Rv1102c (mazF3)

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 MazF3
- NCBI: Toxin MazF3
- updated information (H37Rv4):
  - gene name: mazF3
  - function:
  - reference:
Type: Not Target
Start: 1230660
End: 1230971
Operon:

Trans-membrane region:
Role: V - Conserved hypotheticals
GO terms:
- GO:0090502 - RNA phosphodiester bond hydrolysis, endonucleolytic (Uniprot)
- GO:0090305 - nucleic acid phosphodiester bond hydrolysis (Uniprot)
- GO:0045927 - positive regulation of growth (Uniprot)
- GO:0045926 - negative regulation of growth (Uniprot)
- GO:0045892 - negative regulation of transcription, DNA-templated (Uniprot)
- GO:0017148 - negative regulation of translation (Uniprot)
- GO:0016787 - hydrolase activity (Uniprot)
- GO:0016075 - rRNA catabolic process (Uniprot)
- GO:0006402 - mRNA catabolic process (Uniprot)
- GO:0005515 - protein binding (Uniprot)
- GO:0004521 - endoribonuclease 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

5UCT 100% Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) Mycobacterium tuberculosis toxin MazF-mt6

5CCA 100% Mycobacterium tuberculosis Crystal structure of Mtb toxin
Links to additional information on mazF3:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 0.703 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

PDB	aa ident	species	PDB title
5UCT	100%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Mycobacterium tuberculosis toxin MazF-mt6
5CCA	100%	Mycobacterium tuberculosis	Crystal structure of Mtb toxin

Amino Acid Sequence

MRPIHIAQLDKARPVLILTREVVRPHLTNVTVAPITTTVRGLATEVPVDAVNGLNQPSVVSCDNTQTIPVCDLGRQIGYLLASQEPALAEAIGNAFDLDW
VVA

(Nucleotide sequence available on KEGG)

Additional Information

ESSENTIALITY

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

TnSeqCorr - genes with correlated TnSeq profiles across >100 conditions *new*

Classification	Condition	Strain	Method	Reference	Notes
Non-Essential	Sodium Oleate	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 2 non-insertions in a row out of 8 sites
Non-Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 2 non-insertions in a row out of 8 sites
Non-Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 2 non-insertions in a row out of 8 sites
Non-Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 1 non-insertions in a row out of 9 sites
Non-Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 1 non-insertions in a row out of 9 sites
Non-Essential	7H10-glycerol	H37RvMA	TraSH	Sassetti et al. (2003a)
Non-Essential	C57BL/6J mice (8 weeks)	H37RvMA	TraSH	Sassetti et al. (2003b)	Hybridization Ratio: 3.14
Non-Essential	7H09/7H10 + rich media	H37RvMA	MotifHMM	DeJesus et al. (2017)	Fully saturated (14 reps).

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:
- Rv0260c (-)
- Rv0757 (phoP)

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0757 (phoP) (Direct binding)
- Rv0967 (csoR) (Direct binding)
- Rv1033c (trcR) (Direct binding)
- Rv2324 (-) (Direct binding)
- Rv2989 (-) (Direct binding)
- Rv3681c (whiB4) (Direct binding)
- Rv1990c (-) (Upstream of operon)

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:
- Rv0260c (-)
- Rv0757 (phoP)

TBCAP

Tubculosis Community Annotation Project (

Slayden et al., 2013

Rv1102c (mazF3)

Property	Value	Creator	Evidence	PMID	Comment
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	ISO	20011113	Co-occurrence (Functional linkage)
Interaction	Regulatory Rv1103c	priti.priety	ISO		Co-occurrence (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	Regulatory Rv1103c	priti.priety	ISO		Co-occurrence (Functional linkage) authors,A. Gupta Killing activity and rescue function of genome-wide toxin-antitoxin loci of Mycobacterium tuberculosis. FEMS Microbiol. Lett. 2009
Interaction	Regulatory Rv1103c	priti.priety	ISO		Co-occurrence (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	Killing activity and rescue function of genome-wide toxin-antitoxin loci of Mycobacterium tuberculosis. authors,A. Gupta FEMS Microbiol. Lett. 2009	priti.priety	ISO	19016878	Co-occurrence (Functional linkage)
Interaction	Regulatory Rv1103c	priti.priety	ISO		Co-occurrence (Functional linkage) authors,A. Gupta Killing activity and rescue function of genome-wide toxin-antitoxin loci of Mycobacterium tuberculosis. FEMS Microbiol. Lett. 2009
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, Toxic when expressed in Msmeg, rescued by antitoxin (Rv1103c)
Citation	Characterization of a chromosomal toxin-antitoxin, Rv1102c-Rv1103c system in Mycobacterium tuberculosis. authors,JS. Han,JJ. Lee,T. Anandan,M. Zeng,S. Sripathi,WJ. Jahng,SH. Lee,JW. Suh,CM. Kang Biochem. Biophys. Res. Commun. 2010	jlew		20705052	Cleaves mRNA.. They interact, by pulldown and two-hybrid. Expression of Rv1102c leads to growth arrest in Ecoli, which was recovered when expressed in cis with Rv1102c. Expression of Rv1102c induces growth arrest of Msmeg and increased persisters.
Symbol	MazF3	jlew			Toxic to Ecoli growth. 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	Toxic to Ecoli growth. 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-mt6	jlew			Caused cell growth arrest when induced in Ecoli. mRNA interferase that cleaves at U-rich regions. 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. mRNA interferase that cleaves at U-rich regions.
Other	start:1230660	rslayden			Conserved hypothetical protein, similar to Mycobacterium tuberculosis hypothetical protens e.g. Rv1942c
Other	stop:1230971	rslayden			Conserved hypothetical protein, similar to Mycobacterium tuberculosis hypothetical protens e.g. Rv1942c
Other	strand:+	rslayden			Conserved hypothetical protein, similar to Mycobacterium tuberculosis hypothetical protens e.g. Rv1942c
Other	start:1230660	rslayden			MTCY9F9_22 (109 aa), FASTA scores: opt: 158, E(): 3.6e-05, (33.3% identity in 93 aa overlap); Rv0659c
Other	stop:1230971	rslayden			MTCY9F9_22 (109 aa), FASTA scores: opt: 158, E(): 3.6e-05, (33.3% identity in 93 aa overlap); Rv0659c
Other	strand:+	rslayden			MTCY9F9_22 (109 aa), FASTA scores: opt: 158, E(): 3.6e-05, (33.3% identity in 93 aa overlap); Rv0659c
Other	start:1230660	rslayden			MTCI376_17 (102aa), opt: 140, E(): 0.00072, (40.6% identity in 69aa overlap); and Rv1495. TBparse score is 0.924.
Other	stop:1230971	rslayden			MTCI376_17 (102aa), opt: 140, E(): 0.00072, (40.6% identity in 69aa overlap); and Rv1495. TBparse score is 0.924.
Other	strand:+	rslayden			MTCI376_17 (102aa), opt: 140, E(): 0.00072, (40.6% identity in 69aa overlap); and Rv1495. TBparse score is 0.924.

Property

Value

Creator

Evidence

PMID

Comment

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

ISO

20011113

Co-occurrence (Functional linkage)

Interaction

Regulatory Rv1103c

priti.priety

ISO

Co-occurrence (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

Regulatory Rv1103c

priti.priety

ISO

Co-occurrence (Functional linkage)
authors,A. Gupta Killing activity and rescue function of genome-wide toxin-antitoxin loci of Mycobacterium tuberculosis. FEMS Microbiol. Lett. 2009

Interaction

Regulatory Rv1103c

priti.priety

ISO

Citation

Killing activity and rescue function of genome-wide toxin-antitoxin loci of Mycobacterium tuberculosis. authors,A. Gupta FEMS Microbiol. Lett. 2009

priti.priety

ISO

19016878

Co-occurrence (Functional linkage)

Interaction

Regulatory Rv1103c

priti.priety

ISO

Co-occurrence (Functional linkage)
authors,A. Gupta Killing activity and rescue function of genome-wide toxin-antitoxin loci of Mycobacterium tuberculosis. FEMS Microbiol. Lett. 2009

Citation

jlew

20011113

MazF homolog, Toxic when expressed in Msmeg, rescued by antitoxin (Rv1103c)

Citation

Characterization of a chromosomal toxin-antitoxin, Rv1102c-Rv1103c system in Mycobacterium tuberculosis. authors,JS. Han,JJ. Lee,T. Anandan,M. Zeng,S. Sripathi,WJ. Jahng,SH. Lee,JW. Suh,CM. Kang Biochem. Biophys. Res. Commun. 2010

jlew

20705052

Cleaves mRNA.. They interact, by pulldown and two-hybrid. Expression of Rv1102c leads to growth arrest in Ecoli, which was recovered when expressed in cis with Rv1102c. Expression of Rv1102c induces growth arrest of Msmeg and increased persisters.

Symbol

MazF3

jlew

Toxic to Ecoli growth. 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

Symbol

mazF-mt6

jlew

Caused cell growth arrest when induced in Ecoli. mRNA interferase that cleaves at U-rich regions.
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. mRNA interferase that cleaves at U-rich regions.

Other

start:1230660

rslayden

Conserved hypothetical protein, similar to Mycobacterium tuberculosis hypothetical protens e.g. Rv1942c

Other

stop:1230971

rslayden

Conserved hypothetical protein, similar to Mycobacterium tuberculosis hypothetical protens e.g. Rv1942c

Other

strand:+

rslayden

Conserved hypothetical protein, similar to Mycobacterium tuberculosis hypothetical protens e.g. Rv1942c

Other

start:1230660

rslayden

MTCY9F9_22 (109 aa), FASTA scores: opt: 158, E(): 3.6e-05, (33.3% identity in 93 aa overlap); Rv0659c

Other

stop:1230971

rslayden

MTCY9F9_22 (109 aa), FASTA scores: opt: 158, E(): 3.6e-05, (33.3% identity in 93 aa overlap); Rv0659c

Other

strand:+

rslayden

MTCY9F9_22 (109 aa), FASTA scores: opt: 158, E(): 3.6e-05, (33.3% identity in 93 aa overlap); Rv0659c

Other

start:1230660

rslayden

MTCI376_17 (102aa), opt: 140, E(): 0.00072, (40.6% identity in 69aa overlap); and Rv1495. TBparse score is 0.924.

Other

stop:1230971

rslayden

MTCI376_17 (102aa), opt: 140, E(): 0.00072, (40.6% identity in 69aa overlap); and Rv1495. TBparse score is 0.924.

Other

strand:+

rslayden

MTCI376_17 (102aa), opt: 140, E(): 0.00072, (40.6% identity in 69aa overlap); and Rv1495. TBparse score is 0.924.

Comments