Rv3634c (galE1)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: UDP-glucose 4-epimerase
- REFSEQ: UDP-glucose 4-epimerase GALE1 (galactowaldenase) (UDP-galactose 4-epimerase) (uridine diphosphate galactose 4-epimerase) (uridine diphospho-galactose 4-epimerase)
- PATRIC: UDP-glucose 4-epimerase (EC 5.1.3.2)
- TUBERCULIST: UDP-glucose 4-epimerase GalE1 (galactowaldenase) (UDP-galactose 4-epimerase) (uridine diphosphate galactose 4-epimerase) (uridine diphospho-galactose 4-epimerase)
- NCBI: UDP-glucose 4-epimerase GalE1 (galactowaldenase) (UDP-galactose 4-epimerase) (uridine diphosphate galactose 4-epimerase) (uridine diphospho-galactose 4-epimerase)
- updated information (H37Rv4):
  - gene name: galE1
  - function:
  - reference: Tardeshi (2017), PMID: 28403215
Type: Not Target
Start: 4072667
End: 4073611
Operon:

Trans-membrane region:
Role: I.C.3 - Sugar nucleotides
GO terms:
- GO:0040007 - growth (Uniprot)
- GO:0016853 - isomerase activity (Uniprot)
- GO:0006012 - galactose metabolic process (Uniprot)
- GO:0005975 - carbohydrate metabolic process (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0003978 - UDP-glucose 4-epimerase activity (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
- UDPG[c] <=> UDPGAL[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
4ZRN	45%	Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)	Crystal Structure of UDP-Glucose 4-Epimerase (TM0509) with UDP-glucose from Hyperthermophilic Eubacterium Thermotoga Maritima
4ZRM	45%	Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)	Crystal Structure of UDP-Glucose 4-Epimerase (TM0509) from Hyperthermophilic Eubacterium Thermotoga maritima
2P5Y	44%	Thermus thermophilus HB8	Crystal structure of Thermus thermophilus HB8 UDP-glucose 4-epimerase complex with NAD
2P5U	44%	Thermus thermophilus HB8	Crystal structure of Thermus thermophilus HB8 UDP-glucose 4-epimerase complex with NAD
6WJB	39%	Pseudomonas fluorescens (strain ATCC BAA-477 / NRRL B-23932 / Pf-5)	UDP-GlcNAc C4-epimerase from Pseudomonas protegens in complex with NAD and UDP-GlcNAc
6WJA	38%	Pseudomonas protegens	UDP-GlcNAc C4-epimerase mutant S121A/Y146F from Pseudomonas protegens in complex with UDP-GalNAc
6WJ9	38%	Pseudomonas protegens	UDP-GlcNAc C4-epimerase mutant S121A/Y146F from Pseudomonas protegens in complex with UDP-GlcNAc

Links to additional information on galE1:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -5.264 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

VRALVTGAAGFIGSTLVDRLLADGHSVVGLDNFATGRATNLEHLADNSAHVFVEADIVTADLHAILEQHRPEVVFHLAAQIDVRRSVADPQFDAAVNVIG
TVRLAEAARQTGVRKIVHTSSGGSIYGTPPEYPTPETAPTDPASPYAAGKVAGEIYLNTFRHLYGLDCSHIAPANVYGPRQDPHGEAGVVAIFAQALLSG
KPTRVFGDGTNTRDYVFVDDVVDAFVRVSADVGGGLRFNIGTGKETSDRQLHSAVAAAVGGPDDPEFHPPRLGDLKRSCLDIGLAERVLGWRPQIELADG
VRRTVEYFRHKHTD

(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)	2.18 (0.44)	1.04 (0.34)
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

Rv3634c/galE1, gene len: 944 bp, num TA sites: 20

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	essential	minimal medium	HMM
in-vitro (YM rich medium)	Minato 2019 mSys	essential	YM rich medium	HMM	7H9 supplemented with ~20 metabolites (amino acids, vitamins)
differentially essential in YM rich medium	Minato 2019 mSys	NO (LFC=0.0)	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:
- Rv0260c (-)
- Rv0818 (-)

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:
- Rv0260c (-)
- Rv0818 (-)

Property	Value	Creator	Evidence	PMID	Comment
Interaction	RegulatedBy Rv1221	yamir.moreno	IEP		Microarrays. mRNA levels of regulated element measured and compared between wild-type and trans-element mutation (knockout, over expression etc.) performed by using microarray (or macroarray) experiments.. PA. Fontn, V. Aris et al. Mycobacterium tuberculosis Sigma Factor E Regulon Modulates the Host Inflammatory Response. J. Infect. Dis. 2008
Interaction	RegulatedBy Rv3676	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 Rv3676	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
Name	UDP-Glucose-4-epimerase: formation of UDP-Galactopyranosem, the first step in the formation of UDP-Galactofuranose the donor of galactofuranosyl residues	mjackson	IDA		UDP-Galactofuranose synthesis
Citation	Biosynthetic origin of mycobacterial cell wall galactofuranosyl residues. A. Weston,RJ. Stern,RE. Lee,PM. Nassau,D. Monsey,SL. Martin,MS. Scherman,GS. Besra,K. Duncan,MR. McNeil Tuber. Lung Dis. 1997	mmcneil		9692181	UDP-Glucose-4-epimerase: formation of UDP-Galp the first step in the formation of UDP-Galf the donor of galactofuranosyl residues. Standard pathway; enzymatic evidence
Term	GO:0009226 nucleotide-sugar biosynthetic process - NR	mmcneil	NR		UDP-Glucose-4-epimerase: formation of UDP-Galp the first step in the formation of UDP-Galf the donor of galactofuranosyl residues. Standard pathway; enzymatic evidence A. Weston,RJ. Stern,RE. Lee,PM. Nassau,D. Monsey,SL. Martin,MS. Scherman,GS. Besra,K. Duncan,MR. McNeil Biosynthetic origin of mycobacterial cell wall galactofuranosyl residues. Tuber. Lung Dis. 1997
Citation	Biosynthetic origin of mycobacterial cell wall galactofuranosyl residues. A. Weston,RJ. Stern,RE. Lee,PM. Nassau,D. Monsey,SL. Martin,MS. Scherman,GS. Besra,K. Duncan,MR. McNeil Tuber. Lung Dis. 1997	extern:JZUCKER		9692181	Assay of protein purified to homogeneity from its native host
Term	EC:5.1.3.2 UDP-glucose 4-epimerase. - NR	extern:JZUCKER	NR		Assay of protein purified to homogeneity from its native host A. Weston,RJ. Stern,RE. Lee,PM. Nassau,D. Monsey,SL. Martin,MS. Scherman,GS. Besra,K. Duncan,MR. McNeil Biosynthetic origin of mycobacterial cell wall galactofuranosyl residues. Tuber. Lung Dis. 1997

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