Rv2947c (pks15)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: polyketide synthase 1/15
- REFSEQ: polyketide synthase PKS15
- PATRIC: (MTCY24G1.02) len: 496 aa Probable polyketide synthase almost identical to G560508 PKS002B (495 aa) fasta scores opt: 3270 E(): 0 (99.6% identity in 496 aa overlap); contains PS00606 Beta-ketoacyl synthases active site; similar to MTCY338.20 (49.9% identity in 465 aa overlap) and MTCY24G1.09 (50.2% identity in 454 aa overlap) and MTCY22H8.03 (47.6% identity in 437 aa overlap)
- TUBERCULIST: Probable polyketide synthase Pks15
- NCBI: Probable polyketide synthase Pks15
- updated information (H37Rv4):
  - gene name: pks15
  - function:
  - reference:
Type: Not Target
Start: 3296350
End: 3297840
Operon:

Trans-membrane region:
Role: I.I - Polyketide and non-ribosomal peptide synthesis
GO terms:
- GO:0048037 - cofactor binding (Uniprot)
- GO:0016740 - transferase activity (Uniprot)
- GO:0009247 - glycolipid biosynthetic process (Uniprot)
- GO:0008152 - metabolic process (Uniprot)
- GO:0005829 - cytosol (Uniprot)
- GO:0003824 - catalytic activity (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
2HG4	64%	Saccharopolyspora erythraea	Structure of the ketosynthase-acyltransferase didomain of module 5 from DEBS.
2QO3	61%	Saccharopolyspora erythraea	Crystal Structure of [KS3][AT3] didomain from module 3 of 6-deoxyerthronolide B synthase
6C9U	60%	Saccharopolyspora erythraea	Crystal structure of [KS3][AT3] didomain from module 3 of 6-deoxyerthronolide B synthase in complex with antibody fragment (Fab)
4MZ0	50%	Moorea producens 3L	Structure of a ketosynthase-acyltransferase di-domain from module CurL of the curacin A polyketide synthase
5BP1	48%	Mycobacterium smegmatis (strain ATCC 700084 / mc(2)155)	Condensing di-domain (KS-AT) of a mycocerosic acid synthase-like (MAS-like) PKS
4OQJ	43%	Streptomyces albus	Streptomcyes albus JA3453 oxazolomycin ketosynthase domain OzmQ KS1
4ZDN	42%	Streptomyces platensis subsp. rosaceus	Streptomyces platensis isomigrastatin ketosynthase domain MgsF KS4
4WKY	42%	Streptomyces albus	Streptomcyes albus JA3453 oxazolomycin ketosynthase domain OzmN KS2
4QYR	42%	Streptomyces platensis subsp. rosaceus	Streptomyces platensis isomigrastatin ketosynthase domain MgsE KS3
4NA1	41%	Bacillus subtilis subsp. subtilis	Crystal Structure of the second ketosynthase from the bacillaene polyketide synthase

Links to additional information on pks15:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 1.134 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

VIEEQRTMSVEGADQQSEKLFHYLKKVAVELDETRARLREYEQRATEPVAVVGIGCRFPGGVDGPDGLWDVVSAGRDVVSEFPTDRGWDVEGLYDPDPDA
EGKTYTRWGAFLDDATGFDAGFFGIAPSEVLAMDPQQRLMLEVSWEALEHAGIDPLSLRGSATGVYTGIFAASYGNRDTGGLQGYGLTGTSISVASGRVS
YVLGLQGPAVSVDTACSSSLVAIHWAMSSLRSGECDLALAGGVTVMGLPSIFVGFSRQRGLAADGRCKAFAAAADGTGWGEGAGVVVLERLSDARRLGHS
VLAVVRGSAVNQDGASNGLTAPNGLAQQRVIQVALANAGLSAADVDVVEAHGTATTLGDPIEAQALLSTYGQGGPAEQPLWVGSIKSNMGHTQAAAGVAG
VIKMVQAMRHGVMPATLHVDEPSPRVDWTSGAVSVLTEAREWSVDGRPRRAAVSSFGISGTNAHLILEEAPVPAPAEAPVEASESTGGRGRRWCRG

(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
Non-Essential	Sodium Oleate	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 2 non-insertions in a row out of 22 sites
Non-Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 1 non-insertions in a row out of 22 sites
Non-Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 1 non-insertions in a row out of 22 sites
Non-Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 1 non-insertions in a row out of 21 sites
Non-Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 2 non-insertions in a row out of 21 sites
Non-Essential	7H10-glycerol	H37RvMA	TraSH	Sassetti et al. (2003a)
Non-Essential	C57BL/6J mice (8 weeks)	H37RvMA	TraSH	Sassetti et al. (2003b)	Hybridization Ratio: 1.3
Non-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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0023 (-)
- Rv3295 (-)

Interactions based on ChIPSeq data (Minch et al. 2014)

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0081 (-) (Direct binding)
- Rv0602c (tcrA) (Direct binding)
- Rv0678 (-) (Direct binding)
- Rv1985c (-) (Direct binding)
- Rv3765c (tcrX) (Direct binding)
- Rv0273c (-) (Upstream of operon)

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:
- Rv0023 (-)
- Rv3295 (-)

Property	Value	Creator	Evidence	PMID	Comment
Citation	Identification and substrate specificity of beta -ketoacyl (acyl carrier protein) synthase III (mtFabH) from Mycobacterium tuberculosis. KH. Choi, L. Kremer et al. J. Biol. Chem. 2000	njamshidi	IDA	10840036	mtFABH (Rv0533c) - link between FAS I and FAS II - highest affinity for C12:0, see PMID: 10840036 (since FA synthesis is lumped, does not extend immediately to FAS II).
Term	EC:2.3.1.85 Fatty-acid synthase. - IDA	njamshidi	IDA	10840036	mtFABH (Rv0533c) - link between FAS I and FAS II - highest affinity for C12:0, see PMID: 10840036 (since FA synthesis is lumped, does not extend immediately to FAS II). KH. Choi, L. Kremer et al. Identification and substrate specificity of beta -ketoacyl (acyl carrier protein) synthase III (mtFabH) from Mycobacterium tuberculosis. J. Biol. Chem. 2000
Term	TBRXN:FAS140 fatty acid synthase (n-C14:0) - IDA	njamshidi	IDA	10840036	mtFABH (Rv0533c) - link between FAS I and FAS II - highest affinity for C12:0, see PMID: 10840036 (since FA synthesis is lumped, does not extend immediately to FAS II). KH. Choi, L. Kremer et al. Identification and substrate specificity of beta -ketoacyl (acyl carrier protein) synthase III (mtFabH) from Mycobacterium tuberculosis. J. Biol. Chem. 2000
Interaction	RegulatedBy Rv1221	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.. R. Manganelli, MI. Voskuil et al. The Mycobacterium tuberculosis ECF sigma factor sigmaE: role in global gene expression and survival in macrophages. Mol. Microbiol. 2001
Name	Together with Pks1, type 1 polyketide synthase involved in the elongation of p-hydroxybenzoic acid derivatives with malonyl-CoA to form p-hydroxyphenylalkanoates (precursors of phenolic glycolipids [PGL]); the pks15 and pks1 genes are fused in PGL-producing strains of M. tuberculosis but a frameshift mutation causes this polyketide synthase to be inactive in the H37Rv strain	mjackson	IMP		Phthiocerol dimycocerosates (PDIM), phenolic glycolipids (PGL) and para-hydroxybenzoic acid derivatives
Other	TBPWY:Phthiocerol dimycocerosates, PGL & pHBAD	mjackson			Together with Pks1, type 1 polyketide synthase involved in the elongation of p-hydroxybenzoic acid derivatives with malonyl-CoA to form p-hydroxyphenylalkanoates (precursors of phenolic glycolipids [PGL]); the pks15 and pks1 genes are fused in PGL-producing strains of M. tuberculosis but a frameshift mutation causes this polyketide synthase to be inactive in the H37Rv strain (phenotypic [mycobacterial recombinant strains]). P. Constant, E. Perez et al. Role of the pks15/1 gene in the biosynthesis of phenolglycolipids in the Mycobacterium tuberculosis complex. Evidence that all strains synthesize glycosylated p-hydroxybenzoic methyl esters and that strains devoid of phenolglycolipids harbor a frameshift mutation in the pks15/1 gene. J. Biol. Chem. 2002
Citation	Role of the pks15/1 gene in the biosynthesis of phenolglycolipids in the Mycobacterium tuberculosis complex. Evidence that all strains synthesize glycosylated p-hydroxybenzoic methyl esters and that strains devoid of phenolglycolipids harbor a frameshift mutation in the pks15/1 gene. P. Constant, E. Perez et al. J. Biol. Chem. 2002	mjackson		12138124	Together with Pks1, type 1 polyketide synthase involved in the elongation of p-hydroxybenzoic acid derivatives with malonyl-CoA to form p-hydroxyphenylalkanoates (precursors of phenolic glycolipids [PGL]); the pks15 and pks1 genes are fused in PGL-producing strains of M. tuberculosis but a frameshift mutation causes this polyketide synthase to be inactive in the H37Rv strain (phenotypic [mycobacterial recombinant strains]).
Citation	Role of the pks15/1 gene in the biosynthesis of phenolglycolipids in the Mycobacterium tuberculosis complex. Evidence that all strains synthesize glycosylated p-hydroxybenzoic methyl esters and that strains devoid of phenolglycolipids harbor a frameshift mutation in the pks15/1 gene. P. Constant, E. Perez et al. J. Biol. Chem. 2002	jjmcfadden		12138124	Inferred from direct assay
Other	EC:	jjmcfadden			Inferred from direct assay P. Constant, E. Perez et al. Role of the pks15/1 gene in the biosynthesis of phenolglycolipids in the Mycobacterium tuberculosis complex. Evidence that all strains synthesize glycosylated p-hydroxybenzoic methyl esters and that strains devoid of phenolglycolipids harbor a frameshift mutation in the pks15/1 gene. J. Biol. Chem. 2002

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