Rv3628 (ppa)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: inorganic pyrophosphatase
- REFSEQ: inorganic pyrophosphatase
- PATRIC: Inorganic pyrophosphatase (EC 3.6.1.1)
- TUBERCULIST: Inorganic pyrophosphatase Ppa (pyrophosphate phospho-hydrolase) (PPASE) (inorganic diphosphatase) (diphosphate phospho-hydrolase)
- NCBI: Inorganic pyrophosphatase Ppa (pyrophosphate phospho-hydrolase) (PPASE) (inorganic diphosphatase) (diphosphate phospho-hydrolase)
- updated information (H37Rv4):
  - gene name: ppa
  - function:
  - reference:
Type: Not Target
Start: 4067423
End: 4067911
Operon:

Trans-membrane region:
Role: I.A.4 - Phosphorous compounds
GO terms:
- GO:0046872 - metal ion binding (Uniprot)
- GO:0044228 - host cell surface (Uniprot)
- GO:0016787 - hydrolase activity (Uniprot)
- GO:0006796 - phosphate-containing compound metabolic process (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0005829 - cytosol (Uniprot)
- GO:0005737 - cytoplasm (Uniprot)
- GO:0005576 - extracellular region (Uniprot)
- GO:0004427 - inorganic diphosphatase activity (Uniprot)
- GO:0000287 - magnesium ion binding (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
- PPI[c] -> H[c] + 2 PI[c]
- PPI[c] -> 2 PI[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: 1wcf, 2uxs, 1sxv
Search for Homologs in PDB

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

PDB	aa ident	species	PDB title
2UXS	100%	MYCOBACTERIUM TUBERCULOSIS	2.7A crystal structure of inorganic pyrophosphatase (Rv3628) from Mycobacterium tuberculosis at pH 7.5
5KDF	99%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Inorganic pyrophosphatase from Mycobacterium tuberculosis in complex with inhibitor 6 and inorganic pyrophosphate
5KDE	99%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Inorganic pyrophosphatase from Mycobacterium tuberculosis in complex with inhibitor 1 and inorganic pyrophosphate
4Z74	99%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of inorganic pyrophosphatase from Mycobacterium tuberculosis in complex with inorganic pyrophosphate
4Z73	99%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of inorganic pyrophosphatase from Mycobacterium tuberculosis in complex with a phosphate ion and an inorganic pyrophosphate
4Z72	99%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of inorganic pyrophosphatase from Mycobacterium tuberculosis in complex with two phosphate ions
4Z71	99%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of inorganic pyrophosphatase from Mycobacterium tuberculosis in complex with Mg ions
4Z70	99%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of inorganic pyrophosphatase from Mycobacterium tuberculosis in complex with Ca ions
1WCF	99%	MYCOBACTERIUM TUBERCULOSIS	1.54 A CRYSTAL STRUCTURE OF RV3628, MYCOBACTERIUM TUBERCULOSIS INORGANIC PYROPHOSPHATASE (PPASE) AT PH7.0
1SXV	99%	Mycobacterium tuberculosis	1.3A Crystal structure of rv3628, Mycobacterium tuberculosis inorganic pyrophosphatase (PPase) at pH5.0

Links to additional information on ppa:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -6.243 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

VQFDVTIEIPKGQRNKYEVDHETGRVRLDRYLYTPMAYPTDYGFIEDTLGDDGDPLDALVLLPQPVFPGVLVAARPVGMFRMVDEHGGDDKVLCVPAGDP
RWDHVQDIGDVPAFELDAIKHFFVHYKDLEPGKFVKAADWVDRAEAEAEVQRSVERFKAGTH

(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
Essential	Sodium Oleate	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.993950; 10 non-insertions in a row out of 10 sites
Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.998600; 9 non-insertions in a row out of 10 sites
Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.998800; 9 non-insertions in a row out of 10 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 10 sites
Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.997900; 9 non-insertions in a row out of 10 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

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

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

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

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:

Property	Value	Creator	Evidence	PMID	Comment
Citation	An unusual, His-dependent family I pyrophosphatase from Mycobacterium tuberculosis. authors,M. Tammenkoski,S. Benini,NN. Magretova,AA. Baykov,R. Lahti J. Biol. Chem. 2005	jjmcfadden		16239227	Inferred from direct assay
Term	EC:3.6.1.1 Inorganic diphosphatase. - NR	jjmcfadden	NR		Inferred from direct assay authors,M. Tammenkoski,S. Benini,NN. Magretova,AA. Baykov,R. Lahti An unusual, His-dependent family I pyrophosphatase from Mycobacterium tuberculosis. J. Biol. Chem. 2005

TB Genome Annotation Portal