Rv0301 (vapC2)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: toxin
- REFSEQ: hypothetical protein
- PATRIC: FIG036853: hypothetical protein
- TUBERCULIST: Possible toxin VapC2
- NCBI: Possible toxin VapC2
- updated information (H37Rv4):
  - gene name: vapC2
  - function:
  - reference:
Type: Not Target
Start: 364044
End: 364469
Operon:

Trans-membrane region:
Role: V - Conserved hypotheticals
GO terms:
- GO:0090501 - RNA phosphodiester bond hydrolysis (Uniprot)
- GO:0090305 - nucleic acid phosphodiester bond hydrolysis (Uniprot)
- GO:0046872 - metal ion binding (Uniprot)
- GO:0017148 - negative regulation of translation (Uniprot)
- GO:0016787 - hydrolase activity (Uniprot)
- GO:0004540 - ribonuclease activity (Uniprot)
- GO:0004518 - nuclease activity (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: 3h87
Search for Homologs in PDB

Top 10 Homologs in PDB (as of Nov 2020):

PDB	aa ident	species	PDB title
3H87	100%	Mycobacterium tuberculosis	Rv0301 Rv0300 Toxin Antitoxin Complex from Mycobacterium tuberculosis
5SV2	41%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Toxin VapC21 from Mycobacterium tuberculosis

Links to additional information on vapC2:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 0.757 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

VTDQRWLIDKSALVRLTDSPDMEIWSNRIERGLVHITGVTRLEVGFSAECGEIARREFREPPLSAMPVEYLTPRIEDRALEVQTLLADRGHHRGPSIPDL
LIAATAELSGLTVLHVDKDFDAIAALTGQKTERLTHRPPSA

(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; 0 non-insertions in a row out of 7 sites
Non-Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 0 non-insertions in a row out of 7 sites
Non-Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 0 non-insertions in a row out of 7 sites
Non-Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 0 non-insertions in a row out of 8 sites
Non-Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 0 non-insertions in a row out of 8 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: 1.87
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:
- Rv0324 (-)

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv1219c (-) (Direct binding)
- Rv1353c (-) (Direct binding)
- Rv0047c (-) (Upstream of operon)
- Rv0576 (-) (Upstream of operon)
- Rv3488 (-) (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:
- Rv0324 (-)

TBCAP

Tubculosis Community Annotation Project (

Slayden et al., 2013

Rv0301 (vapC2)

Property	Value	Creator	Evidence	PMID	Comment
Interaction	Regulatory Rv0300	sourish10	IEP		Co-expression (Functional linkage) authors,VL. Arcus,PB. Rainey,SJ. Turner The PIN-domain toxin-antitoxin array in mycobacteria. Trends Microbiol. 2005
Citation	Prokaryotic toxin-antitoxin stress response loci. authors,K. Gerdes,SK. Christensen,A. Lbner-Olesen Nat. Rev. Microbiol. 2005	sourish10	IEP	15864262	Co-expression (Functional linkage)
Interaction	Regulatory Rv0300	sourish10	IEP		Co-expression (Functional linkage) authors,K. Gerdes,SK. Christensen,A. Lbner-Olesen Prokaryotic toxin-antitoxin stress response loci. Nat. Rev. Microbiol. 2005
Interaction	Regulatory Rv0300	sourish10	IEP		Co-expression (Functional linkage) authors,K. Gerdes,SK. Christensen,A. Lbner-Olesen Prokaryotic toxin-antitoxin stress response loci. Nat. Rev. Microbiol. 2005
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	ahal4789	IEP	20011113	Co-expression (Functional linkage)
Interaction	Regulatory Rv0300	ahal4789	IEP		Co-expression (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	The PIN-domain toxin-antitoxin array in mycobacteria. authors,VL. Arcus,PB. Rainey,SJ. Turner Trends Microbiol. 2005	ahal4789	IEP	15993073	Co-expression (Functional linkage)
Interaction	Regulatory Rv0300	ahal4789	IEP		Co-expression (Functional linkage) authors,VL. Arcus,PB. Rainey,SJ. Turner The PIN-domain toxin-antitoxin array in mycobacteria. Trends Microbiol. 2005
Citation	Prokaryotic toxin-antitoxin stress response loci. authors,K. Gerdes,SK. Christensen,A. Lbner-Olesen Nat. Rev. Microbiol. 2005	ahal4789	IEP	15864262	Co-expression (Functional linkage)
Interaction	Regulatory Rv0300	ahal4789	IEP		Co-expression (Functional linkage) authors,K. Gerdes,SK. Christensen,A. Lbner-Olesen Prokaryotic toxin-antitoxin stress response loci. Nat. Rev. Microbiol. 2005
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	sourish10	IEP	20011113	Co-expression (Functional linkage)
Interaction	Regulatory Rv0300	sourish10	IEP		Co-expression (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	The PIN-domain toxin-antitoxin array in mycobacteria. authors,VL. Arcus,PB. Rainey,SJ. Turner Trends Microbiol. 2005	sourish10	IEP	15993073	Co-expression (Functional linkage)
Interaction	Regulatory Rv0300	ahal4789	IEP		Co-expression (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 Rv0300	ahal4789	IEP		Co-expression (Functional linkage) authors,VL. Arcus,PB. Rainey,SJ. Turner The PIN-domain toxin-antitoxin array in mycobacteria. Trends Microbiol. 2005
Interaction	Regulatory Rv0300	ahal4789	IEP		Co-expression (Functional linkage) authors,K. Gerdes,SK. Christensen,A. Lbner-Olesen Prokaryotic toxin-antitoxin stress response loci. Nat. Rev. Microbiol. 2005
Interaction	Regulatory Rv0300	sourish10	IEP		Co-expression (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 Rv0300	sourish10	IEP		Co-expression (Functional linkage) authors,VL. Arcus,PB. Rainey,SJ. Turner The PIN-domain toxin-antitoxin array in mycobacteria. Trends Microbiol. 2005
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	VapC homolog, PIN domain, Toxic when expressed in Msmeg, rescued by antitoxin (Rv0300)
Symbol	VapC2	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.
Other	start:364044	rslayden			Predicted nucleic acid-binding protein, contains PIN domain. Conserved hypothetical protein, similar to other hypothetical Mycobacterium tuberculosis proteins e.g. Rv2757c, Rv0229c, Rv2546, etc.
Other	stop:364469	rslayden			Predicted nucleic acid-binding protein, contains PIN domain. Conserved hypothetical protein, similar to other hypothetical Mycobacterium tuberculosis proteins e.g. Rv2757c, Rv0229c, Rv2546, etc.
Other	strand:+	rslayden			Predicted nucleic acid-binding protein, contains PIN domain. Conserved hypothetical protein, similar to other hypothetical Mycobacterium tuberculosis proteins e.g. Rv2757c, Rv0229c, Rv2546, etc.

Property

Value

Creator

Evidence

PMID

Comment

Interaction

Regulatory Rv0300

sourish10

IEP

Co-expression (Functional linkage)
authors,VL. Arcus,PB. Rainey,SJ. Turner The PIN-domain toxin-antitoxin array in mycobacteria. Trends Microbiol. 2005

Citation

Prokaryotic toxin-antitoxin stress response loci. authors,K. Gerdes,SK. Christensen,A. Lbner-Olesen Nat. Rev. Microbiol. 2005

sourish10

IEP

15864262

Co-expression (Functional linkage)

Interaction

Regulatory Rv0300

sourish10

IEP

Co-expression (Functional linkage)
authors,K. Gerdes,SK. Christensen,A. Lbner-Olesen Prokaryotic toxin-antitoxin stress response loci. Nat. Rev. Microbiol. 2005

Interaction

Regulatory Rv0300

sourish10

IEP

Co-expression (Functional linkage)
authors,K. Gerdes,SK. Christensen,A. Lbner-Olesen Prokaryotic toxin-antitoxin stress response loci. Nat. Rev. Microbiol. 2005

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

ahal4789

IEP

20011113

Co-expression (Functional linkage)

Interaction

Regulatory Rv0300

ahal4789

IEP

Co-expression (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

The PIN-domain toxin-antitoxin array in mycobacteria. authors,VL. Arcus,PB. Rainey,SJ. Turner Trends Microbiol. 2005

ahal4789

IEP

15993073

Co-expression (Functional linkage)

Interaction

Regulatory Rv0300

ahal4789

IEP

Co-expression (Functional linkage)
authors,VL. Arcus,PB. Rainey,SJ. Turner The PIN-domain toxin-antitoxin array in mycobacteria. Trends Microbiol. 2005

Citation

Prokaryotic toxin-antitoxin stress response loci. authors,K. Gerdes,SK. Christensen,A. Lbner-Olesen Nat. Rev. Microbiol. 2005

ahal4789

IEP

15864262

Co-expression (Functional linkage)

Interaction

Regulatory Rv0300

ahal4789

IEP

Co-expression (Functional linkage)
authors,K. Gerdes,SK. Christensen,A. Lbner-Olesen Prokaryotic toxin-antitoxin stress response loci. Nat. Rev. Microbiol. 2005

Citation

sourish10

IEP

20011113

Co-expression (Functional linkage)

Interaction

Regulatory Rv0300

sourish10

IEP

Citation

The PIN-domain toxin-antitoxin array in mycobacteria. authors,VL. Arcus,PB. Rainey,SJ. Turner Trends Microbiol. 2005

sourish10

IEP

15993073

Co-expression (Functional linkage)

Interaction

Regulatory Rv0300

ahal4789

IEP

Interaction

Regulatory Rv0300

ahal4789

IEP

Co-expression (Functional linkage)
authors,VL. Arcus,PB. Rainey,SJ. Turner The PIN-domain toxin-antitoxin array in mycobacteria. Trends Microbiol. 2005

Interaction

Regulatory Rv0300

ahal4789

IEP

Co-expression (Functional linkage)
authors,K. Gerdes,SK. Christensen,A. Lbner-Olesen Prokaryotic toxin-antitoxin stress response loci. Nat. Rev. Microbiol. 2005

Interaction

Regulatory Rv0300

sourish10

IEP

Interaction

Regulatory Rv0300

sourish10

IEP

Co-expression (Functional linkage)
authors,VL. Arcus,PB. Rainey,SJ. Turner The PIN-domain toxin-antitoxin array in mycobacteria. Trends Microbiol. 2005

Citation

jlew

20011113

VapC homolog, PIN domain, Toxic when expressed in Msmeg, rescued by antitoxin (Rv0300)

Symbol

VapC2

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

Other

start:364044

rslayden

Predicted nucleic acid-binding protein, contains PIN domain. Conserved hypothetical protein, similar to other hypothetical Mycobacterium tuberculosis proteins e.g. Rv2757c, Rv0229c, Rv2546, etc.

Other

stop:364469

rslayden

Predicted nucleic acid-binding protein, contains PIN domain. Conserved hypothetical protein, similar to other hypothetical Mycobacterium tuberculosis proteins e.g. Rv2757c, Rv0229c, Rv2546, etc.

Other

strand:+

rslayden

Predicted nucleic acid-binding protein, contains PIN domain. Conserved hypothetical protein, similar to other hypothetical Mycobacterium tuberculosis proteins e.g. Rv2757c, Rv0229c, Rv2546, etc.

Comments