Rv3347c (PPE55)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: hypothetical protein
- REFSEQ: PPE family protein
- PATRIC: PPE family protein
- TUBERCULIST: PPE family protein PPE55
- NCBI: PPE family protein PPE55
- updated information (H37Rv4):
  - gene name: PPE55
  - function:
  - reference:
Type: Not Target
Start: 3743711
End: 3753184
Operon:

Trans-membrane region:
Role: IV.C.2 - PPE family
GO terms:
- GO:0052556 - positive regulation by symbiont of 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
5XFS	51%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of PE8-PPE15 in complex with EspG5 from M. tuberculosis
6VHR	36%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Structure of PE5-PPE4-EspG3 complex from the type VII (ESX-3) secretion system, space group I422
6UUJ	36%	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 PPE55:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 1.211 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

LNFPVLPPEINSVLMYSGAGSSPLLAAAAAWDGLAEELGSAAVSFGQVTSGLTAGVWQGAAAAAMAAAAAPYAGWLGSVAAQAVAVAGQARAAVAAFEAA
LAATVDPAAVAVNRMAMRALAMSNLLGQNAAAIAAVEAEYELMWAADVAAMAGYHSGASAAAAALPAFSPPAQALGGGVGAFLNALFAGPAKMLRLNAGL
GNVGNYNVGLGNVGIFNLGAANVGAQNLGAANAGSGNFGFGNIGNANFGFGNSGLGLPPGMGNIGLGNAGSSNYGLANLGVGNIGFANTGSNNIGIGLTG
DNLTGIGGLNSGTGNLGLFNSGTGNIGFFNSGTGNFGVFNSGSYNTGVGNAGTASTGLFNVGGFNTGVANVGSYNTGSFNAGNTNTGGFNPGNVNTGWLN
TGNTNTGIANSGNVNTGAFISGNFSNGVLWRGDYEGLWGLSGGSTIPAIPIGLELNGGVGPITVLPIQILPTIPLNIHQTFSLGPLVVPDIVIPAFGGGT
AIPISVGPITISPITLFPAQNFNTTFPVGPFFGLGVVNISGIEIKDLAGNVTLQLGNLNIDTRINQSFPVTVNWSTPAVTIFPNGISIPNNPLALLASAS
IGTLGFTIPGFTIPAAPLPLTIDIDGQIDGFSTPPITIDRIPLNLGASVTVGPILINGVNIPATPGFGNTTTAPSSGFFNSGDGGVSGFGNFGAGSSGWW
NQAQTEVAGAGSGFANFGSLGSGVLNFGSGVSGLYNTGGLPPGTPAVVSGIGNVGEQLSGLSSAGTALNQSLIINLGLADVGSVNVGFGNVGDFNLGAAN
IGDLNVGLGNVGGGNVGFGNIGDANFGLGNAGLAAGLAGVGNIGLGNAGSGNVGFGNMGVGNIGFGNTGTNNLGIGLTGDNQTGIGGLNSGAGNIGLFNS
GTGNVGLFNSGTGNFGLFNSGSFNTGIGNGGTGSTGLFNAGNFNTGVANPGSYNTGSFNVGDTNTGGFNPGSINTGWFNTGNANTGVANSGNVDTGALMS
GNFSNGILWRGNFEGLFGLNVGITIPEFPIHWTSTGGIGPIIIPDTTILPPIHLGLTGQANYGFAVPDIPIPAIHIDFDGAADAGFTAPATTLLSALGIT
GQFRFGPITVSNVQLNPFNVNLKLQFLHDAFPNEFPDPTISVQIQVAIPLTSATLGGLALPLQQTIDAIELPAISFSQSIPIDIPPIDIPASTINGISMS
EVVPIDVSVDIPAVTITGTRIDPIPLNFDVLSSAGPINISIIDIPALPGFGNSTELPSSGFFNTGGGGGSGIANFGAGVSGLLNQASSPMVGTLSGLGNA
GSLASGVLNSGVDISGMFNVSTLGSAPAVISGFGNLGNHVSGVSIDGLLAMLTSGGSGGSGQPSIIDAAIAELRHLNPLNIVNLGNVGSYNLGFANVGDV
NLGAGNLGNLNLGGGNLGGQNLGLGNLGDGNVGFGNLGHGNVGFGNSGLGALPGIGNIGLGNAGSNNVGFGNMGLGNIGFGNTGTNNLGIGLTGDNQTGF
GGLNSGAGNLGLFNSGTGNIGFFNTGTGNWGLFNSGSYNTGIGNSGTGSTGLFNAGSFNTGLANAGSYNTGSLNAGNTNTGGFNPGNVNTGWFNAGHTNT
GGFNTGNVNTGAFNSGSFNNGALWTGDHHGLVGFSYSIEITGSTLVDINETLNLGPVHIDQIDIPGMSLFDIHELVNIGPFRIEPIDVPAVVLDIHETMV
IPPIVFLPSMTIGGQTYTIPLDTPPAPAPPPFRLPLLFVNALGDNWIVGASNSTGMSGGFVTAPTQGILIHTGPSSATTGSLALTLPTVTIPTITTSPIP
LKIDVSGGLPAFTLFPGGLNIPQNAIPLTIDASGVLDPITIFPGGFTIDPLPLSLALNISVPDSSVPIIIVPPTPGFGNATATPSSGFFNSGAGGVSGFG
NFGAGSSGWWNQAHAALAGAGSGVLNVGTLNSGVLNVGSGISGLYNTAIVGLGTPALVSGAGNVGQQLSGVLAAGTALTQSPIINLGLADVGNYNLGLGN
VGDFNLGAANLGDLNLGLGNIGNANVGFGNIGHGNVGFGNSGLGAALGIGNIGLGNAGSTNVGLANMGVGNIGFANTGTNNLGIGLTGDNQTGIGGLNSG
AGNIGLFNSGTGNIGFFNSGTGNWGLFNSGSFNTGIGNSGTGSTGLFNAGGFTTGLANAGSYNTGSFNVGDTNTGGFNPGSINTGWFNTGNANTGIANSG
NVDTGALMSGNFSNGILWRGNYEGLFSYSYSLDVPRITILDAHFTGAFGPVVVPPIPVLAINAHLTGNAAMGAFTIPQIDIPALNPNVTGSVGFGPIAVP
SVTIPALTAARAVLDMAASVGATSEIEPFIVWTSSGAIGPTWYSVGRIYNAGDLFVGGNIISGIPTLSTTGPVHAVFNAASQAFNTPALNIHQIPLGFQV
PGSIDAITLFPGGLTFPANSLLNLDVFVGTPGATIPAITFPEIPANADGELYVIAGDIPLINIPPTPGIGNTTTVPSSGFFNTGAGGGSGFGNFGANMSG
WWNQAHTALAGAGSGIANVGTLHSGVLNLGSGLSGIYNTSTLPLGTPALVSGLGNVGDHLSGLLASNVGQNPITIVNIGLANVGNGNVGLGNIGNLNLGA
ANIGDVNLGFGNIGDVNLGFGNIGGGNVGFGNIGDANFGFGNSGLAAGLAGMGNIGLGNAGSGNVGWANMGLGNIGFGNTGTNNLGIGLTGDNQSGIGGL
NSGTGNIGLFNSGTGNIGFFNSGTANFGLFNSGSYNTGIGNSGVASTGLVNAGGFNTGVANAGSYNTGSFNAGDTNTGGFNPGSTNTGWFNTGNANTGVA
NAGNVNTGALITGNFSNGILWRGNYEGLAGFSFGYPIPLFPAVGADVTGDIGPATIIPPIHIPSIPLGFAAIGHIGPISIPNIAIPSIHLGIDPTFDVGP
ITVDPITLTIPGLSLDAAVSEIRMTSGSSSGFKVRPSFSFFAVGPDGMPGGEVSILQPFTVAPINLNPTTLHFPGFTIPTGPIHIGLPLSLTIPGFTIPG
GTLIPQLPLGLGLSGGTPPFDLPTVVIDRIPVELHASTTIGPVSLPIFGFGGAPGFGNDTTAPSSGFFNTGGGGGSGFSNSGSGMSGVLNAISDPLLGSA
SGFANFGTQLSGILNRGAGISGVYNTGTLGLVTSAFVSGFMNVGQQLSGLLFAGTGP

(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?	YES	NO
omega peak height (95%CI lower bound)	4.05 (2.28)	1.86 (0.95)
codons under selection	84, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 2457, 2458, 2459, 2460, 2461, 2462, 2463, 2464, 2465, 2472, 2473, 2474, 2744, 2745, 2746, 2747, 2748, 2749, 2750, 2751, 2752, 2753, 2756, 2757, 2758, 2764, 2765
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

Rv3347c/PPE55, gene len: 9473 bp, num TA sites: 121

condition	dataset	call	medium	method	notes
in-vitro	DeJesus 2017 mBio	growth advantage	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	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=0.09)	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=0.335)	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	growth advantage	YM rich medium	HMM	7H9 supplemented with ~20 metabolites (amino acids, cofactors)
differentially essential in YM rich medium	Minato 2019 mSys	NO (LFC=0.38)	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

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:
- Rv0602c (tcrA) (Direct binding)
- Rv1994c (cmtR) (Direct binding)
- Rv3249c (-) (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:
- Not downregulated by other genes.

Property	Value	Creator	Evidence	PMID	Comment
Interaction	PhysicalInteraction Rv3345c	vashishtrv	IEP		Co-expression (Functional linkage) KK. Singh, Y. Dong et al. Immunogenicity of the Mycobacterium tuberculosis PPE55 (Rv3347c) protein during incipient and clinical tuberculosis. Infect. Immun. 2005
Interaction	PhysicalInteraction Rv3345c	vashishtrv	IEP		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 Rv3345c	vashishtrv	IEP		Co-expression (Functional linkage) AJ. Vallecillo & C. Espitia Expression of Mycobacterium tuberculosis pe_pgrs33 is repressed during stationary phase and stress conditions, and its transcription is mediated by sigma factor A. Microb. Pathog. 2008
Interaction	PhysicalInteraction Rv3345c	vashishtrv	IEP		Co-expression (Functional linkage) V. Dheenadhayalan, G. Delogu et al. Variable expression patterns of Mycobacterium tuberculosis PE_PGRS genes: evidence that PE_PGRS16 and PE_PGRS26 are inversely regulated in vivo. J. Bacteriol. 2006
Citation	Immunogenicity of the Mycobacterium tuberculosis PPE55 (Rv3347c) protein during incipient and clinical tuberculosis. KK. Singh, Y. Dong et al. Infect. Immun. 2005	shahanup86	IEP	16041015	Co-expression (Functional linkage)
Interaction	PhysicalInteraction Rv3345c	shahanup86	IEP		Co-expression (Functional linkage) KK. Singh, Y. Dong et al. Immunogenicity of the Mycobacterium tuberculosis PPE55 (Rv3347c) protein during incipient and clinical tuberculosis. Infect. Immun. 2005
Citation	Immunogenicity of the Mycobacterium tuberculosis PPE55 (Rv3347c) protein during incipient and clinical tuberculosis. KK. Singh, Y. Dong et al. Infect. Immun. 2005	vashishtrv	IEP	16041015	Co-expression (Functional linkage)
Interaction	PhysicalInteraction Rv3345c	shahanup86	IEP		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 Rv3345c	shahanup86	IEP		Co-expression (Functional linkage) AJ. Vallecillo & C. Espitia Expression of Mycobacterium tuberculosis pe_pgrs33 is repressed during stationary phase and stress conditions, and its transcription is mediated by sigma factor A. Microb. Pathog. 2008
Interaction	PhysicalInteraction Rv3345c	shahanup86	IEP		Co-expression (Functional linkage) V. Dheenadhayalan, G. Delogu et al. Variable expression patterns of Mycobacterium tuberculosis PE_PGRS genes: evidence that PE_PGRS16 and PE_PGRS26 are inversely regulated in vivo. J. Bacteriol. 2006

TB Genome Annotation Portal