuberculosis gyrA and gyrB genes and detection of quinolone resistance mutations. Antimicrob. Agents Chemother. 1994
    InteractionRegulatedBy Rv0348yamir.morenoIEPMicroarrays. mRNA levels of regulated element measured and compared between wild-type and trans-element mutation (knockout, over expression etc.) performed by using microarray (or macroarray) experiments..
    B. Abomoelak, EA. Hoye et al. mosR, a novel transcriptional regulator of hypoxia and virulence in Mycobacterium tuberculosis. J. Bacteriol. 2009
    InteractionRegulatedBy Rv3648cyamir.morenoISOE.coli orthology based inference. Orthologous pair regulator-target found in E.coli.
    G. Balzsi, AP. Heath et al. The temporal response of the Mycobacterium tuberculosis gene regulatory network during growth arrest. Mol. Syst. Biol. 2008
    InteractionRegulatedBy Rv3676yamir.morenoISOE.coli orthology based inference. Orthologous pair regulator-target found in E.coli.
    G. Balzsi, AP. Heath et al. The temporal response of the Mycobacterium tuberculosis gene regulatory network during growth arrest. Mol. Syst. Biol. 2008
    InteractionRegulatedBy Rv3648cyamir.morenoISOE.coli orthology based inference. Orthologous pair regulator-target found in E.coli.
    authors,M. Madan Babu,SA. Teichmann,L. Aravind Evolutionary dynamics of prokaryotic transcriptional regulatory networks. J. Mol. Biol. 2006
    InteractionRegulatedBy Rv3676yamir.morenoISOE.coli orthology based inference. Orthologous pair regulator-target found in E.coli.
    authors,M. Madan Babu,SA. Teichmann,L. Aravind Evolutionary dynamics of prokaryotic transcriptional regulatory networks. J. Mol. Biol. 2006

    Comments