Rv1208 (gpgS)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: glucosyl-3-phosphoglycerate synthase
- REFSEQ: putative glucosyl-3-phosphoglycerate synthase
- PATRIC: Glycosyltransferases involved in cell wall biogenesis
- TUBERCULIST: Probable glucosyl-3-phosphoglycerate synthase GpgS
- NCBI: Probable glucosyl-3-phosphoglycerate synthase GpgS
- updated information (H37Rv4):
  - gene name: gpgS
  - function:
  - reference:
Type: Essential
Start: 1352144
End: 1353118
Operon:

Trans-membrane region:
Role: V - Conserved hypotheticals
GO terms:
- GO:0046872 - metal ion binding (Uniprot)
- GO:0042803 - protein homodimerization activity (Uniprot)
- GO:0040007 - growth (Uniprot)
- GO:0016758 - transferase activity, transferring hexosyl groups (Uniprot)
- GO:0016757 - transferase activity, transferring glycosyl groups (Uniprot)
- GO:0016740 - transferase activity (Uniprot)
- GO:0006011 - UDP-glucose metabolic process (Uniprot)
- GO:0000287 - magnesium ion binding (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: 4de7, 3e25, 4ddz, 4dec, 3e26
Search for Homologs in PDB

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

PDB	aa ident	species	PDB title
5JUD	100%	Mycobacterium bovis AF2122/97	Crystal structure of glucosyl-3-phosphoglycerate synthase from Mycobacterium tuberculosis in complex with uridine-diphosphate (UDP) - GpgS*UDP
5JUC	100%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of glucosyl-3-phosphoglycerate synthase from Mycobacterium tuberculosis in complex with Mn2+, uridine-diphosphate (UDP) and glucosyl-3-phosphoglycerate (GPG) - GpgSGPGUDP*Mn2+_2
5JT0	100%	Mycobacterium tuberculosis	Crystal structure of glucosyl-3-phosphoglycerate synthase from Mycobacterium tuberculosis in complex with Mn2+, uridine-diphosphate (UDP) and glucosyl-3-phosphoglycerate (GPG) - GpgSGPGUDP*Mn2+
5JSX	100%	Mycobacterium tuberculosis H37Ra	Crystal structure of glucosyl-3-phosphoglycerate synthase from Mycobacterium tuberculosis in complex with Mn2+ and uridine-diphosphate-glucose (UDP-Glc)
5JQX	100%	Mycobacterium tuberculosis H37Rv	Crystal structure of glucosyl-3-phosphoglycerate synthase from Mycobacterium tuberculosis in complex with phosphoglyceric acid (PGA) - GpgS*PGA
5JQQ	100%	Mycobacterium tuberculosis H37Ra	Crystal structure of glucosyl-3-phosphoglycerate synthase from Mycobacterium tuberculosis - apo form
4Y9X	100%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of glucosyl-3-phosphoglycerate synthase from Mycobacterium tuberculosis in complex with Mn2+, uridine-diphosphate-glucose (UDP-Glc) and phosphoglyceric acid (PGA) - GpgS Mn2+ UDP-Glc PGA-3
4Y7G	100%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of glucosyl-3-phosphoglycerate synthase from Mycobacterium tuberculosis in complex with Mn2+, uridine-diphosphate-glucose (UDP-Glc) and glycerol 3-phosphate (G3P) - GpgS Mn2+ UDP-Glc G3P
4Y7F	100%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of glucosyl-3-phosphoglycerate synthase from Mycobacterium tuberculosis in complex with Mn2+, uridine-diphosphate-glucose (UDP-Glc) and 3-(phosphonooxy)propanoic acid (PPA) - GpgS Mn2+ UDP-Glc PPA
4Y6U	100%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Mycobacterial protein

Links to additional information on gpgS:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -4.054 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MTASELVAGDLAGGRAPGALPLDTTWHRPGWTIGELEAAKAGRTISVVLPALNEEATIESVIDSISPLVDGLVDELIVLDSGSTDDTEIRAIASGARVVS
REQALPEVPVRPGKGEALWRSLAATSGDIVVFIDSDLINPHPLFVPWLVGPLLTGEGIQLVKSFYRRPLQVSDVTSGVCATGGGRVTELVARPLLAALRP
ELGCVLQPLSGEYAASRELLTSLPFAPGYGVEIGLLIDTFDRLGLDAIAQVNLGVRAHRNRPLDELGAMSRQVIATLLSRCGIPDSGVGLTQFLPGGPDD
SDYTRHTWPVSLVDRPPMKVMRPR

(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)	2.07 (0.29)	1.56 (0.54)
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

Rv1208/gpgS, gene len: 974 bp, num TA sites: 14

condition	dataset	call	medium	method	notes
in-vitro	DeJesus 2017 mBio	essential	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	non-essential	minimal medium	HMM
in-vitro (YM rich medium)	Minato 2019 mSys	growth defect	YM rich medium	HMM	7H9 supplemented with ~20 metabolites (amino acids, vitamins)
differentially essential in YM rich medium	Minato 2019 mSys	YES (LFC=-4.55)	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:
- Rv1353c (-)

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv1049 (-) (Direct binding)
- Rv1353c (-) (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:
- Rv1353c (-)

Property	Value	Creator	Evidence	PMID	Comment
Symbol	gpgS	mjackson	IDA		Other (lipo)polysaccharides [Methylglucose lipolysaccharides, glycogen and capsular alpha-1,4 glucan]
Name	Glucosyl-3-phosphoglycerate synthase involved in methylglucose lipolysaccharide synthesis	mjackson	IDA		Other (lipo)polysaccharides [Methylglucose lipolysaccharides, glycogen and capsular alpha-1,4 glucan]
Symbol	gpgS	mjackson	IMP		Other (lipo)polysaccharides [Methylglucose lipolysaccharides, glycogen and capsular alpha-1,4 glucan]
Name	Glucosyl-3-phosphoglycerate synthase involved in methylglucose lipolysaccharide synthesis	mjackson	IMP		Other (lipo)polysaccharides [Methylglucose lipolysaccharides, glycogen and capsular alpha-1,4 glucan]
Symbol	gpgS	mjackson			Glucosyl-3-phosphoglycerate synthase involved in methylglucose lipolysaccharide synthesis (phenotypic [mycobacterial recombinant strains]; enzymatic) N. Empadinhas, L. Albuquerque et al. Identification of the mycobacterial glucosyl-3-phosphoglycerate synthase. FEMS Microbiol. Lett. 2008
Citation	Identification of the mycobacterial glucosyl-3-phosphoglycerate synthase. N. Empadinhas, L. Albuquerque et al. FEMS Microbiol. Lett. 2008	mjackson		18221489	Glucosyl-3-phosphoglycerate synthase involved in methylglucose lipolysaccharide synthesis (phenotypic [mycobacterial recombinant strains]; enzymatic)
Other	TBPWY:(MGLP and alpha-1,4 glucans)	mjackson			Glucosyl-3-phosphoglycerate synthase involved in methylglucose lipolysaccharide synthesis (phenotypic [mycobacterial recombinant strains]; enzymatic) N. Empadinhas, L. Albuquerque et al. Identification of the mycobacterial glucosyl-3-phosphoglycerate synthase. FEMS Microbiol. Lett. 2008
Symbol	gpgS	mjackson			Glucosyl-3-phosphoglycerate synthase involved in methylglucose lipolysaccharide synthesis (phenotypic [mycobacterial recombinant strains]; enzymatic) D. Kaur, H. Pham et al. Initiation of methylglucose lipopolysaccharide biosynthesis in mycobacteria. PLoS ONE 2009
Citation	Initiation of methylglucose lipopolysaccharide biosynthesis in mycobacteria. D. Kaur, H. Pham et al. PLoS ONE 2009	mjackson		19421329	Glucosyl-3-phosphoglycerate synthase involved in methylglucose lipolysaccharide synthesis (phenotypic [mycobacterial recombinant strains]; enzymatic)
Other	TBPWY:(MGLP and alpha-1,4 glucans)	mjackson			Glucosyl-3-phosphoglycerate synthase involved in methylglucose lipolysaccharide synthesis (phenotypic [mycobacterial recombinant strains]; enzymatic) D. Kaur, H. Pham et al. Initiation of methylglucose lipopolysaccharide biosynthesis in mycobacteria. PLoS ONE 2009

TB Genome Annotation Portal