Rv1495 (mazF4)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: toxin
- REFSEQ: hypothetical protein
- PATRIC: FIG00822400: hypothetical protein
- TUBERCULIST: Possible toxin MazF4
- NCBI: Possible toxin MazF4
- updated information (H37Rv4):
  - gene name: mazF4
  - function:
  - reference:
Type: Not Target
Start: 1686570
End: 1686887
Operon:

Trans-membrane region:
Role: V - Conserved hypotheticals
GO terms:
- GO:2000372 - negative regulation of DNA topoisomerase (ATP-hydrolyzing) activity (Uniprot)
- 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):

PDB	aa ident	species	PDB title
5XE3	99%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Endoribonuclease in complex with its cognate antitoxin from Mycobacterial species
5XE2	99%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Endoribonuclease from Mycobacterial species

Links to additional information on mazF4:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = ? (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

VNAPLRGQVYRCDLGYGAKPWLIVSNNARNRHTADVVAVRLTTTRRTIPTWVAMGPSDPLTGYVNADNIETLGKDELGDYLGEVTPATMNKINTALATAL
GLPWP

(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)	1.07 (0.14)	2.36 (0.7)
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

Rv1495/mazF4, gene len: 317 bp, num TA sites: 6

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=0.01)	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=-0.257)	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=0.52)	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

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

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv1353c (-) (Upstream of operon)

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

Upregulates:
- Does not upregulate other genes.
Upregulated by:
- Rv0023 (-)
Downregulates:
- Does not downregulate other genes.
Downregulated by:
- Rv0238 (-)
- Rv2887 (-)

Property	Value	Creator	Evidence	PMID	Comment
Interaction	InhibitedBy Rv1494	sumaavasthi	ISA		Functional linkage ZL. Shang, L. Bao et al. [Molecular cloning and expression of hypothetical proteins Rv1494 and Rv1495 of M.tuberculosis H37Rv strain.] Nan Fang Yi Ke Da Xue Xue Bao 2007
Citation	Occurrence of mazEF-like antitoxin/toxin systems in bacteria. authors,G. Mittenhuber J. Mol. Microbiol. Biotechnol. 1999	sumaavasthi	ISA	10943559	Functional linkage
Interaction	InhibitedBy Rv1494	sumaavasthi	ISA		Functional linkage authors,G. Mittenhuber Occurrence of mazEF-like antitoxin/toxin systems in bacteria. J. Mol. Microbiol. Biotechnol. 1999
Interaction	InhibitedBy Rv1494	sumaavasthi	ISA		Functional linkage ZL. Shang, L. Bao et al. [Molecular cloning and expression of hypothetical proteins Rv1494 and Rv1495 of M.tuberculosis H37Rv strain.] Nan Fang Yi Ke Da Xue Xue Bao 2007
Interaction	InhibitedBy Rv1494	sumaavasthi	ISA		Functional linkage authors,G. Mittenhuber Occurrence of mazEF-like antitoxin/toxin systems in bacteria. J. Mol. Microbiol. Biotechnol. 1999
Citation	[Molecular cloning and expression of hypothetical proteins Rv1494 and Rv1495 of M.tuberculosis H37Rv strain.] ZL. Shang, L. Bao et al. Nan Fang Yi Ke Da Xue Xue Bao 2007	sumaavasthi	ISA	17259135	Functional linkage
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
Citation	Characterization of an interplay between a Mycobacterium tuberculosis MazF homolog, Rv1495 and its sole DNA topoisomerase I. authors,F. Huang,ZG. He Nucleic Acids Res. 2010	jlew		20724443	Through its C-terminal domain, M. tuberculosis DNA topoisomerase I physically interacted with and inhibited the mRNA cleavage activity of Rv1495. Rv1495, in turn, inhibited the DNA cleavage activity of MtbTopA as well as its function of relaxation of supercoiled DNA.
Symbol	MazF4	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-mt7	jlew			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	None
Other	stop:1686887	rslayden			hypothetical protein
Other	strand:+	rslayden			hypothetical protein
Other	start:1686570	rslayden			hypothetical protein

TB Genome Annotation Portal