TB Genome Annotation Portal

Rv0467 (icl1)

Amino Acid Sequence

MSVVGTPKSAEQIQQEWDTNPRWKDVTRTYSAEDVVALQGSVVEEHTLARRGAEVLWEQLHDLEWVNALGALTGNMAVQQVRAGLKAIYLSGWQVAGDAN
LSGHTYPDQSLYPANSVPQVVRRINNALQRADQIAKIEGDTSVENWLAPIVADGEAGFGGALNVYELQKALIAAGVAGSHWEDQLASEKKCGHLGGKVLI
PTQQHIRTLTSARLAADVADVPTVVIARTDAEAATLITSDVDERDQPFITGERTREGFYRTKNGIEPCIARAKAYAPFADLIWMETGTPDLEAARQFSEA
VKAEYPDQMLAYNCSPSFNWKKHLDDATIAKFQKELAAMGFKFQFITLAGFHALNYSMFDLAYGYAQNQMSAYVELQEREFAAEERGYTATKHQREVGAG
YFDRIATTVDPNSSTTALTGSTEEGQFH
(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?NONO

omega peak height (95%CI lower bound)0.91 (0.12)0.67 (0.27)

codons under selection

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

Rv0467/icl1,
gene len: 1286 bp, num TA sites: 19



conditiondatasetcallmediummethodnotes

in-vitroDeJesus 2017 mBiogrowth defect7H9HMMfully 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 PPathessentialM9 minimal+cholesterolGumbel3 replicates; Padj<0.05

differentially essential in cholesterol Griffin 2011 PPathNO (LFC=-2.05)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=-0.101)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 mSysgrowth defectYM rich mediumHMM7H9 supplemented with ~20 metabolites (amino acids, vitamins)

differentially essential in YM rich mediumMinato 2019 mSysNO (LFC=0.92)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
    

    
    

    
    
    

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




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














    

    






    


    


    


    TBCAP
    
Tubculosis Community Annotation Project (    Slayden et al., 2013)
    
Rv0467 (icl1)

    

    PropertyValueCreatorEvidencePMIDComment
    
CitationStructure of isocitrate lyase, a persistence factor of Mycobacterium tuberculosis. V. Sharma, S. Sharma et al. Nat. Struct. Biol. 2000njamshidiIDA10932251PMID: 10932251
    
TermEC:4.1.3.1 Isocitrate lyase. - IDAnjamshidiIDA10932251PMID: 10932251
    V. Sharma, S. Sharma et al. Structure of isocitrate lyase, a persistence factor of Mycobacterium tuberculosis. Nat. Struct. Biol. 2000
    
TermTBRXN:ICL Isocitrate lyase - IDAnjamshidiIDA10932251PMID: 10932251
    V. Sharma, S. Sharma et al. Structure of isocitrate lyase, a persistence factor of Mycobacterium tuberculosis. Nat. Struct. Biol. 2000
    
CitationStructure of isocitrate lyase, a persistence factor of Mycobacterium tuberculosis. V. Sharma, S. Sharma et al. Nat. Struct. Biol. 2000njamshidiISS10932251PMID: 10932251
    
TermEC:4.1.3.1 Isocitrate lyase. - ISSnjamshidiISS10932251PMID: 10932251
    V. Sharma, S. Sharma et al. Structure of isocitrate lyase, a persistence factor of Mycobacterium tuberculosis. Nat. Struct. Biol. 2000
    
TermTBRXN:ICL Isocitrate lyase - ISSnjamshidiISS10932251PMID: 10932251
    V. Sharma, S. Sharma et al. Structure of isocitrate lyase, a persistence factor of Mycobacterium tuberculosis. Nat. Struct. Biol. 2000
    
InteractionRegulatory Rv0757singhpankaj2116IEPSpectrophotometric
    J. Gonzalo-Asensio, S. Mostowy et al. PhoP: a missing piece in the intricate puzzle of Mycobacterium tuberculosis virulence. PLoS ONE 2008
    
InteractionRegulatory Rv0757singhpankaj2116IEPStructural Analysis
    J. Gonzalo-Asensio, S. Mostowy et al. PhoP: a missing piece in the intricate puzzle of Mycobacterium tuberculosis virulence. PLoS ONE 2008
    
InteractionRegulatory Rv0757singhpankaj2116IEPCo-expression (Functional linkage)
    ML. Chesne-Seck, N. Barilone et al. A point mutation in the two-component regulator PhoP-PhoR accounts for the absence of polyketide-derived acyltrehaloses but not that of phthiocerol dimycocerosates in Mycobacterium tuberculosis H37Ra. J. Bacteriol. 2008
    
InteractionRegulatory Rv0757singhpankaj2116IEPCo-expression (Functional linkage)
    authors,A. Sola-Landa,RS. Moura,JF. Martn The two-component PhoR-PhoP system controls both primary metabolism and secondary metabolite biosynthesis in Streptomyces lividans. Proc. Natl. Acad. Sci. U.S.A. 2003
    
InteractionRegulatory Rv0757singhpankaj2116IEPCo-expression (Functional linkage)
    J. Gonzalo Asensio, C. Maia et al. The virulence-associated two-component PhoP-PhoR system controls the biosynthesis of polyketide-derived lipids in Mycobacterium tuberculosis. J. Biol. Chem. 2006
    
InteractionRegulatory Rv0757singhpankaj2116IEPCo-expression (Functional linkage)
    J. Gonzalo-Asensio, CY. Soto et al. The Mycobacterium tuberculosis phoPR operon is positively autoregulated in the virulent strain H37Rv. J. Bacteriol. 2008
    
InteractionRegulatory Rv0757singhpankaj2116IEPCo-expression (Functional linkage)
    A. Sinha, S. Gupta et al. PhoP-PhoP interaction at adjacent PhoP binding sites is influenced by protein phosphorylation. J. Bacteriol. 2008
    
InteractionRegulatory Rv0757singhpankaj2116IEPCo-expression (Functional linkage)
    J. Gonzalo Asensio, C. Maia et al. The virulence-associated two-component PhoP-PhoR system controls the biosynthesis of polyketide-derived lipids in Mycobacterium tuberculosis. J. Biol. Chem. 2006
    
InteractionRegulatory Rv0757singhpankaj2116IEPCo-expression (Functional linkage)
    M. Ryndak, S. Wang et al. PhoP, a key player in Mycobacterium tuberculosis virulence. Trends Microbiol. 2008
    
InteractionRegulatory Rv0757singhpankaj2116IEPCo-expression (Functional linkage)
    JA. Asensio, A. Arbus et al. Live tuberculosis vaccines based on phoP mutants: a step towards clinical trials. Expert opinion on biological therapy 2008
    
InteractionRegulatory Rv0757singhpankaj2116IEPCo-expression (Functional linkage)
    SB. Walters, E. Dubnau et al. The Mycobacterium tuberculosis PhoPR two-component system regulates genes essential for virulence and complex lipid biosynthesis. Mol. Microbiol. 2006
    
InteractionRegulatory Rv0757singhpankaj2116IEPCo-expression (Functional linkage)
    J. Gonzalo-Asensio, S. Mostowy et al. PhoP: a missing piece in the intricate puzzle of Mycobacterium tuberculosis virulence. PLoS ONE 2008
    
InteractionRegulatory Rv0465cpriyadarshinipriyanka2001IDABand shift
    JC. Micklinghoff,KJ. Breitinger,M. Schmidt,R. Geffers,BJ. Eikmanns,FC. Bange Role of the transcriptional regulator RamB (Rv0465c) in the control of the glyoxylate cycle in Mycobacterium tuberculosis. J. Bacteriol. 2009
    
InteractionRegulatory Rv0182cpriti.prietyIEPCo-expression (Functional linkage)
    JH. Lee, DE. Geiman et al. Role of stress response sigma factor SigG in Mycobacterium tuberculosis. J. Bacteriol. 2008
    
InteractionRegulatedBy Rv0182cyamir.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..
    JH. Lee, DE. Geiman et al. Role of stress response sigma factor SigG in Mycobacterium tuberculosis. J. Bacteriol. 2008
    
InteractionRegulatedBy Rv3416yamir.morenoIDAOne hybrid reporter system. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. .
    M. Guo, H. Feng et al. Dissecting transcription regulatory pathways through a new bacterial one-hybrid reporter system. Genome Res. 2009
    
InteractionRegulatedBy Rv3133cyamir.morenoIDAOne hybrid reporter system. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. .
    M. Guo, H. Feng et al. Dissecting transcription regulatory pathways through a new bacterial one-hybrid reporter system. Genome Res. 2009
    
InteractionRegulatedBy Rv2710yamir.morenoIDAOne hybrid reporter system. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. .
    M. Guo, H. Feng et al. Dissecting transcription regulatory pathways through a new bacterial one-hybrid reporter system. Genome Res. 2009
    
InteractionRegulatedBy Rv2017yamir.morenoIDAOne hybrid reporter system. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. .
    M. Guo, H. Feng et al. Dissecting transcription regulatory pathways through a new bacterial one-hybrid reporter system. Genome Res. 2009
    
InteractionRegulatedBy Rv0465cyamir.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.. qRT-PCR. mRNA expression levels of regulated element measured and compared between wild-type  and trans-element mutation (knockout, over expression etc.) performed by using qRT-PCR technique. Electrophoretic mobility shift assays EMSA. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. .
    JC. Micklinghoff,KJ. Breitinger,M. Schmidt,R. Geffers,BJ. Eikmanns,FC. Bange Role of the transcriptional regulator RamB (Rv0465c) in the control of the glyoxylate cycle in Mycobacterium tuberculosis. J. Bacteriol. 2009
    
InteractionRegulatedBy Rv0465cyamir.morenoIDAMicroarrays. 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.. qRT-PCR. mRNA expression levels of regulated element measured and compared between wild-type  and trans-element mutation (knockout, over expression etc.) performed by using qRT-PCR technique. Electrophoretic mobility shift assays EMSA. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. .
    JC. Micklinghoff,KJ. Breitinger,M. Schmidt,R. Geffers,BJ. Eikmanns,FC. Bange Role of the transcriptional regulator RamB (Rv0465c) in the control of the glyoxylate cycle in Mycobacterium tuberculosis. J. Bacteriol. 2009
    
InteractionRegulatedBy Rv0465cyamir.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.. qRT-PCR. mRNA expression levels of regulated element measured and compared between wild-type  and trans-element mutation (knockout, over expression etc.) performed by using qRT-PCR technique. Electrophoretic mobility shift assays EMSA. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. .
    JC. Micklinghoff,KJ. Breitinger,M. Schmidt,R. Geffers,BJ. Eikmanns,FC. Bange Role of the transcriptional regulator RamB (Rv0465c) in the control of the glyoxylate cycle in Mycobacterium tuberculosis. J. Bacteriol. 2009
    
InteractionRegulatedBy Rv0981yamir.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..
    H. He, R. Hovey et al. MprAB is a stress-responsive two-component system that directly regulates expression of sigma factors SigB and SigE in Mycobacterium tuberculosis. J. Bacteriol. 2006
    
InteractionRegulatedBy Rv0757yamir.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..
    J. Gonzalo Asensio, C. Maia et al. The virulence-associated two-component PhoP-PhoR system controls the biosynthesis of polyketide-derived lipids in Mycobacterium tuberculosis. J. Biol. Chem. 2006
    
InteractionRegulatedBy Rv1221yamir.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..
    R. Manganelli, MI. Voskuil et al. The Mycobacterium tuberculosis ECF sigma factor sigmaE: role in global gene expression and survival in macrophages. Mol. Microbiol. 2001
    
InteractionRegulatedBy Rv1785cyamir.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 Rv1221yamir.morenoTASLiterature previously reported link (from Balazsi et al. 2008). Traceable author statement to experimental support.
    G. Balzsi, AP. Heath et al. The temporal response of the Mycobacterium tuberculosis gene regulatory network during growth arrest. Mol. Syst. Biol. 2008
    
InteractionRegulatedBy Rv1785cyamir.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
    
TermEC:4.1.3.30 Methylisocitrate lyase. - NRextern:JZUCKERNRAssay of protein purified to homogeneity from its native host
    EJ. Muoz-Elas, AM. Upton et al. Role of the methylcitrate cycle in Mycobacterium tuberculosis metabolism, intracellular growth, and virulence. Mol. Microbiol. 2006
    
CitationCentral carbon metabolism in Mycobacterium tuberculosis: an unexpected frontier. authors,KY. Rhee,LP. de Carvalho,R. Bryk,S. Ehrt,J. Marrero,SW. Park,D. Schnappinger,A. Venugopal,C. Nathan Trends Microbiol. 2011extern:JZUCKER21561773Traceable author statement to experimental support
    
TermEC:4.1.3.1 Isocitrate lyase. - NRextern:JZUCKERNRTraceable author statement to experimental support
    authors,KY. Rhee,LP. de Carvalho,R. Bryk,S. Ehrt,J. Marrero,SW. Park,D. Schnappinger,A. Venugopal,C. Nathan Central carbon metabolism in Mycobacterium tuberculosis: an unexpected frontier. Trends Microbiol. 2011
    
TermEC:4.1.3.30 Methylisocitrate lyase. - NRextern:JZUCKERNRTraceable author statement to experimental support
    authors,KY. Rhee,LP. de Carvalho,R. Bryk,S. Ehrt,J. Marrero,SW. Park,D. Schnappinger,A. Venugopal,C. Nathan Central carbon metabolism in Mycobacterium tuberculosis: an unexpected frontier. Trends Microbiol. 2011
    
CitationCharacterization of activity and expression of isocitrate lyase in Mycobacterium avium and Mycobacterium tuberculosis. K. Hner Zu Bentrup, A. Miczak et al. J. Bacteriol. 1999extern:JZUCKER10572116Inferred from mutant phenotype
    
TermEC:4.1.3.1 Isocitrate lyase. - NRextern:JZUCKERNRInferred from mutant phenotype
    K. Hner Zu Bentrup, A. Miczak et al. Characterization of activity and expression of isocitrate lyase in Mycobacterium avium and Mycobacterium tuberculosis. J. Bacteriol. 1999
    
TermEC:4.1.3.30 Methylisocitrate lyase. - NRextern:JZUCKERNRInferred from mutant phenotype
    K. Hner Zu Bentrup, A. Miczak et al. Characterization of activity and expression of isocitrate lyase in Mycobacterium avium and Mycobacterium tuberculosis. J. Bacteriol. 1999
    
CitationRole of the methylcitrate cycle in Mycobacterium tuberculosis metabolism, intracellular growth, and virulence. EJ. Muoz-Elas, AM. Upton et al. Mol. Microbiol. 2006extern:JZUCKER16689789Assay of protein purified to homogeneity from its native host
    
TermEC:4.1.3.1 Isocitrate lyase. - NRextern:JZUCKERNRAssay of protein purified to homogeneity from its native host
    EJ. Muoz-Elas, AM. Upton et al. Role of the methylcitrate cycle in Mycobacterium tuberculosis metabolism, intracellular growth, and virulence. Mol. Microbiol. 2006
    

    


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