Rv1018c (glmU)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: glmU protein
- REFSEQ: UDP-N-acetylglucosamine pyrophosphorylase glmU
- PATRIC: N-acetylglucosamine-1-phosphate uridyltransferase (EC 2.7.7.23) / Glucosamine-1-phosphate N-acetyltransferase (EC 2.3.1.157)
- TUBERCULIST: Probable UDP-N-acetylglucosamine pyrophosphorylase GlmU
- NCBI: Probable UDP-N-acetylglucosamine pyrophosphorylase GlmU
- updated information (H37Rv4):
  - gene name: glmU
  - function:
  - reference:
Type: Not Target
Start: 1136573
End: 1138060
Operon:

Trans-membrane region:
Role: II.C.3 - Murein sacculus and peptidoglycan
GO terms:
- GO:0071555 - cell wall organization (Uniprot)
- GO:0070569 - uridylyltransferase activity (Uniprot)
- GO:0046872 - metal ion binding (Uniprot)
- GO:0044650 - adhesion of symbiont to host cell (Uniprot)
- GO:0040007 - growth (Uniprot)
- GO:0035635 - entry of bacterium into host cell (Uniprot)
- GO:0019134 - glucosamine-1-phosphate N-acetyltransferase activity (Uniprot)
- GO:0016779 - nucleotidyltransferase activity (Uniprot)
- GO:0016746 - transferase activity, transferring acyl groups (Uniprot)
- GO:0016740 - transferase activity (Uniprot)
- GO:0009252 - peptidoglycan biosynthetic process (Uniprot)
- GO:0009245 - lipid A biosynthetic process (Uniprot)
- GO:0009103 - lipopolysaccharide biosynthetic process (Uniprot)
- GO:0008360 - regulation of cell shape (Uniprot)
- GO:0008152 - metabolic process (Uniprot)
- GO:0006048 - UDP-N-acetylglucosamine biosynthetic process (Uniprot)
- GO:0005737 - cytoplasm (Uniprot)
- GO:0005515 - protein binding (Uniprot)
- GO:0003977 - UDP-N-acetylglucosamine diphosphorylase activity (Uniprot)
- GO:0003824 - catalytic activity (Uniprot)
- GO:0000902 - cell morphogenesis (Uniprot)
- GO:0000287 - magnesium ion binding (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
- UTP[c] + NAGA1P[c] -> PPI[c] + UDPNAG[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: 3dk5, 3d8v, 3spt, 3d98, 4hcq, 4g87, 3dj4, 2qkx, 3foq, 3st8
Search for Homologs in PDB

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

PDB	aa ident	species	PDB title
6GE9	100%	Mycobacterium tuberculosis (strain ATCC 25177 / H37Ra)	Structure of Mycobacterium tuberculosis GlmU bound to Glc-1P and Ac-CoA
4K6R	100%	Mycobacterium tuberculosis	Crystal structure of GlmU in complex with ATP
4HCQ	100%	Mycobacterium tuberculosis	Crystal structure of GLMU from mycobacterium tuberculosis in complex with glucosamine-1-phosphate
4G87	100%	Mycobacterium tuberculosis	Crystal structure of GLMU from Mycobacterium tuberculosis snapshot 1
4G3S	100%	Mycobacterium tuberculosis	Crystal structure of GlmU from Mycobacterium tuberculosis in complex with uridine-diphosphate-n-acetylglucosamine and pyrophosphate Snapshot 2
4G3Q	100%	Mycobacterium tuberculosis	Crystal structure of GlmU from Mycobacterium tuberculosis Snapshot 4
4G3P	100%	Mycobacterium tuberculosis	Crystal structure of GlmU from Mycobacterium tuberculosis Snapshot 3
3ST8	100%	Mycobacterium tuberculosis	Crystal structure of GlmU from Mycobacterium tuberculosis in complex with COENZYME A, GLUCOSAMINE 1-PHOSPHATE and URIDINE-DIPHOSPHATE-N-ACETYLGLUCOSAMINE
3SPT	100%	Mycobacterium tuberculosis	Crystal structure of GlmU from Mycobacterium tuberculosis in complex with ACETYL COENZYME A and URIDINE-DIPHOSPHATE-N-ACETYLGLUCOSAMINE
3FOQ	100%	Mycobacterium tuberculosis	Crystal structure of N-acetylglucosamine-1-phosphate uridyltransferase (GlmU) from Mycobacterium tuberculosis in a cubic space group.

Links to additional information on glmU:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -8.118 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MTFPGDTAVLVLAAGPGTRMRSDTPKVLHTLAGRSMLSHVLHAIAKLAPQRLIVVLGHDHQRIAPLVGELADTLGRTIDVALQDRPLGTGHAVLCGLSAL
PDDYAGNVVVTSGDTPLLDADTLADLIATHRAVSAAVTVLTTTLDDPFGYGRILRTQDHEVMAIVEQTDATPSQREIREVNAGVYAFDIAALRSALSRLS
SNNAQQELYLTDVIAILRSDGQTVHASHVDDSALVAGVNNRVQLAELASELNRRVVAAHQLAGVTVVDPATTWIDVDVTIGRDTVIHPGTQLLGRTQIGG
RCVVGPDTTLTDVAVGDGASVVRTHGSSSSIGDGAAVGPFTYLRPGTALGADGKLGAFVEVKNSTIGTGTKVPHLTYVGDADIGEYSNIGASSVFVNYDG
TSKRRTTVGSHVRTGSDTMFVAPVTIGDGAYTGAGTVVREDVPPGALAVSAGPQRNIENWVQRKRPGSPAAQASKRASEMACQQPTQPPDADQTP

(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)	1.68 (0.21)	1.5 (0.67)
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

Rv1018c/glmU, gene len: 1487 bp, num TA sites: 24

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	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=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=0.012)	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, cofactors)
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:
- Rv1033c (trcR)
- Rv2250c (-)

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv1033c (trcR) (Direct binding)
- Rv3133c (devR) (Direct binding)
- Rv3574 (kstR) (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:
- Rv1033c (trcR)
- Rv2250c (-)

Property	Value	Creator	Evidence	PMID	Comment
Citation	PknB-Mediated Phosphorylation of a Novel Substrate, N-Acetylglucosamine-1-Phosphate Uridyltransferase, Modulates Its Acetyltransferase Activity. A. Parikh, SK. Verma et al. J. Mol. Biol. 2008	ashwinigbhat	IDA	19121323	Structural Analysis
Interaction	PhysicalInteraction Rv0014c	ashwinigbhat	IDA		Structural Analysis A. Parikh, SK. Verma et al. PknB-Mediated Phosphorylation of a Novel Substrate, N-Acetylglucosamine-1-Phosphate Uridyltransferase, Modulates Its Acetyltransferase Activity. J. Mol. Biol. 2008
Citation	Expression, essentiality, and a microtiter plate assay for mycobacterial GlmU, the bifunctional glucosamine-1-phosphate acetyltransferase and N-acetylglucosamine-1-phosphate uridyltransferase. W. Zhang, VC. Jones et al. Int. J. Biochem. Cell Biol. 2008	priti.priety	IDA	18573680	Structural Analysis
Interaction	PhysicalInteraction Rv0014c	priti.priety	IDA		Structural Analysis W. Zhang, VC. Jones et al. Expression, essentiality, and a microtiter plate assay for mycobacterial GlmU, the bifunctional glucosamine-1-phosphate acetyltransferase and N-acetylglucosamine-1-phosphate uridyltransferase. Int. J. Biochem. Cell Biol. 2008
Citation	PknB-Mediated Phosphorylation of a Novel Substrate, N-Acetylglucosamine-1-Phosphate Uridyltransferase, Modulates Its Acetyltransferase Activity. A. Parikh, SK. Verma et al. J. Mol. Biol. 2008	priti.priety	IDA	19121323	Structural Analysis
Interaction	PhysicalInteraction Rv0014c	priti.priety	IDA		Structural Analysis A. Parikh, SK. Verma et al. PknB-Mediated Phosphorylation of a Novel Substrate, N-Acetylglucosamine-1-Phosphate Uridyltransferase, Modulates Its Acetyltransferase Activity. J. Mol. Biol. 2008
Citation	Expression, essentiality, and a microtiter plate assay for mycobacterial GlmU, the bifunctional glucosamine-1-phosphate acetyltransferase and N-acetylglucosamine-1-phosphate uridyltransferase. W. Zhang, VC. Jones et al. Int. J. Biochem. Cell Biol. 2008	ashwinigbhat	IDA	18573680	Structural Analysis
Interaction	PhysicalInteraction Rv0014c	ashwinigbhat	IDA		Structural Analysis W. Zhang, VC. Jones et al. Expression, essentiality, and a microtiter plate assay for mycobacterial GlmU, the bifunctional glucosamine-1-phosphate acetyltransferase and N-acetylglucosamine-1-phosphate uridyltransferase. Int. J. Biochem. Cell Biol. 2008
Interaction	RegulatedBy Rv0485	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 Rv0485	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	Bifunctional enzyme: N-acetylation of GlcNH2-1-P to form GlcNAc-1-P and GlcNAc-1-P uridylyltransferase that forms UDP-GlcNAc	mjackson	IDA		UDP-GlcNAc synthesis
Citation	Expression, essentiality, and a microtiter plate assay for mycobacterial GlmU, the bifunctional glucosamine-1-phosphate acetyltransferase and N-acetylglucosamine-1-phosphate uridyltransferase. W. Zhang, VC. Jones et al. Int. J. Biochem. Cell Biol. 2008	mmcneil		18573680	Conversion of glcNH2-6-P to glcNH2-1-P (unpublished data Michael McNeil; enzymatic evidence)
Term	GO:0006048 UDP-N-acetylglucosamine biosynthetic process - NR	mmcneil	NR		Conversion of glcNH2-6-P to glcNH2-1-P (unpublished data Michael McNeil; enzymatic evidence) W. Zhang, VC. Jones et al. Expression, essentiality, and a microtiter plate assay for mycobacterial GlmU, the bifunctional glucosamine-1-phosphate acetyltransferase and N-acetylglucosamine-1-phosphate uridyltransferase. Int. J. Biochem. Cell Biol. 2008
Citation	Expression, essentiality, and a microtiter plate assay for mycobacterial GlmU, the bifunctional glucosamine-1-phosphate acetyltransferase and N-acetylglucosamine-1-phosphate uridyltransferase. W. Zhang, VC. Jones et al. Int. J. Biochem. Cell Biol. 2008	mmcneil		18573680	N-acetylation of GlcNH2-1-P to form GlcNAc-1-P by the bifunctional enzyme GlmU; enzymatic evidence
Term	GO:0006048 UDP-N-acetylglucosamine biosynthetic process - NR	mmcneil	NR		N-acetylation of GlcNH2-1-P to form GlcNAc-1-P by the bifunctional enzyme GlmU; enzymatic evidence W. Zhang, VC. Jones et al. Expression, essentiality, and a microtiter plate assay for mycobacterial GlmU, the bifunctional glucosamine-1-phosphate acetyltransferase and N-acetylglucosamine-1-phosphate uridyltransferase. Int. J. Biochem. Cell Biol. 2008

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