Rv1818c (PE_PGRS33)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: PE-PGRS family protein
- REFSEQ: PE-PGRS family protein
- PATRIC: PE family protein
- TUBERCULIST: PE-PGRS family protein PE_PGRS33
- NCBI: PE-PGRS family protein PE_PGRS33
- updated information (H37Rv4):
  - gene name: PE_PGRS33
  - function:
  - reference:
Type: Conditional
Start: 2061178
End: 2062674
Operon:

Trans-membrane region:
Role: IV.C.1.b - PE_PGRS subfamily
GO terms:
- GO:0070482 - response to oxygen levels (Uniprot)
- GO:0052167 - modulation by symbiont of host innate immune response (Uniprot)
- GO:0046789 - host cell surface receptor binding (Uniprot)
- GO:0044650 - adhesion of symbiont to host cell (Uniprot)
- GO:0042594 - response to starvation (Uniprot)
- GO:0016020 - membrane (Uniprot)
- GO:0009986 - cell surface (Uniprot)
- GO:0009405 - pathogenesis (Uniprot)
- GO:0009279 - cell outer membrane (Uniprot)
- GO:0005618 - cell wall (Uniprot)
- GO:0005576 - extracellular region (Uniprot)
- GO:0005515 - protein binding (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): (none with >35% aa id)
Links to additional information on PE_PGRS33:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 0.14 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MSFVVTIPEALAAVATDLAGIGSTIGTANAAAAVPTTTVLAAAADEVSAAMAALFSGHAQAYQALSAQAALFHEQFVRALTAGAGSYAAAEAASAAPLEG
VLDVINAPALALLGRPLIGNGANGAPGTGANGGDGGILIGNGGAGGSGAAGMPGGNGGAAGLFGNGGAGGAGGNVASGTAGFGGAGGAGGLLYGAGGAGG
AGGRAGGGVGGIGGAGGAGGNGGLLFGAGGAGGVGGLAADAGDGGAGGDGGLFFGVGGAGGAGGTGTNVTGGAGGAGGNGGLLFGAGGVGGVGGDGVAFL
GTAPGGPGGAGGAGGLFGVGGAGGAGGIGLVGNGGAGGSGGSALLWGDGGAGGAGGVGSTTGGAGGAGGNAGLLVGAGGAGGAGALGGGATGVGGAGGNG
GTAGLLFGAGGAGGFGFGGAGGAGGLGGKAGLIGDGGDGGAGGNGTGAKGGDGGAGGGAILVGNGGNGGNAGSGTPNGSAGTGGAGGLLGKNGMNGLP

(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 *new*

Classification	Condition	Strain	Method	Reference	Notes
Non-Essential	Sodium Oleate	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 3 non-insertions in a row out of 16 sites
Non-Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 3 non-insertions in a row out of 16 sites
Non-Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 3 non-insertions in a row out of 16 sites
Uncertain	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.062500; 3 non-insertions in a row out of 17 sites
Non-Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 2 non-insertions in a row out of 17 sites
Non-Essential	7H10-glycerol	H37RvMA	TraSH	Sassetti et al. (2003a)
Non-Essential	C57BL/6J mice (8 weeks)	H37RvMA	TraSH	Sassetti et al. (2003b)	Hybridization Ratio: 0.93
Non-Essential	7H09/7H10 + rich media	H37RvMA	MotifHMM	DeJesus et al. (2017)	Fully saturated (14 reps).

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:
- Rv0081 (-)
- Rv1167c (-)

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0691c (-) (Direct binding)
- Rv0967 (csoR) (Direct binding)
- Rv3133c (devR) (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:
- Rv0081 (-)
- Rv1167c (-)

Property	Value	Creator	Evidence	PMID	Comment
Interaction	PhysicalInteraction Rv2250c	sourish10	IPI		Yeast two-hybrid (Physical interaction) J. Zeng, L. Zhang et al. Over-producing soluble protein complex and validating protein-protein interaction through a new bacterial co-expression system. Protein Expr. Purif. 2010
Interaction	RegulatedBy Rv2710	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.. JH. Lee, PC. Karakousis et al. Roles of SigB and SigF in the Mycobacterium tuberculosis sigma factor network. J. Bacteriol. 2008
Citation	Functional dissection of the PE domain responsible for translocation of PE_PGRS33 across the mycobacterial cell wall. authors,A. Cascioferro,MH. Daleke,M. Ventura,V. Don,G. Delogu,G. Pal,W. Bitter,R. Manganelli PLoS ONE 2011	jlew		22110736	In this paper, we characterize the PE domain of PE_PGRS33 (PERv1818c), one of the best characterized PE proteins. We confirmed that the PE domain is essential for PE_PGRS33 surface localization. Using Mycobacterium marinum we could show that the type VII secretion system ESX-5 is essential for PE_PGRS33 export.
Citation	Over-producing soluble protein complex and validating protein-protein interaction through a new bacterial co-expression system. J. Zeng, L. Zhang et al. Protein Expr. Purif. 2010	jlew		19747546	Rv2250c and Rv1818c interact. Using an in vivo pull-down assay, for the first time we have confirmed the presence of three pairs of PE/PPE-related novel protein interactions in this pathogen.
Citation	A comparative study of host response to three Mycobacterium tuberculosis PE_PGRS proteins. PP. Singh, M. Parra et al. Microbiology (Reading, Engl.) 2008	jlew		18957600	More persistent. Overexpress in MS and infect macrophages and mice.
Citation	PE is a functional domain responsible for protein translocation and localization on mycobacterial cell wall. A. Cascioferro, G. Delogu et al. Mol. Microbiol. 2007	jlew		18028308	Protein is surface exposed and localizes in the cell wall. PE domain for cell wall localization
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. quantitative real-time RT-PCR (QRT-PCR) was implemented to assess expression of three PE_PGRS genes under different experimental conditions.
Citation	Variable expression patterns of Mycobacterium tuberculosis PE_PGRS genes: evidence that PE_PGRS16 and PE_PGRS26 are inversely regulated in vivo. V. Dheenadhayalan, G. Delogu et al. J. Bacteriol. 2006	jlew		16672626	Constitutively expressed in all in vitro conditions examined. Evaluation of expression of 16 PE_PGRS genes present in Mycobacterium tuberculosis under various growth conditions

TB Genome Annotation Portal