Rv2548 (vapC19)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: toxin
- REFSEQ: hypothetical protein
- PATRIC: PIN domain protein
- TUBERCULIST: Possible toxin VapC19
- NCBI: Possible toxin VapC19
- updated information (H37Rv4):
  - gene name: vapC19
  - function:
  - reference:
Type: Not Target
Start: 2868860
End: 2869237
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:0045926 - negative regulation of growth (Uniprot)
- GO:0044119 - growth of symbiont in host cell (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 vapC19:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 1.014 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

VKLIDTTIAVDHLRGEPAAAVLLAELINNGEEIAASELVRFELLAGVRESELAALEAFFSAVVWTLVTEDIARIGGRLARRYRSSHRGIDDVDYLIAATA
IVVDADLLTTNVRHFPMFPDLQPPY

(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 5 sites
Non-Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 2 non-insertions in a row out of 5 sites
Non-Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 2 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; 2 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; 2 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: 0.37
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:
- Rv0047c (-)

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv1049 (-) (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:
- Rv0047c (-)

TBCAP

Tubculosis Community Annotation Project (

Slayden et al., 2013

Rv2548 (vapC19)

Property	Value	Creator	Evidence	PMID	Comment
Interaction	Regulatory Rv2547	soumisengupta	ISO		Gene Neighborhood (Functional linkage) authors,VL. Arcus,PB. Rainey,SJ. Turner The PIN-domain toxin-antitoxin array in mycobacteria. Trends Microbiol. 2005
Interaction	Regulatory Rv2547	soumisengupta	ISO		Gene Neighborhood (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	soumisengupta	ISO	15993073	Gene Neighborhood (Functional linkage)
Interaction	Regulatory Rv2547	soumisengupta	ISO		Gene Neighborhood (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	soumisengupta	ISO	20011113	Gene Neighborhood (Functional linkage)
Interaction	Regulatory Rv2547	soumisengupta	ISO		Gene Neighborhood (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	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 (Rv2547)
Symbol	VapC-mt19	jlew			Expression resulted in growth arrest in E coli. Expressed 23 VapC toxins in EC lacking TA modules. 4 inhibited growth. authors,JD. Sharp,JW. Cruz,S. Raman,M. Inouye,RN. Husson,NA. Woychik Growth and translation inhibition through sequence specific RNA binding by a mycobacterium tuberculosis VAPC toxin. The Journal of biological chemistry 2012
Citation	Growth and translation inhibition through sequence specific RNA binding by a mycobacterium tuberculosis VAPC toxin. authors,JD. Sharp,JW. Cruz,S. Raman,M. Inouye,RN. Husson,NA. Woychik The Journal of biological chemistry 2012	jlew		22354968	Expression resulted in growth arrest in E coli. Expressed 23 VapC toxins in EC lacking TA modules. 4 inhibited growth.
Symbol	VapC	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	VapC19	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	stop:2869237	rslayden			MTCY21B4.14c HYPOTHETICAL 15.0 KDA PROTEIN from Mycobacterium tuberculosis (133 aa), FASTA scores: opt: 265, E(): 7.1e-12, (42.3% identity in 123 aa overlap); Q97WY5
Other	strand:+	rslayden			MTCY21B4.14c HYPOTHETICAL 15.0 KDA PROTEIN from Mycobacterium tuberculosis (133 aa), FASTA scores: opt: 265, E(): 7.1e-12, (42.3% identity in 123 aa overlap); Q97WY5
Other	start:2868860	rslayden			SSO1975 HYPOTHETICAL PROTEIN from Sulfolobus solfataricus (125 aa), FASTA scores: opt: 131, E(): 0.018, (30.0% identity in 110 aa overlap); O52285
Other	stop:2869237	rslayden			SSO1975 HYPOTHETICAL PROTEIN from Sulfolobus solfataricus (125 aa), FASTA scores: opt: 131, E(): 0.018, (30.0% identity in 110 aa overlap); O52285
Other	strand:+	rslayden			SSO1975 HYPOTHETICAL PROTEIN from Sulfolobus solfataricus (125 aa), FASTA scores: opt: 131, E(): 0.018, (30.0% identity in 110 aa overlap); O52285
Other	start:2868860	rslayden			YLE HYPOTHETICAL 14.9 KDA PROTEIN from Agrobacterium radiobacter (133 aa), FASTA scores: opt: 128, E(): 0.03,(32.8% identity in 125 aa overlap); etc. TBscore is 0.865
Other	stop:2869237	rslayden			YLE HYPOTHETICAL 14.9 KDA PROTEIN from Agrobacterium radiobacter (133 aa), FASTA scores: opt: 128, E(): 0.03,(32.8% identity in 125 aa overlap); etc. TBscore is 0.865
Other	strand:+	rslayden			YLE HYPOTHETICAL 14.9 KDA PROTEIN from Agrobacterium radiobacter (133 aa), FASTA scores: opt: 128, E(): 0.03,(32.8% identity in 125 aa overlap); etc. TBscore is 0.865
Other	start:2868860	rslayden			Conserved hypothetical protein. Some similarity to various proteins e.g. P71665
Other	stop:2869237	rslayden			Conserved hypothetical protein. Some similarity to various proteins e.g. P71665
Other	strand:+	rslayden			Conserved hypothetical protein. Some similarity to various proteins e.g. P71665
Other	start:2868860	rslayden			Rv1397c
Other	stop:2869237	rslayden			Rv1397c
Other	strand:+	rslayden			Rv1397c
Other	start:2868860	rslayden			MTCY21B4.14c HYPOTHETICAL 15.0 KDA PROTEIN from Mycobacterium tuberculosis (133 aa), FASTA scores: opt: 265, E(): 7.1e-12, (42.3% identity in 123 aa overlap); Q97WY5

Property

Value

Creator

Evidence

PMID

Comment

Interaction

Regulatory Rv2547

soumisengupta

ISO

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

Interaction

Regulatory Rv2547

soumisengupta

ISO

Gene Neighborhood (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

soumisengupta

ISO

15993073

Gene Neighborhood (Functional linkage)

Interaction

Regulatory Rv2547

soumisengupta

ISO

Gene Neighborhood (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

soumisengupta

ISO

20011113

Gene Neighborhood (Functional linkage)

Interaction

Regulatory Rv2547

soumisengupta

ISO

Citation

jlew

20011113

VapC homolog, PIN domain, Toxic when expressed in Msmeg, rescued by antitoxin (Rv2547)

Symbol

VapC-mt19

jlew

Expression resulted in growth arrest in E coli. Expressed 23 VapC toxins in EC lacking TA modules. 4 inhibited growth.
authors,JD. Sharp,JW. Cruz,S. Raman,M. Inouye,RN. Husson,NA. Woychik Growth and translation inhibition through sequence specific RNA binding by a mycobacterium tuberculosis VAPC toxin. The Journal of biological chemistry 2012

Citation

Growth and translation inhibition through sequence specific RNA binding by a mycobacterium tuberculosis VAPC toxin. authors,JD. Sharp,JW. Cruz,S. Raman,M. Inouye,RN. Husson,NA. Woychik The Journal of biological chemistry 2012

jlew

22354968

Expression resulted in growth arrest in E coli. Expressed 23 VapC toxins in EC lacking TA modules. 4 inhibited growth.

Symbol

VapC

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

VapC19

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

stop:2869237

rslayden

MTCY21B4.14c HYPOTHETICAL 15.0 KDA PROTEIN from Mycobacterium tuberculosis (133 aa), FASTA scores: opt: 265, E(): 7.1e-12, (42.3% identity in 123 aa overlap); Q97WY5

Other

strand:+

rslayden

MTCY21B4.14c HYPOTHETICAL 15.0 KDA PROTEIN from Mycobacterium tuberculosis (133 aa), FASTA scores: opt: 265, E(): 7.1e-12, (42.3% identity in 123 aa overlap); Q97WY5

Other

start:2868860

rslayden

SSO1975 HYPOTHETICAL PROTEIN from Sulfolobus solfataricus (125 aa), FASTA scores: opt: 131, E(): 0.018, (30.0% identity in 110 aa overlap); O52285

Other

stop:2869237

rslayden

SSO1975 HYPOTHETICAL PROTEIN from Sulfolobus solfataricus (125 aa), FASTA scores: opt: 131, E(): 0.018, (30.0% identity in 110 aa overlap); O52285

Other

strand:+

rslayden

SSO1975 HYPOTHETICAL PROTEIN from Sulfolobus solfataricus (125 aa), FASTA scores: opt: 131, E(): 0.018, (30.0% identity in 110 aa overlap); O52285

Other

start:2868860

rslayden

YLE HYPOTHETICAL 14.9 KDA PROTEIN from Agrobacterium radiobacter (133 aa), FASTA scores: opt: 128, E(): 0.03,(32.8% identity in 125 aa overlap); etc. TBscore is 0.865

Other

stop:2869237

rslayden

YLE HYPOTHETICAL 14.9 KDA PROTEIN from Agrobacterium radiobacter (133 aa), FASTA scores: opt: 128, E(): 0.03,(32.8% identity in 125 aa overlap); etc. TBscore is 0.865

Other

strand:+

rslayden

YLE HYPOTHETICAL 14.9 KDA PROTEIN from Agrobacterium radiobacter (133 aa), FASTA scores: opt: 128, E(): 0.03,(32.8% identity in 125 aa overlap); etc. TBscore is 0.865

Other

start:2868860

rslayden

Conserved hypothetical protein. Some similarity to various proteins e.g. P71665

Other

stop:2869237

rslayden

Conserved hypothetical protein. Some similarity to various proteins e.g. P71665

Other

strand:+

rslayden

Conserved hypothetical protein. Some similarity to various proteins e.g. P71665

Other

start:2868860

rslayden

Rv1397c

Other

stop:2869237

rslayden

Rv1397c

Other

strand:+

rslayden

Rv1397c

Other

start:2868860

rslayden

MTCY21B4.14c HYPOTHETICAL 15.0 KDA PROTEIN from Mycobacterium tuberculosis (133 aa), FASTA scores: opt: 265, E(): 7.1e-12, (42.3% identity in 123 aa overlap); Q97WY5

Comments