Rv3478 (PPE60)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: PPE family protein
- REFSEQ: PE family protein
- PATRIC: PPE family protein
- TUBERCULIST: PE family protein PPE60
- NCBI: PE family protein PPE60
- updated information (H37Rv4):
  - gene name: PPE60
  - function:
  - reference:
Type: Not Target
Start: 3894426
End: 3895607
Operon:

Trans-membrane region:
Role: IV.C.2 - PPE family
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 Homologs in PDB

Top 10 Homologs in PDB (as of Nov 2020):

PDB	aa ident	species	PDB title
5XFS	52%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of PE8-PPE15 in complex with EspG5 from M. tuberculosis
6VHR	38%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Structure of PE5-PPE4-EspG3 complex from the type VII (ESX-3) secretion system, space group I422
6UUJ	38%	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 PPE60:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -0.333 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

VVDFGALPPEINSARMYAGPGSASLVAAAKMWDSVASDLFSAASAFQSVVWGLTVGSWIGSSAGLMAAAASPYVAWMSVTAGQAQLTAAQVRVAAAAYET
AYRLTVPPPVIAENRTELMTLTATNLLGQNTPAIEANQAAYSQMWGQDAEAMYGYAATAATATEALLPFEDAPLITNPGGLLEQAVAVEEAIDTAAANQL
MNNVPQALQQLAQPAQGVVPSSKLGGLWTAVSPHLSPLSNVSSIANNHMSMMGTGVSMTNTLHSMLKGLAPAAAQAVETAAENGVWAMSSLGSQLGSSLG
SSGLGAGVAANLGRAASVGSLSVPPAWAAANQAVTPAARALPLTSLTSAAQTAPGHMLGGLPLGHSVNAGSGINNALRVPARAYAIPRTPAAG

(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; 2 non-insertions in a row out of 18 sites
Non-Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 4 non-insertions in a row out of 18 sites
Non-Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 2 non-insertions in a row out of 18 sites
Non-Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 2 non-insertions in a row out of 16 sites
Uncertain	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.177750; 4 non-insertions in a row out of 16 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: 0.45
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

RNA processing and modification

Energy production and conversion

Chromatin structure and dynamics

Amino acid transport and metabolism

Cell cycle control, cell division, chromosome partitioning

Carbohydrate transport and metabolism

Nucleotide transport and metabolism

Lipid transport and metabolism

Coenzyme transport and metabolism

Transcription

Translation, ribosomal structure and biogenesis

Cell wall/membrane/envelope biogenesis

Replication, recombination and repair

Posttranslational modification, protein turnover, chaperones

Cell motility

Secondary metabolites biosynthesis, transport and catabolism

Inorganic ion transport and metabolism

Function unknown

General function prediction only

Intracellular trafficking, secretion, and vesicular transport

Signal transduction mechanisms

Extracellular structures

Defense mechanisms

Nuclear structure

Cytoskeleton

BioCyc Co-regulated genes based on gene expression profiling (Systems Biology, Inferelator Network)

Differentially expressed as result of RNASeq in glycerol environment (Only top 20 genes shown sorted by log fold change with p_adj 0.05).

Conditionally essential as result of TNSeq (Only top 20 genes shown sorted by log fold change with p_adj 0.05).

BioCyc Transcription factor binding based on ChIP-Seq (Systems Biology)

Binds To:
- No bindings to other targets were found.
Bound By:
- No bindings from other targets were found.

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0047c (-) (Direct binding)
- Rv2034 (-) (Direct binding)
- Rv0042c (-) (Upstream of operon)
- Rv0081 (-) (Upstream of operon)
- Rv0602c (tcrA) (Upstream of operon)
- Rv0757 (phoP) (Upstream of operon)
- Rv1049 (-) (Upstream of operon)
- Rv1423 (whiA) (Upstream of operon)
- Rv1985c (-) (Upstream of operon)
- Rv2887 (-) (Upstream of operon)
- Rv3488 (-) (Upstream of operon)
- Rv3597c (lsr2) (Upstream of operon)
- Rv3681c (whiB4) (Upstream of operon)
- Rv3736 (-) (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:
- Rv0818 (-)

Property	Value	Creator	Evidence	PMID	Comment
Citation	Evolution and expansion of the Mycobacterium tuberculosis PE and PPE multigene families and their association with the duplication of the ESAT-6 (esx) gene cluster regions. authors,NC. Gey van Pittius,SL. Sampson,H. Lee,Y. Kim,PD. van Helden,RM. Warren BMC Evol. Biol. 2006	raj252000	RCA	17105670	Co-expression (Functional Linkage)
Interaction	PhysicalInteraction Rv3477	raj252000	RCA		Co-expression (Functional Linkage) authors,NC. Gey van Pittius,SL. Sampson,H. Lee,Y. Kim,PD. van Helden,RM. Warren Evolution and expansion of the Mycobacterium tuberculosis PE and PPE multigene families and their association with the duplication of the ESAT-6 (esx) gene cluster regions. BMC Evol. Biol. 2006
Interaction	PhysicalInteraction Rv3477	raj252000	RCA		Co-expression (Functional Linkage) authors,R. Riley,M. Pellegrini,D. Eisenberg Identifying cognate binding pairs among a large set of paralogs: the case of PE/PPE proteins of Mycobacterium tuberculosis. PLoS Comput. Biol. 2008
Interaction	PhysicalInteraction Rv3477	raj252000	RCA		Co-expression (Functional Linkage) authors,NC. Gey van Pittius,SL. Sampson,H. Lee,Y. Kim,PD. van Helden,RM. Warren Evolution and expansion of the Mycobacterium tuberculosis PE and PPE multigene families and their association with the duplication of the ESAT-6 (esx) gene cluster regions. BMC Evol. Biol. 2006
Citation	Identifying cognate binding pairs among a large set of paralogs: the case of PE/PPE proteins of Mycobacterium tuberculosis. authors,R. Riley,M. Pellegrini,D. Eisenberg PLoS Comput. Biol. 2008	raj252000	RCA	18787688	Co-expression (Functional Linkage)
Interaction	PhysicalInteraction Rv3477	raj252000	RCA		Co-expression (Functional Linkage) authors,R. Riley,M. Pellegrini,D. Eisenberg Identifying cognate binding pairs among a large set of paralogs: the case of PE/PPE proteins of Mycobacterium tuberculosis. PLoS Comput. Biol. 2008
Interaction	RegulatedBy Rv3911	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.. S. Raman, X. Puyang et al. Mycobacterium tuberculosis SigM positively regulates Esx secreted protein and nonribosomal peptide synthetase genes and down regulates virulence-associated surface lipid synthesis. J. Bacteriol. 2006
Interaction	RegulatedBy Rv0348	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.. B. Abomoelak, EA. Hoye et al. mosR, a novel transcriptional regulator of hypoxia and virulence in Mycobacterium tuberculosis. J. Bacteriol. 2009
Interaction	RegulatedBy Rv0757	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.. SB. Walters, E. Dubnau et al. The Mycobacterium tuberculosis PhoPR two-component system regulates genes essential for virulence and complex lipid biosynthesis. Mol. Microbiol. 2006

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