Rv2958c (-)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: inactive PGL/p-HBAD biosynthesis glycosyltransferase
- REFSEQ: glycosyl transferase
- PATRIC: UDP-glucoronosyl and UDP-glucosyltransferases family protein
- TUBERCULIST: Possible glycosyl transferase
- NCBI: Possible glycosyl transferase
- updated information (H37Rv4):
  - gene name: -
  - function:
  - reference:
Type: Not Target
Start: 3310714
End: 3312000
Operon:

Trans-membrane region:
Role: IV.H - Miscellaneous transferases
GO terms:
- GO:0043231 - intracellular membrane-bounded organelle (Uniprot)
- GO:0020012 - evasion or tolerance of host immune response (Uniprot)
- GO:0016758 - transferase activity, transferring hexosyl groups (Uniprot)
- GO:0016757 - transferase activity, transferring glycosyl groups (Uniprot)
- GO:0016740 - transferase activity (Uniprot)
- GO:0009405 - pathogenesis (Uniprot)
- GO:0009247 - glycolipid biosynthetic process (Uniprot)
- GO:0008194 - UDP-glycosyltransferase activity (Uniprot)
- GO:0008152 - metabolic process (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
- HBA[c] + DTDPRHAM[c] -> DTDP[c] + HBARHAM2[c]
- DTDPRHAM[c] + PHDIMRHAM1[c] -> DTDP[c] + PHDIMRHAM2[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 Rv2958c:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 0.759 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MEETSVAGDPGPDAGTSTAPNAAPEPVARRQRILFVGEAATLAHVVRPFVLARSLDPSRYEVHFACDPRFNKLLGPLPFPHHPIHTVPSEEVLLKIAQGR
LFYNTRTLRKYIAADRKILNEIAPDVVVGDNRLSLSVSARLAGIPYIAIANAYWSPQARRRFPLPDVPWTRFFGVRPVSILYRLYRPLIFALYCLPLNWL
RRKHGLSSLGWDLCRIFTDGDYTLYADVPELVPTYNLPANHRYLGPVLWSPDVKPPTWWHSLPTDRPIIYATLGSSGGKNLLQVVLNALADLPVTVIAAT
AGRNHLKNVPANAFVADYLPGEAAAARSAVVLCNGGSPTTQQALAAGVPVIGLPSNMDQHLNMEALERAGAGVLLRTERLNTEGVAAAVKQVLSGAEFRQ
AARRLAEAFGPDFAGFPQHIESALRLVC

(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)	1.78 (0.4)	1.65 (0.79)
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

Rv2958c/-, gene len: 1286 bp, num TA sites: 26

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	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=0.67)	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=0.208)	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=0.46)	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:
- Rv0047c (-) (Direct binding)

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

Upregulates:
- Does not upregulate other genes.
Upregulated by:
- Rv1994c (cmtR)
Downregulates:
- Does not downregulate other genes.
Downregulated by:

Property	Value	Creator	Evidence	PMID	Comment
Term	TBRXN:RRPPDIMAS rhamnose rhamnose phenol phthiocerol dimycocerosate synthesis - IMP	njamshidi	IMP	15292272	See PMID: 15292272 and 10540187. Whether rhamnose or methoxy-ramnose is transfered is not yet clear, also the rhamnose donor has not been shown specifically to be dtdprmn authors,J. Fldt,C. Dahlgren,A. Karlsson,AM. Ahmed,DE. Minnikin,M. Ridell Activation of human neutrophils by mycobacterial phenolic glycolipids. Clin. Exp. Immunol. 1999
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	njamshidi	ISS	15292272	See PMID: 15292272 and 10540187. Whether rhamnose or methoxy-ramnose is transfered is not yet clear, also the rhamnose donor has not been shown specifically to be dtdprmn
Term	TBRXN:RRPPDIMAS rhamnose rhamnose phenol phthiocerol dimycocerosate synthesis - ISS	njamshidi	ISS	15292272	See PMID: 15292272 and 10540187. Whether rhamnose or methoxy-ramnose is transfered is not yet clear, also the rhamnose donor has not been shown specifically to be dtdprmn 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
Citation	Activation of human neutrophils by mycobacterial phenolic glycolipids. authors,J. Fldt,C. Dahlgren,A. Karlsson,AM. Ahmed,DE. Minnikin,M. Ridell Clin. Exp. Immunol. 1999	njamshidi	ISS	15292272\|10540187	See PMID: 15292272 and 10540187. Whether rhamnose or methoxy-ramnose is transfered is not yet clear, also the rhamnose donor has not been shown specifically to be dtdprmn
Term	TBRXN:RRPPDIMAS rhamnose rhamnose phenol phthiocerol dimycocerosate synthesis - ISS	njamshidi	ISS	15292272	See PMID: 15292272 and 10540187. Whether rhamnose or methoxy-ramnose is transfered is not yet clear, also the rhamnose donor has not been shown specifically to be dtdprmn authors,J. Fldt,C. Dahlgren,A. Karlsson,AM. Ahmed,DE. Minnikin,M. Ridell Activation of human neutrophils by mycobacterial phenolic glycolipids. Clin. Exp. Immunol. 1999
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	njamshidi	IMP	15292272	See PMID: 15292272 and 10540187. Whether rhamnose or methoxy-ramnose is transfered is not yet clear, also the rhamnose donor has not been shown specifically to be dtdprmn
Term	TBRXN:RRPPDIMAS rhamnose rhamnose phenol phthiocerol dimycocerosate synthesis - IMP	njamshidi	IMP	15292272	See PMID: 15292272 and 10540187. Whether rhamnose or methoxy-ramnose is transfered is not yet clear, also the rhamnose donor has not been shown specifically to be dtdprmn 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
Citation	Activation of human neutrophils by mycobacterial phenolic glycolipids. authors,J. Fldt,C. Dahlgren,A. Karlsson,AM. Ahmed,DE. Minnikin,M. Ridell Clin. Exp. Immunol. 1999	njamshidi	IMP	15292272\|10540187	See PMID: 15292272 and 10540187. Whether rhamnose or methoxy-ramnose is transfered is not yet clear, also the rhamnose donor has not been shown specifically to be dtdprmn
Interaction	Operon Rv2959c	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
Name	Rhamnosyltransferase responsible for the transfer of the second rhamnosyl residue of the triglycosyl appendage of phenolic glycolipids and p-hydroxybenzoic acid derivatives	mjackson	IMP		Phthiocerol dimycocerosates (PDIM), phenolic glycolipids (PGL) and para-hydroxybenzoic acid derivatives
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	mjackson		15292272	Rhamnosyltransferase responsible for the transfer of the second rhamnosyl residue of the triglycosyl appendage of phenolic glycolipids and p-hydroxybenzoic acid derivatives (phenotypic [mycobacterial recombinant strains])
Other	TBPWY:Phthiocerol dimycocerosates, PGL & pHBAD	mjackson			Rhamnosyltransferase responsible for the transfer of the second rhamnosyl residue of the triglycosyl appendage of phenolic glycolipids and p-hydroxybenzoic acid derivatives (phenotypic [mycobacterial recombinant strains]) 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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