Rv0946c (pgi)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: glucose-6-phosphate isomerase
- REFSEQ: glucose-6-phosphate isomerase
- PATRIC: Glucose-6-phosphate isomerase (EC 5.3.1.9)
- TUBERCULIST: Probable glucose-6-phosphate isomerase Pgi (GPI) (phosphoglucose isomerase) (phosphohexose isomerase) (phi)
- NCBI: Probable glucose-6-phosphate isomerase Pgi (GPI) (phosphoglucose isomerase) (phosphohexose isomerase) (phi)
- updated information (H37Rv4):
  - gene name: pgi
  - function:
  - reference:
Type: Not Target
Start: 1055024
End: 1056685
Operon:

Trans-membrane region:
Role: I.B.1 - Glycolysis
GO terms:
- GO:0040007 - growth (Uniprot)
- GO:0016853 - isomerase activity (Uniprot)
- GO:0006096 - glycolytic process (Uniprot)
- GO:0006094 - gluconeogenesis (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0005737 - cytoplasm (Uniprot)
- GO:0004347 - glucose-6-phosphate isomerase activity (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: 2wu8
Search for Homologs in PDB

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

PDB	aa ident	species	PDB title
2WU8	99%	MYCOBACTERIUM TUBERCULOSIS	Structural studies of phosphoglucose isomerase from Mycobacterium tuberculosis H37Rv
4EM6	53%	Brucella melitensis bv. 1	The structure of Glucose-6-phosphate isomerase (GPI) from Brucella melitensis
3HJB	51%	Vibrio cholerae	1.5 Angstrom Crystal Structure of Glucose-6-phosphate Isomerase from Vibrio cholerae.
3NBU	51%	Escherichia coli	Crystal structure of pGI glucosephosphate isomerase
4WMJ	49%	Colias eurytheme	Colias eurytheme Phosphoglucose isomerase. Homodimer from 4-5(18) genotype.
1XTB	49%	Oryctolagus cuniculus	Crystal Structure of Rabbit Phosphoglucose Isomerase Complexed with Sorbitol-6-Phosphate
1N8T	49%	Oryctolagus cuniculus	The crystal structure of phosphoglucose isomerase from rabbit muscle
1KOJ	49%	Oryctolagus cuniculus	Crystal structure of rabbit phosphoglucose isomerase complexed with 5-phospho-D-arabinonohydroxamic acid
1HOX	49%	Oryctolagus cuniculus	CRYSTAL STRUCTURE OF RABBIT PHOSPHOGLUCOSE ISOMERASE COMPLEXED WITH FRUCTOSE-6-PHOSPHATE
1HM5	49%	Oryctolagus cuniculus	CRYSTAL STRUCTURE ANALYSIS OF THE RABBIT D-GLUCOSE 6-PHOSPHATE ISOMERASE (NO LIGAND BOUND)

Links to additional information on pgi:
- TBDB (updated)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MTSAPIPDITATPAWDALRRHHDQIGNTHLRQFFADDPGRGRELTVSVGDLYIDYSKHRVTRETLALLIDLARTAHLEERRDQMFAGVHINTSEDRAVLH
TALRLPRDAELVVDGQDVVTDVHAVLDAMGAFTDRLRSGEWTGATGKRISTVVNIGIGGSDLGPVMVYQALRHYADAGISARFVSNVDPADLIATLADLD
PATTLFIVASKTFSTLETLTNATAARRWLTDALGDAAVSRHFVAVSTNKRLVDDFGINTDNMFGFWDWVGGRYSVDSAIGLSLMTVIGRDAFADFLAGFH
IIDRHFATAPLESNAPVLLGLIGLWYSNFFGAQSRTVLPYSNDLSRFPAYLQQLTMESNGKSTRADGSPVSADTGEIFWGEPGTNGQHAFYQLLHQGTRL
VPADFIGFAQPLDDLPTAEGTGSMHDLLMSNFFAQTQVLAFGKTAEEIAADGTPAHVVAHKVMPGNRPSTSILASRLTPSVLGQLIALYEHQVFTEGVVW
GIDSFDQWGVELGKTQAKALLPVITGAGSPPPQSDSSTDGLVRRYRTERGRAG

(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?	NO	NO
omega peak height (95%CI lower bound)	1.86 (0.5)	1.33 (0.49)
codons under selection
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

Rv0946c/pgi, gene len: 1661 bp, num TA sites: 20

condition	dataset	call	medium	method	notes
in-vitro	DeJesus 2017 mBio	growth defect	7H9	HMM	fully saturated, 14 TnSeq libraries combined
in-vitro	Sassetti 2003 Mol Micro	essential	7H9	TRASH	essential if hybridization ratio<0.2
in-vivo (mice)	Sassetti 2003 PNAS	no data	BL6 mice	TRASH	essential if hybridization ratio<0.4, min over 4 timepoints (1-8 weeks)
in-vitro (glycerol)	Griffin 2011 PPath	essential	M9 minimal+glycerol	Gumbel	2 replicates; Padj<0.05
in-vitro (cholesterol)	Griffin 2011 PPath	essential	M9 minimal+cholesterol	Gumbel	3 replicates; Padj<0.05
differentially essential in cholesterol	Griffin 2011 PPath	NO (LFC=0.0)	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	essential	7H9	HMM	6 replicates (raw data in Subramaniam 2017, PMID 31752678)
in-vivo (mice)	Smith 2022 eLife	essential	BL6 mice	HMM	6 replicates (raw data in Subramaniam 2017, PMID 31752678)
differentially essential in mice	Smith 2022 eLife	NO (LFC=0.0)	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	growth defect	minimal medium	HMM
in-vitro (YM rich medium)	Minato 2019 mSys	essential	YM rich medium	HMM	7H9 supplemented with ~20 metabolites (amino acids, cofactors)
differentially essential in YM rich medium	Minato 2019 mSys	NO (LFC=-0.81)	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:
- Rv0576 (-)

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:
- Rv0576 (-)

Property	Value	Creator	Evidence	PMID	Comment
Citation	Biochemical characterization of recombinant phosphoglucose isomerase of Mycobacterium tuberculosis. D. Mathur, Z. Ahsan et al. Biochem. Biophys. Res. Commun. 2005	njamshidi	IDA	16212940	see PMID: 16212940
Term	EC:5.3.1.9 Glucose-6-phosphate isomerase. - IDA	njamshidi	IDA	16212940	see PMID: 16212940 D. Mathur, Z. Ahsan et al. Biochemical characterization of recombinant phosphoglucose isomerase of Mycobacterium tuberculosis. Biochem. Biophys. Res. Commun. 2005
Term	TBRXN:PGI glucose-6-phosphate isomerase - IDA	njamshidi	IDA	16212940	see PMID: 16212940 D. Mathur, Z. Ahsan et al. Biochemical characterization of recombinant phosphoglucose isomerase of Mycobacterium tuberculosis. Biochem. Biophys. Res. Commun. 2005
Citation	Biochemical characterization of recombinant phosphoglucose isomerase of Mycobacterium tuberculosis. D. Mathur, Z. Ahsan et al. Biochem. Biophys. Res. Commun. 2005	njamshidi	ISS	16212940	see PMID: 16212940
Term	EC:5.3.1.9 Glucose-6-phosphate isomerase. - ISS	njamshidi	ISS	16212940	see PMID: 16212940 D. Mathur, Z. Ahsan et al. Biochemical characterization of recombinant phosphoglucose isomerase of Mycobacterium tuberculosis. Biochem. Biophys. Res. Commun. 2005
Term	TBRXN:PGI glucose-6-phosphate isomerase - ISS	njamshidi	ISS	16212940	see PMID: 16212940 D. Mathur, Z. Ahsan et al. Biochemical characterization of recombinant phosphoglucose isomerase of Mycobacterium tuberculosis. Biochem. Biophys. Res. Commun. 2005
Citation	Central carbon metabolism in Mycobacterium tuberculosis: an unexpected frontier. authors,KY. Rhee,LP. de Carvalho,R. Bryk,S. Ehrt,J. Marrero,SW. Park,D. Schnappinger,A. Venugopal,C. Nathan Trends Microbiol. 2011	extern:JZUCKER		21561773	Traceable author statement to experimental support
Term	EC:5.3.1.9 Glucose-6-phosphate isomerase. - NR	extern:JZUCKER	NR		Traceable author statement to experimental support authors,KY. Rhee,LP. de Carvalho,R. Bryk,S. Ehrt,J. Marrero,SW. Park,D. Schnappinger,A. Venugopal,C. Nathan Central carbon metabolism in Mycobacterium tuberculosis: an unexpected frontier. Trends Microbiol. 2011
Citation	Structural studies of phosphoglucose isomerase from Mycobacterium tuberculosis H37Rv. K. Anand, D. Mathur et al. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 2010	extern:JZUCKER		20445242	Inferred from mutant phenotype
Term	EC:5.3.1.9 Glucose-6-phosphate isomerase. - NR	extern:JZUCKER	NR		Inferred from mutant phenotype K. Anand, D. Mathur et al. Structural studies of phosphoglucose isomerase from Mycobacterium tuberculosis H37Rv. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 2010

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