Rv2549c (vapC20)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: toxin
- REFSEQ: hypothetical protein
- PATRIC: hypothetical protein Rv2549c
- TUBERCULIST: Possible toxin VapC20
- NCBI: Possible toxin VapC20
- updated information (H37Rv4):
  - gene name: vapC20
  - function:
  - reference:
Type: Not Target
Start: 2869727
End: 2870122
Operon:

Trans-membrane region:
Role: VI - Unknowns
GO terms:
- GO:0090502 - RNA phosphodiester bond hydrolysis, endonucleolytic (Uniprot)
- 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:0016075 - rRNA catabolic process (Uniprot)
- GO:0005515 - protein binding (Uniprot)
- GO:0004540 - ribonuclease activity (Uniprot)
- GO:0004521 - endoribonuclease activity (Uniprot)
- GO:0004519 - endonuclease 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
5WZF	100%	Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh)	Crystal structure of Mycobacterium tuberculosis VapC20 (Rv2549c), Sarcin-Ricin loop cleaving toxin
5WZF	100%	Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh)	Crystal structure of Mycobacterium tuberculosis VapC20 (Rv2549c), Sarcin-Ricin loop cleaving toxin
5WZ4	99%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of Mycobacterium tuberculosis VapC20 (Rv2549c), Sarcin-Ricin loop cleaving toxin

Links to additional information on vapC20:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 0.642 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MIFVDTSFWAALGNAGDARHGTAKRLWASKPPVVMTSNHVLGETWTLLNRRCGHRAAVAAAAIRLSTVVRVEHVTADLEEQAWEWLVRHDEREYSFVDAT
SFAVMRKKGIQNAYAFDGDFSAAGFVEVRPE

(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; 0 non-insertions in a row out of 5 sites
Non-Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 0 non-insertions in a row out of 5 sites
Non-Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 0 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; 0 non-insertions in a row out of 6 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 6 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: 0.93
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:
- Rv1404 (-)
- Rv3849 (espR)

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0047c (-) (Direct binding)
- Rv0081 (-) (Direct binding)
- Rv1033c (trcR) (Direct binding)
- Rv1404 (-) (Direct binding)
- Rv1985c (-) (Direct binding)
- Rv2011c (-) (Direct binding)
- Rv3557c (-) (Direct binding)
- Rv3597c (lsr2) (Direct binding)

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:
- Rv1404 (-)
- Rv3849 (espR)

TBCAP

Tubculosis Community Annotation Project (

Slayden et al., 2013

Rv2549c (vapC20)

Property	Value	Creator	Evidence	PMID	Comment
Interaction	Inhibition Rv2550c	gaurisd10	IDA		Structural Analysis authors,A. Gupta Killing activity and rescue function of genome-wide toxin-antitoxin loci of Mycobacterium tuberculosis. FEMS Microbiol. Lett. 2009
Interaction	Inhibition Rv2550c	gaurisd10	IDA		Structural Analysis authors,DP. Pandey,K. Gerdes Toxin-antitoxin loci are highly abundant in free-living but lost from host-associated prokaryotes. Nucleic Acids Res. 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 Rv2550c	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
Interaction	Inhibition Rv2550c	gaurisd10	IDA		Spectrophotometric authors,VL. Arcus,PB. Rainey,SJ. Turner The PIN-domain toxin-antitoxin array in mycobacteria. Trends Microbiol. 2005
Interaction	Inhibition Rv2550c	gaurisd10	IDA		Spectrophotometric authors,A. Gupta Killing activity and rescue function of genome-wide toxin-antitoxin loci of Mycobacterium tuberculosis. FEMS Microbiol. Lett. 2009
Interaction	Inhibition Rv2550c	gaurisd10	IDA		Spectrophotometric 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	Inhibition Rv2550c	gaurisd10	IDA		Structural Analysis authors,VL. Arcus,PB. Rainey,SJ. Turner The PIN-domain toxin-antitoxin array in mycobacteria. Trends Microbiol. 2005
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 Rv2550c	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	jlew		20011113	VapC homolog, PIN domain, Not toxic when expressed in Msmeg
Symbol	VapC-mt20	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			Growth inhibitory in Mt and MS. In MS, not rescued by Rv0596c or Rv2830c. Rv2549c interacts with Rv2550c 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 Rv0596c or Rv2830c. Rv2549c interacts with Rv2550c but not the other 3 VapBs, by Y2H.
Symbol	VapC20	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:2869727	rslayden			VNG0072H from Halobacterium sp. strain NRC-1 (144 aa), FASTA scores: opt: 113, E(): 0.29,(25.75% identity in 136 aa overlap)
Other	stop:2870122	rslayden			VNG0072H from Halobacterium sp. strain NRC-1 (144 aa), FASTA scores: opt: 113, E(): 0.29,(25.75% identity in 136 aa overlap)
Other	strand:+	rslayden			VNG0072H from Halobacterium sp. strain NRC-1 (144 aa), FASTA scores: opt: 113, E(): 0.29,(25.75% identity in 136 aa overlap)
Other	start:2869727	rslayden			Conserved hypothetical protein, showing some similarity to P73415
Other	stop:2870122	rslayden			Conserved hypothetical protein, showing some similarity to P73415
Other	strand:+	rslayden			Conserved hypothetical protein, showing some similarity to P73415
Other	start:2869727	rslayden			SLL1715 from Synechocystis sp. strain PCC 6803 (157aa), FASTA scores: opt: 167, E(): 4.2e-05, (29.45% identity in 129 aa overlap); Q9HHY6
Other	stop:2870122	rslayden			SLL1715 from Synechocystis sp. strain PCC 6803 (157aa), FASTA scores: opt: 167, E(): 4.2e-05, (29.45% identity in 129 aa overlap); Q9HHY6
Other	strand:+	rslayden			SLL1715 from Synechocystis sp. strain PCC 6803 (157aa), FASTA scores: opt: 167, E(): 4.2e-05, (29.45% identity in 129 aa overlap); Q9HHY6
Other	start:2869727	rslayden			VNG6166H from Halobacterium sp. plasmid pNRC200 strain NRC-1 (144 aa),FASTA scores: opt: 133, E(): 0.011, (29.6% identity in 125aa overlap); and Q9HSU3
Other	stop:2870122	rslayden			VNG6166H from Halobacterium sp. plasmid pNRC200 strain NRC-1 (144 aa),FASTA scores: opt: 133, E(): 0.011, (29.6% identity in 125aa overlap); and Q9HSU3
Other	strand:+	rslayden			VNG6166H from Halobacterium sp. plasmid pNRC200 strain NRC-1 (144 aa),FASTA scores: opt: 133, E(): 0.011, (29.6% identity in 125aa overlap); and Q9HSU3

Property

Value

Creator

Evidence

PMID

Comment

Interaction

Inhibition Rv2550c

gaurisd10

IDA

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

Interaction

Inhibition Rv2550c

gaurisd10

IDA

Structural Analysis
authors,DP. Pandey,K. Gerdes Toxin-antitoxin loci are highly abundant in free-living but lost from host-associated prokaryotes. Nucleic Acids Res. 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 Rv2550c

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

Interaction

Inhibition Rv2550c

gaurisd10

IDA

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

Interaction

Inhibition Rv2550c

gaurisd10

IDA

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

Interaction

Inhibition Rv2550c

gaurisd10

IDA

Spectrophotometric
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

Inhibition Rv2550c

gaurisd10

IDA

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

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 Rv2550c

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

jlew

20011113

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

Symbol

VapC-mt20

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

Growth inhibitory in Mt and MS. In MS, not rescued by Rv0596c or Rv2830c. Rv2549c interacts with Rv2550c 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 Rv0596c or Rv2830c. Rv2549c interacts with Rv2550c but not the other 3 VapBs, by Y2H.

Symbol

VapC20

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:2869727

rslayden

VNG0072H from Halobacterium sp. strain NRC-1 (144 aa), FASTA scores: opt: 113, E(): 0.29,(25.75% identity in 136 aa overlap)

Other

stop:2870122

rslayden

VNG0072H from Halobacterium sp. strain NRC-1 (144 aa), FASTA scores: opt: 113, E(): 0.29,(25.75% identity in 136 aa overlap)

Other

strand:+

rslayden

VNG0072H from Halobacterium sp. strain NRC-1 (144 aa), FASTA scores: opt: 113, E(): 0.29,(25.75% identity in 136 aa overlap)

Other

start:2869727

rslayden

Conserved hypothetical protein, showing some similarity to P73415

Other

stop:2870122

rslayden

Conserved hypothetical protein, showing some similarity to P73415

Other

strand:+

rslayden

Conserved hypothetical protein, showing some similarity to P73415

Other

start:2869727

rslayden

SLL1715 from Synechocystis sp. strain PCC 6803 (157aa), FASTA scores: opt: 167, E(): 4.2e-05, (29.45% identity in 129 aa overlap); Q9HHY6

Other

stop:2870122

rslayden

SLL1715 from Synechocystis sp. strain PCC 6803 (157aa), FASTA scores: opt: 167, E(): 4.2e-05, (29.45% identity in 129 aa overlap); Q9HHY6

Other

strand:+

rslayden

SLL1715 from Synechocystis sp. strain PCC 6803 (157aa), FASTA scores: opt: 167, E(): 4.2e-05, (29.45% identity in 129 aa overlap); Q9HHY6

Other

start:2869727

rslayden

VNG6166H from Halobacterium sp. plasmid pNRC200 strain NRC-1 (144 aa),FASTA scores: opt: 133, E(): 0.011, (29.6% identity in 125aa overlap); and Q9HSU3

Other

stop:2870122

rslayden

VNG6166H from Halobacterium sp. plasmid pNRC200 strain NRC-1 (144 aa),FASTA scores: opt: 133, E(): 0.011, (29.6% identity in 125aa overlap); and Q9HSU3

Other

strand:+

rslayden

VNG6166H from Halobacterium sp. plasmid pNRC200 strain NRC-1 (144 aa),FASTA scores: opt: 133, E(): 0.011, (29.6% identity in 125aa overlap); and Q9HSU3

Comments