Rv2611c (-)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: phosphatidylinositol mannoside acyltransferase
- REFSEQ: lipid A biosynthesis lauroyl acyltransferase
- PATRIC: Lauroyl/myristoyl acyltransferase involved in lipid A biosynthesis (Lauroyl/myristoyl acyltransferase)
- TUBERCULIST: Probable acyltransferase
- NCBI: Probable acyltransferase
- updated information (H37Rv4):
  - gene name: acylT
  - function: PIM synthesis
  - reference: Kordulakova 2003, PMID: 12851411
Type: Essential
Start: 2939012
End: 2939962
Operon:

Trans-membrane region:
Role: V - Conserved hypotheticals
GO terms:
- GO:0046488 - phosphatidylinositol metabolic process (Uniprot)
- GO:0040007 - growth (Uniprot)
- GO:0016746 - transferase activity, transferring acyl groups (Uniprot)
- GO:0016740 - transferase activity (Uniprot)
- GO:0016021 - integral component of membrane (Uniprot)
- GO:0016020 - membrane (Uniprot)
- GO:0009247 - glycolipid biosynthetic process (Uniprot)
- GO:0005886 - plasma membrane (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:
Search for Homologs in PDB

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

PDB	aa ident	species	PDB title
5OCE	73%	Mycobacterium smegmatis (strain ATCC 700084 / mc(2)155)	THE MOLECULAR MECHANISM OF SUBSTRATE RECOGNITION AND CATALYSIS OF THE MEMBRANE ACYLTRANSFERASE PatA -- Complex of PatA with palmitate, mannose, and palmitoyl-6-mannose
5F34	73%	Mycobacterium smegmatis str. MC2 155	Crystal structure of membrane associated PatA from Mycobacterium smegmatis in complex with S-hexadecyl Coenzyme A - P21 space group
5F31	73%	Mycobacterium smegmatis str. MC2 155	Crystal structure of membrane associated PatA from Mycobacterium smegmatis in complex with palmitate - P 42 21 2 space group
5F2Z	73%	Mycobacterium smegmatis str. MC2 155	Crystal structure of membrane associated PatA from Mycobacterium smegmatis in complex with palmitate - P21 space group
5F2T	73%	Mycobacterium smegmatis	Crystal structure of membrane associated PatA from Mycobacterium smegmatis in complex with palmitate - C 2 space group

Links to additional information on Rv2611c:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -7.73 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology
- Photo of spot titer

Amino Acid Sequence

VIAGLKGLKLPKDPRSSVTRTATDWAYAAGWMAVRALPEFAVRNAFDTGARYFARHGGPEQLRKNLARVLGVPPAAVPDPLMCASLESYGRYWREVFRLP
TINHRKLARQLDRVIGGLDHLDAALAAGLGAVLALPHSGNWDMAGMWLVQRHGTFTTVAERLKPESLYQRFIDYRESLGFEVLPLSGGERPPFEVLSERL
RNNRVVCLMAERDLTRTGVEVDFFGEPTRMPVGPAKLAVETGAALLPTHCWFEGRGWGFQVYPALDCTSGDVAAITQALADRFAQNIAAHPADWHMLQPQ
WLADLSESRRAQLRSR

(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)	1.17 (0.17)	1.94 (0.64)
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

Rv2611c/-, gene len: 950 bp, num TA sites: 15

condition	dataset	call	medium	method	notes
in-vitro	DeJesus 2017 mBio	essential	7H9	HMM	fully saturated, 14 TnSeq libraries combined
in-vitro	Sassetti 2003 Mol Micro	essential	7H9	TRASH	essential if hybridization ratio<0.2
in-vivo (mice)	Sassetti 2003 PNAS	no data	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	essential	M9 minimal+cholesterol	Gumbel	3 replicates; Padj<0.05
differentially essential in cholesterol	Griffin 2011 PPath	NO (LFC=0.0)	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=-0.018)	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	growth defect	minimal medium	HMM
in-vitro (YM rich medium)	Minato 2019 mSys	essential	YM rich medium	HMM	7H9 supplemented with ~20 metabolites (amino acids, cofactors)
differentially essential in YM rich medium	Minato 2019 mSys	NO (LFC=-2.43)	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

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
Term	TBRXN:MANAT2 mannosyl acyl transferase - ISS	njamshidi	ISS	14627436	presently only adding C16:0 onto PIM core - R3 position may be C16 or C19; R4 may be C16, C18, or C19 - see for example PMID: 14627436 authors,YS. Morita,JH. Patterson,H. Billman-Jacobe,MJ. McConville Biosynthesis of mycobacterial phosphatidylinositol mannosides. Biochem. J. 2004
Citation	Biosynthesis of mycobacterial phosphatidylinositol mannosides. authors,YS. Morita,JH. Patterson,H. Billman-Jacobe,MJ. McConville Biochem. J. 2004	njamshidi	IPI	14627436	presently only adding C16:0 onto PIM core - R3 position may be C16 or C19; R4 may be C16, C18, or C19 - see for example PMID: 14627436
Term	TBRXN:MANAT2 mannosyl acyl transferase - IPI	njamshidi	IPI	14627436	presently only adding C16:0 onto PIM core - R3 position may be C16 or C19; R4 may be C16, C18, or C19 - see for example PMID: 14627436 authors,YS. Morita,JH. Patterson,H. Billman-Jacobe,MJ. McConville Biosynthesis of mycobacterial phosphatidylinositol mannosides. Biochem. J. 2004
Citation	Biosynthesis of mycobacterial phosphatidylinositol mannosides. authors,YS. Morita,JH. Patterson,H. Billman-Jacobe,MJ. McConville Biochem. J. 2004	njamshidi	ISS	14627436	presently only adding C16:0 onto PIM core - R3 position may be C16 or C19; R4 may be C16, C18, or C19 - see for example PMID: 14627436
Term	TBRXN:MANAT1 mannosyl acyl transferase - ISS	njamshidi	ISS	14627436	presently only adding C16:0 onto PIM core - R3 position may be C16 or C19; R4 may be C16, C18, or C19 - see for example PMID: 14627436 authors,YS. Morita,JH. Patterson,H. Billman-Jacobe,MJ. McConville Biosynthesis of mycobacterial phosphatidylinositol mannosides. Biochem. J. 2004
Citation	Biosynthesis of mycobacterial phosphatidylinositol mannosides. authors,YS. Morita,JH. Patterson,H. Billman-Jacobe,MJ. McConville Biochem. J. 2004	njamshidi	IPI	14627436	presently only adding C16:0 onto PIM core - R3 position may be C16 or C19; R4 may be C16, C18, or C19 - see for example PMID: 14627436
Term	TBRXN:MANAT1 mannosyl acyl transferase - IPI	njamshidi	IPI	14627436	presently only adding C16:0 onto PIM core - R3 position may be C16 or C19; R4 may be C16, C18, or C19 - see for example PMID: 14627436 authors,YS. Morita,JH. Patterson,H. Billman-Jacobe,MJ. McConville Biosynthesis of mycobacterial phosphatidylinositol mannosides. Biochem. J. 2004
Citation	Biosynthesis of mycobacterial phosphatidylinositol mannosides. authors,YS. Morita,JH. Patterson,H. Billman-Jacobe,MJ. McConville Biochem. J. 2004	njamshidi	ISS	14627436	presently only adding C16:0 onto PIM core - R3 position may be C16 or C19; R4 may be C16, C18, or C19 - see for example PMID: 14627436
Citation	Structure, function, and biogenesis of the cell wall of Mycobacterium tuberculosis. authors,PJ. Brennan Tuberculosis (Edinb) 2003	shahanup86	NAS	12758196	Operon (Functional linkage)
Interaction	PhysicalInteraction Rv2609c	shahanup86	NAS		Operon (Functional linkage) authors,PJ. Brennan Structure, function, and biogenesis of the cell wall of Mycobacterium tuberculosis. Tuberculosis (Edinb) 2003
Interaction	PhysicalInteraction Rv2610c	shahanup86	NAS		Operon (Functional linkage) authors,PJ. Brennan Structure, function, and biogenesis of the cell wall of Mycobacterium tuberculosis. Tuberculosis (Edinb) 2003
Interaction	PhysicalInteraction Rv2609c	shahanup86	NAS		Operon (Functional linkage) authors,PJ. Brennan Structure, function, and biogenesis of the cell wall of Mycobacterium tuberculosis. Tuberculosis (Edinb) 2003
Interaction	PhysicalInteraction Rv2610c	shahanup86	NAS		Operon (Functional linkage) authors,PJ. Brennan Structure, function, and biogenesis of the cell wall of Mycobacterium tuberculosis. Tuberculosis (Edinb) 2003
Name	Acyltransferase involved in the 6-O-acylation of the Man residue linked to the 2-position of myo-Inositol in PIM1 and PIM2; essential gene in M. tb (Barilone, Stadthagen, Jackson; unpublished result)	mjackson	IMP		PIM, LM and LAM biosynthesis
Name	Acyltransferase involved in the 6-O-acylation of the Man residue linked to the 2-position of myo-Inositol in PIM1 and PIM2; essential gene in M. tb (Barilone, Stadthagen, Jackson; unpublished result)	mjackson	IDA		PIM, LM and LAM biosynthesis
Other	TBPWY:PIM, LM and LAM biosynthesis	mjackson			Acyltransferase involved in the 6-O-acylation of the Man residue linked to the 2-position of myo-Inositol in PIM1 and PIM2 (phenotypic [mycobacterial recombinant strains]; enzymatic); essential gene in M. tb (Barilone, Stadthagen, Jackson; unpublished) ME. Guerin, D. Kaur et al. New insights into the early steps of phosphatidylinositol mannoside biosynthesis in mycobacteria: PimB' is an essential enzyme of Mycobacterium smegmatis. J. Biol. Chem. 2009
Citation	Identification of the required acyltransferase step in the biosynthesis of the phosphatidylinositol mannosides of mycobacterium species. J. Kordulkov, M. Gilleron et al. J. Biol. Chem. 2003	mjackson		12851411	Acyltransferase involved in the 6-O-acylation of the Man residue linked to the 2-position of myo-Inositol in PIM1 and PIM2 (phenotypic [mycobacterial recombinant strains]; enzymatic); essential gene in M. tb (Barilone, Stadthagen, Jackson; unpublished)
Other	TBPWY:PIM, LM and LAM biosynthesis	mjackson			Acyltransferase involved in the 6-O-acylation of the Man residue linked to the 2-position of myo-Inositol in PIM1 and PIM2 (phenotypic [mycobacterial recombinant strains]; enzymatic); essential gene in M. tb (Barilone, Stadthagen, Jackson; unpublished) J. Kordulkov, M. Gilleron et al. Identification of the required acyltransferase step in the biosynthesis of the phosphatidylinositol mannosides of mycobacterium species. J. Biol. Chem. 2003
Citation	New insights into the early steps of phosphatidylinositol mannoside biosynthesis in mycobacteria: PimB' is an essential enzyme of Mycobacterium smegmatis. ME. Guerin, D. Kaur et al. J. Biol. Chem. 2009	mjackson		19638342	Acyltransferase involved in the 6-O-acylation of the Man residue linked to the 2-position of myo-Inositol in PIM1 and PIM2 (phenotypic [mycobacterial recombinant strains]; enzymatic); essential gene in M. tb (Barilone, Stadthagen, Jackson; unpublished)

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