Rv2959c (-)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: rhamnosyl O-methyltransferase
- REFSEQ: methyltransferase (methylase)
- PATRIC: POSSIBLE METHYLTRANSFERASE (METHYLASE)
- TUBERCULIST: Possible methyltransferase (methylase)
- NCBI: Possible methyltransferase (methylase)
- updated information (H37Rv4):
  - gene name: -
  - function:
  - reference:
Type: Not Target
Start: 3312101
End: 3312838
Operon:

Trans-membrane region:
Role: IV.H - Miscellaneous transferases
GO terms:
- GO:0071770 - DIM/DIP cell wall layer assembly (Uniprot)
- GO:0032259 - methylation (Uniprot)
- GO:0030206 - chondroitin sulfate biosynthetic process (Uniprot)
- GO:0016740 - transferase activity (Uniprot)
- GO:0008610 - lipid biosynthetic process (Uniprot)
- GO:0008168 - methyltransferase activity (Uniprot)
- GO:0006629 - lipid metabolic process (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
- SAM[c] + HBARHAM2[c] -> SAH[c] + PHBAD1[c]
- SAM[c] + PHDIMRHAM2[c] -> SAH[c] + MYCOSIDE[B][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): (none with >35% aa id)
Links to additional information on Rv2959c:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 1.412 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MGLVWRSRTSLVGQLIGLVRLVASFAAQLFYRPSDAVAEEYHKWYYGNLVWTKTTYMGINCWKSVSDMWNYQEILSELQPSLVIEFGTRYGGSAVYFANI
MRQIGQPFKVLTVDNSHKALDPRARREPDVLFVESSSTDPAIAEQIQRLKNEYPGKIFAILDSDHSMNHVLAEMKLLRPLLSAGDYLVVEDSNINGHPVL
PGFGPGPYEAIEAYEDEFPNDYKHDAERENKFGWTSAPNGFLIRN

(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)	1.83 (0.37)	1.29 (0.66)
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

Rv2959c/-, gene len: 737 bp, num TA sites: 32

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	no data	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=0.44)	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	non-essential	7H9	HMM	6 replicates (raw data in Subramaniam 2017, PMID 31752678)
in-vivo (mice)	Smith 2022 eLife	non-essential	BL6 mice	HMM	6 replicates (raw data in Subramaniam 2017, PMID 31752678)
differentially essential in mice	Smith 2022 eLife	NO (LFC=-0.004)	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=0.65)	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:
- Rv0967 (csoR) (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:

Property	Value	Creator	Evidence	PMID	Comment
Interaction	Operon Rv2958c	priti.priety	IMP		Methylation interface E. Prez, P. Constant et al. Molecular dissection of the role of two methyltransferases in the biosynthesis of phenolglycolipids and phthiocerol dimycoserosate in the Mycobacterium tuberculosis complex. J. Biol. Chem. 2004
Citation	Molecular dissection of the role of two methyltransferases in the biosynthesis of phenolglycolipids and phthiocerol dimycoserosate in the Mycobacterium tuberculosis complex. E. Prez, P. Constant et al. J. Biol. Chem. 2004	priti.priety	IMP	15292265	Methylation interface
Interaction	RegulatedBy Rv0348	yamir.moreno	IEP		Microarrays. mRNA levels of regulated element measured and compared between wild-type and trans-element mutation (knockout, over expression etc.) performed by using microarray (or macroarray) experiments.. B. Abomoelak, EA. Hoye et al. mosR, a novel transcriptional regulator of hypoxia and virulence in Mycobacterium tuberculosis. J. Bacteriol. 2009
Name	SAM-dependent methyltransferase responsible for the O-methylation of the hydroxyl group at position 2 of the rhamnosyl residue linked to the phenolic group of phenolic glycolipids and p-hydroxybenzoic acid derivatives	mjackson	IMP		Phthiocerol dimycocerosates (PDIM), phenolic glycolipids (PGL) and para-hydroxybenzoic acid derivatives
Citation	Molecular dissection of the role of two methyltransferases in the biosynthesis of phenolglycolipids and phthiocerol dimycoserosate in the Mycobacterium tuberculosis complex. E. Prez, P. Constant et al. J. Biol. Chem. 2004	mjackson		15292265	SAM-dependent methyltransferase responsible for the O-methylation of the hydroxyl group at position 2 of the rhamnosyl residue linked to the phenolic group of phenolic glycolipids and p-hydroxybenzoic acid derivatives (phenotypic [mycobacterial recombinant strains])
Other	TBPWY:Phthiocerol dimycocerosates, PGL & pHBAD	mjackson			SAM-dependent methyltransferase responsible for the O-methylation of the hydroxyl group at position 2 of the rhamnosyl residue linked to the phenolic group of phenolic glycolipids and p-hydroxybenzoic acid derivatives (phenotypic [mycobacterial recombinant strains]) E. Prez, P. Constant et al. Molecular dissection of the role of two methyltransferases in the biosynthesis of phenolglycolipids and phthiocerol dimycoserosate in the Mycobacterium tuberculosis complex. J. Biol. Chem. 2004
Citation	Characterization of three glycosyltransferases involved in the biosynthesis of the phenolic glycolipid antigens from the Mycobacterium tuberculosis complex. E. Prez, P. Constant et al. J. Biol. Chem. 2004	jjmcfadden		15292272	Inferred from direct assay
Term	EC:2.1.1.- Transferases. Transferring one-carbon groups. Methyltransferases. - NR	jjmcfadden	NR		Inferred from direct assay E. Prez, P. Constant et al. Characterization of three glycosyltransferases involved in the biosynthesis of the phenolic glycolipid antigens from the Mycobacterium tuberculosis complex. J. Biol. Chem. 2004

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