Rv0746 (PE_PGRS9)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: PE-PGRS family protein
- REFSEQ: PE-PGRS family protein
- PATRIC: PE-PGRS virulence associated protein
- TUBERCULIST: PE-PGRS family protein PE_PGRS9
- NCBI: PE-PGRS family protein PE_PGRS9
- updated information (H37Rv4):
  - gene name: PE_PGRS9
  - function:
  - reference:
Coordinates in H37Rv: 835701 - 838052
Gene length: 2352 bp (with stop codon), 783 aa (without stop codon)
Operon:

Trans-membrane region:
Role: IV.C.1.b - PE_PGRS subfamily
GO terms:
- No terms assigned.
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 Latest Homologs in PDB
Top 10 Homologs in PDB (as of Apr 2026):

PDB aa ident species PDB title

5XFS 51% Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) Crystal structure of PE8-PPE15 in complex with EspG5 from M. tuberculosis
Links to additional information on PE_PGRS9:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 0.794 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

PDB	aa ident	species	PDB title
5XFS	51%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of PE8-PPE15 in complex with EspG5 from M. tuberculosis

Amino Acid Sequence

MSFVLAMPEVLGSAATDLAALGSVLGAADAAAAATTTGIVAAAQDEVSAAIAALFSAHGRAYQVASAQAAAVHAQFVEALSAGAGAYASAEAAGAAVLAN
PAQSVQQDLLAAVNAQSVALTGRPLIGNGANGAPGTGANGAPGGWLLGNGGAGGSAAAGSGLPGGAGGAAGLFGTGGAGGAGGSSTVGDGEAGGAGGSGG
WLLGTGGVGGVGGLGAGAGGAGGVGGAGGLLGAGGHGGAGGLGAVTGGVGGTGGAGGLLAGLLAGPGGAGGTGGRGFLNNGGVGGAGGNAGLLFGAGGTG
GSGGAGLGGDGGAGGAGGNTGVLFGNAGSGGTGGFGDTDGGAGGAGGDAGWLGSGGVGGAGGFGETGDGGVGGAGGKAGLLIGNGGAGGAGGQGAVTGGT
GGAGGDGVLIGNGGNAGIGGTGPTAGDTGAGGISGLLLGADGFNTPASASPLHTLKQQALAAINAPTQTLTGRPLIGNGTPGAVGSGATGAPGGWLLGDG
GAGGSGAAGSGAPGGAGGAAGLWGTGGAGGAGGSSAGGGGAGGAGGAGGWLLGDGGAGGIGGASTVLGGTGGGGGVGGLWGAGGAGGAGGTGLVGGDGGA
GGAGGTGGLLAGLIGAGGGHGGTGGLSTNGDGGVGGAGGNAGMLAGPGGAGGAGGDGENLDTGGDGGAGGSAGLLFGSGGAGGAGGFGFLGGDGGAGGNA
GLLLSSGGAGGFGGFGTAGGVGGAGGNAGWLGFGGAGGVGGSAGLIGTGGNGGNGGTGANAGSPGTGGAGGLLLGQNGLNGLP

(Nucleotide sequence available on KEGG)

Additional Information

ESSENTIALITY

MtbTnDB - interactive tool for exploring a database of published TnSeq datasets for Mtb

TnSeqCorr - genes with correlated TnSeq profiles across ~100 conditions

Rv0746/PE_PGRS9, gene len: 2351 bp, num TA sites: 15

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	no data	7H9	TRASH	essential if hybridization ratio<0.2
in-vivo (mice)	Sassetti 2003 PNAS	no data	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=-0.03)	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=0.098)	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=-0.94)	YM rich vs minimal medium	resampling

Analysis of Positive Selection in Clinical Isolates new

data from Culviner et al (2025) (55,259 Mtb clinical isolates)
- overall pN/pS for Rv0746:
- lineage-specific pN/pS in L1:
- lineage-specific pN/pS in L2:
- lineage-specific pN/pS in L3:
- lineage-specific pN/pS in L4:

Analysis of dN/dS (omega) in a global collection of 10k Mtb clinical isolates using GenomegaMap (Window model)
clinical isolates collection: global set of 10,626 Mtb genomes
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.

	global set of 10,626 Mtb clinical isolates
under significant positive selection?	NO
omega peak height (95%CI lower bound)	1.38 (0.57)
codons under selection
omega plots
genetic variants*	link

* example format for variants: "D27 (GAC): D27H (CAC,11)" means "Asp27 (native codon GAC) mutated to His (codon CAC) in 11 isolates"

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: see table of TFOE interactions below

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:
- Rv1404 (-) (Direct binding)
- Rv1990c (-) (Direct binding)

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

TFOE = Transcription Factor Over-Expression study
significance criteria used in paper: greater than 2-fold change (|LFC|>=1.0) and Padj<0.01

gene	dysregulated by OE of	LFC
Rv0746/PE_PGRS9	Rv2242/mabR	-1.03
Rv0746/PE_PGRS9	Rv3765c/tcrX	-1.07
Rv0746/PE_PGRS9	Rv3417c/groEL1	-1.18
Rv0746/PE_PGRS9	Rv2374c/hrcA	-1.24
Rv0746/PE_PGRS9	Rv0054/ssb	-1.25
Rv0746/PE_PGRS9	Rv0348/mosR1	-1.29
Rv0746/PE_PGRS9	Rv1167c/-	-1.31
Rv0746/PE_PGRS9	Rv0735/sigL	-1.34
Rv0746/PE_PGRS9	Rv0818/glnR	-1.73
Rv0746/PE_PGRS9	Rv1404/-	-1.82

Upregulates:
- Does not upregulate other genes.
Upregulated by:
- Not upregulated by other genes.
Downregulates:
- Does not downregulate other genes.
Downregulated by:

Property	Value	Creator	Evidence	PMID	Comment
Citation	PE_PGRS proteins are differentially expressed by Mycobacterium tuberculosis in host tissues. G. Delogu, M. Sanguinetti et al. Microbes Infect. 2006	sourish10	IEP	16798044	Co-expression (Functional linkage)
Interaction	Transcription Rv0745	sourish10	IEP		Co-expression (Functional linkage) G. Delogu, M. Sanguinetti et al. PE_PGRS proteins are differentially expressed by Mycobacterium tuberculosis in host tissues. Microbes Infect. 2006
Citation	In vitro analysis of rates and spectra of mutations in a polymorphic region of the Rv0746 PE_PGRS gene of Mycobacterium tuberculosis. EE. Machowski, S. Barichievy et al. J. Bacteriol. 2007	sourish10	IEP	17172340	Co-expression (Functional linkage)
Interaction	Transcription Rv0745	sourish10	IEP		Co-expression (Functional linkage) EE. Machowski, S. Barichievy et al. In vitro analysis of rates and spectra of mutations in a polymorphic region of the Rv0746 PE_PGRS gene of Mycobacterium tuberculosis. J. Bacteriol. 2007
Citation	PE_PGRS proteins are differentially expressed by Mycobacterium tuberculosis in host tissues. G. Delogu, M. Sanguinetti et al. Microbes Infect. 2006	jlew		16798044	in axenic cultures, significant up-regulation occurring at late log and early stationary phases. Significant upreglation in mice in the spleen. quantitative real-time RT-PCR (QRT-PCR) was implemented to assess expression of three PE_PGRS genes under different experimental conditions.

TB Genome Annotation Portal