Rv1960c (parD1)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: antitoxin
- REFSEQ: hypothetical protein
- PATRIC: Antitoxin ParD1
- TUBERCULIST: Possible antitoxin ParD1
- NCBI: Possible antitoxin ParD1
- updated information (H37Rv4):
  - gene name: parD1
  - function:
  - reference:
Type: Not Target
Start: 2203974
End: 2204225
Operon:

Trans-membrane region:
Role: VI - Unknowns
GO terms:
- GO:0045927 - positive regulation of growth (Uniprot)
- GO:0006355 - regulation of transcription, DNA-templated (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

3KXE 59% Caulobacter crescentus NA1000 A conserved mode of protein recognition and binding in a ParD-ParE toxin-antitoxin complex
Links to additional information on parD1:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 0.418 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

PDB	aa ident	species	PDB title
3KXE	59%	Caulobacter crescentus NA1000	A conserved mode of protein recognition and binding in a ParD-ParE toxin-antitoxin complex

Amino Acid Sequence

VGKNTSFVLDEHYSAFIDGEIAAGRYRSASEVIRSALRLLEDRETQLRALREALEAGERSGSSTPFDFDGFLGRKRADASRGR

(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)	1.15 (0.07)	1.2 (0.42)
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

Rv1960c/parD1, gene len: 251 bp, num TA sites: 4

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	non-essential	BL6 mice	TRASH	essential if hybridization ratio<0.4, min over 4 timepoints (1-8 weeks)
in-vitro (glycerol)	Griffin 2011 PPath	non-essential	M9 minimal+glycerol	Gumbel	2 replicates; Padj<0.05
in-vitro (cholesterol)	Griffin 2011 PPath	non-essential	M9 minimal+cholesterol	Gumbel	3 replicates; Padj<0.05
differentially essential in cholesterol	Griffin 2011 PPath	NO (LFC=-1.46)	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=-0.792)	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, vitamins)
differentially essential in YM rich medium	Minato 2019 mSys	NO (LFC=0.33)	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:

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv2034 (-) (Direct binding)
- Rv3574 (kstR) (Direct binding)

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

Upregulates:
Upregulated by:
- Rv0023 (-)
- Rv1960c (parD1)
Downregulates:
- Does not downregulate other genes.
Downregulated by:

Property	Value	Creator	Evidence	PMID	Comment
Interaction	InhibitedBy Rv2142c	harsharohiratruefriend	ISA		operon(Functional linkage) authors,K. Simola,RK. Selander,A. de la Chapelle,G. Corneo,E. Ginelli Molecular basis of chromosome banding. I. The effect of mouse DNA fractions on two fluorescent dyes in vitro. Chromosoma 1975
Interaction	InhibitedBy Rv2142c	harsharohiratruefriend	ISA		operon(Functional linkage) authors,KM. Dalton,S. Crosson A conserved mode of protein recognition and binding in a ParD-ParE toxin-antitoxin complex. Biochemistry 2010
Interaction	InhibitedBy Rv2142c	harsharohiratruefriend	ISA		operon(Functional linkage) authors,V. Anantharaman,L. Aravind New connections in the prokaryotic toxin-antitoxin network: relationship with the eukaryotic nonsense-mediated RNA decay system. Genome Biol. 2003
Interaction	InhibitedBy Rv2142c	harsharohiratruefriend	ISA		operon(Functional linkage) authors,K. Gerdes,SK. Christensen,A. Lbner-Olesen Prokaryotic toxin-antitoxin stress response loci. Nat. Rev. Microbiol. 2005
Interaction	Inhibits Rv1959c	akankshajain.21	IDA		Spectrophotometric analysis authors,A. Gupta Killing activity and rescue function of genome-wide toxin-antitoxin loci of Mycobacterium tuberculosis. FEMS Microbiol. Lett. 2009
Interaction	Inhibits Rv1959c	prabhakarsmail	IDA		Spectrophotometric analysis 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	akankshajain.21	IDA	19016878	Spectrophotometric analysis
Interaction	Inhibits Rv1959c	akankshajain.21	IDA		Spectrophotometric analysis 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	prabhakarsmail	IDA	19016878	Spectrophotometric analysis
Interaction	Inhibits Rv1959c	prabhakarsmail	IDA		Spectrophotometric analysis authors,A. Gupta Killing activity and rescue function of genome-wide toxin-antitoxin loci of Mycobacterium tuberculosis. FEMS Microbiol. Lett. 2009
Symbol	ParD1	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.
Symbol	Par DE-1	rslayden			Conserved hypothetical protein, similar to O85269
Other	start:2203974	rslayden			Conserved hypothetical protein, similar to O85269
Other	stop:2204225	rslayden			Conserved hypothetical protein, similar to O85269
Other	strand:+	rslayden			Conserved hypothetical protein, similar to O85269
Symbol	Par DE-1	rslayden			AF102990
Other	start:2203974	rslayden			AF102990
Other	stop:2204225	rslayden			AF102990
Other	strand:+	rslayden			AF102990
Symbol	Par DE-1	rslayden			AF102990_51 hypothetical protein of Yersinia enterocolitica (80 aa), FASTA scores: opt: 149, E(): 0.00037, (42 .1% identity in 57 aa overlap).
Other	start:2203974	rslayden			AF102990_51 hypothetical protein of Yersinia enterocolitica (80 aa), FASTA scores: opt: 149, E(): 0.00037, (42 .1% identity in 57 aa overlap).
Other	stop:2204225	rslayden			AF102990_51 hypothetical protein of Yersinia enterocolitica (80 aa), FASTA scores: opt: 149, E(): 0.00037, (42 .1% identity in 57 aa overlap).
Other	strand:+	rslayden			AF102990_51 hypothetical protein of Yersinia enterocolitica (80 aa), FASTA scores: opt: 149, E(): 0.00037, (42 .1% identity in 57 aa overlap).

TB Genome Annotation Portal