Rv1170 (mshB)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: 1D-myo-inositol 2-acetamido-2-deoxy-alpha-D-glucopyranoside deacetylase
- REFSEQ: N-Acetyl-1-D-myo-Inosityl-2-amino-2-deoxy-alpha- D-glucopyranoside deacetylase mshB (GlcNAc-Ins deacetylase)
- PATRIC: N-acetyl-1-D-myo-inosityl-2-amino-2-deoxy-alpha-D-glucopyranoside deacetylase MshB
- TUBERCULIST: N-acetyl-1-D-myo-inosityl-2-amino-2-deoxy-alpha-D-glucopyranoside deacetylase MshB (GlcNAc-Ins deacetylase)
- NCBI: N-acetyl-1-D-myo-inosityl-2-amino-2-deoxy-alpha- D-glucopyranoside deacetylase MshB (GlcNAc-Ins deacetylase)
- updated information (H37Rv4):
  - gene name: mshB
  - function:
  - reference:
Coordinates in H37Rv: 1300304 - 1301215
Gene length: 912 bp (with stop codon), 303 aa (without stop codon)
Operon:

Trans-membrane region:
Role: IV.D - Antibiotic production and resistance
GO terms:
- GO:0046872 - metal ion binding (Uniprot)
- GO:0035595 - N-acetylglucosaminylinositol deacetylase activity (Uniprot)
- GO:0016811 - hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides (Uniprot)
- GO:0016787 - hydrolase activity (Uniprot)
- GO:0010125 - mycothiol biosynthetic process (Uniprot)
- GO:0008270 - zinc ion binding (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
- NAG_INS[c] -> AC[c] + NG_INS[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: 1q7t, 4ewl, 1q74
Search for Homologs in PDB

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

PDB	aa ident	species	PDB title
4EWL	100%	Mycobacterium tuberculosis	Crystal Structure of MshB with glycerol and Acetate bound in the active site
1Q7T	100%	Mycobacterium tuberculosis	Rv1170 (MshB) from Mycobacterium tuberculosis
1Q74	100%	Mycobacterium tuberculosis	The Crystal Structure of 1D-myo-inositol 2-acetamido-2-deoxy-alpha-D-glucopyranoside Deacetylase (MshB)

Links to additional information on mshB:
- 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 = 0.311 (from Jeremy Rock's lab)

Amino Acid Sequence

MSETPRLLFVHAHPDDESLSNGATIAHYTSRGAQVHVVTCTLGEEGEVIGDRWAQLTADHADQLGGYRIGELTAALRALGVSAPIYLGGAGRWRDSGMAG
TDQRSQRRFVDADPRQTVGALVAIIRELRPHVVVTYDPNGGYGHPDHVHTHTVTTAAVAAAGVGSGTADHPGDPWTVPKFYWTVLGLSALISGARALVPD
DLRPEWVLPRADEIAFGYSDDGIDAVVEADEQARAAKVAALAAHATQVVVGPTGRAAALSNNLALPILADEHYVLAGGSAGARDERGWETDLLAGLGFTA
SGT

(Nucleotide sequence available on KEGG)

Additional Information

ESSENTIALITY

MtbTnDB - interactive tool for exploring a database of published TnSeq datasets for Mtb

TnSeqCorr - genes with correlated TnSeq profiles across ~100 conditions

Rv1170/mshB, gene len: 911 bp, num TA sites: 12

condition	dataset	call	medium	method	notes
in-vitro	DeJesus 2017 mBio	non-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	non-essential	M9 minimal+glycerol	Gumbel	2 replicates; Padj<0.05
in-vitro (cholesterol)	Griffin 2011 PPath	non-essential	M9 minimal+cholesterol	Gumbel	3 replicates; Padj<0.05
differentially essential in cholesterol	Griffin 2011 PPath	NO (LFC=2.49)	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	growth defect	7H9	HMM	6 replicates (raw data in Subramaniam 2017, PMID 31752678)
in-vivo (mice)	Smith 2022 eLife	growth defect	BL6 mice	HMM	6 replicates (raw data in Subramaniam 2017, PMID 31752678)
differentially essential in mice	Smith 2022 eLife	NO (LFC=0.018)	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	non-essential	YM rich medium	HMM	7H9 supplemented with ~20 metabolites (amino acids, cofactors)
differentially essential in YM rich medium	Minato 2019 mSys	NO (LFC=0.28)	YM rich vs minimal medium	resampling

Analysis of Positive Selection in Clinical Isolates new

data from Culviner et al (2025) (55,259 Mtb clinical isolates)
- overall pN/pS for Rv1170: 0.578007464
- lineage-specific pN/pS in L1: 0.569630544
- lineage-specific pN/pS in L2: 1.250953351
- lineage-specific pN/pS in L3: 0.482510578
- lineage-specific pN/pS in L4: 0.511134087

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)	2.37 (0.47)	1.24 (0.57)
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"

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:
- Rv0081 (-)
- Rv3223c (sigH)

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0023 (-) (Direct binding)
- Rv0135c (-) (Direct binding)
- Rv0602c (tcrA) (Direct binding)
- Rv0967 (csoR) (Direct binding)
- Rv1167c (-) (Direct binding)
- Rv2011c (-) (Direct binding)
- Rv3133c (devR) (Direct binding)
- Rv3246c (mtrA) (Direct binding)
- Rv3597c (lsr2) (Direct binding)

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

Upregulates:
- Does not upregulate other genes.
Upregulated by:
- Rv0081 (-)
- Rv3676 (crp)
Downregulates:
- Does not downregulate other genes.
Downregulated by:
- Rv3223c (sigH)

Property	Value	Creator	Evidence	PMID	Comment
Term	TBRXN:IGAMD 1D-myo-inositol 2-Acetamido-2-deoxy-D-glucopyranoside deacetylase - ISS	njamshidi	ISS	11092856\|14698305	see PMID: 11092856, 14698305 GL. Newton, Y. Av-Gay et al. N-Acetyl-1-D-myo-inosityl-2-amino-2-deoxy-alpha-D-glucopyranoside deacetylase (MshB) is a key enzyme in mycothiol biosynthesis. J. Bacteriol. 2000
Citation	Crystal structure of MshB from Mycobacterium tuberculosis, a deacetylase involved in mycothiol biosynthesis. AA. McCarthy, NA. Peterson et al. J. Mol. Biol. 2004	njamshidi	ISS	11092856\|14698305	see PMID: 11092856, 14698305
Term	TBRXN:IGAMD 1D-myo-inositol 2-Acetamido-2-deoxy-D-glucopyranoside deacetylase - ISS	njamshidi	ISS	11092856\|14698305	see PMID: 11092856, 14698305 AA. McCarthy, NA. Peterson et al. Crystal structure of MshB from Mycobacterium tuberculosis, a deacetylase involved in mycothiol biosynthesis. J. Mol. Biol. 2004
Citation	N-Acetyl-1-D-myo-inosityl-2-amino-2-deoxy-alpha-D-glucopyranoside deacetylase (MshB) is a key enzyme in mycothiol biosynthesis. GL. Newton, Y. Av-Gay et al. J. Bacteriol. 2000	njamshidi	IDA	11092856\|14698305	see PMID: 11092856, 14698305
Term	TBRXN:IGAMD 1D-myo-inositol 2-Acetamido-2-deoxy-D-glucopyranoside deacetylase - IDA	njamshidi	IDA	11092856\|14698305	see PMID: 11092856, 14698305 GL. Newton, Y. Av-Gay et al. N-Acetyl-1-D-myo-inosityl-2-amino-2-deoxy-alpha-D-glucopyranoside deacetylase (MshB) is a key enzyme in mycothiol biosynthesis. J. Bacteriol. 2000
Citation	Crystal structure of MshB from Mycobacterium tuberculosis, a deacetylase involved in mycothiol biosynthesis. AA. McCarthy, NA. Peterson et al. J. Mol. Biol. 2004	njamshidi	IDA	11092856\|14698305	see PMID: 11092856, 14698305
Term	TBRXN:IGAMD 1D-myo-inositol 2-Acetamido-2-deoxy-D-glucopyranoside deacetylase - IDA	njamshidi	IDA	11092856\|14698305	see PMID: 11092856, 14698305 AA. McCarthy, NA. Peterson et al. Crystal structure of MshB from Mycobacterium tuberculosis, a deacetylase involved in mycothiol biosynthesis. J. Mol. Biol. 2004
Citation	N-Acetyl-1-D-myo-inosityl-2-amino-2-deoxy-alpha-D-glucopyranoside deacetylase (MshB) is a key enzyme in mycothiol biosynthesis. GL. Newton, Y. Av-Gay et al. J. Bacteriol. 2000	njamshidi	ISS	11092856\|14698305	see PMID: 11092856, 14698305
Citation	The glycosyltransferase gene encoding the enzyme catalyzing the first step of mycothiol biosynthesis (mshA). GL. Newton, T. Koledin et al. J. Bacteriol. 2003	jjmcfadden		12754249	Inferred from direct assay
Other	EC:	jjmcfadden			Inferred from direct assay GL. Newton, T. Koledin et al. The glycosyltransferase gene encoding the enzyme catalyzing the first step of mycothiol biosynthesis (mshA). J. Bacteriol. 2003

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