Rv2610c (pimA)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: GDP-mannose-dependent alpha-(1-2)-phosphatidylinositol mannosyltransferase
- REFSEQ: alpha-mannosyltransferase PIMA
- PATRIC: Phosphatidylinositol alpha-mannosyltransferase (EC 2.4.1.57)
- TUBERCULIST: Alpha-mannosyltransferase PimA
- NCBI: Alpha-mannosyltransferase PimA
- updated information (H37Rv4):
  - gene name: pimA
  - function:
  - reference:
Type: Not Target
Start: 2937865
End: 2939001
Operon:

Trans-membrane region:
Role: IV.H - Miscellaneous transferases
GO terms:
- GO:0097502 - mannosylation (Uniprot)
- GO:0046488 - phosphatidylinositol metabolic process (Uniprot)
- GO:0043750 - phosphatidylinositol alpha-mannosyltransferase activity (Uniprot)
- GO:0016757 - transferase activity, transferring glycosyl groups (Uniprot)
- GO:0016740 - transferase activity (Uniprot)
- GO:0016020 - membrane (Uniprot)
- GO:0009405 - pathogenesis (Uniprot)
- GO:0009247 - glycolipid biosynthetic process (Uniprot)
- GO:0008654 - phospholipid biosynthetic process (Uniprot)
- GO:0006629 - lipid metabolic process (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0004377 - GDP-Man:Man3GlcNAc2-PP-Dol alpha-1,2-mannosyltransferase activity (Uniprot)
- GO:0000287 - magnesium ion binding (Uniprot)
- GO:0000030 - mannosyltransferase activity (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
- GDPMAN[c] + PI_TBA[c] -> GDP[c] + AC1PIM1[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
4NC9	82%	Mycobacterium smegmatis	Crystal structure of phosphatidyl mannosyltransferase PimA
4N9W	82%	Mycobacterium smegmatis	Crystal structure of phosphatidyl mannosyltransferase PimA
2GEK	82%	Mycobacterium smegmatis	Crystal Structure of phosphatidylinositol mannosyltransferase (PimA) from Mycobacterium smegmatis in complex with GDP
2GEJ	82%	Mycobacterium smegmatis	Crystal Structure of phosphatidylinositol mannosyltransferase (PimA) from Mycobacterium smegmatis in complex with GDP-Man

Links to additional information on pimA:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -5.252 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MRIGMICPYSFDVPGGVQSHVLQLAEVMRTRGHLVSVLAPASPHAALPDYFVSGGRAVPIPYNGSVARLRFGPATHRKVKKWLAHGDFDVLHLHEPNAPS
LSMLALNIAEGPIVATFHTSTTKSLTLTVFQGILRPMHEKIVGRIAVSDLARRWQMEALGSDAVEIPNGVDVDSFASAARLDGYPRQGKTVLFLGRYDEP
RKGMAVLLDALPKVVQRFPDVQLLIVGHGDADQLRGQAGRLAAHLRFLGQVDDAGKASAMRSADVYCAPNTGGESFGIVLVEAMAAGTAVVASDLDAFRR
VLRDGEVGHLVPVDPPDLQAAALADGLIAVLENDVLRERYVAAGNAAVRRYDWSVVASQIMRVYETVAGSGAKVQVAS

(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: 0.999900; 16 non-insertions in a row out of 16 sites
Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 1.000000; 16 non-insertions in a row out of 16 sites
Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 1.000000; 16 non-insertions in a row out of 16 sites
Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 1.000000; 16 non-insertions in a row out of 16 sites
Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.999950; 16 non-insertions in a row out of 16 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
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:
- Rv0966c (-) (Direct binding)
- Rv0967 (csoR) (Direct binding)
- Rv1460 (-) (Direct binding)
- Rv1953 (vapC14) (Direct binding)
- Rv1954c (-) (Direct binding)
- Rv2621c (-) (Direct binding)
- Rv2622 (-) (Direct binding)
- Rv3065 (mmr) (Direct binding)
- Rv3290c (lat) (Direct binding)
- Rv3746c (PE34) (Direct binding)
- Rv3747 (-) (Direct binding)
- Rv0965c (-) (Upstream of operon)
- Rv1461 (-) (Upstream of operon)
- Rv1462 (-) (Upstream of operon)
- Rv1463 (-) (Upstream of operon)
- Rv1464 (csd) (Upstream of operon)
- Rv1465 (-) (Upstream of operon)
- Rv1466 (-) (Upstream of operon)
- Rv2619c (-) (Upstream of operon)
- Rv2620c (-) (Upstream of operon)
- Rv3066 (-) (Upstream of operon)
- Rv3288c (usfY) (Upstream of operon)
- Rv3289c (-) (Upstream of operon)
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	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	njamshidi	ISS	12851411	known to occur physiologically see for example PMID: 12851411
Term	EC:2.4.1.131 GDP-Man:Man(3)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase. - ISS	njamshidi	ISS	12851411	known to occur physiologically see for example PMID: 12851411 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
Term	TBRXN:G16MTM1 Glycolipid 1,6-alpha-D-mannosyltransferase - ISS	njamshidi	ISS	12851411	known to occur physiologically see for example PMID: 12851411 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	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	njamshidi	IPI	12851411	known to occur physiologically see for example PMID: 12851411
Term	EC:2.4.1.131 GDP-Man:Man(3)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase. - IPI	njamshidi	IPI	12851411	known to occur physiologically see for example PMID: 12851411 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
Term	TBRXN:G16MTM1 Glycolipid 1,6-alpha-D-mannosyltransferase - IPI	njamshidi	IPI	12851411	known to occur physiologically see for example PMID: 12851411 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
Interaction	PhysicalInteraction Rv2611c	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
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 Rv2611c	shahanup86	NAS		Operon (Functional linkage) authors,PJ. Brennan Structure, function, and biogenesis of the cell wall of Mycobacterium tuberculosis. Tuberculosis (Edinb) 2003
Name	GDP-Man-dependent alpha-1,2-phosphatidylinositol mannosyltransferase; essential gene in M. tb (Barilone, Stadthagen, Jackson; unpublished result)	mjackson	IMP		PIM, LM and LAM biosynthesis
Name	GDP-Man-dependent alpha-1,2-phosphatidylinositol mannosyltransferase; essential gene in M. tb (Barilone, Stadthagen, Jackson; unpublished result)	mjackson	IDA		PIM, LM and LAM biosynthesis
Citation	Definition of the first mannosylation step in phosphatidylinositol mannoside synthesis. PimA is essential for growth of mycobacteria. J. Kordulkov, M. Gilleron et al. J. Biol. Chem. 2002	mjackson		12068013	GDP-Man-dependent alpha-1,2-phosphatidylinositol mannosyltransferase (phenotypic [mycobacterial recombinant strains]; enzymatic); essential gene in M. tb (Barilone, Stadthagen, Jackson; unpublished)
Other	TBPWY:PIM, LM and LAM biosynthesis	mjackson			GDP-Man-dependent alpha-1,2-phosphatidylinositol mannosyltransferase (phenotypic [mycobacterial recombinant strains]; enzymatic); essential gene in M. tb (Barilone, Stadthagen, Jackson; unpublished) J. Kordulkov, M. Gilleron et al. Definition of the first mannosylation step in phosphatidylinositol mannoside synthesis. PimA is essential for growth of mycobacteria. J. Biol. Chem. 2002
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	GDP-Man-dependent alpha-1,2-phosphatidylinositol mannosyltransferase (phenotypic [mycobacterial recombinant strains]; enzymatic); essential gene in M. tb (Barilone, Stadthagen, Jackson; unpublished)
Other	TBPWY:PIM, LM and LAM biosynthesis	mjackson			GDP-Man-dependent alpha-1,2-phosphatidylinositol mannosyltransferase (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

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