Rv0549c (vapC3)

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 VapC3
- NCBI: Possible toxin VapC3
- updated information (H37Rv4):
  - gene name: vapC3
  - function:
  - reference:
Type: Not Target
Start: 640228
End: 640641
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:0075136 - response to host (Uniprot)
- GO:0046872 - metal ion binding (Uniprot)
- GO:0045927 - positive regulation of growth (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 vapC3:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 0.276 (from Jeremy Rock's lab)
- Mycobrowser
- PATRIC
- KEGG - nucleotide and amino acid sequences of gene
- BioCyc
- Systems Biology

Amino Acid Sequence

VRASPTSPPEQVVVDASAMVDLLARTSDRCSAVRARLARTAMHAPAHFDAEVLSALGRMQRAGALTVAYVDAALEELRQVPVTRHGLSSLLAGAWSRRDT
LRLTDALYVELAETAGLVLLTTDERLARAWPSAHAIG

(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 4 sites
Non-Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 0 non-insertions in a row out of 4 sites
Non-Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 0 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 4 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 4 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: 1.08
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:

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv1049 (-) (Direct binding)

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

Upregulates:
- Does not upregulate other genes.
Upregulated by:
- Rv0023 (-)
Downregulates:
- Does not downregulate other genes.
Downregulated by:

Property	Value	Creator	Evidence	PMID	Comment
Citation	Killing activity and rescue function of genome-wide toxin-antitoxin loci of Mycobacterium tuberculosis. authors,A. Gupta FEMS Microbiol. Lett. 2009	sourish10	IDA	19016878	Spectrophototmetric assay
Interaction	Inhibits Rv0550c	sourish10	IDA		Spectrophototmetric assay authors,A. Gupta Killing activity and rescue function of genome-wide toxin-antitoxin loci of Mycobacterium tuberculosis. FEMS Microbiol. Lett. 2009
Interaction	Inhibits Rv0550c	sourish10	IDA		Spectrophototmetric assay 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	VapC homolog, PIN domain, Toxic when expressed in Msmeg, rescued by antitoxin (Rv0550c)
Symbol	VapC	jlew			Growth inhibitory in Mt and MS. 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	Growth inhibitory in Mt and MS.
Symbol	VapC3	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:640228	rslayden			Predicted nucleic acid-binding protein, contains PIN domain. Conserved hypothetical protein, similar to Rv0960, Rv0065, and Rv1720c from Mycobacterium tuberculosis.
Other	stop:640641	rslayden			Predicted nucleic acid-binding protein, contains PIN domain. Conserved hypothetical protein, similar to Rv0960, Rv0065, and Rv1720c from Mycobacterium tuberculosis.
Other	strand:+	rslayden			Predicted nucleic acid-binding protein, contains PIN domain. Conserved hypothetical protein, similar to Rv0960, Rv0065, and Rv1720c from Mycobacterium tuberculosis.

TB Genome Annotation Portal