Rv1302 (rfe)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: undecaprenyl-phosphate alpha-N-acetylglucosaminyl 1-phosphate transferase
- REFSEQ: undecapaprenyl-phosphate alpha-N-acetylglucosaminyltransferase rfe (UDP-GlcNAc transferase)
- PATRIC: Undecaprenyl-phosphate N-acetylglucosaminyl 1-phosphate transferase (EC 2.7.8.-)
- TUBERCULIST: Probable undecapaprenyl-phosphate alpha-N-acetylglucosaminyltransferase Rfe (UDP-GlcNAc transferase)
- NCBI: Probable undecapaprenyl-phosphate alpha-N-acetylglucosaminyltransferase Rfe (UDP-GlcNAc transferase)
- updated information (H37Rv4):
  - gene name: wecA
  - function: N-Acetylglucosamine-1-Phosphate Transferase
  - reference: Huszar (2017) PMID: 28874370
Type: Not Target
Start: 1458295
End: 1459509
Operon:

Trans-membrane region:
Role: II.C.2 - Surface polysaccharides, lipopolysaccharides, proteins and antigens
GO terms:
- GO:0071555 - cell wall organization (Uniprot)
- GO:0045227 - capsule polysaccharide biosynthetic process (Uniprot)
- GO:0044038 - cell wall macromolecule biosynthetic process (Uniprot)
- GO:0030145 - manganese ion binding (Uniprot)
- GO:0016780 - phosphotransferase activity, for other substituted phosphate groups (Uniprot)
- GO:0016757 - transferase activity, transferring glycosyl groups (Uniprot)
- GO:0016740 - transferase activity (Uniprot)
- GO:0016021 - integral component of membrane (Uniprot)
- GO:0016020 - membrane (Uniprot)
- GO:0008963 - phospho-N-acetylmuramoyl-pentapeptide-transferase activity (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0000287 - magnesium ion binding (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
- UDPNAG[c] + UDCPP[c] -> UMP[c] + UNAGA[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): (none with >35% aa id)
Links to additional information on rfe:
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -5.018 (from Jeremy Rock's lab)
- Photo of spot titer

Amino Acid Sequence

VQYGLEVSSDVAGVAGGLLALSYRGAGVPLRELALVGLTAAIITYFATGPVRMLASRLGAVAYPRERDVHVTPTPRMGGLAMFLGIVGAVFLASQLPALT
RGFVYSTGMPAVLVAGAVIMGIGLIDDRWGLDALTKFAGQITAASVLVTMGVAWSVLYIPVGGVGTIVLDQASSILLTLALTVSIVNAMNFVDGLDGLAA
GLGLITALAICMFSVGLLRDHGGDVLYYPPAVISVVLAGACLGFLPHNFHRAKIFMGDSGSMLIGLMLAAASTTAAGPISQNAYGARDVFALLSPFLLVV
AVMFVPMLDLLLAIVRRTRAGRSAFSPDKMHLHHRLLQIGHSHRRVVLIIYLWVGIVAFGAASSIFFNPRDTAAVMLGAIVVAGVATLIPLLRRGDDYYD
PDLD

(Nucleotide sequence available on KEGG)

Additional Information

WecA.
Huzar et al (2017). N-Acetylglucosamine-1-Phosphate Transferase, WecA, as a Validated Drug Target in Mycobacterium tuberculosis. AAC. https://aac.asm.org/content/61/11/e01310-17

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)	1.21 (0.11)	0.58 (0.16)
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

Rv1302/rfe, gene len: 1214 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	non-essential	7H9	TRASH	essential if hybridization ratio<0.2
in-vivo (mice)	Sassetti 2003 PNAS	non-essential	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=-1.1)	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=-0.065)	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=-0.38)	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:
- Rv0757 (phoP)
- Rv3765c (tcrX)

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0081 (-) (Direct binding)
- Rv0465c (-) (Direct binding)
- Rv0757 (phoP) (Direct binding)

Interactions based on TFOE data (Rustad et al. 2014)

Upregulates:
- Does not upregulate other genes.
Upregulated by:
- Rv0757 (phoP)
- Rv3765c (tcrX)
Downregulates:
- Does not downregulate other genes.
Downregulated by:
- Not downregulated by other genes.

Property	Value	Creator	Evidence	PMID	Comment
Term	TBRXN:ACGAMT UDP-N-acetylglucosamine:undecaprenylphosphate N-acetylglucosamine -1-phosphate transferase - ISS	njamshidi	ISS	\|10934214	See PMID: 10934214, Text by Cole et al (Tuberculosis and the tubercle bacillus) chap 18. K. Mikusov, T. Yagi et al. Biosynthesis of the galactan component of the mycobacterial cell wall. J. Biol. Chem. 2000
Citation	Biosynthesis of the galactan component of the mycobacterial cell wall. K. Mikusov, T. Yagi et al. J. Biol. Chem. 2000	njamshidi	IPI	\|10934214	See PMID: 10934214, Text by Cole et al (Tuberculosis and the tubercle bacillus) chap 18.
Term	TBRXN:ACGAMT UDP-N-acetylglucosamine:undecaprenylphosphate N-acetylglucosamine -1-phosphate transferase - IPI	njamshidi	IPI	\|10934214	See PMID: 10934214, Text by Cole et al (Tuberculosis and the tubercle bacillus) chap 18. K. Mikusov, T. Yagi et al. Biosynthesis of the galactan component of the mycobacterial cell wall. J. Biol. Chem. 2000
Citation	Biosynthesis of the galactan component of the mycobacterial cell wall. K. Mikusov, T. Yagi et al. J. Biol. Chem. 2000	njamshidi	ISS	\|10934214	See PMID: 10934214, Text by Cole et al (Tuberculosis and the tubercle bacillus) chap 18.
Interaction	RegulatedBy Rv0757	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.. SB. Walters, E. Dubnau et al. The Mycobacterium tuberculosis PhoPR two-component system regulates genes essential for virulence and complex lipid biosynthesis. Mol. Microbiol. 2006
Interaction	RegulatedBy Rv3286c	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.. EP. Williams, JH. Lee et al. Mycobacterium tuberculosis SigF regulates genes encoding cell wall-associated proteins and directly regulates the transcriptional regulatory gene phoY1. J. Bacteriol. 2007
Symbol	wecA	mjackson	IMP		GlcNAc-1-phosphate transferase
Name	GlcNAc-1-P transferase. Transfers GlcNAc-1-P to decaprenyl phosphate to make GlcNAc-P-P-decaprenyl	mjackson	IMP		GlcNAc-1-phosphate transferase
Symbol	wecA	mmcneil			GlcNAc-1-P transferase. Transfers GlcNAc-1-P to decaprenyl phosphate to make GlcNAc-P-P-decaprenyl (complementation of an E. coli LPS mutant) authors,Y. Jin,Y. Xin,W. Zhang,Y. Ma Mycobacterium tuberculosis Rv1302 and Mycobacterium smegmatis MSMEG_4947 have WecA function and MSMEG_4947 is required for the growth of M. smegmatis. FEMS Microbiol. Lett. 2010
Citation	Mycobacterium tuberculosis Rv1302 and Mycobacterium smegmatis MSMEG_4947 have WecA function and MSMEG_4947 is required for the growth of M. smegmatis. authors,Y. Jin,Y. Xin,W. Zhang,Y. Ma FEMS Microbiol. Lett. 2010	mmcneil		20637039	GlcNAc-1-P transferase. Transfers GlcNAc-1-P to decaprenyl phosphate to make GlcNAc-P-P-decaprenyl (complementation of an E. coli LPS mutant)
Term	GO:0003975 UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase activity - NR	mmcneil	NR		GlcNAc-1-P transferase. Transfers GlcNAc-1-P to decaprenyl phosphate to make GlcNAc-P-P-decaprenyl (complementation of an E. coli LPS mutant) authors,Y. Jin,Y. Xin,W. Zhang,Y. Ma Mycobacterium tuberculosis Rv1302 and Mycobacterium smegmatis MSMEG_4947 have WecA function and MSMEG_4947 is required for the growth of M. smegmatis. FEMS Microbiol. Lett. 2010
Citation	Biosynthesis of the linkage region of the mycobacterial cell wall. authors,K. Mikusov,M. Mikus,GS. Besra,I. Hancock,PJ. Brennan J. Biol. Chem. 1996	extern:JZUCKER		8631826	Assay of unpurified protein expressed in its native host
Term	EC:2.4.1.- Transferases. Glycosyltransferases. Hexosyltransferases. - NR	extern:JZUCKER	NR		Assay of unpurified protein expressed in its native host authors,K. Mikusov,M. Mikus,GS. Besra,I. Hancock,PJ. Brennan Biosynthesis of the linkage region of the mycobacterial cell wall. J. Biol. Chem. 1996

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