Rv0470c (pcaA)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: cyclopropane mycolic acid synthase 3
- REFSEQ: mycolic acid synthase pcaA (cyclopropane synthase)
- PATRIC: Cyclopropane-fatty-acyl-phospholipid synthase 1 CmaA1 (EC 2.1.1.79)
- TUBERCULIST: Mycolic acid synthase PcaA (cyclopropane synthase)
- NCBI: Mycolic acid synthase PcaA (cyclopropane synthase)
- updated information (H37Rv4):
  - gene name: pcaA
  - function:
  - reference:
Type: Not Target
Start: 560848
End: 561711
Operon:

Trans-membrane region:
Role: I.H.2 - Modification of fatty and mycolic acids
GO terms:
- GO:0071768 - mycolic acid biosynthetic process (Uniprot)
- GO:0052167 - modulation by symbiont of host innate immune response (Uniprot)
- GO:0046500 - S-adenosylmethionine metabolic process (Uniprot)
- GO:0042783 - active evasion of host immune response (Uniprot)
- GO:0032259 - methylation (Uniprot)
- GO:0016740 - transferase activity (Uniprot)
- GO:0009405 - pathogenesis (Uniprot)
- GO:0008825 - cyclopropane-fatty-acyl-phospholipid synthase activity (Uniprot)
- GO:0008610 - lipid biosynthetic process (Uniprot)
- GO:0008168 - methyltransferase activity (Uniprot)
- GO:0006629 - lipid metabolic process (Uniprot)
- GO:0005737 - cytoplasm (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: 1l1e
Search for Homologs in PDB

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

PDB	aa ident	species	PDB title
1L1E	100%	Mycobacterium tuberculosis	Crystal Structure of Mycolic Acid Cyclopropane Synthase PcaA Complexed with S-adenosyl-L-homocysteine
1TPY	73%	Mycobacterium tuberculosis	Structure of the cyclopropane synthase MmaA2 from Mycobacterium tuberculosis
1KPH	72%	Mycobacterium tuberculosis	Crystal Structure of mycolic acid cyclopropane synthase CmaA1 complexed with SAH and DDDMAB
1KPG	72%	Mycobacterium tuberculosis	Crystal Structure of mycolic acid cyclopropane synthase CmaA1 complexed with SAH and CTAB
1KP9	72%	Mycobacterium tuberculosis	Crystal structure of mycolic acid cyclopropane synthase CmaA1, apo-form
3HEM	57%	Mycobacterium tuberculosis	Structure of Mycobacterium tuberculosis Mycolic Acid Cyclopropane Synthase CmaA2 in Complex with Dioctylamine
1KPI	57%	Mycobacterium tuberculosis	Crystal Structure of mycolic acid cyclopropane synthase CmaA2 complexed with SAH and DDDMAB
3HA7	55%	Mycobacterium tuberculosis	Crystal structure of HMA (MMAA4) from mycobacterium tuberculosis complexed with S-adenosyl-N-decyl-aminoethyl (SADAE)
3HA5	55%	Mycobacterium tuberculosis	Crystal structure of HMA (MMAA4) from mycobacterium tuberculosis complexed with sinefungin
3HA3	55%	Mycobacterium tuberculosis	Crystal structure of HMA (MMAA4) from mycobacterium tuberculosis complexed with S-adenosylhomocysteine

Links to additional information on pcaA:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 0.29 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MSVQLTPHFGNVQAHYDLSDDFFRLFLDPTQTYSCAYFERDDMTLQEAQIAKIDLALGKLNLEPGMTLLDIGCGWGATMRRAIEKYDVNVVGLTLSENQA
GHVQKMFDQMDTPRSRRVLLEGWEKFDEPVDRIVSIGAFEHFGHQRYHHFFEVTHRTLPADGKMLLHTIVRPTFKEGREKGLTLTHELVHFTKFILAEIF
PGGWLPSIPTVHEYAEKVGFRVTAVQSLQLHYARTLDMWATALEANKDQAIAIQSQTVYDRYMKYLTGCAKLFRQGYTDVDQFTLEK

(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 11 sites
Non-Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 0 non-insertions in a row out of 11 sites
Non-Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 0 non-insertions in a row out of 11 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 12 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 12 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: 0.77
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:
- Rv3849 (espR)

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0047c (-) (Direct binding)
- Rv1049 (-) (Direct binding)
- Rv1353c (-) (Direct binding)
- Rv2324 (-) (Direct binding)
- Rv2989 (-) (Direct binding)
- Rv3597c (lsr2) (Direct binding)

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:
- Rv3849 (espR)

Property	Value	Creator	Evidence	PMID	Comment
Citation	Further insight into S-adenosylmethionine-dependent methyltransferases: structural characterization of Hma, an enzyme essential for the biosynthesis of oxygenated mycolic acids in Mycobacterium tuberculosis. F. Boissier, F. Bardou et al. J. Biol. Chem. 2006	njamshidi	IDA	16356931	PMID: 16356931
Term	TBRXN:MYC1CYC3 Mycolic Acid Cyclopropanation - IDA	njamshidi	IDA	16356931	PMID: 16356931 F. Boissier, F. Bardou et al. Further insight into S-adenosylmethionine-dependent methyltransferases: structural characterization of Hma, an enzyme essential for the biosynthesis of oxygenated mycolic acids in Mycobacterium tuberculosis. J. Biol. Chem. 2006
Citation	Further insight into S-adenosylmethionine-dependent methyltransferases: structural characterization of Hma, an enzyme essential for the biosynthesis of oxygenated mycolic acids in Mycobacterium tuberculosis. F. Boissier, F. Bardou et al. J. Biol. Chem. 2006	njamshidi	ISS	16356931	PMID: 16356931
Term	TBRXN:MYC1CYC3 Mycolic Acid Cyclopropanation - ISS	njamshidi	ISS	16356931	PMID: 16356931 F. Boissier, F. Bardou et al. Further insight into S-adenosylmethionine-dependent methyltransferases: structural characterization of Hma, an enzyme essential for the biosynthesis of oxygenated mycolic acids in Mycobacterium tuberculosis. J. Biol. Chem. 2006
Citation	Further insight into S-adenosylmethionine-dependent methyltransferases: structural characterization of Hma, an enzyme essential for the biosynthesis of oxygenated mycolic acids in Mycobacterium tuberculosis. F. Boissier, F. Bardou et al. J. Biol. Chem. 2006	njamshidi	IDA	16356931	PMID: 16356931
Term	TBRXN:MYC1CYC1 Mycolic Acid Cyclopropanation - IDA	njamshidi	IDA	16356931	PMID: 16356931 F. Boissier, F. Bardou et al. Further insight into S-adenosylmethionine-dependent methyltransferases: structural characterization of Hma, an enzyme essential for the biosynthesis of oxygenated mycolic acids in Mycobacterium tuberculosis. J. Biol. Chem. 2006
Citation	Further insight into S-adenosylmethionine-dependent methyltransferases: structural characterization of Hma, an enzyme essential for the biosynthesis of oxygenated mycolic acids in Mycobacterium tuberculosis. F. Boissier, F. Bardou et al. J. Biol. Chem. 2006	njamshidi	ISS	16356931	PMID: 16356931
Term	TBRXN:MYC1CYC1 Mycolic Acid Cyclopropanation - ISS	njamshidi	ISS	16356931	PMID: 16356931 F. Boissier, F. Bardou et al. Further insight into S-adenosylmethionine-dependent methyltransferases: structural characterization of Hma, an enzyme essential for the biosynthesis of oxygenated mycolic acids in Mycobacterium tuberculosis. J. Biol. Chem. 2006
Citation	Further insight into S-adenosylmethionine-dependent methyltransferases: structural characterization of Hma, an enzyme essential for the biosynthesis of oxygenated mycolic acids in Mycobacterium tuberculosis. F. Boissier, F. Bardou et al. J. Biol. Chem. 2006	njamshidi	IDA	16356931	PMID: 16356931
Term	TBRXN:MYC1CYC2 Mycolic Acid Cyclopropanation - IDA	njamshidi	IDA	16356931	PMID: 16356931 F. Boissier, F. Bardou et al. Further insight into S-adenosylmethionine-dependent methyltransferases: structural characterization of Hma, an enzyme essential for the biosynthesis of oxygenated mycolic acids in Mycobacterium tuberculosis. J. Biol. Chem. 2006
Citation	Further insight into S-adenosylmethionine-dependent methyltransferases: structural characterization of Hma, an enzyme essential for the biosynthesis of oxygenated mycolic acids in Mycobacterium tuberculosis. F. Boissier, F. Bardou et al. J. Biol. Chem. 2006	njamshidi	ISS	16356931	PMID: 16356931
Term	TBRXN:MYC1CYC2 Mycolic Acid Cyclopropanation - ISS	njamshidi	ISS	16356931	PMID: 16356931 F. Boissier, F. Bardou et al. Further insight into S-adenosylmethionine-dependent methyltransferases: structural characterization of Hma, an enzyme essential for the biosynthesis of oxygenated mycolic acids in Mycobacterium tuberculosis. J. Biol. Chem. 2006
Interaction	RegulatedBy Rv1395	yamir.moreno	TAS		Literature previously reported link (from Balazsi et al. 2008). Traceable author statement to experimental support. G. Balzsi, AP. Heath et al. The temporal response of the Mycobacterium tuberculosis gene regulatory network during growth arrest. Mol. Syst. Biol. 2008
Name	PcaA (UmaA2) MYCOLIC ACID SYNTHASE PCAA; adds the cyclopropane rings to the proximal positions of the alpha mycolate	mjackson	IMP		S-adenosyl-methionine-dependent mycolic acid methyltransferases
Citation	A novel mycolic acid cyclopropane synthetase is required for cording, persistence, and virulence of Mycobacterium tuberculosis. MS. Glickman, JS. Cox et al. Mol. Cell 2000	extern:JZUCKER		10882107	Reaction blocked in mutant
Term	EC:2.1.1.- Transferases. Transferring one-carbon groups. Methyltransferases. - NR	extern:JZUCKER	NR		Reaction blocked in mutant MS. Glickman, JS. Cox et al. A novel mycolic acid cyclopropane synthetase is required for cording, persistence, and virulence of Mycobacterium tuberculosis. Mol. Cell 2000
Term	EC:2.1.1.79 Cyclopropane-fatty-acyl-phospholipid synthase. - NR	extern:JZUCKER	NR		Reaction blocked in mutant MS. Glickman, JS. Cox et al. A novel mycolic acid cyclopropane synthetase is required for cording, persistence, and virulence of Mycobacterium tuberculosis. Mol. Cell 2000

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