Rv0486 (mshA)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: D-inositol-3-phosphate glycosyltransferase
- REFSEQ: mannosyltransferase
- PATRIC: Glycosyltransferase MshA involved in mycothiol biosynthesis (EC 2.4.1.-)
- TUBERCULIST: Glycosyltransferase MshA
- NCBI: Glycosyltransferase MshA
- updated information (H37Rv4):
  - gene name: mshA
  - function:
  - reference:
Type: Essential
Start: 575348
End: 576790
Operon:

Trans-membrane region:
Role: V - Conserved hypotheticals
GO terms:
- GO:0102710 - D-inositol-3-phosphate glycosyltransferase activity (Uniprot)
- GO:0046872 - metal ion binding (Uniprot)
- GO:0016757 - transferase activity, transferring glycosyl groups (Uniprot)
- GO:0016740 - transferase activity (Uniprot)
- GO:0010125 - mycothiol biosynthetic process (Uniprot)
- GO:0008375 - acetylglucosaminyltransferase activity (Uniprot)
- GO:0005829 - cytosol (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
- IP[c] + UDPNAG[c] -> PI[c] + UDP[c] + NAG_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:
Search for Homologs in PDB

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

PDB	aa ident	species	PDB title
3C4V	51%	Corynebacterium glutamicum	Structure of the retaining glycosyltransferase MshA:The first step in mycothiol biosynthesis. Organism: Corynebacterium glutamicum : Complex with UDP and 1L-INS-1-P.
3C4Q	51%	Corynebacterium glutamicum	Structure of the retaining glycosyltransferase MshA : The first step in mycothiol biosynthesis. Organism : Corynebacterium glutamicum- Complex with UDP
3C48	51%	Corynebacterium glutamicum	Structure of the retaining glycosyltransferase MshA: The first step in mycothiol biosynthesis. Organism: Corynebacterium glutamicum- APO (OPEN) structure.
5ZFK	35%	Synechococcus elongatus PCC 7942	UDP Glucose alpha tetrahydrobiopterin glycosyltransferase from Synechococcus species PCC 7942 - UDP-BH2 complex
5ZFK	35%	Synechococcus elongatus PCC 7942	UDP Glucose alpha tetrahydrobiopterin glycosyltransferase from Synechococcus species PCC 7942 - UDP-BH2 complex
5ZES	35%	Synechococcus elongatus (strain PCC 7942)	UDP Glucose alpha tetrahydrobiopterin glycosyltransferase from Synechococcus species PCC 7942 - UDP complex
5ZER	35%	Synechococcus elongatus PCC 7942	UDP Glucose alpha tetrahydrobiopterin glycosyltransferase from Synechococcus species PCC 7942 - BH2 complex form
5ZE7	35%	Synechococcus elongatus (strain PCC 7942)	UDP Glucose alpha tetrahydrobiopterin glycosyltransferase from Synechococcus species PCC 7942 - apo form
6KIH	35%	Thermosynechococcus elongatus	Sucrose-phosphate synthase (tll1590) from Thermosynechococcus elongatus

Links to additional information on mshA:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -0.729 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MAGVRHDDGSGLIAQRRPVRGEGATRSRGPSGPSNRNVSAADDPRRVALLAVHTSPLAQPGTGDAGGMNVYMLQSALHLARRGIEVEIFTRATASADPPV
VRVAPGVLVRNVVAGPFEGLDKYDLPTQLCAFAAGVLRAEAVHEPGYYDIVHSHYWLSGQVGWLARDRWAVPLVHTAHTLAAVKNAALADGDGPEPPLRT
VGEQQVVDEADRLIVNTDDEARQVISLHGADPARIDVVHPGVDLDVFRPGDRRAARAALGLPVDERVVAFVGRIQPLKAPDIVLRAAAKLPGVRIIVAGG
PSGSGLASPDGLVRLADELGISARVTFLPPQSHTDLATLFRAADLVAVPSYSESFGLVAVEAQACGTPVVAAAVGGLPVAVRDGITGTLVSGHEVGQWAD
AIDHLLRLCAGPRGRVMSRAAARHAATFSWENTTDALLASYRRAIGEYNAERQRRGGEVISDLVAVGKPRHWTPRRGVGA

(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 *new*

Classification	Condition	Strain	Method	Reference	Notes
Essential	Sodium Oleate	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.995250; 10 non-insertions in a row out of 13 sites
Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.999450; 10 non-insertions in a row out of 13 sites
Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.999750; 10 non-insertions in a row out of 13 sites
Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.999500; 10 non-insertions in a row out of 13 sites
Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.998800; 10 non-insertions in a row out of 13 sites
No-Data	7H10-glycerol	H37RvMA	TraSH	Sassetti et al. (2003a)
Too-Short	C57BL/6J mice (8 weeks)	H37RvMA	TraSH	Sassetti et al. (2003b)	Hybridization Ratio: -1
Non-Essential	7H09/7H10 + rich media	H37RvMA	MotifHMM	DeJesus et al. (2017)	Fully saturated (14 reps).

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

RNA processing and modification

Energy production and conversion

Chromatin structure and dynamics

Amino acid transport and metabolism

Cell cycle control, cell division, chromosome partitioning

Carbohydrate transport and metabolism

Nucleotide transport and metabolism

Lipid transport and metabolism

Coenzyme transport and metabolism

Transcription

Translation, ribosomal structure and biogenesis

Cell wall/membrane/envelope biogenesis

Replication, recombination and repair

Posttranslational modification, protein turnover, chaperones

Cell motility

Secondary metabolites biosynthesis, transport and catabolism

Inorganic ion transport and metabolism

Function unknown

General function prediction only

Intracellular trafficking, secretion, and vesicular transport

Signal transduction mechanisms

Extracellular structures

Defense mechanisms

Nuclear structure

Cytoskeleton

BioCyc Co-regulated genes based on gene expression profiling (Systems Biology, Inferelator Network)

Differentially expressed as result of RNASeq in glycerol environment (Only top 20 genes shown sorted by log fold change with p_adj 0.05).

Conditionally essential as result of TNSeq (Only top 20 genes shown sorted by log fold change with p_adj 0.05).

BioCyc Transcription factor binding based on ChIP-Seq (Systems Biology)

Binds To:
- No bindings to other targets were found.
Bound By:
- No bindings from other targets were found.

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:
- Not downregulated by other genes.

Property	Value	Creator	Evidence	PMID	Comment
Citation	The glycosyltransferase gene encoding the enzyme catalyzing the first step of mycothiol biosynthesis (mshA). GL. Newton, T. Koledin et al. J. Bacteriol. 2003	njamshidi	IDA	\|12754249	See PMID: 12754249, Cole et al text: Tuberculosis and Tubercle Bacillus
Term	TBRXN:IACGAMS 1D-myo-inositol 2-Acetamido-2-deoxy-D-glucopyranoside synthesis - IDA	njamshidi	IDA	\|12754249	See PMID: 12754249, Cole et al text: Tuberculosis and Tubercle Bacillus GL. Newton, T. Koledin et al. The glycosyltransferase gene encoding the enzyme catalyzing the first step of mycothiol biosynthesis (mshA). J. Bacteriol. 2003
Citation	The glycosyltransferase gene encoding the enzyme catalyzing the first step of mycothiol biosynthesis (mshA). GL. Newton, T. Koledin et al. J. Bacteriol. 2003	njamshidi	ISS	\|12754249	See PMID: 12754249, Cole et al text: Tuberculosis and Tubercle Bacillus
Term	TBRXN:IACGAMS 1D-myo-inositol 2-Acetamido-2-deoxy-D-glucopyranoside synthesis - ISS	njamshidi	ISS	\|12754249	See PMID: 12754249, Cole et al text: Tuberculosis and Tubercle Bacillus GL. Newton, T. Koledin et al. The glycosyltransferase gene encoding the enzyme catalyzing the first step of mycothiol biosynthesis (mshA). J. Bacteriol. 2003
Interaction	Regulatory Rv0485	shahanup86	NAS		GL. Newton, N. Buchmeier et al. Biosynthesis and functions of mycothiol, the unique protective thiol of Actinobacteria. Microbiol. Mol. Biol. Rev. 2008
Citation	Biosynthesis and functions of mycothiol, the unique protective thiol of Actinobacteria. GL. Newton, N. Buchmeier et al. Microbiol. Mol. Biol. Rev. 2008	gaat3s	NAS	18772286	None
Interaction	Regulatory Rv0485	gaat3s	NAS		GL. Newton, N. Buchmeier et al. Biosynthesis and functions of mycothiol, the unique protective thiol of Actinobacteria. Microbiol. Mol. Biol. Rev. 2008
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
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

TB Genome Annotation Portal