Rv0595c (vapC4)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: toxin
- REFSEQ: hypothetical protein
- PATRIC: FIG00822047: hypothetical protein
- TUBERCULIST: Possible toxin VapC4
- NCBI: Possible toxin VapC4
- updated information (H37Rv4):
  - gene name: vapC4
  - function:
  - reference:
Type: Not Target
Start: 694839
End: 695231
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:0005576 - extracellular region (Uniprot)
- GO:0005515 - protein binding (Uniprot)
- GO:0004540 - ribonuclease activity (Uniprot)
- GO:0004518 - nuclease activity (Uniprot)
- GO:0003723 - RNA binding (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

3DBO 40% Mycobacterium tuberculosis Crystal structure of a member of the VapBC family of toxin-antitoxin systems, VapBC-5, from Mycobacterium tuberculosis
Links to additional information on vapC4:
- 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 = 0.493 (from Jeremy Rock's lab)

PDB	aa ident	species	PDB title
3DBO	40%	Mycobacterium tuberculosis	Crystal structure of a member of the VapBC family of toxin-antitoxin systems, VapBC-5, from Mycobacterium tuberculosis

Amino Acid Sequence

VNVRRALADTSVFIGIEATRFDPDRFAGYEWGVSVVTLGELRLGVLQASGPEAAARRLSTYQLAQRFEPLGIDEAVSEAWALLVSKLRAAKLRVPINDSW
IAATAVAHGIAILTQDNDYAAMPDVEVITI

(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 8 sites
Non-Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 1 non-insertions in a row out of 8 sites
Non-Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 1 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; 0 non-insertions in a row out of 8 sites
Non-Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 0 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: 1.5
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:
- Rv1423 (whiA) (Direct binding)

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

Upregulates:
- Does not upregulate other genes.
Upregulated by:
- Rv0818 (-)
Downregulates:
- Does not downregulate other genes.
Downregulated by:

TBCAP

Tubculosis Community Annotation Project (

Slayden et al., 2013

Rv0595c (vapC4)

Property	Value	Creator	Evidence	PMID	Comment
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	shahanup86	IEP	20011113	Co-expression (Functional linkage)
Interaction	Inhibition Rv0596c	shahanup86	IEP		Co-expression (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	Inhibition Rv0596c	shahanup86	IEP		Co-expression (Functional linkage) authors,DJ. Beste,M. Espasa,B. Bonde,AM. Kierzek,GR. Stewart,J. McFadden The genetic requirements for fast and slow growth in mycobacteria. PLoS ONE 2009
Interaction	Inhibition Rv0596c	shahanup86	IEP		Co-expression (Functional linkage) authors,VL. Arcus,PB. Rainey,SJ. Turner The PIN-domain toxin-antitoxin array in mycobacteria. Trends Microbiol. 2005
Interaction	Inhibition Rv0596c	shahanup86	IEP		Co-expression (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 genetic requirements for fast and slow growth in mycobacteria. authors,DJ. Beste,M. Espasa,B. Bonde,AM. Kierzek,GR. Stewart,J. McFadden PLoS ONE 2009	shahanup86	IEP	19479006	Co-expression (Functional linkage)
Interaction	Inhibition Rv0596c	shahanup86	IEP		Co-expression (Functional linkage) authors,DJ. Beste,M. Espasa,B. Bonde,AM. Kierzek,GR. Stewart,J. McFadden The genetic requirements for fast and slow growth in mycobacteria. PLoS ONE 2009
Citation	The PIN-domain toxin-antitoxin array in mycobacteria. authors,VL. Arcus,PB. Rainey,SJ. Turner Trends Microbiol. 2005	shahanup86	IEP	15993073	Co-expression (Functional linkage)
Interaction	Inhibition Rv0596c	shahanup86	IEP		Co-expression (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	jlew		20011113	VapC homolog, PIN domain, Not toxic when expressed in Msmeg
Symbol	vapC-mt4	jlew			VapC-mt4 expression resulted in growth arrest in E coli, M. smeg and Mtb. Its expression led to translation inhibition accompanied by a gradual decrease in the steady-state levels of several mRNAs. VapC-mt4 exhibited sequence-specific endoribonuclease activity on mRNA templates at ACGC and AC(A/U)GC sequences. VapC-mt4 is mechanistically distinct from other TA toxins since it appears to primarily inhibit translation through selective, stable binding to RNA.. 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	VapC-mt4 expression resulted in growth arrest in E coli, M. smeg and Mtb. Its expression led to translation inhibition accompanied by a gradual decrease in the steady-state levels of several mRNAs. VapC-mt4 exhibited sequence-specific endoribonuclease activity on mRNA templates at ACGC and AC(A/U)GC sequences. VapC-mt4 is mechanistically distinct from other TA toxins since it appears to primarily inhibit translation through selective, stable binding to RNA.. Expressed 23 VapC toxins in EC lacking TA modules. 4 inhibited growth.
Symbol	VapC	jlew			Growth inhibitory in Mt and MS. In MS, not rescued by Rv2550c or Rv2830c. Rv0595c interacts with Rv0596c but not the other 3 VapBs, by Y2H. 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. In MS, not rescued by Rv2550c or Rv2830c. Rv0595c interacts with Rv0596c but not the other 3 VapBs, by Y2H.
Symbol	VapC4	jlew			Toxic to Ecoli growth. 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	Toxic to Ecoli growth. 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:694839	rslayden			Conserved hypothetical protein, similar to other conserved hypothetical proteins e.g. Rv0627 (135 aa) and Rv0665 (112 aa) from Mycobacterium tuberculosis; and STBB_PSESM
Other	stop:695231	rslayden			Conserved hypothetical protein, similar to other conserved hypothetical proteins e.g. Rv0627 (135 aa) and Rv0665 (112 aa) from Mycobacterium tuberculosis; and STBB_PSESM
Other	strand:+	rslayden			Conserved hypothetical protein, similar to other conserved hypothetical proteins e.g. Rv0627 (135 aa) and Rv0665 (112 aa) from Mycobacterium tuberculosis; and STBB_PSESM
Other	start:694839	rslayden			Q52562 plasmid stability protein from Pseudomonas syringae (139 aa), FASTA scores: opt: 131, E(): 0.0035, (35.2% identity in 88 aa overlap).
Other	stop:695231	rslayden			Q52562 plasmid stability protein from Pseudomonas syringae (139 aa), FASTA scores: opt: 131, E(): 0.0035, (35.2% identity in 88 aa overlap).
Other	strand:+	rslayden			Q52562 plasmid stability protein from Pseudomonas syringae (139 aa), FASTA scores: opt: 131, E(): 0.0035, (35.2% identity in 88 aa overlap).

Property

Value

Creator

Evidence

PMID

Comment

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

shahanup86

IEP

20011113

Co-expression (Functional linkage)

Interaction

Inhibition Rv0596c

shahanup86

IEP

Co-expression (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

Inhibition Rv0596c

shahanup86

IEP

Co-expression (Functional linkage)
authors,DJ. Beste,M. Espasa,B. Bonde,AM. Kierzek,GR. Stewart,J. McFadden The genetic requirements for fast and slow growth in mycobacteria. PLoS ONE 2009

Interaction

Inhibition Rv0596c

shahanup86

IEP

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

Interaction

Inhibition Rv0596c

shahanup86

IEP

Citation

The genetic requirements for fast and slow growth in mycobacteria. authors,DJ. Beste,M. Espasa,B. Bonde,AM. Kierzek,GR. Stewart,J. McFadden PLoS ONE 2009

shahanup86

IEP

19479006

Co-expression (Functional linkage)

Interaction

Inhibition Rv0596c

shahanup86

IEP

Co-expression (Functional linkage)
authors,DJ. Beste,M. Espasa,B. Bonde,AM. Kierzek,GR. Stewart,J. McFadden The genetic requirements for fast and slow growth in mycobacteria. PLoS ONE 2009

Citation

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

shahanup86

IEP

15993073

Co-expression (Functional linkage)

Interaction

Inhibition Rv0596c

shahanup86

IEP

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

Citation

jlew

20011113

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

Symbol

vapC-mt4

jlew

VapC-mt4 expression resulted in growth arrest in E coli, M. smeg and Mtb. Its expression led to translation inhibition accompanied by a gradual decrease in the steady-state levels of several mRNAs. VapC-mt4 exhibited sequence-specific endoribonuclease activity on mRNA templates at ACGC and AC(A/U)GC sequences. VapC-mt4 is mechanistically distinct from other TA toxins since it appears to primarily inhibit translation through selective, stable binding to RNA.. 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

Symbol

VapC

jlew

Growth inhibitory in Mt and MS. In MS, not rescued by Rv2550c or Rv2830c. Rv0595c interacts with Rv0596c but not the other 3 VapBs, by Y2H.
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. In MS, not rescued by Rv2550c or Rv2830c. Rv0595c interacts with Rv0596c but not the other 3 VapBs, by Y2H.

Symbol

VapC4

jlew

Toxic to Ecoli growth. 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

start:694839

rslayden

Conserved hypothetical protein, similar to other conserved hypothetical proteins e.g. Rv0627 (135 aa) and Rv0665 (112 aa) from Mycobacterium tuberculosis; and STBB_PSESM

Other

stop:695231

rslayden

Conserved hypothetical protein, similar to other conserved hypothetical proteins e.g. Rv0627 (135 aa) and Rv0665 (112 aa) from Mycobacterium tuberculosis; and STBB_PSESM

Other

strand:+

rslayden

Conserved hypothetical protein, similar to other conserved hypothetical proteins e.g. Rv0627 (135 aa) and Rv0665 (112 aa) from Mycobacterium tuberculosis; and STBB_PSESM

Other

start:694839

rslayden

Q52562 plasmid stability protein from Pseudomonas syringae (139 aa), FASTA scores: opt: 131, E(): 0.0035, (35.2% identity in 88 aa overlap).

Other

stop:695231

rslayden

Q52562 plasmid stability protein from Pseudomonas syringae (139 aa), FASTA scores: opt: 131, E(): 0.0035, (35.2% identity in 88 aa overlap).

Other

strand:+

rslayden

Q52562 plasmid stability protein from Pseudomonas syringae (139 aa), FASTA scores: opt: 131, E(): 0.0035, (35.2% identity in 88 aa overlap).

Comments