Rv2794c (pptT)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: hypothetical protein
- REFSEQ: hypothetical protein
- PATRIC: 4'-phosphopantetheinyl transferase EntD (EC 2.7.8.-)
- TUBERCULIST: Phosphopantetheinyl transferase PptT (CoA:APO-[ACP]pantetheinephosphotransferase) (CoA:APO-[acyl-carrier protein]pantetheinephosphotransferase)
- NCBI: Phosphopantetheinyl transferase PptT (CoA:APO-[ACP]pantetheinephosphotransferase) (CoA:APO-[acyl-carrier protein]pantetheinephosphotransferase)
- updated information (H37Rv4):
  - gene name: pptT
  - function: phosphopantetheine transferase
  - reference: Balligner (2019) PMID 30705156
Type: Essential
Start: 3103257
End: 3103940
Operon:

Trans-membrane region:
Role: V - Conserved hypotheticals
GO terms:
- GO:0046872 - metal ion binding (Uniprot)
- GO:0019540 - siderophore biosynthetic process from catechol (Uniprot)
- GO:0016780 - phosphotransferase activity, for other substituted phosphate groups (Uniprot)
- GO:0016740 - transferase activity (Uniprot)
- GO:0009366 - enterobactin synthetase complex (Uniprot)
- GO:0009239 - enterobactin biosynthetic process (Uniprot)
- GO:0008897 - holo-[acyl-carrier-protein] synthase activity (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0005515 - protein binding (Uniprot)
- GO:0000287 - magnesium ion binding (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
- COA[c] -> ACP[c]
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
6CT5	100%	Mycobacterium tuberculosis	PptT PAP(CoA) 8918 complex
4U89	100%	Mycobacterium tuberculosis	4'-phosphopantetheinyl transferase PptT from Mycobacterium tuberculosis
4QVH	100%	Escherichia coli	Crystal structure of the essential Mycobacterium tuberculosis phosphopantetheinyl transferase PptT, solved as a fusion protein with maltose binding protein
4QJK	100%	Mycobacterium tuberculosis	Crystal structure of M. tuberculosis phosphopantetheinyl transferase PptT
4QJL	83%	Mycobacterium ulcerans	Crystal structure of M. ulcerans phosphopantetheinyl transferase MuPPT
6RCX	67%	Mycobacteroides abscessus ATCC 19977	Mycobacterial 4'-phosphopantetheinyl transferase PptAb in complex with the ACP domain of PpsC.
6QYG	67%	Mycobacterium abscessus (strain ATCC 19977 / DSM 44196 / CIP 104536 / JCM 13569 / NCTC 13031 / TMC 1543)	4'-phosphopantetheinyl transferase PptAb from Mycobacterium abscessus at pH 8.5 with Mg2+ and CoA.
6QYF	67%	Mycobacteroides abscessus ATCC 19977	4'-phosphopantetheinyl transferase PptAb from Mycobacterium abscessus at pH 4.6 with Mg2+ and CoA.
6QXR	67%	Mycobacterium abscessus (strain ATCC 19977 / DSM 44196 / CIP 104536 / JCM 13569 / NCTC 13031 / TMC 1543)	4'-phosphopantetheinyl transferase PptAb from Mycobacterium abscessus at pH 8.5 with Mn2+ and CoA.
6QXQ	67%	Mycobacteroides abscessus ATCC 19977	4'-phosphopantetheinyl transferase PptAb from Mycobacterium abscessus at pH 7 with Mn2+ and CoA.

Links to additional information on pptT:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -4.522 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MTVGTLVASVLPATVFEDLAYAELYSDPPGLTPLPEEAPLIARSVAKRRNEFITVRHCARIALDQLGVPPAPILKGDKGEPCWPDGMVGSLTHCAGYRGA
VVGRRDAVRSVGIDAEPHDVLPNGVLDAISLPAERADMPRTMPAALHWDRILFCAKEATYKAWFPLTKRWLGFEDAHITFETDSTGWTGRFVSRILIDGS
TLSGPPLTTLRGRWSVERGLVLTAIVL

(Nucleotide sequence available on KEGG)

Additional Information

PptT - phosphopantetheine transferase
Ballinger et al (2019). Opposing reactions in coenzyme A metabolism sensitize Mycobacterium tuberculosis to enzyme inhibition. Science. https://pubmed.ncbi.nlm.nih.gov/30705156/

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
Uncertain	Sodium Oleate	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.982650; 9 non-insertions in a row out of 9 sites
Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.997650; 9 non-insertions in a row out of 9 sites
Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.998800; 9 non-insertions in a row out of 9 sites
Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.997600; 9 non-insertions in a row out of 9 sites
Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.996500; 9 non-insertions in a row out of 9 sites
No-Data	7H10-glycerol	H37RvMA	TraSH	Sassetti et al. (2003a)
Too-Short	C57BL/6J mice (8 weeks)	H37RvMA	TraSH	Sassetti et al. (2003b)	Hybridization Ratio: -1
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:
- Rv0767c (-) (Upstream of operon)
- Rv3133c (devR) (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:
- Not downregulated by other genes.

Property	Value	Creator	Evidence	PMID	Comment
Citation	The nonredundant roles of two 4'-phosphopantetheinyl transferases in vital processes of Mycobacteria. C. Chalut, L. Botella et al. Proc. Natl. Acad. Sci. U.S.A. 2006	shahanup86	IDA	16709676	Affinity purification (Physical interaction)
Interaction	Activates Rv3800c	shahanup86	IDA		Affinity purification (Physical interaction) C. Chalut, L. Botella et al. The nonredundant roles of two 4'-phosphopantetheinyl transferases in vital processes of Mycobacteria. Proc. Natl. Acad. Sci. U.S.A. 2006
Interaction	RegulatedBy Rv2359	yamir.moreno	ISO		E.coli orthology based inference. Orthologous pair regulator-target found in E.coli. G. Balzsi, AP. Heath et al. The temporal response of the Mycobacterium tuberculosis gene regulatory network during growth arrest. Mol. Syst. Biol. 2008
Interaction	RegulatedBy Rv2359	yamir.moreno	ISO		E.coli orthology based inference. Orthologous pair regulator-target found in E.coli. authors,M. Madan Babu,SA. Teichmann,L. Aravind Evolutionary dynamics of prokaryotic transcriptional regulatory networks. J. Mol. Biol. 2006
Symbol	pptT	mjackson	ISS		Claisen-type condensation
Name	PHOSPHOPANTETHEINYL TRANSFERASE; CoA + APO-[ACYL-CARRIER PROTEIN] = ADENOSINE 3',5'-BISPHOSPHATE + HOLO-[ACYL-CARRIER PROTEIN]	mjackson	ISS		Claisen-type condensation
Symbol	pptT	mjackson	IMP		Claisen-type condensation
Name	PHOSPHOPANTETHEINYL TRANSFERASE; CoA + APO-[ACYL-CARRIER PROTEIN] = ADENOSINE 3',5'-BISPHOSPHATE + HOLO-[ACYL-CARRIER PROTEIN]	mjackson	IMP		Claisen-type condensation

TB Genome Annotation Portal