Rv2494 (vapC38)

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 VapC38. Contains PIN domain.
- NCBI: Possible toxin VapC38 Contains PIN domain
- updated information (H37Rv4):
  - gene name: vapC38
  - function:
  - reference:
Type: Not Target
Start: 2808310
End: 2808735
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:0016788 - hydrolase activity, acting on ester bonds (Uniprot)
- GO:0016787 - hydrolase activity (Uniprot)
- GO:0005576 - extracellular region (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 vapC38:
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 1.181 (from Jeremy Rock's lab)

Amino Acid Sequence

VALLDVNALVALAWDSHIHHARIREWFTANATLGWATCPLTEAGFVRVSTNPKVLPSAIGIADARRVLVALRAVGGHRFLADDVSLVDDDVPLIVGYRQV
TDAHLLTLARRRGVRLVTFDAGVFTLAQQRPKTPVELLTIL

(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 5 sites
Non-Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 1 non-insertions in a row out of 5 sites
Non-Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 3 non-insertions in a row out of 5 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 6 sites
Non-Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 2 non-insertions in a row out of 6 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: 0.9
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

RNA processing and modification

Energy production and conversion

Chromatin structure and dynamics

Amino acid transport and metabolism

Cell cycle control, cell division, chromosome partitioning

Carbohydrate transport and metabolism

Nucleotide transport and metabolism

Lipid transport and metabolism

Coenzyme transport and metabolism

Transcription

Translation, ribosomal structure and biogenesis

Cell wall/membrane/envelope biogenesis

Replication, recombination and repair

Posttranslational modification, protein turnover, chaperones

Cell motility

Secondary metabolites biosynthesis, transport and catabolism

Inorganic ion transport and metabolism

Function unknown

General function prediction only

Intracellular trafficking, secretion, and vesicular transport

Signal transduction mechanisms

Extracellular structures

Defense mechanisms

Nuclear structure

Cytoskeleton

BioCyc Co-regulated genes based on gene expression profiling (Systems Biology, Inferelator Network)

Differentially expressed as result of RNASeq in glycerol environment (Only top 20 genes shown sorted by log fold change with p_adj 0.05).

Conditionally essential as result of TNSeq (Only top 20 genes shown sorted by log fold change with p_adj 0.05).

BioCyc Transcription factor binding based on ChIP-Seq (Systems Biology)

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

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0678 (-) (Direct binding)
- Rv1985c (-) (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:
- Not downregulated by other genes.

Property	Value	Creator	Evidence	PMID	Comment
Interaction	PhysicalInteraction Rv2492	vmevada102	IGC		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	PhysicalInteraction Rv2493	vmevada102	IGC		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	PhysicalInteraction Rv2493	vmevada102	IGC		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	Contribution of horizontally acquired genomic islands to the evolution of the tubercle bacilli. authors,J. Becq,MC. Gutierrez,V. Rosas-Magallanes,J. Rauzier,B. Gicquel,O. Neyrolles,P. Deschavanne Mol. Biol. Evol. 2007	vmevada102	IGC	17545187	Co-occurrence (Functional linkage)
Interaction	PhysicalInteraction Rv2491	vmevada102	IGC		Co-occurrence (Functional linkage) authors,J. Becq,MC. Gutierrez,V. Rosas-Magallanes,J. Rauzier,B. Gicquel,O. Neyrolles,P. Deschavanne Contribution of horizontally acquired genomic islands to the evolution of the tubercle bacilli. Mol. Biol. Evol. 2007
Interaction	PhysicalInteraction Rv2492	vmevada102	IGC		Co-occurrence (Functional linkage) authors,J. Becq,MC. Gutierrez,V. Rosas-Magallanes,J. Rauzier,B. Gicquel,O. Neyrolles,P. Deschavanne Contribution of horizontally acquired genomic islands to the evolution of the tubercle bacilli. Mol. Biol. Evol. 2007
Interaction	PhysicalInteraction Rv2493	vmevada102	IGC		Co-occurrence (Functional linkage) authors,J. Becq,MC. Gutierrez,V. Rosas-Magallanes,J. Rauzier,B. Gicquel,O. Neyrolles,P. Deschavanne Contribution of horizontally acquired genomic islands to the evolution of the tubercle bacilli. Mol. Biol. Evol. 2007
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	vmevada102	IGC	20011113	Co-occurrence (Functional linkage)
Interaction	PhysicalInteraction Rv2491	vmevada102	IGC		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	PhysicalInteraction Rv2492	vmevada102	IGC		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	PhysicalInteraction Rv2493	vmevada102	IGC		Co-occurrence (Functional linkage) authors,J. Becq,MC. Gutierrez,V. Rosas-Magallanes,J. Rauzier,B. Gicquel,O. Neyrolles,P. Deschavanne Contribution of horizontally acquired genomic islands to the evolution of the tubercle bacilli. Mol. Biol. Evol. 2007
Interaction	PhysicalInteraction Rv2491	vmevada102	IGC		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	PhysicalInteraction Rv2492	vmevada102	IGC		Co-occurrence (Functional linkage) authors,J. Becq,MC. Gutierrez,V. Rosas-Magallanes,J. Rauzier,B. Gicquel,O. Neyrolles,P. Deschavanne Contribution of horizontally acquired genomic islands to the evolution of the tubercle bacilli. Mol. Biol. Evol. 2007
Interaction	PhysicalInteraction Rv2491	vmevada102	IGC		Co-occurrence (Functional linkage) authors,J. Becq,MC. Gutierrez,V. Rosas-Magallanes,J. Rauzier,B. Gicquel,O. Neyrolles,P. Deschavanne Contribution of horizontally acquired genomic islands to the evolution of the tubercle bacilli. Mol. Biol. Evol. 2007
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

TB Genome Annotation Portal