Rv0482 (murB)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: UDP-N-acetylenolpyruvoylglucosamine reductase
- REFSEQ: UDP-N-acetylenolpyruvoylglucosamine reductase
- PATRIC: UDP-N-acetylenolpyruvoylglucosamine reductase (EC 1.1.1.158)
- TUBERCULIST: Probable UDP-N-acetylenolpyruvoylglucosamine reductase MurB (UDP-N-acetylmuramate dehydrogenase)
- NCBI: Probable UDP-N-acetylenolpyruvoylglucosamine reductase MurB (UDP-N-acetylmuramate dehydrogenase)
- updated information (H37Rv4):
  - gene name: murB
  - function:
  - reference:
Type: Not Target
Start: 570539
End: 571648
Operon:

Trans-membrane region:
Role: II.C.3 - Murein sacculus and peptidoglycan
GO terms:
- GO:0071555 - cell wall organization (Uniprot)
- GO:0055114 - oxidation-reduction process (Uniprot)
- GO:0051301 - cell division (Uniprot)
- GO:0050660 - flavin adenine dinucleotide binding (Uniprot)
- GO:0016614 - oxidoreductase activity, acting on CH-OH group of donors (Uniprot)
- GO:0016491 - oxidoreductase activity (Uniprot)
- GO:0009252 - peptidoglycan biosynthetic process (Uniprot)
- GO:0008762 - UDP-N-acetylmuramate dehydrogenase activity (Uniprot)
- GO:0008360 - regulation of cell shape (Uniprot)
- GO:0007049 - cell cycle (Uniprot)
- GO:0005737 - cytoplasm (Uniprot)
- GO:0003824 - catalytic activity (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
- NADPH[c] + UDPNAGPEE[c] -> NADP[c] + UDPNAM[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
5JZX	100%	Mycobacterium tuberculosis H37Rv	Crystal Structure of UDP-N-acetylenolpyruvoylglucosamine reductase (MurB) from Mycobacterium tuberculosis
4JB1	37%	Pseudomonas aeruginosa	Crystal structure of P. aeruginosa MurB in complex with NADP+
4JAY	37%	Pseudomonas aeruginosa	Crystal structure of P. aeruginosa MurB in complex with NADP+

Links to additional information on murB:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -12.167 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MKRSGVGSLFAGAHIAEAVPLAPLTTLRVGPIARRVITCTSAEQVVAALRHLDSAAKTGADRPLVFAGGSNLVIAENLTDLTVVRLANSGITIDGNLVRA
EAGAVFDDVVVRAIEQGLGGLECLSGIPGSAGATPVQNVGAYGAEVSDTITRVRLLDRCTGEVRWVSARDLRFGYRTSVLKHADGLAVPTVVLEVEFALD
PSGRSAPLRYGELIAALNATSGERADPQAVREAVLALRARKGMVLDPTDHDTWSVGSFFTNPVVTQDVYERLAGDAATRKDGPVPHYPAPDGVKLAAGWL
VERAGFGKGYPDAGAAPCRLSTKHALALTNRGGATAEDVVTLARAVRDGVHDVFGITLKPEPVLIGCML

(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)	1.74 (0.39)	1.53 (0.6)
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

Rv0482/murB, gene len: 1109 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	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=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=-0.83)	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:

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv1353c (-) (Direct binding)
- Rv2034 (-) (Direct binding)

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

Upregulates:
- Does not upregulate other genes.
Upregulated by:
- Rv3765c (tcrX)
Downregulates:
- Does not downregulate other genes.
Downregulated by:
- Rv3223c (sigH)
- Rv3286c (sigF)

Property	Value	Creator	Evidence	PMID	Comment
Citation	The Mycobacterium tuberculosis IdeR is a dual functional regulator that controls transcription of genes involved in iron acquisition, iron storage and survival in macrophages. B. Gold, GM. Rodriguez et al. Mol. Microbiol. 2001	akankshajain.21	IEP	11722747	Footprinting
Interaction	Regulatory Rv2711	akankshajain.21	IEP		Footprinting B. Gold, GM. Rodriguez et al. The Mycobacterium tuberculosis IdeR is a dual functional regulator that controls transcription of genes involved in iron acquisition, iron storage and survival in macrophages. Mol. Microbiol. 2001
Citation	The Mycobacterium tuberculosis IdeR is a dual functional regulator that controls transcription of genes involved in iron acquisition, iron storage and survival in macrophages. B. Gold, GM. Rodriguez et al. Mol. Microbiol. 2001	prabhakarsmail	IEP	11722747	Footprinting
Interaction	Regulatory Rv2711	prabhakarsmail	IEP		Footprinting B. Gold, GM. Rodriguez et al. The Mycobacterium tuberculosis IdeR is a dual functional regulator that controls transcription of genes involved in iron acquisition, iron storage and survival in macrophages. Mol. Microbiol. 2001
Interaction	RegulatedBy Rv2711	yamir.moreno	TAS		Literature previously reported link (from Balazsi et al. 2008). Traceable author statement to experimental support. G. Balzsi, AP. Heath et al. The temporal response of the Mycobacterium tuberculosis gene regulatory network during growth arrest. Mol. Syst. Biol. 2008
Name	UDP-N-acetylenolpyruvoylglucosamine reductase	mjackson	ISS		Peptidoglycan precursor synthesis

TB Genome Annotation Portal