Rv2009 (vapB15)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: antitoxin
- REFSEQ: hypothetical protein
- PATRIC: FIG00821114: hypothetical protein
- TUBERCULIST: Antitoxin VapB15
- NCBI: Antitoxin VapB15
- updated information (H37Rv4):
  - gene name: vapB15
  - function:
  - reference:
Type: Not Target
Start: 2258030
End: 2258272
Operon:

Trans-membrane region:
Role: V - Conserved hypotheticals
GO terms:
- GO:0046872 - metal ion binding (Uniprot)
- GO:0045927 - positive regulation of growth (Uniprot)
- GO:0001666 - response to hypoxia (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
4CHG	100%	MYCOBACTERIUM TUBERCULOSIS	Crystal structure of VapBC15 complex from Mycobacterium tuberculosis
6A7V	56%	Mycobacterium tuberculosis H37Rv	Crystal structure of Mycobacterium tuberculosis VapBC11 toxin-antitoxin complex

Links to additional information on vapB15:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 1.817 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

VYSGVVSRTNIEIDDELVAAAQRMYRLDSKRSAVDLALRRLVGEPLGRDEALALQGSGFDFSNDEIESFSDTDRKLADES

(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 4 sites
Non-Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 2 non-insertions in a row out of 4 sites
Non-Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 2 non-insertions in a row out of 4 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 5 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 5 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: 1.31
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:
Bound By:

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

Binds To:
- Rv0167 (yrbE1A) (Direct binding)
- Rv0178 (-) (Direct binding)
- Rv0179c (lprO) (Direct binding)
- Rv0317c (glpQ2) (Direct binding)
- Rv1016c (lpqT) (Direct binding)
- Rv1168c (PPE17) (Direct binding)
- Rv1795 (eccD5) (Direct binding)
- Rv2009 (vapB15) (Direct binding)
- Rv2010 (vapC15) (Direct binding)
- Rv3140 (fadE23) (Direct binding)
- Rv3492c (-) (Direct binding)
- Rv3614c (espD) (Direct binding)
- Rv3799c (accD4) (Direct binding)
- Rv3800c (pks13) (Direct binding)
- Rv0168 (yrbE1B) (Upstream of operon)
- Rv0169 (mce1A) (Upstream of operon)
- Rv0170 (mce1B) (Upstream of operon)
- Rv0171 (mce1C) (Upstream of operon)
- Rv0172 (mce1D) (Upstream of operon)
- Rv0173 (lprK) (Upstream of operon)
- Rv0174 (mce1F) (Upstream of operon)
- Rv0175 (-) (Upstream of operon)
- Rv0176 (-) (Upstream of operon)
- Rv0177 (-) (Upstream of operon)
- Rv1796 (mycP5) (Upstream of operon)
- Rv1797 (eccE5) (Upstream of operon)
- Rv1798 (eccA5) (Upstream of operon)
Bound By:
- Rv0081 (-) (Direct binding)
- Rv1033c (trcR) (Direct binding)
- Rv2009 (vapB15) (Direct binding)

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

Upregulates:
Upregulated by:
- Not upregulated by other genes.
Downregulates:
- Rv1799 (lppT)
- Rv2493 (vapB38)
Downregulated by:

Property	Value	Creator	Evidence	PMID	Comment
Citation	The vapBC operon from Mycobacterium smegmatis is an autoregulated toxin-antitoxin module that controls growth via inhibition of translation. authors,J. Robson,JL. McKenzie,R. Cursons,GM. Cook,VL. Arcus J. Mol. Biol. 2009	shahanup86	IEP	19445953	coexpression(Functional Linkage)
Interaction	Inhibits Rv2010	shahanup86	IEP		coexpression(Functional Linkage) authors,J. Robson,JL. McKenzie,R. Cursons,GM. Cook,VL. Arcus The vapBC operon from Mycobacterium smegmatis is an autoregulated toxin-antitoxin module that controls growth via inhibition of translation. J. Mol. Biol. 2009
Interaction	Inhibits Rv2010	shahanup86	IEP		coexpression(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	Inhibits Rv2010	shahanup86	IEP		coexpression(Functional Linkage) authors,J. Robson,JL. McKenzie,R. Cursons,GM. Cook,VL. Arcus The vapBC operon from Mycobacterium smegmatis is an autoregulated toxin-antitoxin module that controls growth via inhibition of translation. J. Mol. Biol. 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	shahanup86	IEP	20011113	coexpression(Functional Linkage)
Interaction	Inhibits Rv2010	shahanup86	IEP		coexpression(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	RegulatedBy Rv0757	yamir.moreno	IEP		Microarrays. 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.. 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
Symbol	VapB	jlew			authors,BA. Ahidjo,D. Kuhnert,JL. McKenzie,EE. Machowski,BG. Gordhan,V. Arcus,GL. Abrahams,V. Mizrahi VapC toxins from Mycobacterium tuberculosis are ribonucleases that differentially inhibit growth and are neutralized by cognate VapB antitoxins. PLoS ONE 2011
Citation	VapC toxins from Mycobacterium tuberculosis are ribonucleases that differentially inhibit growth and are neutralized by cognate VapB antitoxins. authors,BA. Ahidjo,D. Kuhnert,JL. McKenzie,EE. Machowski,BG. Gordhan,V. Arcus,GL. Abrahams,V. Mizrahi PLoS ONE 2011	jlew		21738782	None
Symbol	VapB15	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	Vap BC-15	rslayden			Conserved hypothetical protein, very similar to Rv1560
Other	start:2258030	rslayden			Conserved hypothetical protein, very similar to Rv1560
Other	stop:258272	rslayden			Conserved hypothetical protein, very similar to Rv1560
Other	strand:+	rslayden			Conserved hypothetical protein, very similar to Rv1560
Symbol	Vap BC-15	rslayden			MTCY48.05c (54.4% identity in 68 aa overlap).
Other	start:2258030	rslayden			MTCY48.05c (54.4% identity in 68 aa overlap).
Other	stop:258272	rslayden			MTCY48.05c (54.4% identity in 68 aa overlap).
Other	strand:+	rslayden			MTCY48.05c (54.4% identity in 68 aa overlap).

TB Genome Annotation Portal