Rv2546 (vapC18)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: toxin
- REFSEQ: hypothetical protein
- PATRIC: Cell division protein DivIC (FtsB) stabilizes FtsL against RasP cleavage
- TUBERCULIST: Possible toxin VapC18
- NCBI: Possible toxin VapC18
- updated information (H37Rv4):
  - gene name: vapC18
  - function:
  - reference:
Type: Not Target
Start: 2868154
End: 2868567
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):

PDB	aa ident	species	PDB title
3H87	51%	Mycobacterium tuberculosis	Rv0301 Rv0300 Toxin Antitoxin Complex from Mycobacterium tuberculosis
5SV2	37%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Toxin VapC21 from Mycobacterium tuberculosis

Links to additional information on vapC18:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 1 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MVFCVDTSAWHHAARPEVARRWLAALSADQIGICDHVRLEILYSANSATDYDALADELDGLARIPVGAETFTRACQVQRELAHVAGLHHRSVKIADLVIA
AAAELSGTIVWHYDENYDRVAAITGQPTEWIVPRGTL

(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 9 sites
Non-Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 1 non-insertions in a row out of 9 sites
Non-Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 2 non-insertions in a row out of 9 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 10 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 10 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: 2.71
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:
- Rv0022c (whiB5)

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:
- Rv0022c (whiB5)
Downregulates:
- Does not downregulate other genes.
Downregulated by:
- Not downregulated by other genes.

TBCAP

Tubculosis Community Annotation Project (

Slayden et al., 2013

Rv2546 (vapC18)

Property	Value	Creator	Evidence	PMID	Comment
Interaction	Regulatory Rv2545	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 Rv2545	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 Rv2545	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 Rv2545	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, Not toxic when expressed in Msmeg
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	VapC18	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	strand:+	rslayden			MTCY08D5.24c (226 aa), FASTA scores: opt: 272, E(): 1.3e-11, (39.7% identity in 136 aa overlap); O33299
Other	start:2868154	rslayden			Rv2757c
Other	stop:2868567	rslayden			Rv2757c
Other	strand:+	rslayden			Rv2757c
Other	start:2868154	rslayden			MTV002.22c (138 aa), FASTA scores: opt: 265, E(): 2.5e-11, (38.5% identity in 135 aa overlap); P95026
Other	stop:2868567	rslayden			MTV002.22c (138 aa), FASTA scores: opt: 265, E(): 2.5e-11, (38.5% identity in 135 aa overlap); P95026
Other	strand:+	rslayden			MTV002.22c (138 aa), FASTA scores: opt: 265, E(): 2.5e-11, (38.5% identity in 135 aa overlap); P95026
Other	start:2868154	rslayden			Rv2527
Other	stop:2868567	rslayden			Rv2527
Other	strand:+	rslayden			Rv2527
Other	start:2868154	rslayden			MTCY159.29c (133 aa), FASTA scores: opt: 206, E(): 2.6e-07, (38.0% identity in 100 aa overlap); etc.
Other	stop:2868567	rslayden			MTCY159.29c (133 aa), FASTA scores: opt: 206, E(): 2.6e-07, (38.0% identity in 100 aa overlap); etc.
Other	strand:+	rslayden			MTCY159.29c (133 aa), FASTA scores: opt: 206, E(): 2.6e-07, (38.0% identity in 100 aa overlap); etc.
Other	start:2868154	rslayden			Conserved hypothetical protein. Some similarity to several HYPOTHETICAL PROTEINS from Mycobacterium tuberculosis (strain H37Rv and CDC1551) e.g. P96411
Other	stop:2868567	rslayden			Conserved hypothetical protein. Some similarity to several HYPOTHETICAL PROTEINS from Mycobacterium tuberculosis (strain H37Rv and CDC1551) e.g. P96411
Other	strand:+	rslayden			Conserved hypothetical protein. Some similarity to several HYPOTHETICAL PROTEINS from Mycobacterium tuberculosis (strain H37Rv and CDC1551) e.g. P96411
Other	start:2868154	rslayden			Rv0229c
Other	stop:2868567	rslayden			Rv0229c
Other	strand:+	rslayden			Rv0229c
Other	start:2868154	rslayden			MTCY08D5.24c (226 aa), FASTA scores: opt: 272, E(): 1.3e-11, (39.7% identity in 136 aa overlap); O33299
Other	stop:2868567	rslayden			MTCY08D5.24c (226 aa), FASTA scores: opt: 272, E(): 1.3e-11, (39.7% identity in 136 aa overlap); O33299

Property

Value

Creator

Evidence

PMID

Comment

Interaction

Regulatory Rv2545

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 Rv2545

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 Rv2545

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 Rv2545

soumisengupta

ISO

Citation

jlew

20011113

VapC homolog, PIN domain, Not toxic when expressed in Msmeg

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

VapC18

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

strand:+

rslayden

MTCY08D5.24c (226 aa), FASTA scores: opt: 272, E(): 1.3e-11, (39.7% identity in 136 aa overlap); O33299

Other

start:2868154

rslayden

Rv2757c

Other

stop:2868567

rslayden

Rv2757c

Other

strand:+

rslayden

Rv2757c

Other

start:2868154

rslayden

MTV002.22c (138 aa), FASTA scores: opt: 265, E(): 2.5e-11, (38.5% identity in 135 aa overlap); P95026

Other

stop:2868567

rslayden

MTV002.22c (138 aa), FASTA scores: opt: 265, E(): 2.5e-11, (38.5% identity in 135 aa overlap); P95026

Other

strand:+

rslayden

MTV002.22c (138 aa), FASTA scores: opt: 265, E(): 2.5e-11, (38.5% identity in 135 aa overlap); P95026

Other

start:2868154

rslayden

Rv2527

Other

stop:2868567

rslayden

Rv2527

Other

strand:+

rslayden

Rv2527

Other

start:2868154

rslayden

MTCY159.29c (133 aa), FASTA scores: opt: 206, E(): 2.6e-07, (38.0% identity in 100 aa overlap); etc.

Other

stop:2868567

rslayden

MTCY159.29c (133 aa), FASTA scores: opt: 206, E(): 2.6e-07, (38.0% identity in 100 aa overlap); etc.

Other

strand:+

rslayden

MTCY159.29c (133 aa), FASTA scores: opt: 206, E(): 2.6e-07, (38.0% identity in 100 aa overlap); etc.

Other

start:2868154

rslayden

Conserved hypothetical protein. Some similarity to several HYPOTHETICAL PROTEINS from Mycobacterium tuberculosis (strain H37Rv and CDC1551) e.g. P96411

Other

stop:2868567

rslayden

Conserved hypothetical protein. Some similarity to several HYPOTHETICAL PROTEINS from Mycobacterium tuberculosis (strain H37Rv and CDC1551) e.g. P96411

Other

strand:+

rslayden

Conserved hypothetical protein. Some similarity to several HYPOTHETICAL PROTEINS from Mycobacterium tuberculosis (strain H37Rv and CDC1551) e.g. P96411

Other

start:2868154

rslayden

Rv0229c

Other

stop:2868567

rslayden

Rv0229c

Other

strand:+

rslayden

Rv0229c

Other

start:2868154

rslayden

MTCY08D5.24c (226 aa), FASTA scores: opt: 272, E(): 1.3e-11, (39.7% identity in 136 aa overlap); O33299

Other

stop:2868567

rslayden

MTCY08D5.24c (226 aa), FASTA scores: opt: 272, E(): 1.3e-11, (39.7% identity in 136 aa overlap); O33299

Comments