Rv3350c (PPE56)

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 PPE56
- NCBI: PPE family protein PPE56
- updated information (H37Rv4):
  - gene name: PPE56
  - function:
  - reference:
Type: Essential
Start: 3755952
End: 3767102
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	51%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of PE8-PPE15 in complex with EspG5 from M. tuberculosis
6VHR	35%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Structure of PE5-PPE4-EspG3 complex from the type VII (ESX-3) secretion system, space group I422
6UUJ	35%	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 PPE56:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 1.018 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MEFPVLPPEINSVLMYSGAGSSPLLAAAAAWDGLAEELGSAAVSFGQVTSGLTAGVWQGAAAAAMAAAAAPYAGWLGSVAAAAEAVAGQARVVVGVFEAA
LAATVDPALVAANRARLVALAVSNLLGQNTPAIAAAEAEYELMWAADVAAMAGYHSGASAAAAALPAFSPPAQALGGGVGAFLTALFASPAKALSLNAGL
GNVGNYNVGLGNVGVFNLGAGNVGGQNLGFGNAGGTNVGFGNLGNGNVGFGNSGLGAGLAGLGNIGLGNAGSSNYGFANLGVGNIGFGNTGTNNVGVGLT
GNHLTGIGGLNSGTGNIGLFNSGTGNVGFFNSGTGNFGVFNSGNYNTGVGNAGTASTGLFNAGNFNTGVVNVGSYNTGSFNAGDTNTGGFNPGGVNTGWL
NTGNTNTGIANSGNVNTGAFISGNFNNGVLWVGDYQGLFGVSAGSSIPAIPIGLVLNGDIGPITIQPIPILPTIPLSIHQTVNLGPLVVPDIVIPAFGGG
IGIPINIGPLTITPITLFAQQTFVNQLPFPTFSLGKITIPQIQTFDSNGQLVSFIGPIVIDTTIPGPTNPQIDLTIRWDTPPITLFPNGISAPDNPLGLL
VSVSISNPGFTIPGFSVPAQPLPLSIDIEGQIDGFSTPPITIDRIPLTVGGGVTIGPITIQGLHIPAAPGVGNTTTAPSSGFFNSGAGGVSGFGNVGAGS
SGWWNQAPSALLGAGSGVGNVGTLGSGVLNLGSGISGFYNTSVLPFGTPAAVSGIGNLGQQLSGVSAAGTTLRSMLAGNLGLANVGNFNTGFGNVGDVNL
GAANIGGHNLGLGNVGDGNLGLGNIGHGNLGFANLGLTAGAAGVGNVGFGNAGINNYGLANMGVGNIGFANTGTGNIGIGLVGDHRTGIGGLNSGIGNIG
LFNSGTGNVGFFNSGTGNFGIGNSGRFNTGIGNSGTASTGLFNAGSFSTGIANTGDYNTGSFNAGDTNTGGFNPGGINTGWFNTGHANTGLANAGTFGTG
AFMTGDYSNGLLWRGGYEGLVGVRVGPTISQFPVTVHAIGGVGPLHVAPVPVPAVHVEITDATVGLGPFTVPPISIPSLPIASITGSVDLAANTISPIRA
LDPLAGSIGLFLEPFRLSDPFITIDAFQVVAGVLFLENIIVPGLTVSGQILVTPTPIPLTLNLDTTPWTLFPNGFTIPAQTPVTVGMEVANDGFTFFPGG
LTFPRASAGVTGLSVGLDAFTLLPDGFTLDTVPATFDGTILIGDIPIPIIDVPAVPGFGNTTTAPSSGFFNTGGGGGSGFANVGAGTSGWWNQGHDVLAG
AGSGVANAGTLSSGVLNVGSGISGWYNTSTLGAGTPAVVSGIGNLGQQLSGFLANGTVLNRSPIVNIGWADVGAFNTGLGNVGDLNWGAANIGAQNLGLG
NLGSGNVGFGNIGAGNVGFANSGPAVGLAGLGNVGLSNAGSNNWGLANLGVGNIGLANTGTGNIGIGLVGDYQTGIGGLNSGSGNIGLFNSGTGNVGFFN
TGTGNFGLFNSGSFNTGIGNSGTGSTGLFNAGNFNTGIANPGSYNTGSFNVGDTNTGGFNPGDINTGWFNTGIMNTGTRNTGALMSGTDSNGMLWRGDHE
GLFGLSYGITIPQFPIRITTTGGIGPIVIPDTTILPPLHLQITGDADYSFTVPDIPIPAIHIGINGVVTVGFTAPEATLLSALKNNGSFISFGPITLSNI
DIPPMDFTLGLPVLGPITGQLGPIHLEPIVVAGIGVPLEIEPIPLDAISLSESIPIRIPVDIPASVIDGISMSEVVPIDASVDIPAVTITGTTISAIPLG
FDIRTSAGPLNIPIIDIPAAPGFGNSTQMPSSGFFNTGAGGGSGIGNLGAGVSGLLNQAGAGSLVGTLSGLGNAGTLASGVLNSGTAISGLFNVSTLDAT
TPAVISGFSNLGDHMSGVSIDGLIAILTFPPAESVFDQIIDAAIAELQHLDIGNALALGNVGGVNLGLANVGEFNLGAGNVGNINVGAGNLGGSNLGLGN
VGTGNLGFGNIGAGNFGFGNAGLTAGAGGLGNVGLGNAGSGSWGLANVGVGNIGLANTGTGNIGIGLTGDYRTGIGGLNSGTGNLGLFNSGTGNIGFFNT
GTGNFGLFNSGSYSTGVGNAGTASTGLFNAGNFNTGLANAGSYNTGSLNVGSFNTGGVNPGTVNTGWFNTGHTNTGLFNTGNVNTGAFNSGSFNNGALWT
GDYHGLVGFSFSIDIAGSTLLDLNETLNLGPIHIEQIDIPGMSLFDVHEIVEIGPFTIPQVDVPAIPLEIHESIHMDPIVLVPATTIPAQTRTIPLDIPA
SPGSTMTLPLISMRFEGEDWILGSTAAIPNFGDPFPAPTQGITIHTGPGPGTTGELKISIPGFEIPQIATTRFLLDVNISGGLPAFTLFAGGLTIPTNAI
PLTIDASGALDPITIFPGGYTIDPLPLHLALNLTVPDSSIPIIDVPPTPGFGNTTATPSSGFFNSGAGGVSGFGNVGSNLSGWWNQAASALAGSGSGVLN
VGTLGSGVLNVGSGVSGIYNTSVLPLGTPAVLSGLGNVGHQLSGVSAAGTALNQIPILNIGLADVGNFNVGFGNVGDVNLGAANLGAQNLGLGNVGTGNL
GFANVGHGNIGFGNSGLTAGAAGLGNTGFGNAGSANYGFANQGVRNIGLANTGTGNIGIGLVGDNLTGIGGLNSGAGNIGLFNSGTGNIGFFNSGTGNFG
IGNSGSFNTGIGNSGTGSTGLFNAGSFNTGVANAGSYNTGSFNAGDTNTGGFNPGTINTGWFNTGHTNTGIANSGNVGTGAFMSGNFSNGLLWRGDHEGL
FSLFYSLDVPRITIVDAHLDGGFGPVVLPPIPVPAVNAHLTGNVAMGAFTIPQIDIPALTPNITGSAAFRIVVGSVRIPPVSVIVEQIINASVGAEMRID
PFEMWTQGTNGLGITFYSFGSADGSPYATGPLVFGAGTSDGSHLTISASSGAFTTPQLETGPITLGFQVPGSVNAITLFPGGLTFPATSLLNLDVTAGAG
GVDIPAITWPEIAASADGSVYVLASSIPLINIPPTPGIGNSTITPSSGFFNAGAGGGSGFGNFGAGTSGWWNQAHTALAGAGSGFANVGTLHSGVLNLGS
GVSGIYNTSTLGVGTPALVSGLGNVGHQLSGLLSGGSAVNPVTVLNIGLANVGSHNAGFGNVGEVNLGAANLGAHNLGFGNIGAGNLGFGNIGHGNVGVG
NSGLTAGVPGLGNVGLGNAGGNNWGLANVGVGNIGLANTGTGNIGIGLTGDYQTGIGGLNSGAGNLGLFNSGAGNVGFFNTGTGNFGLFNSGSFNTGVGN
SGTGSTGLFNAGSFNTGVANAGSYNTGSFNVGDTNTGGFNPGSINTGWLNAGNANTGVANAGNVNTGAFVTGNFSNGILWRGDYQGLAGFAVGYTLPLFP
AVGADVSGGIGPITVLPPIHIPPIPVGFAAVGGIGPIAIPDISVPSIHLGLDPAVHVGSITVNPITVRTPPVLVSYSQGAVTSTSGPTSEIWVKPSFFPG
IRIAPSSGGGATSTQGAYFVGPISIPSGTVTFPGFTIPLDPIDIGLPVSLTIPGFTIPGGTLIPTLPLGLALSNGIPPVDIPAIVLDRILLDLHADTTIG
PINVPIAGFGGAPGFGNSTTLPSSGFFNTGAGGGSGFSNTGAGMSGLLNAMSDPLLGSASGFANFGTQLSGILNRGAGISGVYNTGALGVVTAAVVSGFG
NVGQQLSGLLFTGVGP

(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	YES
omega peak height (95%CI lower bound)	6.43 (3.77)	2.35 (1.36)
codons under selection	82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135	109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121
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

Rv3350c/PPE56, gene len: 11150 bp, num TA sites: 130

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	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=-0.2)	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=0.176)	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=0.11)	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:
- Rv3286c (sigF)
- Rv3417c (groEL1)

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0023 (-) (Direct binding)
- Rv0302 (-) (Direct binding)
- Rv0339c (-) (Direct binding)
- Rv0653c (-) (Direct binding)
- Rv3133c (devR) (Direct binding)
- Rv3223c (sigH) (Direct binding)

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

Upregulates:
- Does not upregulate other genes.
Upregulated by:
- Rv3286c (sigF)
Downregulates:
- Does not downregulate other genes.
Downregulated by:
- Rv3417c (groEL1)

TB Genome Annotation Portal