Rv3824c (papA1)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: SL659 acyltransferase papA1
- REFSEQ: polyketide synthase associated protein
- PATRIC: Polyketide synthase associated protein PapA1
- TUBERCULIST: Conserved polyketide synthase associated protein PapA1
- NCBI: Conserved polyketide synthase associated protein PapA1
- updated information (H37Rv4):
  - gene name: papA1
  - function: sulfolipid-1 synthesis
  - reference: Seeliger (2012) PMID: 22194604
Type: Not Target
Start: 4291639
End: 4293174
Operon:

Trans-membrane region:
Role: I.I - Polyketide and non-ribosomal peptide synthesis
GO terms:
- GO:0046506 - sulfolipid biosynthetic process (Uniprot)
- GO:0016747 - transferase activity, transferring acyl groups other than amino-acyl groups (Uniprot)
- GO:0016746 - transferase activity, transferring acyl groups (Uniprot)
- GO:0016740 - transferase 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

6AEF 53% Mycobacterium tuberculosis CAS/NITR204 PapA2 acyl transferase
Links to additional information on papA1:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 1.362 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

PDB	aa ident	species	PDB title
6AEF	53%	Mycobacterium tuberculosis CAS/NITR204	PapA2 acyl transferase

Amino Acid Sequence

VRIGPVELSAVKDWDPAPGVLVSWHPTPASCAKALAAPVSAVPPSYVQARQIRSFSEQAARGLDHSRLLIASVEVFGHCDLRAMTYVINAHLRRHDTYRS
WFELRDTDHIVRHSIADPADIEFVPTTHGEMTSADLRQHIVATPDSLHWDCFSFGVIQRADSFTFYASIDHLHADGQFVGVGLMEFQSMYTALIMGEPPI
GLSEAGSYVDFCVRQHEYTSALTVDSPEVRAWIDFAEINNGTFPEFPLPLGDPSVRCGGDLLSMMLMDEQQTQRFESACMAANARFIGGMLACIAIAIHE
LTGADTYFGITPKDIRTPADLMTQGWFTGQIPVTVPVAGLSFNEIARIAQTSFDTGADLAKVPFERVVELSPSLRRPQPLFSLVNFFDAQVGPLSAVTKL
FEGLNVGTYSDGRVTYPLSTMVGRFDETAASVLFPDNPVARESVTAYLRAIRSVCMRIANGGTAERVGNVVALSPGRRNNIERMTWRSCRAGDFIDICNL
KVANVTVDREA

(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 46 sites
Non-Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 4 non-insertions in a row out of 46 sites
Non-Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 4 non-insertions in a row out of 46 sites
Non-Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 5 non-insertions in a row out of 47 sites
Non-Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 5 non-insertions in a row out of 47 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: 2.97
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:
- Rv0047c (-) (Direct binding)
- Rv1353c (-) (Direct binding)
- Rv3133c (devR) (Direct binding)
- Rv3597c (lsr2) (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:

Property	Value	Creator	Evidence	PMID	Comment
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
Citation	PapA1 and PapA2 are acyltransferases essential for the biosynthesis of the Mycobacterium tuberculosis virulence factor sulfolipid-1. P. Kumar, MW. Schelle et al. Proc. Natl. Acad. Sci. U.S.A. 2007	sourish10	TAS	17592143	Spectrophotometric
Interaction	Operon Rv3825c	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
Citation	PapA1 and PapA2 are acyltransferases essential for the biosynthesis of the Mycobacterium tuberculosis virulence factor sulfolipid-1. P. Kumar, MW. Schelle et al. Proc. Natl. Acad. Sci. U.S.A. 2007	sourish10	TAS	17592143	Structural Analysis
Interaction	Operon Rv3825c	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
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
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.. 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	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	Acyltransferase responsible for the transfer of (hydroxy-)phthioceranic acids to the 3'-position of trehalose-2-sulfate-2'-palmitate to form a diacylated precursor of sulfolipid-I	mjackson	IDA		Polymethyl-branched acyltrehaloses
Name	Acyltransferase responsible for the transfer of (hydroxy-)phthioceranic acids to the 3'-position of trehalose-2-sulfate-2'-palmitate to form a diacylated precursor of sulfolipid-I	mjackson	IMP		Polymethyl-branched acyltrehaloses
Citation	PapA1 and PapA2 are acyltransferases essential for the biosynthesis of the Mycobacterium tuberculosis virulence factor sulfolipid-1. P. Kumar, MW. Schelle et al. Proc. Natl. Acad. Sci. U.S.A. 2007	mjackson		17592143	Acyltransferase responsible for the transfer of (hydroxy-)phthioceranic acids to the 3'-position of trehalose-2-sulfate-2'-palmitate to form a diacylated precursor of sulfolipid-I (phenotypic [mycobacterial recombinant strains]; enzymatic)
Other	TBPWY:Polymethyl-branched acyltrehaloses	mjackson			Acyltransferase responsible for the transfer of (hydroxy-)phthioceranic acids to the 3'-position of trehalose-2-sulfate-2'-palmitate to form a diacylated precursor of sulfolipid-I (phenotypic [mycobacterial recombinant strains]; enzymatic) 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

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