Rv2949c (-)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: chorismate-pyruvate lyase
- REFSEQ: hypothetical protein
- PATRIC: Chorismate--pyruvate lyase (EC 4.1.3.40)
- TUBERCULIST: Chorismate pyruvate lyase
- NCBI: Chorismate pyruvate lyase
- updated information (H37Rv4):
  - gene name: -
  - function: synthesis of p-Hydroxybenzoic acid
  - reference: Stadthagen (2005) PMID: 16210318
Type: Essential
Start: 3299971
End: 3300570
Operon:

Trans-membrane region:
Role: VI - Unknowns
GO terms:
- GO:0072330 - monocarboxylic acid biosynthetic process (Uniprot)
- GO:0071770 - DIM/DIP cell wall layer assembly (Uniprot)
- GO:0046417 - chorismate metabolic process (Uniprot)
- GO:0016829 - lyase activity (Uniprot)
- GO:0008813 - chorismate lyase activity (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
- CHOR[c] -> PYR[c] + HBA[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 Rv2949c:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 1.653 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MTECFLSDQEIRKLNRDLRILIAANGTLTRVLNIVADDEVIVQIVKQRIHDVSPKLSEFEQLGQVGVGRVLQRYIILKGRNSEHLFVAAESLIAIDRLPA
AIITRLTQTNDPLGEVMAASHIETFKEEAKVWVGDLPGWLALHGYQNSRKRAVARRYRVISGGQPIMVVTEHFLRSVFRDAPHEEPDRWQFSNAITLAR

(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)	2.09 (0.53)	1.38 (0.62)
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

Rv2949c/-, gene len: 599 bp, num TA sites: 23

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=2.47)	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=0.264)	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=-0.2)	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

RNA processing and modification

Energy production and conversion

Chromatin structure and dynamics

Amino acid transport and metabolism

Cell cycle control, cell division, chromosome partitioning

Carbohydrate transport and metabolism

Nucleotide transport and metabolism

Lipid transport and metabolism

Coenzyme transport and metabolism

Transcription

Translation, ribosomal structure and biogenesis

Cell wall/membrane/envelope biogenesis

Replication, recombination and repair

Posttranslational modification, protein turnover, chaperones

Cell motility

Secondary metabolites biosynthesis, transport and catabolism

Inorganic ion transport and metabolism

Function unknown

General function prediction only

Intracellular trafficking, secretion, and vesicular transport

Signal transduction mechanisms

Extracellular structures

Defense mechanisms

Nuclear structure

Cytoskeleton

BioCyc Co-regulated genes based on gene expression profiling (Systems Biology, Inferelator Network)

Differentially expressed as result of RNASeq in glycerol environment (Only top 20 genes shown sorted by log fold change with p_adj 0.05).

Conditionally essential as result of TNSeq (Only top 20 genes shown sorted by log fold change with p_adj 0.05).

BioCyc Transcription factor binding based on ChIP-Seq (Systems Biology)

Binds To:
- No bindings to other targets were found.
Bound By:
- No bindings from other targets were found.

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv1994c (cmtR) (Direct binding)
- Rv0273c (-) (Upstream of operon)

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:
- Not downregulated by other genes.

Property	Value	Creator	Evidence	PMID	Comment
Citation	p-Hydroxybenzoic acid synthesis in Mycobacterium tuberculosis. G. Stadthagen, J. Kordulkov et al. J. Biol. Chem. 2005	njamshidi	IDA	16210318	see PMID: 16210318
Term	TBRXN:CHRPL Chorismate pyruvate lyase - IDA	njamshidi	IDA	16210318	see PMID: 16210318 G. Stadthagen, J. Kordulkov et al. p-Hydroxybenzoic acid synthesis in Mycobacterium tuberculosis. J. Biol. Chem. 2005
Interaction	Operon Rv2949c	ashwinigbhat	IDA		Co-expression (Functional linkage) B. Abomoelak, EA. Hoye et al. mosR, a novel transcriptional regulator of hypoxia and virulence in Mycobacterium tuberculosis. J. Bacteriol. 2009
Interaction	Operon Rv2950c	ashwinigbhat	IDA		Co-expression (Functional linkage) B. Abomoelak, EA. Hoye et al. mosR, a novel transcriptional regulator of hypoxia and virulence in Mycobacterium tuberculosis. J. Bacteriol. 2009
Citation	mosR, a novel transcriptional regulator of hypoxia and virulence in Mycobacterium tuberculosis. B. Abomoelak, EA. Hoye et al. J. Bacteriol. 2009	ashwinigbhat	IEP	19648248	Co-expression (Functional linkage)
Interaction	Regulatory Rv0348	ashwinigbhat	IEP		Co-expression (Functional linkage) B. Abomoelak, EA. Hoye et al. mosR, a novel transcriptional regulator of hypoxia and virulence in Mycobacterium tuberculosis. J. Bacteriol. 2009
Interaction	Operon Rv2950c	ashwinigbhat	IEP		Co-expression (Functional linkage) B. Abomoelak, EA. Hoye et al. mosR, a novel transcriptional regulator of hypoxia and virulence in Mycobacterium tuberculosis. J. Bacteriol. 2009
Interaction	Operon Rv2948c	ashwinigbhat	NAS		Co-expression (Functional linkage) B. Abomoelak, EA. Hoye et al. mosR, a novel transcriptional regulator of hypoxia and virulence in Mycobacterium tuberculosis. J. Bacteriol. 2009
Citation	mosR, a novel transcriptional regulator of hypoxia and virulence in Mycobacterium tuberculosis. B. Abomoelak, EA. Hoye et al. J. Bacteriol. 2009	ashwinigbhat	IDA	19648248	Co-expression (Functional linkage)
Interaction	Operon Rv2949c	ashwinigbhat	IDA		Co-expression (Functional linkage) B. Abomoelak, EA. Hoye et al. mosR, a novel transcriptional regulator of hypoxia and virulence in Mycobacterium tuberculosis. J. Bacteriol. 2009
Interaction	RegulatedBy Rv0348	yamir.moreno	IEP		Microarrays. mRNA levels of regulated element measured and compared between wild-type and trans-element mutation (knockout, over expression etc.) performed by using microarray (or macroarray) experiments.. B. Abomoelak, EA. Hoye et al. mosR, a novel transcriptional regulator of hypoxia and virulence in Mycobacterium tuberculosis. J. Bacteriol. 2009
Name	p-hydroxybenzoic acid synthase	mjackson	IMP		Phthiocerol dimycocerosates (PDIM), phenolic glycolipids (PGL) and para-hydroxybenzoic acid derivatives
Name	p-hydroxybenzoic acid synthase	mjackson	IDA		Phthiocerol dimycocerosates (PDIM), phenolic glycolipids (PGL) and para-hydroxybenzoic acid derivatives
Citation	p-Hydroxybenzoic acid synthesis in Mycobacterium tuberculosis. G. Stadthagen, J. Kordulkov et al. J. Biol. Chem. 2005	mjackson		16210318	p-hydroxybenzoic acid synthase (phenotypic [mycobacterial recombinant strains]; enzymatic)
Other	TBPWY:Phthiocerol dimycocerosates, PGL & pHBAD	mjackson			p-hydroxybenzoic acid synthase (phenotypic [mycobacterial recombinant strains]; enzymatic) G. Stadthagen, J. Kordulkov et al. p-Hydroxybenzoic acid synthesis in Mycobacterium tuberculosis. J. Biol. Chem. 2005
Term	EC:4.-.-.- Lyases. - NR	jjmcfadden	NR		Inferred from direct assay G. Stadthagen, J. Kordulkov et al. p-Hydroxybenzoic acid synthesis in Mycobacterium tuberculosis. J. Biol. Chem. 2005
Citation	p-Hydroxybenzoic acid synthesis in Mycobacterium tuberculosis. G. Stadthagen, J. Kordulkov et al. J. Biol. Chem. 2005	jjmcfadden		16210318	Inferred from direct assay

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