Rv2757c (vapC21)

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 VapC21
- NCBI: Possible toxin VapC21
- updated information (H37Rv4):
  - gene name: vapC21
  - function:
  - reference:
Type: Not Target
Start: 3070170
End: 3070586
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: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
5SV2	99%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Toxin VapC21 from Mycobacterium tuberculosis
3H87	42%	Mycobacterium tuberculosis	Rv0301 Rv0300 Toxin Antitoxin Complex from Mycobacterium tuberculosis

Links to additional information on vapC21:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 1.923 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MTTRYLLDKSAAYRAHLPAVRHRLEPLMERGLLARCGITDLEFGVSARSREDHRTLGTYRRDALEYVNTPDTVWVRAWEIQEALTDKGFHRSVKIPDLII
AAVAEHHGIPVMHYDQDFERIAAITRQPVEWVVAPGTA

(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; 3 non-insertions in a row out of 8 sites
Non-Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 4 non-insertions in a row out of 8 sites
Non-Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 4 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; 4 non-insertions in a row out of 8 sites
Uncertain	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.020700; 5 non-insertions in a row out of 8 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: 0.32
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:
- No bindings to other targets were found.

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:
- Rv0078 (-)
- Rv0238 (-)

TBCAP

Tubculosis Community Annotation Project (

Slayden et al., 2013

Rv2757c (vapC21)

Property	Value	Creator	Evidence	PMID	Comment
Citation	The PIN-domain toxin-antitoxin array in mycobacteria. authors,VL. Arcus,PB. Rainey,SJ. Turner Trends Microbiol. 2005	vizhi.gurusamy	IEP	15993073	Co-expression (Functional linkage)
Interaction	InhibitedBy Rv2758c	vizhi.gurusamy	IEP		Co-expression (Functional linkage) authors,VL. Arcus,PB. Rainey,SJ. Turner The PIN-domain toxin-antitoxin array in mycobacteria. Trends Microbiol. 2005
Citation	Killing activity and rescue function of genome-wide toxin-antitoxin loci of Mycobacterium tuberculosis. authors,A. Gupta FEMS Microbiol. Lett. 2009	vizhi.gurusamy	IEP	19016878	Co-expression (Functional linkage)
Interaction	InhibitedBy Rv2758c	vizhi.gurusamy	IEP		Co-expression (Functional linkage) authors,A. Gupta Killing activity and rescue function of genome-wide toxin-antitoxin loci of Mycobacterium tuberculosis. FEMS Microbiol. Lett. 2009
Interaction	InhibitedBy Rv2758c	vizhi.gurusamy	IEP		Co-expression (Functional linkage) authors,DP. Pandey,K. Gerdes Toxin-antitoxin loci are highly abundant in free-living but lost from host-associated prokaryotes. Nucleic Acids Res. 2005
Interaction	InhibitedBy Rv2758c	vizhi.gurusamy	IEP		Co-expression (Functional linkage) authors,VL. Arcus,PB. Rainey,SJ. Turner The PIN-domain toxin-antitoxin array in mycobacteria. Trends Microbiol. 2005
Interaction	Regulatory Rv0616c	akankshajain.21	IEP		Co-expression (Functional linkage) T. Parish, DA. Smith et al. The senX3-regX3 two-component regulatory system of Mycobacterium tuberculosis is required for virulence. Microbiology (Reading, Engl.) 2003
Interaction	RegulatedBy Rv0491	yamir.moreno	IEP		Microarrays. mRNA levels of regulated element measured and compared between wild-type and trans-element mutation (knockout, over expression etc.) performed by using microarray (or macroarray) experiments.. T. Parish, DA. Smith et al. The senX3-regX3 two-component regulatory system of Mycobacterium tuberculosis is required for virulence. Microbiology (Reading, Engl.) 2003
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 (Rv2758c)
Symbol	VapC21	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:3070586	rslayden			MTCY159.10c (137 aa), FASTA scores: opt: 265, E(): 7.5e-12, (38.5% identity in 135 aa overlap); O07228
Other	strand:+	rslayden			MTCY159.10c (137 aa), FASTA scores: opt: 265, E(): 7.5e-12, (38.5% identity in 135 aa overlap); O07228
Other	start:3070170	rslayden			Rv0301
Other	stop:3070586	rslayden			Rv0301
Other	strand:+	rslayden			Rv0301
Other	start:3070170	rslayden			MTCY63.06 (141 aa), FASTA scores: opt: 259, E(): 2.1e-11, (42.4% identity in 132 aa overlap); etc.
Other	stop:3070586	rslayden			MTCY63.06 (141 aa), FASTA scores: opt: 259, E(): 2.1e-11, (42.4% identity in 132 aa overlap); etc.
Other	strand:+	rslayden			MTCY63.06 (141 aa), FASTA scores: opt: 259, E(): 2.1e-11, (42.4% identity in 132 aa overlap); etc.
Other	start:3070170	rslayden			Conserved hypothetical protein, similar to several other M. tuberculosis hypothetical proteins e.g. P96411
Other	stop:3070586	rslayden			Conserved hypothetical protein, similar to several other M. tuberculosis hypothetical proteins e.g. P96411
Other	strand:+	rslayden			Conserved hypothetical protein, similar to several other M. tuberculosis hypothetical proteins e.g. P96411
Other	start:3070170	rslayden			Rv0229c
Other	stop:3070586	rslayden			Rv0229c
Other	strand:+	rslayden			Rv0229c
Other	start:3070170	rslayden			MTCY08D5.24c (226 aa), FASTA scores: opt: 354, E():4.6e-18, (45.25% identity in 137 aa overlap) (N-terminus longer 89 aa); P95007
Other	stop:3070586	rslayden			MTCY08D5.24c (226 aa), FASTA scores: opt: 354, E():4.6e-18, (45.25% identity in 137 aa overlap) (N-terminus longer 89 aa); P95007
Other	strand:+	rslayden			MTCY08D5.24c (226 aa), FASTA scores: opt: 354, E():4.6e-18, (45.25% identity in 137 aa overlap) (N-terminus longer 89 aa); P95007
Other	start:3070170	rslayden			Rv2546
Other	stop:3070586	rslayden			Rv2546
Other	strand:+	rslayden			Rv2546
Other	start:3070170	rslayden			MTCY159.10c (137 aa), FASTA scores: opt: 265, E(): 7.5e-12, (38.5% identity in 135 aa overlap); O07228

Property

Value

Creator

Evidence

PMID

Comment

Citation

The PIN-domain toxin-antitoxin array in mycobacteria. authors,VL. Arcus,PB. Rainey,SJ. Turner Trends Microbiol. 2005

vizhi.gurusamy

IEP

15993073

Co-expression (Functional linkage)

Interaction

InhibitedBy Rv2758c

vizhi.gurusamy

IEP

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

Citation

Killing activity and rescue function of genome-wide toxin-antitoxin loci of Mycobacterium tuberculosis. authors,A. Gupta FEMS Microbiol. Lett. 2009

vizhi.gurusamy

IEP

19016878

Co-expression (Functional linkage)

Interaction

InhibitedBy Rv2758c

vizhi.gurusamy

IEP

Co-expression (Functional linkage)
authors,A. Gupta Killing activity and rescue function of genome-wide toxin-antitoxin loci of Mycobacterium tuberculosis. FEMS Microbiol. Lett. 2009

Interaction

InhibitedBy Rv2758c

vizhi.gurusamy

IEP

Co-expression (Functional linkage)
authors,DP. Pandey,K. Gerdes Toxin-antitoxin loci are highly abundant in free-living but lost from host-associated prokaryotes. Nucleic Acids Res. 2005

Interaction

InhibitedBy Rv2758c

vizhi.gurusamy

IEP

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

Interaction

Regulatory Rv0616c

akankshajain.21

IEP

Co-expression (Functional linkage)
T. Parish, DA. Smith et al. The senX3-regX3 two-component regulatory system of Mycobacterium tuberculosis is required for virulence. Microbiology (Reading, Engl.) 2003

Interaction

RegulatedBy Rv0491

yamir.moreno

IEP

Microarrays. mRNA levels of regulated element measured and compared between wild-type and trans-element mutation (knockout, over expression etc.) performed by using microarray (or macroarray) experiments..
T. Parish, DA. Smith et al. The senX3-regX3 two-component regulatory system of Mycobacterium tuberculosis is required for virulence. Microbiology (Reading, Engl.) 2003

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 (Rv2758c)

Symbol

VapC21

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:3070586

rslayden

MTCY159.10c (137 aa), FASTA scores: opt: 265, E(): 7.5e-12, (38.5% identity in 135 aa overlap); O07228

Other

strand:+

rslayden

MTCY159.10c (137 aa), FASTA scores: opt: 265, E(): 7.5e-12, (38.5% identity in 135 aa overlap); O07228

Other

start:3070170

rslayden

Rv0301

Other

stop:3070586

rslayden

Rv0301

Other

strand:+

rslayden

Rv0301

Other

start:3070170

rslayden

MTCY63.06 (141 aa), FASTA scores: opt: 259, E(): 2.1e-11, (42.4% identity in 132 aa overlap); etc.

Other

stop:3070586

rslayden

MTCY63.06 (141 aa), FASTA scores: opt: 259, E(): 2.1e-11, (42.4% identity in 132 aa overlap); etc.

Other

strand:+

rslayden

MTCY63.06 (141 aa), FASTA scores: opt: 259, E(): 2.1e-11, (42.4% identity in 132 aa overlap); etc.

Other

start:3070170

rslayden

Conserved hypothetical protein, similar to several other M. tuberculosis hypothetical proteins e.g. P96411

Other

stop:3070586

rslayden

Conserved hypothetical protein, similar to several other M. tuberculosis hypothetical proteins e.g. P96411

Other

strand:+

rslayden

Conserved hypothetical protein, similar to several other M. tuberculosis hypothetical proteins e.g. P96411

Other

start:3070170

rslayden

Rv0229c

Other

stop:3070586

rslayden

Rv0229c

Other

strand:+

rslayden

Rv0229c

Other

start:3070170

rslayden

MTCY08D5.24c (226 aa), FASTA scores: opt: 354, E():4.6e-18, (45.25% identity in 137 aa overlap) (N-terminus longer 89 aa); P95007

Other

stop:3070586

rslayden

MTCY08D5.24c (226 aa), FASTA scores: opt: 354, E():4.6e-18, (45.25% identity in 137 aa overlap) (N-terminus longer 89 aa); P95007

Other

strand:+

rslayden

MTCY08D5.24c (226 aa), FASTA scores: opt: 354, E():4.6e-18, (45.25% identity in 137 aa overlap) (N-terminus longer 89 aa); P95007

Other

start:3070170

rslayden

Rv2546

Other

stop:3070586

rslayden

Rv2546

Other

strand:+

rslayden

Rv2546

Other

start:3070170

rslayden

MTCY159.10c (137 aa), FASTA scores: opt: 265, E(): 7.5e-12, (38.5% identity in 135 aa overlap); O07228

Comments