Rv2951c (-)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: phthiodiolone/phenolphthiodiolone dimycocerosates ketoreductase
- REFSEQ: oxidoreductase
- PATRIC: Phthiodiolone/phenolphthiodiolone dimycocerosates ketoreductase
- TUBERCULIST: Possible oxidoreductase
- NCBI: Possible oxidoreductase
- updated information (H37Rv4):
  - gene name: -
  - function:
  - reference:
Type: Not Target
Start: 3303103
End: 3304248
Operon:

Trans-membrane region:
Role: I.B.7 - Miscellaneous oxidoreductases and oxygenases
GO terms:
- GO:0055114 - oxidation-reduction process (Uniprot)
- GO:0016705 - oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen (Uniprot)
- GO:0016491 - oxidoreductase activity (Uniprot)
- GO:0006629 - lipid metabolic process (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0005829 - cytosol (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
- NADPH[c] + PHENOLPHTHIODIOLONE[A][c] -> NADP[c] + PPTT[c]
- NADPH[c] + PHTHIODIOLONE[A][c] -> NADP[c] + PTT[c]
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): (none with >35% aa id)
Links to additional information on Rv2951c:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 0.953 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

VGGLRFGFVDALVHSRLPPTLPARSSMAAATVMGADSYWVGDHLNALVPRSIATSEYLGIAAKFVPKIDANYEPWTMLGNLAFGLPSRLRLGVCVTDAGR
RNPAVTAQAAATLHLLTRGRAILGIGVGEREGNEPYGVEWTKPVARFEEALATIRALWNSNGELISRESPYFPLHNALFDLPPYRGKWPEIWVAAHGPRM
LRATGRYADAWIPIVVVRPSDYSRALEAVRSAASDAGRDPMSITPAAVRGIITGRNRDDVEEALESVVVKMTALGVPGEAWARHGVEHPMGADFSGVQDI
IPQTMDKQTVLSYAAKVPAALMKEVVFSGTPDEVIDQVAEWRDHGLRYVVLINGSLVNPSLRKTVTAVLPHAKVLRGLKKL

(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)	1.68 (0.26)	1.81 (0.84)
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

Rv2951c/-, gene len: 1145 bp, num TA sites: 24

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=0.16)	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=-0.111)	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=-0.26)	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:
- No bindings to other targets were found.
Bound By:
- Rv3058c (-)

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0302 (-) (Direct binding)
- Rv3133c (devR) (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:
- Rv3058c (-)

Property	Value	Creator	Evidence	PMID	Comment
Name	Ketoreductase catalyzing the reduction of (phenol)phthiodiolone to yield (phenol)phthiotriol in the biosynthesis of phthiocerol dimycocerosates and phenolic glycolipids	mjackson	IMP		Phthiocerol dimycocerosates (PDIM), phenolic glycolipids (PGL) and para-hydroxybenzoic acid derivatives
Citation	Identification of phthiodiolone ketoreductase, an enzyme required for production of mycobacterial diacyl phthiocerol virulence factors. authors,KC. Onwueme,CJ. Vos,J. Zurita,CE. Soll,LE. Quadri J. Bacteriol. 2005	mjackson		15995190	Ketoreductase catalyzing the reduction of (phenol)phthiodiolone to yield (phenol)phthiotriol in the biosynthesis of phthiocerol dimycocerosates and phenolic glycolipids (phenotypic [mycobacterial recombinant strains])
Other	TBPWY:Phthiocerol dimycocerosates, PGL & pHBAD	mjackson			Ketoreductase catalyzing the reduction of (phenol)phthiodiolone to yield (phenol)phthiotriol in the biosynthesis of phthiocerol dimycocerosates and phenolic glycolipids (phenotypic [mycobacterial recombinant strains]) authors,KC. Onwueme,CJ. Vos,J. Zurita,CE. Soll,LE. Quadri Identification of phthiodiolone ketoreductase, an enzyme required for production of mycobacterial diacyl phthiocerol virulence factors. J. Bacteriol. 2005
Citation	Molecular dissection of the biosynthetic relationship between phthiocerol and phthiodiolone dimycocerosates and their critical role in the virulence and permeability of Mycobacterium tuberculosis. R. Simone, P. Constant et al. FEBS J. 2007	mjackson		17371506	Ketoreductase catalyzing the reduction of (phenol)phthiodiolone to yield (phenol)phthiotriol in the biosynthesis of phthiocerol dimycocerosates and phenolic glycolipids (phenotypic [mycobacterial recombinant strains])
Other	TBPWY:Phthiocerol dimycocerosates, PGL & pHBAD	mjackson			Ketoreductase catalyzing the reduction of (phenol)phthiodiolone to yield (phenol)phthiotriol in the biosynthesis of phthiocerol dimycocerosates and phenolic glycolipids (phenotypic [mycobacterial recombinant strains]) R. Simone, P. Constant et al. Molecular dissection of the biosynthetic relationship between phthiocerol and phthiodiolone dimycocerosates and their critical role in the virulence and permeability of Mycobacterium tuberculosis. FEBS J. 2007
Citation	Role of the pks15/1 gene in the biosynthesis of phenolglycolipids in the Mycobacterium tuberculosis complex. Evidence that all strains synthesize glycosylated p-hydroxybenzoic methyl esters and that strains devoid of phenolglycolipids harbor a frameshift mutation in the pks15/1 gene. P. Constant, E. Perez et al. J. Biol. Chem. 2002	jjmcfadden		12138124	Inferred from direct assay
Term	EC:1.-.-.- Oxidoreductases. - NR	jjmcfadden	NR		Inferred from direct assay P. Constant, E. Perez et al. Role of the pks15/1 gene in the biosynthesis of phenolglycolipids in the Mycobacterium tuberculosis complex. Evidence that all strains synthesize glycosylated p-hydroxybenzoic methyl esters and that strains devoid of phenolglycolipids harbor a frameshift mutation in the pks15/1 gene. J. Biol. Chem. 2002

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