Rv0659c (mazF2)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: toxin
- REFSEQ: hypothetical protein
- PATRIC: Death on curing protein Doc toxin
- TUBERCULIST: Toxin MazF2
- NCBI: Toxin MazF2
- updated information (H37Rv4):
  - gene name: mazF2
  - function:
  - reference:
Type: Not Target
Start: 754685
End: 754993
Operon:

Trans-membrane region:
Role: V - Conserved hypotheticals
GO terms:
- GO:0090305 - nucleic acid phosphodiester bond hydrolysis (Uniprot)
- GO:0016787 - hydrolase activity (Uniprot)
- GO:0004519 - endonuclease activity (Uniprot)
- GO:0004518 - nuclease activity (Uniprot)
- GO:0003677 - DNA binding (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
Gene Expression Profile (Transcriptional Responses to Drugs; Boshoff et al, 2004)
Gene Modules extracted from cluster analysis of 249 transcriptomic datasets using ICA
Orthologs among selected mycobacteria
Protein structure:
Search for Homologs in PDB
Top 10 Homologs in PDB (as of Nov 2020): (none with >35% aa id)
Links to additional information on mazF2:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 0.95 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MRRGELWFAATPGGDRPVLVLTRDPVADRIGAVVVVALTRTRRGLVSELELTAVENRVPSDCVVNFDNIHTLPRTAFRRRITRLSPARLHEACQTLRAST
GC

(Nucleotide sequence available on KEGG)

Additional Information

Analysis of Positive Selection in Clinical Isolates new

Analysis of dN/dS (omega) in two collections of Mtb clinical isolates using GenomegaMap (Window model) (see description of methods)
- Moldova: 2,057 clinical isolates
- global set: 5,195 clinical isolates from 15 other countries
In the omega plots, the black line shows the mean estimate of omega (dN/dS) at each codon, and the blue lines are the bounds for the 95% credible interval (95%CI, from MCMC sampling).
A gene is under significant positive selection if the lower-bound of the 95%CI of omega (lower blue line) exceeds 1.0 at any codon.

	Moldova (2,057)	global set (5,195)
under significant positive selection?	NO	NO
omega peak height (95%CI lower bound)	1.72 (0.31)	1.09 (0.36)
codons under selection
omega plots
genetic variants*	link	link
statistics at each codon	link	link

* 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

Rv0659c/mazF2, gene len: 308 bp, num TA sites: 4

condiion	dataset	call	medium	method	notes
in-vitro	DeJesus 2017 mBio	non-essential	7H9	HMM	14 TnSeq libraries combined
in-vitro	Sassetti 2003 Mol Micro	non-essential	7H9	TRASH	essential if hybridization ratio<0.2
in-vivo (mice)	Sassetti 2003 PNAS	non-essential	BL6 mice	TRASH	essential if hybridization ratio<0.4, min over 4 timepoints (1-8 weeks)
in-vitro (glycerol)	Griffin 2011 PPath	non-essential	M9 minimal+glycerol	Gumbel	2 replicates; Padj<0.05
in-vitro (cholesterol)	Griffin 2011 PPath	non-essential	M9 minimal+cholesterol	Gumbel	3 replicates; Padj<0.05
differentially essential in cholesterol	Griffin 2011 PPath	NO (LFC=-0.59)	cholesterol vs glycerol	resampling-SR	YES if Padj<0.05, else not significant; LFC<0 means less insertions/more essential in cholesterol
in-vitro	Smith 2022 eLife	non-essential	7H9	HMM	6 replicates (raw data in Subramaniam 2017, PMID 31752678)
in-vivo (mice)	Smith 2022 eLife	non-essential	BL6 mice	HMM	6 replicates (raw data in Subramaniam 2017, PMID 31752678)
differentially essential in mice	Smith 2022 eLife	NO (LFC=0.256)	in-vivo vs in-vitro	ZINB	YES if Padj<0.05, else not significant; LFC<0 means less insertions/more essential in mice
in-vitro (minimal)	Minato 2019 mSys	non-essential	minimal medium	HMM
in-vitro (YM rich medium)	Minato 2019 mSys	non-essential	YM rich medium	HMM	7H9 supplemented with ~20 metabolites (amino acids, vitamins)
differentially essential in YM rich medium	Minato 2019 mSys	NO (LFC=0.16)	YM rich vs minimal medium	resampling

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

RNA processing and modification

Energy production and conversion

Chromatin structure and dynamics

Amino acid transport and metabolism

Cell cycle control, cell division, chromosome partitioning

Carbohydrate transport and metabolism

Nucleotide transport and metabolism

Lipid transport and metabolism

Coenzyme transport and metabolism

Transcription

Translation, ribosomal structure and biogenesis

Cell wall/membrane/envelope biogenesis

Replication, recombination and repair

Posttranslational modification, protein turnover, chaperones

Cell motility

Secondary metabolites biosynthesis, transport and catabolism

Inorganic ion transport and metabolism

Function unknown

General function prediction only

Intracellular trafficking, secretion, and vesicular transport

Signal transduction mechanisms

Extracellular structures

Defense mechanisms

Nuclear structure

Cytoskeleton

BioCyc Co-regulated genes based on gene expression profiling (Systems Biology, Inferelator Network)

Differentially expressed as result of RNASeq in glycerol environment (Only top 20 genes shown sorted by log fold change with p_adj 0.05).

Conditionally essential as result of TNSeq (Only top 20 genes shown sorted by log fold change with p_adj 0.05).

BioCyc Transcription factor binding based on ChIP-Seq (Systems Biology)

Binds To:
- No bindings to other targets were found.
Bound By:
- No bindings from other targets were found.

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0135c (-) (Direct binding)
- Rv0691c (-) (Direct binding)

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:
- Not downregulated by other genes.

Property	Value	Creator	Evidence	PMID	Comment
Interaction	InhibitedBy Rv0660c	priti.priety	IGC		Gene Neighborhood (Functional linkage) authors,HR. Ramage,LE. Connolly,JS. Cox Comprehensive functional analysis of Mycobacterium tuberculosis toxin-antitoxin systems: implications for pathogenesis, stress responses, and evolution. PLoS Genet. 2009
Interaction	InhibitedBy Rv0660c	priti.priety	IGC		Gene Neighborhood (Functional linkage) authors,L. Zhu,Y. Zhang,JS. Teh,J. Zhang,N. Connell,H. Rubin,M. Inouye Characterization of mRNA interferases from Mycobacterium tuberculosis. J. Biol. Chem. 2006
Interaction	InhibitedBy Rv0660c	ashwinigbhat	IGC		Gene Neighborhood (Functional linkage) authors,HR. Ramage,LE. Connolly,JS. Cox Comprehensive functional analysis of Mycobacterium tuberculosis toxin-antitoxin systems: implications for pathogenesis, stress responses, and evolution. PLoS Genet. 2009
Interaction	InhibitedBy Rv0660c	ashwinigbhat	IGC		Gene Neighborhood (Functional linkage) authors,L. Zhu,Y. Zhang,JS. Teh,J. Zhang,N. Connell,H. Rubin,M. Inouye Characterization of mRNA interferases from Mycobacterium tuberculosis. J. Biol. Chem. 2006
Citation	Comprehensive functional analysis of Mycobacterium tuberculosis toxin-antitoxin systems: implications for pathogenesis, stress responses, and evolution. authors,HR. Ramage,LE. Connolly,JS. Cox PLoS Genet. 2009	priti.priety	IGC	20011113	Gene Neighborhood (Functional linkage)
Interaction	InhibitedBy Rv0660c	priti.priety	IGC		Gene Neighborhood (Functional linkage) authors,HR. Ramage,LE. Connolly,JS. Cox Comprehensive functional analysis of Mycobacterium tuberculosis toxin-antitoxin systems: implications for pathogenesis, stress responses, and evolution. PLoS Genet. 2009
Citation	Characterization of mRNA interferases from Mycobacterium tuberculosis. authors,L. Zhu,Y. Zhang,JS. Teh,J. Zhang,N. Connell,H. Rubin,M. Inouye J. Biol. Chem. 2006	priti.priety	IGC	16611633	Gene Neighborhood (Functional linkage)
Interaction	InhibitedBy Rv0660c	priti.priety	IGC		Gene Neighborhood (Functional linkage) authors,L. Zhu,Y. Zhang,JS. Teh,J. Zhang,N. Connell,H. Rubin,M. Inouye Characterization of mRNA interferases from Mycobacterium tuberculosis. J. Biol. Chem. 2006
Citation	Comprehensive functional analysis of Mycobacterium tuberculosis toxin-antitoxin systems: implications for pathogenesis, stress responses, and evolution. authors,HR. Ramage,LE. Connolly,JS. Cox PLoS Genet. 2009	ashwinigbhat	IGC	20011113	Gene Neighborhood (Functional linkage)
Interaction	InhibitedBy Rv0660c	ashwinigbhat	IGC		Gene Neighborhood (Functional linkage) authors,HR. Ramage,LE. Connolly,JS. Cox Comprehensive functional analysis of Mycobacterium tuberculosis toxin-antitoxin systems: implications for pathogenesis, stress responses, and evolution. PLoS Genet. 2009
Citation	Characterization of mRNA interferases from Mycobacterium tuberculosis. authors,L. Zhu,Y. Zhang,JS. Teh,J. Zhang,N. Connell,H. Rubin,M. Inouye J. Biol. Chem. 2006	ashwinigbhat	IGC	16611633	Gene Neighborhood (Functional linkage)
Interaction	InhibitedBy Rv0660c	ashwinigbhat	IGC		Gene Neighborhood (Functional linkage) authors,L. Zhu,Y. Zhang,JS. Teh,J. Zhang,N. Connell,H. Rubin,M. Inouye Characterization of mRNA interferases from Mycobacterium tuberculosis. J. Biol. Chem. 2006
Citation	Comprehensive functional analysis of Mycobacterium tuberculosis toxin-antitoxin systems: implications for pathogenesis, stress responses, and evolution. authors,HR. Ramage,LE. Connolly,JS. Cox PLoS Genet. 2009	jlew		20011113	MazF homolog, Not toxic when expressed in Msmeg
Symbol	MazF2	jlew			We report the heterologous toxicity of these TA loci in Escherichia coli and show that only a few of the M. tuberculosis-encoded toxins can inhibit E. coli growth and have a killing effect. This killing effect can be suppressed by coexpression of the cognate antitoxin. authors,A. Gupta Killing activity and rescue function of genome-wide toxin-antitoxin loci of Mycobacterium tuberculosis. FEMS Microbiol. Lett. 2009
Citation	Killing activity and rescue function of genome-wide toxin-antitoxin loci of Mycobacterium tuberculosis. authors,A. Gupta FEMS Microbiol. Lett. 2009	jlew		19016878	We report the heterologous toxicity of these TA loci in Escherichia coli and show that only a few of the M. tuberculosis-encoded toxins can inhibit E. coli growth and have a killing effect. This killing effect can be suppressed by coexpression of the cognate antitoxin.
Symbol	mazF-mt4	jlew			Caused cell growth arrest when induced in Ecoli. authors,L. Zhu,Y. Zhang,JS. Teh,J. Zhang,N. Connell,H. Rubin,M. Inouye Characterization of mRNA interferases from Mycobacterium tuberculosis. J. Biol. Chem. 2006
Citation	Characterization of mRNA interferases from Mycobacterium tuberculosis. authors,L. Zhu,Y. Zhang,JS. Teh,J. Zhang,N. Connell,H. Rubin,M. Inouye J. Biol. Chem. 2006	jlew		16611633	Caused cell growth arrest when induced in Ecoli.
Other	start:754685	rslayden			Conserved hypothetical protein, weakly similar to other Mycobacterium tuberculosis hypothetical proteins e.g. Rv1942c, Rv1495, etc.
Other	stop:754993	rslayden			Conserved hypothetical protein, weakly similar to other Mycobacterium tuberculosis hypothetical proteins e.g. Rv1942c, Rv1495, etc.
Other	strand:+	rslayden			Conserved hypothetical protein, weakly similar to other Mycobacterium tuberculosis hypothetical proteins e.g. Rv1942c, Rv1495, etc.

TB Genome Annotation Portal