Rv2108 (PPE36)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: PPE family protein
- REFSEQ: PPE family protein
- PATRIC: PPE family protein
- TUBERCULIST: PPE family protein PPE36
- NCBI: PPE family protein PPE36
- updated information (H37Rv4):
  - gene name: PPE36
  - function: implicated in heme uptake
  - reference: Mitra 2017; PMID: 28119467
Type: Not Target
Start: 2367711
End: 2368442
Operon:

Trans-membrane region:
Role: IV.C.2 - PPE family
GO terms:
- GO:0016020 - membrane (Uniprot)
- GO:0005886 - plasma membrane (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
5XFS	46%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of PE8-PPE15 in complex with EspG5 from M. tuberculosis
6VHR	40%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Structure of PE5-PPE4-EspG3 complex from the type VII (ESX-3) secretion system, space group I422
6UUJ	40%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Structure of PE5-PPE4-EspG3 complex from the type VII (ESX-3) secretion system, space group P212121

Links to additional information on PPE36:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 1.079 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MPNFWALPPEINSTRIYLGPGSGPILAAAQGWNALASELEKTKVGLQSALDTLLESYRGQSSQALIQQTLPYVQWLTTTAEHAHKTAIQLTAAANAYEQA
RAAMVPPAMVRANRVQTTVLKAINWFGQFSTRIADKEADYEQMWFQDALVMENYWEAVQEAIQSTSHFEDPPEMADDYDEAWMLNTVFDYHNENAKEEVI
HLVPDVNKERGPIELVTKVDKEGTIRLVYDGEPTFSYKEHPKF

(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)	1.0 (0.18)	1.16 (0.4)
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

Rv2108/PPE36, gene len: 731 bp, num TA sites: 21

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=0.18)	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=0.217)	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=0.4)	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:

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0023 (-) (Direct binding)
- Rv0047c (-) (Direct binding)
- Rv0081 (-) (Direct binding)
- Rv2887 (-) (Direct binding)
- Rv3133c (devR) (Direct binding)
- Rv3249c (-) (Direct binding)
- Rv3574 (kstR) (Direct binding)

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

Upregulates:
- Does not upregulate other genes.
Upregulated by:
Downregulates:
- Does not downregulate other genes.
Downregulated by:
- Rv0260c (-)
- Rv0465c (-)

Property	Value	Creator	Evidence	PMID	Comment
Interaction	PhysicalInteraction Rv2107	kholia.trupti	IGC		Neighbourhood (Functional linkage) S. Tundup, Y. Akhter et al. Clusters of PE and PPE genes of Mycobacterium tuberculosis are organized in operons: evidence that PE Rv2431c is co-transcribed with PPE Rv2430c and their gene products interact with each other. FEBS Lett. 2006
Interaction	PhysicalInteraction Rv2107	kholia.trupti	IGC		Neighbourhood (Functional linkage) authors,M. Strong,MR. Sawaya,S. Wang,M. Phillips,D. Cascio,D. Eisenberg Toward the structural genomics of complexes: crystal structure of a PE/PPE protein complex from Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. U.S.A. 2006
Citation	Clusters of PE and PPE genes of Mycobacterium tuberculosis are organized in operons: evidence that PE Rv2431c is co-transcribed with PPE Rv2430c and their gene products interact with each other. S. Tundup, Y. Akhter et al. FEBS Lett. 2006	kholia.trupti	IGC	16458305	Neighbourhood (Functional linkage)
Interaction	PhysicalInteraction Rv2107	kholia.trupti	IGC		Neighbourhood (Functional linkage) S. Tundup, Y. Akhter et al. Clusters of PE and PPE genes of Mycobacterium tuberculosis are organized in operons: evidence that PE Rv2431c is co-transcribed with PPE Rv2430c and their gene products interact with each other. FEBS Lett. 2006
Citation	Toward the structural genomics of complexes: crystal structure of a PE/PPE protein complex from Mycobacterium tuberculosis. authors,M. Strong,MR. Sawaya,S. Wang,M. Phillips,D. Cascio,D. Eisenberg Proc. Natl. Acad. Sci. U.S.A. 2006	kholia.trupti	IGC	16690741	Neighbourhood (Functional linkage)
Interaction	PhysicalInteraction Rv2107	kholia.trupti	IGC		Neighbourhood (Functional linkage) authors,M. Strong,MR. Sawaya,S. Wang,M. Phillips,D. Cascio,D. Eisenberg Toward the structural genomics of complexes: crystal structure of a PE/PPE protein complex from Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. U.S.A. 2006
Symbol	PPE36, p27	jlew			Mouse immune response to p27 V. Le Moigne, G. Robreau et al. Flagellin as a good carrier and potent adjuvant for Th1 response: study of mice immune response to the p27 (Rv2108) Mycobacterium tuberculosis antigen. Mol. Immunol. 2008
Citation	Flagellin as a good carrier and potent adjuvant for Th1 response: study of mice immune response to the p27 (Rv2108) Mycobacterium tuberculosis antigen. V. Le Moigne, G. Robreau et al. Mol. Immunol. 2008	jlew		18289677	Mouse immune response to p27
Symbol	p27	jlew			Western blot and immunoelectron microscopic analysis of BCG strain indicated that the p27 protein is localized in the membrane of the cell. V. Le Moigne, G. Robreau et al. Expression, immunochemical characterization and localization of the Mycobacterium tuberculosis protein p27. Tuberculosis (Edinburgh, Scotland) 2005
Citation	Expression, immunochemical characterization and localization of the Mycobacterium tuberculosis protein p27. V. Le Moigne, G. Robreau et al. Tuberculosis (Edinburgh, Scotland) 2005	jlew		15958258	Western blot and immunoelectron microscopic analysis of BCG strain indicated that the p27 protein is localized in the membrane of the cell.

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