Rv2596 (vapC40)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: toxin
- REFSEQ: hypothetical protein
- PATRIC: Toxin 1 PIN domain
- TUBERCULIST: Possible toxin VapC40. Contains PIN domain.
- NCBI: Possible toxin VapC40 Contains PIN domain
- updated information (H37Rv4):
  - gene name: vapC40
  - function:
  - reference:
Type: Not Target
Start: 2925734
End: 2926138
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: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:
Search for Homologs in PDB
Top 10 Homologs in PDB (as of Nov 2020): (none with >35% aa id)
Links to additional information on vapC40:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 0.192 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

VIAPDTSVLVAGFATWHEGHEAAVRALNRGVHLIAHAAVETYSVLTRLPPPHRIAPVAVHAYLADITSSNYLALDACSYRGLTDHLAEHDVTGGATYDAL
VGFTAKAAGAKLLTRDLRAVETYERLRVEVELVT

(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; 1 non-insertions in a row out of 8 sites
Non-Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 1 non-insertions in a row out of 8 sites
Non-Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 1 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; 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
No-Data	7H10-glycerol	H37RvMA	TraSH	Sassetti et al. (2003a)
Too-Short	C57BL/6J mice (8 weeks)	H37RvMA	TraSH	Sassetti et al. (2003b)	Hybridization Ratio: -1
Growth-Advantage	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:

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0081 (-) (Upstream of operon)
- Rv1423 (whiA) (Upstream of operon)
- Rv2595 (vapB40) (Upstream of operon)
- Rv3736 (-) (Upstream of operon)

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

Upregulates:
- Does not upregulate other genes.
Upregulated by:
- Rv2595 (vapB40)
Downregulates:
- Does not downregulate other genes.
Downregulated by:
- Rv0324 (-)
- Rv2887 (-)

Property	Value	Creator	Evidence	PMID	Comment
Interaction	Operon Rv2595	xaccheus	TAS		Structural Analysis 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	Distant structural homology leads to the functional characterization of an archaeal PIN domain as an exonuclease. authors,VL. Arcus,K. Bckbro,A. Roos,EL. Daniel,EN. Baker J. Biol. Chem. 2004	xaccheus	TAS	14734548	Spectrophotometric
Interaction	Operon Rv2595	xaccheus	TAS		Spectrophotometric authors,VL. Arcus,K. Bckbro,A. Roos,EL. Daniel,EN. Baker Distant structural homology leads to the functional characterization of an archaeal PIN domain as an exonuclease. J. Biol. Chem. 2004
Citation	Distant structural homology leads to the functional characterization of an archaeal PIN domain as an exonuclease. authors,VL. Arcus,K. Bckbro,A. Roos,EL. Daniel,EN. Baker J. Biol. Chem. 2004	xaccheus	TAS	14734548	Structural Analysis
Interaction	Operon Rv2595	xaccheus	TAS		Structural Analysis authors,VL. Arcus,K. Bckbro,A. Roos,EL. Daniel,EN. Baker Distant structural homology leads to the functional characterization of an archaeal PIN domain as an exonuclease. J. Biol. Chem. 2004
Interaction	Operon Rv2595	xaccheus	TAS		Spectrophotometric authors,VL. Arcus,PB. Rainey,SJ. Turner The PIN-domain toxin-antitoxin array in mycobacteria. Trends Microbiol. 2005
Interaction	Operon Rv2595	xaccheus	TAS		Spectrophotometric 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	Operon Rv2595	xaccheus	TAS		Structural Analysis 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, Not toxic when expressed in Msmeg
Symbol	vapC-mt25	jlew			No growth when mazF-mt1 expressed in Ecoli but restored when mazE-mt1 was co-induced. mazF-mt1 could also be partially neutralized by vapB-mt24 or vapB-mt25. Growth inhibition by mazF-mt3; normal growth if mazE-mt1, mazE-mt3, vapB-mt24 or vapB-mt25 were co-expressed. Each pair shows interaction by pull-down. authors,L. Zhu,JD. Sharp,H. Kobayashi,NA. Woychik,M. Inouye Noncognate Mycobacterium tuberculosis toxin-antitoxins can physically and functionally interact. J. Biol. Chem. 2010
Citation	Noncognate Mycobacterium tuberculosis toxin-antitoxins can physically and functionally interact. authors,L. Zhu,JD. Sharp,H. Kobayashi,NA. Woychik,M. Inouye J. Biol. Chem. 2010	jlew		20876537	No growth when mazF-mt1 expressed in Ecoli but restored when mazE-mt1 was co-induced. mazF-mt1 could also be partially neutralized by vapB-mt24 or vapB-mt25. Growth inhibition by mazF-mt3; normal growth if mazE-mt1, mazE-mt3, vapB-mt24 or vapB-mt25 were co-expressed. Each pair shows interaction by pull-down.

TB Genome Annotation Portal