Rv2123 (PPE37)

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 PPE37
- NCBI: PPE family protein PPE37
- updated information (H37Rv4):
  - gene name: PPE37
  - function: implicated in heme uptake
  - reference: Tullius 2019; PMID: 30455201
Type: Not Target
Start: 2381071
End: 2382492
Operon:

Trans-membrane region:
Role: IV.C.2 - PPE family
GO terms:
- GO:0075139 - response to host iron concentration (Uniprot)
- GO:0052572 - response to host immune response (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
6VHR	59%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Structure of PE5-PPE4-EspG3 complex from the type VII (ESX-3) secretion system, space group I422
6UUJ	59%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Structure of PE5-PPE4-EspG3 complex from the type VII (ESX-3) secretion system, space group P212121
5XFS	38%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of PE8-PPE15 in complex with EspG5 from M. tuberculosis

Links to additional information on PPE37:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 1.636 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

VTFPMWFAVPPEVPSAWLSTGMGPGPLLAAARAWHALAAQYTEIATELASVLAAVQASSWQGPSADRFVVAHQPFRYWLTHAATVATAAAAAHETAAAGY
TSALGGMPTLAELAANHAMHGALVTTNFFGVNTIPIALNEADYLRMWIQAATVMSHYQAVAHESVAATPSTPPAPQIVTSAASSAASSSFPDPTKLILQL
LKDFLELLRYLAVELLPGPLGDLIAQVLDWFISFVSGPVFTFLAYLVLDPLIYFGPFAPLTSPVLLPAGLTGLAGLGAVSGPAGPMVERVHSDGPSRQSW
PAATGVTLVGTNPAALVTTPAPAPTTSAAPTAPSTPGSSAAQGLYAVGGPDGEGFNPIAKTTALAGVTTDAAAPAAKLPGDQAQSSASKATRLRRRLRQH
RFEFLADDGRLTMPNTPEMADVAAGNRGLDALGFAGTIPKSAPGSATGLTHLGGGFADVLSQPMLPHTWDGSD

(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)	2.96 (0.97)	1.49 (0.72)
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

Rv2123/PPE37, gene len: 1421 bp, num TA sites: 23

condiion	dataset	call	medium	method	notes
in-vitro	DeJesus 2017 mBio	non-essential	7H9	HMM	14 TnSeq libraries combined
in-vitro	Sassetti 2003 Mol Micro	no data	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=-0.67)	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	NO (LFC=0.6)	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:
- No bindings to other targets were found.

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:
- Not downregulated by other genes.

Property	Value	Creator	Evidence	PMID	Comment
Interaction	Regulatory Rv2122c	ahal4789	IDA		Footprinting GM. Rodriguez, MI. Voskuil et al. ideR, An essential gene in mycobacterium tuberculosis: role of IdeR in iron-dependent gene expression, iron metabolism, and oxidative stress response. Infect. Immun. 2002
Citation	Computational prediction and experimental verification of novel IdeR binding sites in the upstream sequences of Mycobacterium tuberculosis open reading frames. P. Prakash, S. Yellaboina et al. Bioinformatics 2005	sourish10	IDA	15746274	Footprinting
Interaction	Regulatory Rv2711	sourish10	IDA		Footprinting P. Prakash, S. Yellaboina et al. Computational prediction and experimental verification of novel IdeR binding sites in the upstream sequences of Mycobacterium tuberculosis open reading frames. Bioinformatics 2005
Interaction	Regulatory Rv2122c	sourish10	IDA		Footprinting P. Prakash, S. Yellaboina et al. Computational prediction and experimental verification of novel IdeR binding sites in the upstream sequences of Mycobacterium tuberculosis open reading frames. Bioinformatics 2005
Citation	ideR, An essential gene in mycobacterium tuberculosis: role of IdeR in iron-dependent gene expression, iron metabolism, and oxidative stress response. GM. Rodriguez, MI. Voskuil et al. Infect. Immun. 2002	sourish10	IDA	12065475	Footprinting
Interaction	Regulatory Rv2711	sourish10	IDA		Footprinting GM. Rodriguez, MI. Voskuil et al. ideR, An essential gene in mycobacterium tuberculosis: role of IdeR in iron-dependent gene expression, iron metabolism, and oxidative stress response. Infect. Immun. 2002
Interaction	Regulatory Rv2122c	sourish10	IDA		Footprinting GM. Rodriguez, MI. Voskuil et al. ideR, An essential gene in mycobacterium tuberculosis: role of IdeR in iron-dependent gene expression, iron metabolism, and oxidative stress response. Infect. Immun. 2002
Citation	Computational prediction and experimental verification of novel IdeR binding sites in the upstream sequences of Mycobacterium tuberculosis open reading frames. P. Prakash, S. Yellaboina et al. Bioinformatics 2005	ahal4789	IDA	15746274	Footprinting
Interaction	Regulatory Rv2711	ahal4789	IDA		Footprinting P. Prakash, S. Yellaboina et al. Computational prediction and experimental verification of novel IdeR binding sites in the upstream sequences of Mycobacterium tuberculosis open reading frames. Bioinformatics 2005
Interaction	Regulatory Rv2122c	ahal4789	IDA		Footprinting P. Prakash, S. Yellaboina et al. Computational prediction and experimental verification of novel IdeR binding sites in the upstream sequences of Mycobacterium tuberculosis open reading frames. Bioinformatics 2005
Citation	ideR, An essential gene in mycobacterium tuberculosis: role of IdeR in iron-dependent gene expression, iron metabolism, and oxidative stress response. GM. Rodriguez, MI. Voskuil et al. Infect. Immun. 2002	ahal4789	IDA	12065475	Footprinting
Interaction	Regulatory Rv2711	ahal4789	IDA		Footprinting GM. Rodriguez, MI. Voskuil et al. ideR, An essential gene in mycobacterium tuberculosis: role of IdeR in iron-dependent gene expression, iron metabolism, and oxidative stress response. Infect. Immun. 2002
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 Rv2711	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
Interaction	RegulatedBy Rv2711	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.. GM. Rodriguez, MI. Voskuil et al. ideR, An essential gene in mycobacterium tuberculosis: role of IdeR in iron-dependent gene expression, iron metabolism, and oxidative stress response. Infect. Immun. 2002

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