Rv2942 (mmpL7)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: hypothetical protein
- REFSEQ: transmembrane transport protein MmpL7
- PATRIC: Putative membrane protein MmpL7
- TUBERCULIST: Conserved transmembrane transport protein MmpL7
- NCBI: Conserved transmembrane transport protein MmpL7
- updated information (H37Rv4):
  - gene name: mmpL7
  - function:
  - reference:
Type: Not Target
Start: 3285070
End: 3287832
Operon:

Trans-membrane region:
Role: II.C.4 - Conserved membrane proteins
GO terms:
- GO:0071555 - cell wall organization (Uniprot)
- GO:0052572 - response to host immune response (Uniprot)
- GO:0044119 - growth of symbiont in host cell (Uniprot)
- GO:0016021 - integral component of membrane (Uniprot)
- GO:0016020 - membrane (Uniprot)
- GO:0009405 - pathogenesis (Uniprot)
- GO:0006869 - lipid transport (Uniprot)
- GO:0006855 - drug transmembrane transport (Uniprot)
- GO:0005887 - integral component of plasma membrane (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
- 0.436 DIM_CYTO[c] -> DIM[c]
- PHDIM_CYTO[c] -> PHDIM[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 mmpL7:
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 1.397 (from Jeremy Rock's lab)

Amino Acid Sequence

MPSPAGRLHRIRYIRLKKSSPDCRATITSGSADGQRRSPRLTNLLVVAAWVAAAVIANLLLTFTQAEPHDTSPALLPQDAKTAAATSRIAQAFPGTGSNA
IAYLVVEGGSTLEPQDQPYYDAAVGALRADTRHVGSVLDWWSDPVTAPLGTSPDGRSATAMVWLRGEAGTTQAAESLDAVRSVLRQLPPSEGLRASIVVP
AITNDMPMQITAWQSATIVTVAAVIAVLLLLRARLSVRAAAIVLLTADLSLAVAWPLAAVVRGHDWGTDSVFSWTLAAVLTIGTITAATMLAARLGSDAG
HSAAPTYRDSLPAFALPGACVAIFTGPLLLARTPALHGVGTAGLGVFVALAASLTVLPALIALAGASRQLPAPTTGAGWTGRLSLPVSSASALGTAAVLA
ICMLPIIGMRWGVAENPTRQGGAQVLPGNALPDVVVIKSARDLRDPAALIAINQVSHRLVEVPGVRKVESAAWPAGVPWTDASLSSAAGRLADQLGQQAG
SFVPAVTAIKSMKSIIEQMSGAVDQLDSTVNVTLAGARQAQQYLDPMLAAARNLKNKTTELSEYLETIHTWIVGFTNCPDDVLCTAMRKVIEPYDIVVTG
MNELSTGADRISAISTQTMSALSSAPRMVAQMRSALAQVRSFVPKLETTIQDAMPQIAQASAMLKNLSADFADTGEGGFHLSRKDLADPSYRHVRESMFS
SDGTATRLFLYSDGQLDLAAAARAQQLEIAAGKAMKYGSLVDSQVTVGGAAQIAAAVRDALIHDAVLLAVILLTVVALASMWRGAVHGAAVGVGVLASYL
AALGVSIALWQHLLDRELNALVPLVSFAVLASCGVPYLVAGIKAGRIADEATGARSKGAVSGRGAVAPLAALGGVFGAGLVLVSGGSFSVLSQIGTVVVL
GLGVLITVQRAWLPTTPGRR

(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)	1.58 (0.3)	1.87 (0.85)
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

Rv2942/mmpL7, gene len: 2762 bp, num TA sites: 43

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	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	YES (LFC=2.11)	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	YES (LFC=-1.803)	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=0.44)	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:
- Rv0023 (-)

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv1816 (-) (Direct binding)
- Rv1049 (-) (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:
- Rv0023 (-)

Property	Value	Creator	Evidence	PMID	Comment
Interaction	Signaling Rv0931c	priyadarshinipriyanka2001	IDA		spectrophotometric Analysis J. Prez, R. Garcia et al. Mycobacterium tuberculosis transporter MmpL7 is a potential substrate for kinase PknD. Biochem. Biophys. Res. Commun. 2006
Name	RND superfamily inner membrane transporter involved in phthiocerol dimycocerosates translocation across the plasma membrane	mjackson	IMP		Phthiocerol dimycocerosates (PDIM), phenolic glycolipids (PGL) and para-hydroxybenzoic acid derivatives
Other	TBPWY:Phthiocerol dimycocerosates, PGL & pHBAD	mjackson			RND superfamily inner membrane transporter involved in phthiocerol dimycocerosates translocation across the plasma membrane authors,JS. Cox,B. Chen,M. McNeil,WR. Jacobs Complex lipid determines tissue-specific replication of Mycobacterium tuberculosis in mice. Nature 1999
Citation	Analysis of the phthiocerol dimycocerosate locus of Mycobacterium tuberculosis. Evidence that this lipid is involved in the cell wall permeability barrier. LR. Camacho, P. Constant et al. J. Biol. Chem. 2001	mjackson		11279114	RND superfamily inner membrane transporter involved in phthiocerol dimycocerosates translocation across the plasma membrane
Other	TBPWY:Phthiocerol dimycocerosates, PGL & pHBAD	mjackson			RND superfamily inner membrane transporter involved in phthiocerol dimycocerosates translocation across the plasma membrane LR. Camacho, P. Constant et al. Analysis of the phthiocerol dimycocerosate locus of Mycobacterium tuberculosis. Evidence that this lipid is involved in the cell wall permeability barrier. J. Biol. Chem. 2001
Citation	Interaction between polyketide synthase and transporter suggests coupled synthesis and export of virulence lipid in M. tuberculosis. M. Jain & JS. Cox PLoS Pathog. 2005	mjackson		16201014	RND superfamily inner membrane transporter involved in phthiocerol dimycocerosates translocation across the plasma membrane
Other	TBPWY:Phthiocerol dimycocerosates, PGL & pHBAD	mjackson			RND superfamily inner membrane transporter involved in phthiocerol dimycocerosates translocation across the plasma membrane M. Jain & JS. Cox Interaction between polyketide synthase and transporter suggests coupled synthesis and export of virulence lipid in M. tuberculosis. PLoS Pathog. 2005
Citation	Complex lipid determines tissue-specific replication of Mycobacterium tuberculosis in mice. authors,JS. Cox,B. Chen,M. McNeil,WR. Jacobs Nature 1999	mjackson		10573420	RND superfamily inner membrane transporter involved in phthiocerol dimycocerosates translocation across the plasma membrane
Citation	Interaction between polyketide synthase and transporter suggests coupled synthesis and export of virulence lipid in M. tuberculosis. M. Jain & JS. Cox PLoS Pathog. 2005	jjmcfadden		16201014	Inferred from direct assay
Other	EC:	jjmcfadden			Inferred from direct assay M. Jain & JS. Cox Interaction between polyketide synthase and transporter suggests coupled synthesis and export of virulence lipid in M. tuberculosis. PLoS Pathog. 2005

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