Rv1561 (vapC11)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: toxin
- REFSEQ: hypothetical protein
- PATRIC: FIG00820947: hypothetical protein
- TUBERCULIST: Possible toxin VapC11
- NCBI: Possible toxin VapC11
- updated information (H37Rv4):
  - gene name: vapC11
  - function:
  - reference:
Type: Not Target
Start: 1764979
End: 1765383
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:0075136 - response to host (Uniprot)
- GO:0046872 - metal ion binding (Uniprot)
- GO:0045926 - negative regulation of growth (Uniprot)
- GO:0017148 - negative regulation of translation (Uniprot)
- GO:0016787 - hydrolase activity (Uniprot)
- GO:0005515 - protein binding (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
6A7V	100%	Mycobacterium tuberculosis H37Rv	Crystal structure of Mycobacterium tuberculosis VapBC11 toxin-antitoxin complex
4CHG	37%	MYCOBACTERIUM TUBERCULOSIS	Crystal structure of VapBC15 complex from Mycobacterium tuberculosis

Links to additional information on vapC11:
- 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 = 0.196 (from Jeremy Rock's lab)

Amino Acid Sequence

MILIDTSAWVEYFRATGSIAAVEVRRLLSEEAARIAMCEPIAMEILSGALDDNTHTTLERLVNGLPSLNVDDAIDFRAAAGIYRAARRAGETVRSINDCL
IAALAIRHGARIVHRDADFDVIARITNLQAASFR

(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 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; 1 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; 3 non-insertions in a row out of 9 sites
Non-Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.002700; 6 non-insertions in a row out of 9 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: 0.75
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:
- Rv0047c (-) (Direct binding)
- Rv2250c (-) (Direct binding)
- Rv0135c (-) (Upstream of operon)
- Rv1353c (-) (Upstream of operon)
- Rv1556 (-) (Upstream of operon)

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

Upregulates:
- Does not upregulate other genes.
Upregulated by:
- Rv1560 (vapB11)
Downregulates:
- Does not downregulate other genes.
Downregulated by:

Property	Value	Creator	Evidence	PMID	Comment
Interaction	InhibitedBy Rv1560	vizhi.gurusamy	NAS		Functional linkage (Gene neighborhood) 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	vizhi.gurusamy	NAS	19016878	Functional linkage (Gene neighborhood)
Interaction	Inhibits Rv1560	vizhi.gurusamy	NAS		Functional linkage (Gene neighborhood) authors,A. Gupta Killing activity and rescue function of genome-wide toxin-antitoxin loci of Mycobacterium tuberculosis. FEMS Microbiol. Lett. 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	vizhi.gurusamy	NAS	20011113	Functional linkage (Gene neighborhood)
Interaction	Inhibits Rv1560	vizhi.gurusamy	NAS		Functional linkage (Gene neighborhood) 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 (Rv1560)
Symbol	VapC-mt11	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	VapC11	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:1764979	rslayden			Conserved hypothetical protein, similar to others from Mycobacterium tuberculosis e.g. Q10847
Other	stop:1765383	rslayden			Conserved hypothetical protein, similar to others from Mycobacterium tuberculosis e.g. Q10847
Other	strand:+	rslayden			Conserved hypothetical protein, similar to others from Mycobacterium tuberculosis e.g. Q10847
Other	start:1764979	rslayden			Rv2010
Other	stop:1765383	rslayden			Rv2010
Other	strand:+	rslayden			Rv2010
Other	start:1764979	rslayden			MTCY39.07c (132 aa), FASTA scores: (37.0% identity in 127 aa overlap); and O06566
Other	stop:1765383	rslayden			MTCY39.07c (132 aa), FASTA scores: (37.0% identity in 127 aa overlap); and O06566
Other	strand:+	rslayden			MTCY39.07c (132 aa), FASTA scores: (37.0% identity in 127 aa overlap); and O06566
Other	start:1764979	rslayden			Rv1114
Other	stop:1765383	rslayden			Rv1114
Other	strand:+	rslayden			Rv1114
Other	start:1764979	rslayden			MTCY22G8.03 (124 aa).
Other	stop:1765383	rslayden			MTCY22G8.03 (124 aa).
Other	strand:+	rslayden			MTCY22G8.03 (124 aa).

TB Genome Annotation Portal