Rv0819 (mshD)
Current annotations:
TBCAP: (community-based annotations - see table at bottom of page )
TBDB: mycothiol acetyltransferase
REFSEQ: hypothetical protein
PATRIC: Acetyl-CoA:Cys-GlcN-Ins acetyltransferase mycothiol synthase MshD
TUBERCULIST: GCN5-related N-acetyltransferase MshD
NCBI: GCN5-related N-acetyltransferase, MshD
updated information (H37Rv4):
gene name: mshD
function:
reference:
Type: Essential
Start: 911736
End: 912683
Operon:
Trans-membrane region:
Role: V - Conserved hypotheticals
GO terms:
GO:0071468 - cellular response to acidic pH (Uniprot)
GO:0070301 - cellular response to hydrogen peroxide (Uniprot)
GO:0044119 - growth of symbiont in host cell (Uniprot)
GO:0035447 - mycothiol synthase activity (Uniprot)
GO:0016747 - transferase activity, transferring acyl groups other than amino-acyl groups (Uniprot)
GO:0016746 - transferase activity, transferring acyl groups (Uniprot)
GO:0016740 - transferase activity (Uniprot)
GO:0010126 - mycothiol metabolic process (Uniprot)
GO:0010125 - mycothiol biosynthetic process (Uniprot)
GO:0008080 - N-acetyltransferase activity (Uniprot)
GO:0005829 - cytosol (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
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: 1p0h , 1ozp , 2c27
Search for Homologs in PDB
Top 10 Homologs in PDB (as of Nov 2020): PDB aa ident species PDB title 2C27 99% MYCOBACTERIUM TUBERCULOSIS The Structure of Mycothiol Synthase in Complex with des- AcetylMycothiol and CoenzymeA. 1P0H 99% Mycobacterium tuberculosis Crystal Structure of Rv0819 from Mycobacterium Tuberculosis MshD-Mycothiol Synthase Coenzyme A Complex 1OZP 99% Mycobacterium tuberculosis Crystal Structure of Rv0819 from Mycobacterium tuberculosis MshD-Mycothiol Synthase Acetyl-Coenzyme A Complex.
Links to additional information on mshD:
Amino Acid Sequence
VTALDWRSALTADEQRSVRALVTATTAVDGVAPVGEQVLRELGQQRTEHLLVAGSRPGGPIIGYLNLSPPRGAGGAMAELVVHPQSRRRGIGTAMARAAL
AKTAGRNQFWAHGTLDPARATASALGLVGVRELIQMRRPLRDIPEPTIPDGVVIRTYAGTSDDAELLRVNNAAFAGHPEQGGWTAVQLAERRGEAWFDPD
GLILAFGDSPRERPGRLLGFHWTKVHPDHPGLGEVYVLGVDPAAQRRGLGQMLTSIGIVSLARRLGGRKTLDPAVEPAVLLYVESDNVAAVRTYQSLGFT
TYSVDTAYALAGTDN
(
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 (0.38) 1.84 (0.78)
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"
MtbTnDB - interactive tool for exploring a database of published TnSeq datasets for Mtb
TnSeqCorr - genes with correlated TnSeq profiles across ~100 conditions
Rv0819/mshD,
gene len: 947 bp, num TA sites: 14
condition dataset call medium method notes
in-vitro DeJesus 2017 mBio growth advantage 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 uncertain M9 minimal+cholesterol Gumbel 3 replicates; Padj<0.05
differentially essential in cholesterol Griffin 2011 PPath NO (LFC=2.11) 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 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, vitamins)
differentially essential in YM rich medium Minato 2019 mSys NO (LFC=-0.36) 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
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
Translation, ribosomal structure and biogenesis
Cell wall/membrane/envelope biogenesis
Replication, recombination and repair
Posttranslational modification, protein turnover, chaperones
Secondary metabolites biosynthesis, transport and catabolism
Inorganic ion transport and metabolism
General function prediction only
Intracellular trafficking, secretion, and vesicular transport
Signal transduction mechanisms
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).
Binds To:
No bindings to other targets were found.
Bound By:
No bindings from other targets were found.
Binds To:
No bindings to other targets were found.
Bound By:
No bindings to other targets were found.
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
Term TBRXN:MSHS mycothiol synthase - IDA njamshidi IDA |12754249|12930994 see PMID: 12754249, 12930994, Cole et al textMW. Vetting, SL. Roderick et al. Crystal structure of mycothiol synthase (Rv0819) from Mycobacterium tuberculosis shows structural homology to the GNAT family of N-acetyltransferases. Protein Sci. 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|12930994 see PMID: 12754249, 12930994, Cole et al text
Term TBRXN:MSHS mycothiol synthase - ISS njamshidi ISS |12754249|12930994 see PMID: 12754249, 12930994, Cole et al textGL. Newton, T. Koledin et al. The glycosyltransferase gene encoding the enzyme catalyzing the first step of mycothiol biosynthesis (mshA). J. Bacteriol. 2003
Citation Crystal structure of mycothiol synthase (Rv0819) from Mycobacterium tuberculosis shows structural homology to the GNAT family of N-acetyltransferases. MW. Vetting, SL. Roderick et al. Protein Sci. 2003 njamshidi ISS |12754249|12930994 see PMID: 12754249, 12930994, Cole et al text
Term TBRXN:MSHS mycothiol synthase - ISS njamshidi ISS |12754249|12930994 see PMID: 12754249, 12930994, Cole et al textMW. Vetting, SL. Roderick et al. Crystal structure of mycothiol synthase (Rv0819) from Mycobacterium tuberculosis shows structural homology to the GNAT family of N-acetyltransferases. Protein Sci. 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 IDA |12754249|12930994 see PMID: 12754249, 12930994, Cole et al text
Term TBRXN:MSHS mycothiol synthase - IDA njamshidi IDA |12754249|12930994 see PMID: 12754249, 12930994, Cole et al textGL. Newton, T. Koledin et al. The glycosyltransferase gene encoding the enzyme catalyzing the first step of mycothiol biosynthesis (mshA). J. Bacteriol. 2003
Citation Crystal structure of mycothiol synthase (Rv0819) from Mycobacterium tuberculosis shows structural homology to the GNAT family of N-acetyltransferases. MW. Vetting, SL. Roderick et al. Protein Sci. 2003 njamshidi IDA |12754249|12930994 see PMID: 12754249, 12930994, Cole et al text
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 assayGL. Newton, T. Koledin et al. The glycosyltransferase gene encoding the enzyme catalyzing the first step of mycothiol biosynthesis (mshA). J. Bacteriol. 2003
Citation Crystal structure of mycothiol synthase (Rv0819) from Mycobacterium tuberculosis shows structural homology to the GNAT family of N-acetyltransferases. MW. Vetting, SL. Roderick et al. Protein Sci. 2003 extern:JZUCKER 12930994 Assay of protein purified to homogeneity
Term EC:2.3.1.189 Mycothiol synthase. - NR extern:JZUCKER NR Assay of protein purified to homogeneityMW. Vetting, SL. Roderick et al. Crystal structure of mycothiol synthase (Rv0819) from Mycobacterium tuberculosis shows structural homology to the GNAT family of N-acetyltransferases. Protein Sci. 2003