Rv0483 (lprQ)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: lipoprotein lprQ
- REFSEQ: lipoprotein LprQ
- PATRIC: Possible lipoprotein LprQ
- TUBERCULIST: Probable conserved lipoprotein LprQ
- NCBI: Probable conserved lipoprotein LprQ
- updated information (H37Rv4):
  - gene name: ldtC
  - function: (3,3-) L,D-transpeptidase, peptidoglycan synthesis
  - reference: Cordillot (2013) PMC3837840
Type: Not Target
Start: 571710
End: 573065
Operon:

Trans-membrane region:
Role: V - Conserved hypotheticals
GO terms:
- GO:0071555 - cell wall organization (Uniprot)
- GO:0016746 - transferase activity, transferring acyl groups (Uniprot)
- GO:0016740 - transferase activity (Uniprot)
- GO:0009252 - peptidoglycan biosynthetic process (Uniprot)
- GO:0008360 - regulation of cell shape (Uniprot)
- GO:0005576 - extracellular region (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
6D5A	100%	Mycobacterium tuberculosis	Crystal structure of L,D-transpeptidase 5 from Mycobacterium tuberculosis in apo form
4ZFQ	100%	Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh)	Structure of M. tuberculosis (3,3) L,D-Transpeptidase, LdtMt5. (Meropenen-adduct form)
4Z7A	100%	Mycobacterium tuberculosis (strain ATCC 25177 / H37Ra)	Structural and biochemical characterization of a non-functionally redundant M. tuberculosis (3,3) L,D-Transpeptidase, LdtMt5.
4HU2	38%	Mycobacterium tuberculosis	Crystal structure of LdtMt2, a L,D-transpeptidase from Mycobacterium tuberculosis: domain A and B
5LBG	36%	Mycobacterium tuberculosis	Crystal structure of the Mycobacterium tuberculosis L,D-transpeptidase-2 (LdtMt2) BC-module with faropenem-derived adduct at the active site cysteine-354
5LB1	36%	Mycobacterium tuberculosis	Crystal structure of the Mycobacterium tuberculosis L,D-transpeptidase-2 (LdtMt2) BC-module with thionitrobenzoate (TNB) adduct at the active site cysteine-354
4HUC	36%	Mycobacterium tuberculosis	Crystal structure of LdtMt2, a L,D-transpeptidase from Mycobacterium tuberculosis: domain B and C
6RRM	35%	Mycobacterium tuberculosis CDC1551	Crystal structure of LdtMt2 from Mycobacterium tuberculosis bound to Ebselen
6RLG	35%	Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh)	Crystal structure of LdtMt2 from Mycobacterium tuberculosis
6BOI	35%	Mycobacterium tuberculosis (strain ATCC 25177 / H37Ra)	Crystal Structure of LdtMt2 (56-408) with a panipenem adduct at the active site cysteine-354

Links to additional information on lprQ:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 1.228 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

VVIRVLFRPVSLIPVNNSSTPQSQGPISRRLALTALGFGVLAPNVLVACAGKVTKLAEKRPPPAPRLTFRPADSAADVVPIAPISVEVGDGWFQRVALTN
SAGKVVAGAYSRDRTIYTITEPLGYDTTYTWSGSAVGHDGKAVPVAGKFTTVAPVKTINAGFQLADGQTVGIAAPVIIQFDSPISDKAAVERALTVTTDP
PVEGGWAWLPDEAQGARVHWRPREYYPAGTTVDVDAKLYGLPFGDGAYGAQDMSLHFQIGRRQVVKAEVSSHRIQVVTDAGVIMDFPCSYGEADLARNVT
RNGIHVVTEKYSDFYMSNPAAGYSHIHERWAVRISNNGEFIHANPMSAGAQGNSNVTNGCINLSTENAEQYYRSAVYGDPVEVTGSSIQLSYADGDIWDW
AVDWDTWVSMSALPPPAAKPAATQIPVTAPVTPSDAPTPSGTPTTTNGPGG

(Nucleotide sequence available on KEGG)

Additional Information

LdtC, L,D-transpeptidase, peptidoglycan synthesis

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)	1.22 (0.18)	1.27 (0.56)
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

Rv0483/lprQ, gene len: 1355 bp, num TA sites: 30

condition	dataset	call	medium	method	notes
in-vitro	DeJesus 2017 mBio	growth advantage	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=-0.29)	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=-0.048)	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	YES (LFC=-1.05)	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:
- Rv1049 (-) (Direct binding)
- Rv1423 (whiA) (Direct binding)
- Rv1994c (cmtR) (Direct binding)
- Rv2324 (-) (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:
- Not downregulated by other genes.

Property	Value	Creator	Evidence	PMID	Comment
Interaction	Transcription Rv3676	priya29sep	IMP		ChIP (Physical interaction) authors,IC. Sutcliffe,DJ. Harrington Lipoproteins of Mycobacterium tuberculosis: an abundant and functionally diverse class of cell envelope components. FEMS Microbiol. Rev. 2004
Citation	A member of the cAMP receptor protein family of transcription regulators in Mycobacterium tuberculosis is required for virulence in mice and controls transcription of the rpfA gene coding for a resuscitation promoting factor. L. Rickman, C. Scott et al. Mol. Microbiol. 2005	priya29sep	IMP	15882420	ChIP (Physical interaction)
Interaction	Transcription Rv3676	priya29sep	IMP		ChIP (Physical interaction) L. Rickman, C. Scott et al. A member of the cAMP receptor protein family of transcription regulators in Mycobacterium tuberculosis is required for virulence in mice and controls transcription of the rpfA gene coding for a resuscitation promoting factor. Mol. Microbiol. 2005
Citation	Lipoproteins of Mycobacterium tuberculosis: an abundant and functionally diverse class of cell envelope components. authors,IC. Sutcliffe,DJ. Harrington FEMS Microbiol. Rev. 2004	priya29sep	IMP	15539077	ChIP (Physical interaction)
Interaction	RegulatedBy Rv0981	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.. H. He, R. Hovey et al. MprAB is a stress-responsive two-component system that directly regulates expression of sigma factors SigB and SigE in Mycobacterium tuberculosis. J. Bacteriol. 2006
Interaction	RegulatedBy Rv3676	yamir.moreno	TAS		Literature previously reported link (from Balazsi et al. 2008). Traceable author statement to experimental support. G. Balzsi, AP. Heath et al. The temporal response of the Mycobacterium tuberculosis gene regulatory network during growth arrest. Mol. Syst. Biol. 2008
Symbol	ldtC	mjackson	ISS		Peptidoglycan assembly/maturation
Name	Homologous to L,D-transpeptidase	mjackson	ISS		Peptidoglycan assembly/maturation
Symbol	LprQ	jlew			Contains a functional tat sequence. Test for functional tat sequences using a BlaC reporter. 13 identified. JA. McDonough, JR. McCann et al. Identification of functional Tat signal sequences in Mycobacterium tuberculosis proteins. J. Bacteriol. 2008
Citation	Identification of functional Tat signal sequences in Mycobacterium tuberculosis proteins. JA. McDonough, JR. McCann et al. J. Bacteriol. 2008	jlew		18658266	Contains a functional tat sequence. Test for functional tat sequences using a BlaC reporter. 13 identified.

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