Rv1560 (vapB11)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: antitoxin
- REFSEQ: hypothetical protein
- PATRIC: FIG00821924: hypothetical protein
- TUBERCULIST: Possible antitoxin VapB11
- NCBI: Possible antitoxin VapB11
- updated information (H37Rv4):
  - gene name: vapB11
  - function:
  - reference:
Type: Conditional
Start: 1764755
End: 1764973
Operon:

Trans-membrane region:
Role: V - Conserved hypotheticals
GO terms:
- GO:0075136 - response to host (Uniprot)
- GO:0045927 - positive regulation of growth (Uniprot)
- GO:0045727 - positive regulation of translation (Uniprot)
- GO:0005515 - protein 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
6A7V	100%	Mycobacterium tuberculosis H37Rv	Crystal structure of Mycobacterium tuberculosis VapBC11 toxin-antitoxin complex
4CHG	52%	MYCOBACTERIUM TUBERCULOSIS	Crystal structure of VapBC15 complex from Mycobacterium tuberculosis

Links to additional information on vapB11:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 0.107 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

VYRWCMSRTNIDIDDELAAEVMRRFGLTTKRAAVDLALRRLVGSPLSREFLLGLEGVGWEGDLDDLRSDRPD

(Nucleotide sequence available on KEGG)

Additional Information

Analysis of Positive Selection in Clinical Isolates new

Analysis of dN/dS (omega) in two collections of Mtb clinical isolates using GenomegaMap (Window model) (see description of methods)
- Moldova: 2,057 clinical isolates
- global set: 5,195 clinical isolates from 15 other countries
In the omega plots, the black line shows the mean estimate of omega (dN/dS) at each codon, and the blue lines are the bounds for the 95% credible interval (95%CI, from MCMC sampling).
A gene is under significant positive selection if the lower-bound of the 95%CI of omega (lower blue line) exceeds 1.0 at any codon.

	Moldova (2,057)	global set (5,195)
under significant positive selection?	NO	NO
omega peak height (95%CI lower bound)	0.57 (0.01)	1.14 (0.3)
codons under selection
omega plots
genetic variants*	link	link
statistics at each codon	link	link

* example format for variants: "D27 (GAC): D27H (CAC,11)" means "Asp27 (native codon GAC) mutated to His (codon CAC) in 11 isolates"

ESSENTIALITY

MtbTnDB - interactive tool for exploring a database of published TnSeq datasets for Mtb

TnSeqCorr - genes with correlated TnSeq profiles across ~100 conditions

Rv1560/vapB11, gene len: 218 bp, num TA sites: 3

condition	dataset	call	medium	method	notes
in-vitro	DeJesus 2017 mBio	non-essential	7H9	HMM	fully saturated, 14 TnSeq libraries combined
in-vitro	Sassetti 2003 Mol Micro	non-essential	7H9	TRASH	essential if hybridization ratio<0.2
in-vivo (mice)	Sassetti 2003 PNAS	essential	BL6 mice	TRASH	essential if hybridization ratio<0.4, min over 4 timepoints (1-8 weeks)
in-vitro (glycerol)	Griffin 2011 PPath	too short	M9 minimal+glycerol	Gumbel	2 replicates; Padj<0.05
in-vitro (cholesterol)	Griffin 2011 PPath	too short	M9 minimal+cholesterol	Gumbel	3 replicates; Padj<0.05
differentially essential in cholesterol	Griffin 2011 PPath	NO (LFC=-2.27)	cholesterol vs glycerol	resampling-SR	YES if Padj<0.05, else not significant; LFC<0 means less insertions/more essential in cholesterol
in-vitro	Smith 2022 eLife	non-essential	7H9	HMM	6 replicates (raw data in Subramaniam 2017, PMID 31752678)
in-vivo (mice)	Smith 2022 eLife	non-essential	BL6 mice	HMM	6 replicates (raw data in Subramaniam 2017, PMID 31752678)
differentially essential in mice	Smith 2022 eLife	NO (LFC=-0.271)	in-vivo vs in-vitro	ZINB	YES if Padj<0.05, else not significant; LFC<0 means less insertions/more essential in mice
in-vitro (minimal)	Minato 2019 mSys	non-essential	minimal medium	HMM
in-vitro (YM rich medium)	Minato 2019 mSys	non-essential	YM rich medium	HMM	7H9 supplemented with ~20 metabolites (amino acids, cofactors)
differentially essential in YM rich medium	Minato 2019 mSys	NO (LFC=0.75)	YM rich vs minimal medium	resampling

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:
Bound By:
- Rv0238 (-)

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:
- Rv1560 (vapB11)
- Rv1561 (vapC11)
Upregulated by:
- Rv1560 (vapB11)
Downregulates:
- Does not downregulate other genes.
Downregulated by:
- Rv0238 (-)

Property	Value	Creator	Evidence	PMID	Comment
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 Rv1561	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
Interaction	InhibitedBy Rv1561	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
Interaction	InhibitedBy Rv1561	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
Symbol	VapB11	jlew			Relieves toxin activity. 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	Relieves toxin activity. 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			Rv2009
Symbol	Vap BC-11	rslayden			MTCY39.08c (80 aa), FASTA score: (54.4% identity in 68 aa overlap); Q10799
Other	start:1764755	rslayden			MTCY39.08c (80 aa), FASTA score: (54.4% identity in 68 aa overlap); Q10799
Other	stop:1764973	rslayden			MTCY39.08c (80 aa), FASTA score: (54.4% identity in 68 aa overlap); Q10799
Other	strand:+	rslayden			MTCY39.08c (80 aa), FASTA score: (54.4% identity in 68 aa overlap); Q10799
Symbol	Vap BC-11	rslayden			Rv2871
Other	start:1764755	rslayden			Rv2871
Other	stop:1764973	rslayden			Rv2871
Other	strand:+	rslayden			Rv2871
Symbol	Vap BC-11	rslayden			MTCY274.02 (85 aa); O50456
Other	start:1764755	rslayden			MTCY274.02 (85 aa); O50456
Other	stop:1764973	rslayden			MTCY274.02 (85 aa); O50456
Other	strand:+	rslayden			MTCY274.02 (85 aa); O50456
Symbol	Vap BC-11	rslayden			Rv1241
Other	start:1764755	rslayden			Rv1241
Other	stop:1764973	rslayden			Rv1241
Other	strand:+	rslayden			Rv1241
Symbol	Vap BC-11	rslayden			MTV006.13 (86 aa), O06243
Other	start:1764755	rslayden			MTV006.13 (86 aa), O06243
Other	stop:1764973	rslayden			MTV006.13 (86 aa), O06243
Other	strand:+	rslayden			MTV006.13 (86 aa), O06243
Symbol	Vap BC-11	rslayden			Rv2132
Other	start:1764755	rslayden			Rv2132
Other	stop:1764973	rslayden			Rv2132
Other	strand:+	rslayden			Rv2132
Symbol	Vap BC-11	rslayden			MTCY270.36C (76 aa); etc.
Other	start:1764755	rslayden			MTCY270.36C (76 aa); etc.
Other	stop:1764973	rslayden			MTCY270.36C (76 aa); etc.
Other	strand:+	rslayden			MTCY270.36C (76 aa); etc.
Symbol	Vap BC-11	rslayden			Conserved hypothetical protein, part of a Mycobacterial tuberculosis family of proteins e.g. Q10848
Other	start:1764755	rslayden			Conserved hypothetical protein, part of a Mycobacterial tuberculosis family of proteins e.g. Q10848
Other	stop:1764973	rslayden			Conserved hypothetical protein, part of a Mycobacterial tuberculosis family of proteins e.g. Q10848
Other	strand:+	rslayden			Conserved hypothetical protein, part of a Mycobacterial tuberculosis family of proteins e.g. Q10848
Symbol	Vap BC-11	rslayden			Rv2009
Other	start:1764755	rslayden			Rv2009
Other	stop:1764973	rslayden			Rv2009

TB Genome Annotation Portal