Rv3825c (pks2)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: phthioceranic/hydroxyphthioceranic acid synthase
- REFSEQ: polyketide synthase PKS2
- PATRIC: Polyketide synthase
- TUBERCULIST: Polyketide synthase Pks2
- NCBI: Polyketide synthase Pks2
- updated information (H37Rv4):
  - gene name: pks2
  - function: sulfolipid-1 synthesis
  - reference: Seeliger (2012) PMID: 22194604
Type: Not Target
Start: 4293225
End: 4299605
Operon:

Trans-membrane region:
Role: I.I - Polyketide and non-ribosomal peptide synthesis
GO terms:
- GO:0055114 - oxidation-reduction process (Uniprot)
- GO:0031177 - phosphopantetheine binding (Uniprot)
- GO:0016746 - transferase activity, transferring acyl groups (Uniprot)
- GO:0016740 - transferase activity (Uniprot)
- GO:0016491 - oxidoreductase activity (Uniprot)
- GO:0010106 - cellular response to iron ion starvation (Uniprot)
- GO:0008152 - metabolic process (Uniprot)
- GO:0006633 - fatty acid biosynthetic process (Uniprot)
- GO:0006631 - fatty acid metabolic process (Uniprot)
- GO:0006629 - lipid metabolic process (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0005829 - cytosol (Uniprot)
- GO:0005618 - cell wall (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
5BP1	69%	Mycobacterium smegmatis (strain ATCC 700084 / mc(2)155)	Condensing di-domain (KS-AT) of a mycocerosic acid synthase-like (MAS-like) PKS
5BP4	61%	Mycobacterium smegmatis	Modifying region (DH-ER-KR) of a mycocerosic acid synthase-like (MAS-like) PKS
5BP3	55%	Mycobacterium smegmatis	Dehydratase domain (DH) of a mycocerosic acid synthase-like (MAS-like) PKS, crystal form 2
5BP2	55%	Mycobacterium smegmatis	Dehydratase domain (DH) of a mycocerosic acid synthase-like (MAS-like) PKS, crystal form 1
1PQW	46%	Mycobacterium tuberculosis	Putative enoyl reductase domain of polyketide synthase
4OKI	43%	Mycobacterium tuberculosis	X-ray structure of the nucleotide-binding subdomain of the enoylreductase domain of PpsC from Mycobacterium tuberculosis
5XUO	42%	Mycobacterium tuberculosis H37Rv	Pks13 AT domain fragment from Mycobacterium tuberculosis
2HG4	41%	Saccharopolyspora erythraea	Structure of the ketosynthase-acyltransferase didomain of module 5 from DEBS.
6C9U	40%	Saccharopolyspora erythraea	Crystal structure of [KS3][AT3] didomain from module 3 of 6-deoxyerthronolide B synthase in complex with antibody fragment (Fab)
2QO3	40%	Saccharopolyspora erythraea	Crystal Structure of [KS3][AT3] didomain from module 3 of 6-deoxyerthronolide B synthase

Links to additional information on pks2:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 1.454 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

LGLGSAASGTGADRGAWTLAEPRVTPVAVIGMACRLPGGIDSPELLWKALLRGDDLITEVPPDRWDCDEFYDPQPGVPGRTVCKWGGFLDNPADFDCEFF
GIGEREAIAIDPQQRLLLETSWEAMEHAGLTQQTLAGSATGVFAGVTHGDYTMVAADAKQLEEPYGYLGNSFSMASGRVAYAMRLHGPAITVDTACSSGL
TAVHMACRSLHEGESDVALAGGVALMLEPRKAAAGSALGMLSPTGRCRAFDVAADGFVSGEGCAVVVLKRLPDALADGDRILAVIRGTSANQDGHTVNIA
TPSQPAQVAAYRAALAAGGVDAATVGMVEAHGPGTPIGDPIEYASVSEVYGVDGPCALASVKTNFGHTQSTAGVLGLIKVVLALKHGVVPRNLHFTRLPD
EIAGITTNLFVPEVTTPWPTNGRQVPRRAAVSSYGFSGTNVHAVVEQAPQTEAQPHAASTPPTGTPALFTLSASSADALRQTAQRLTDWIQQHADSLVLS
DLAYTLARRRTHRSVRTAVIASSVDELIAGLGEVADGDTVYQPAVGQDDRGPVWLFSGQGSQWAAMGADLLTNESVFAATVAELEPLIAAESGFSVTEAM
TAPETVTGIDRVQPTIFAMQVALAATMAAYGVRPGAVIGHSMGESAAAVVAGVLSAEDGVRVICRRSKLMATIAGSAAMASVELPALAVQSELTALGIDD
VVVAVVTAPQSTVIAGGTESVRKLVDIWERRDVLARAVAVDVASHSPQVDPILDELIAALADLNPKAPEIPYYSATLFDPREAPACDARYWADNLRHTVR
FSAAVRSALDDGYRVFAELSPHPLLTHAVDQIAGSVGMPVAALAGMRREQPLPLGLRRLLTDLHNAGAAVDFSVLCPQGRLVDAPLPAWSHRFLFYDREG
VDNRSPGGSTVAVHPLLGAHVRLPEEPERHAWQADVGTATLPWLGDHRIHNVAALPGAAYCEMALSAARAVLGEQSEVRDMRFEAMLLLDDQTPVSTVAT
VTSPGVVDFAVEALQEGVGHHLRRASAVLQQVSGECEPPAYDMASLLEAHPCRVDGEDLRRQFDKHGVQYGPAFTGLAVAYVAEDATATMLAEVALPGSI
RSQQGLYAIHPALLDACFQSVGAHPDSQSVGSGLLVPLGVRRVRAYAPVRTARYCYTRVTKVELVGVEADIDVLDAHGTVLLAVCGLRIGTGVSERDKHN
RVLNERLLTIEWHQRELPEMDPSGAGKWLLISDCAASDVTATRLADAFREHSAACTTMRWPLHDDQLAAADQLRDQVGSDEFSGVVVLTGSNTGTPHQGS
ADRGAEYVRRLVGIARELSDLPGAVPRMYVVTRGAQRVLADDCVNLEQGGLRGLLRTIGAEHPHLRATQIDVDEQTGVEQLARQLLATSEEDETAWRDNE
WYVARLCPTPLRPQERRTIVADHQQSGMRLQIRTPGDMQTIELAAFHRVPPGPGQIEVAVRASSVNFADVLIAFGRYPSFEGHLPQLGTDFAGVVTAVGP
GVTDHKVGDHVGGMSPNGCWGTFVTCDARLAATLPPGLGDAQAAAVTTAHATAWYGLHELARIRAGDTVLIHSGTGGVGQAAIAIARAAGAEIFATAGTP
QRRELLRNMGIEHVYDSRSIEFAEQIRRDTNGRGVDVVLNSVTGAAQLAGLKLLAFRGRFVEIGKRDIYGDTKLGLFPFRRNLSFYAVDLGLLSATHPEE
LRDLLGTVYRLTAAGELPMPQSTHYPLVEAATAIRVMGNAEHTGKLVLHIPQTGKSLVTLPPEQAQVFRPDGSYIITGGLGGLGLFLAEKMAAAGCGRIV
LNSRTQPTQKMRETIEAIAAMGSEVVVECGDIAQPGTAERLVATAVATGLPVRGVLHAAAVVEDATLANITDELLARDWAPKVHGAWELHEATSGQPLDW
FCLFSSAAALTGSPGQSAYSAANSWLDAFAHWRQAQGLPATAIAWGAWSDIGQLGWWSASPARASALEESNYTAITPDEGAYAFEALLRHNRVYTGYAPV
IGAPWLVAFAERSRFFEVFSSSNGSGTSKFRVELNELPRDEWPARLRQLVAEQVSLILRRTVDPDRPLPEYGLDSLGALELRTRIETETGIRLAPKNVSA
TVRGLADHLYEQLAPDDAPAAALSSQ

(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; 5 non-insertions in a row out of 116 sites
Non-Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 3 non-insertions in a row out of 116 sites
Non-Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 3 non-insertions in a row out of 116 sites
Non-Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 2 non-insertions in a row out of 117 sites
Non-Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 3 non-insertions in a row out of 117 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: 0.37
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:

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0757 (phoP) (Direct binding)
- Rv1033c (trcR) (Direct binding)
- Rv1353c (-) (Direct binding)
- Rv3681c (whiB4) (Direct binding)

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

Upregulates:
- Does not upregulate other genes.
Upregulated by:
Downregulates:
- Does not downregulate other genes.
Downregulated by:
- Rv0022c (whiB5)
- Rv3416 (whiB3)

Property	Value	Creator	Evidence	PMID	Comment
Citation	Sequence analysis corresponding to the PPE and PE proteins in Mycobacterium tuberculosis and other genomes. authors,S. Adindla,L. Guruprasad J. Biosci. 2003	sourish10	IEP	12711809	Co-expression (Functional linkage)
Interaction	Transcription Rv0757	sourish10	IEP		Co-expression (Functional linkage) authors,S. Adindla,L. Guruprasad Sequence analysis corresponding to the PPE and PE proteins in Mycobacterium tuberculosis and other genomes. J. Biosci. 2003
Citation	The Mycobacterium tuberculosis PhoPR two-component system regulates genes essential for virulence and complex lipid biosynthesis. SB. Walters, E. Dubnau et al. Mol. Microbiol. 2006	sourish10	IEP	16573683	Co-expression (Functional linkage)
Interaction	Transcription Rv0757	sourish10	IEP		Co-expression (Functional linkage) SB. Walters, E. Dubnau et al. The Mycobacterium tuberculosis PhoPR two-component system regulates genes essential for virulence and complex lipid biosynthesis. Mol. Microbiol. 2006
Interaction	Operon Rv3824c	sourish10	TAS		Spectrophotometric P. Kumar, MW. Schelle et al. PapA1 and PapA2 are acyltransferases essential for the biosynthesis of the Mycobacterium tuberculosis virulence factor sulfolipid-1. Proc. Natl. Acad. Sci. U.S.A. 2007
Interaction	Operon Rv3824c	sourish10	TAS		Structural Analysis P. Kumar, MW. Schelle et al. PapA1 and PapA2 are acyltransferases essential for the biosynthesis of the Mycobacterium tuberculosis virulence factor sulfolipid-1. Proc. Natl. Acad. Sci. U.S.A. 2007
Interaction	Signaling Rv1571	razeeth.new	IEP		Co-expression AH. Li, WL. Lam et al. Characterization of genes differentially expressed within macrophages by virulent and attenuated Mycobacterium tuberculosis identifies candidate genes involved in intracellular growth. Microbiology (Reading, Engl.) 2008
Interaction	Signaling Rv1571	razeeth.new	IEP		Co-expression AH. Li, WL. Lam et al. Bacterial artificial chromosome fingerprint arrays for the differentiation of transcriptomic differences in mycobacteria. J. Microbiol. Methods 2008
Interaction	Regulatory Rv0757	singhpankaj2116	IEP		Co-expression (Functional linkage) ML. Chesne-Seck, N. Barilone et al. A point mutation in the two-component regulator PhoP-PhoR accounts for the absence of polyketide-derived acyltrehaloses but not that of phthiocerol dimycocerosates in Mycobacterium tuberculosis H37Ra. J. Bacteriol. 2008
Interaction	Regulatory Rv0757	singhpankaj2116	IEP		Co-expression (Functional linkage) authors,A. Sola-Landa,RS. Moura,JF. Martn The two-component PhoR-PhoP system controls both primary metabolism and secondary metabolite biosynthesis in Streptomyces lividans. Proc. Natl. Acad. Sci. U.S.A. 2003
Interaction	Regulatory Rv0757	singhpankaj2116	IEP		Co-expression (Functional linkage) J. Gonzalo Asensio, C. Maia et al. The virulence-associated two-component PhoP-PhoR system controls the biosynthesis of polyketide-derived lipids in Mycobacterium tuberculosis. J. Biol. Chem. 2006
Interaction	Regulatory Rv0757	singhpankaj2116	IEP		Co-expression (Functional linkage) J. Gonzalo-Asensio, CY. Soto et al. The Mycobacterium tuberculosis phoPR operon is positively autoregulated in the virulent strain H37Rv. J. Bacteriol. 2008
Interaction	Regulatory Rv0757	singhpankaj2116	IEP		Co-expression (Functional linkage) A. Sinha, S. Gupta et al. PhoP-PhoP interaction at adjacent PhoP binding sites is influenced by protein phosphorylation. J. Bacteriol. 2008
Interaction	Regulatory Rv0757	singhpankaj2116	IEP		Co-expression (Functional linkage) J. Gonzalo Asensio, C. Maia et al. The virulence-associated two-component PhoP-PhoR system controls the biosynthesis of polyketide-derived lipids in Mycobacterium tuberculosis. J. Biol. Chem. 2006
Interaction	Regulatory Rv0757	singhpankaj2116	IEP		Co-expression (Functional linkage) M. Ryndak, S. Wang et al. PhoP, a key player in Mycobacterium tuberculosis virulence. Trends Microbiol. 2008
Interaction	Regulatory Rv0757	singhpankaj2116	IEP		Co-expression (Functional linkage) JA. Asensio, A. Arbus et al. Live tuberculosis vaccines based on phoP mutants: a step towards clinical trials. Expert opinion on biological therapy 2008
Interaction	Regulatory Rv0757	singhpankaj2116	IEP		Co-expression (Functional linkage) SB. Walters, E. Dubnau et al. The Mycobacterium tuberculosis PhoPR two-component system regulates genes essential for virulence and complex lipid biosynthesis. Mol. Microbiol. 2006
Interaction	Regulatory Rv0757	singhpankaj2116	IEP		Co-expression (Functional linkage) J. Gonzalo-Asensio, S. Mostowy et al. PhoP: a missing piece in the intricate puzzle of Mycobacterium tuberculosis virulence. PLoS ONE 2008
Interaction	RegulatedBy Rv3911	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.. S. Raman, X. Puyang et al. Mycobacterium tuberculosis SigM positively regulates Esx secreted protein and nonribosomal peptide synthetase genes and down regulates virulence-associated surface lipid synthesis. J. Bacteriol. 2006
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
Interaction	RegulatedBy Rv0757	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.. J. Gonzalo Asensio, C. Maia et al. The virulence-associated two-component PhoP-PhoR system controls the biosynthesis of polyketide-derived lipids in Mycobacterium tuberculosis. J. Biol. Chem. 2006
Interaction	RegulatedBy Rv0757	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.. SB. Walters, E. Dubnau et al. The Mycobacterium tuberculosis PhoPR two-component system regulates genes essential for virulence and complex lipid biosynthesis. Mol. Microbiol. 2006
Name	Polyketide synthase involved in the synthesis of phthioceranic and hydroxyphthioceranic acids	mjackson	IMP		Polymethyl-branched acyltrehaloses
Citation	The Mycobacterium tuberculosis pks2 gene encodes the synthase for the hepta- and octamethyl-branched fatty acids required for sulfolipid synthesis. TD. Sirakova, AK. Thirumala et al. J. Biol. Chem. 2001	mjackson		11278910	Polyketide synthase involved in the synthesis of phthioceranic and hydroxyphthioceranic acids (phenotypic [mycobacterial recombinant strains])
Other	TBPWY:Polymethyl-branched acyltrehaloses	mjackson			Polyketide synthase involved in the synthesis of phthioceranic and hydroxyphthioceranic acids (phenotypic [mycobacterial recombinant strains]) TD. Sirakova, AK. Thirumala et al. The Mycobacterium tuberculosis pks2 gene encodes the synthase for the hepta- and octamethyl-branched fatty acids required for sulfolipid synthesis. J. Biol. Chem. 2001
Citation	The Mycobacterium tuberculosis pks2 gene encodes the synthase for the hepta- and octamethyl-branched fatty acids required for sulfolipid synthesis. TD. Sirakova, AK. Thirumala et al. J. Biol. Chem. 2001	jjmcfadden		11278910	Inferred from direct assay
Other	EC:	jjmcfadden			Inferred from direct assay TD. Sirakova, AK. Thirumala et al. The Mycobacterium tuberculosis pks2 gene encodes the synthase for the hepta- and octamethyl-branched fatty acids required for sulfolipid synthesis. J. Biol. Chem. 2001

TB Genome Annotation Portal