TB Genome Annotation Portal

Rv0503c (cmaA2)

• Current annotations:
  • TBCAP: (community-based annotations - see table at bottom of page)
  • TBDB: cyclopropane mycolic acid synthase 2
  • REFSEQ: cyclopropane-fatty-acyl-phospholipid synthase 2 CMAA2 (cyclopropane fatty acid synthase) (CFA synthase) (cyclopropane mycolic acid synthase 2) (mycolic acid trans-cyclopropane synthetase)
  • PATRIC: Cyclopropane-fatty-acyl-phospholipid synthase 2 CmaA2 (EC 2.1.1.79)
  • TUBERCULIST: Cyclopropane-fatty-acyl-phospholipid synthase 2 CmaA2 (cyclopropane fatty acid synthase) (CFA synthase) (cyclopropane mycolic acid synthase 2) (mycolic acid trans-cyclopropane synthetase)
  • NCBI: Cyclopropane-fatty-acyl-phospholipid synthase 2 CmaA2 (cyclopropane fatty acid synthase) (CFA synthase) (cyclopropane mycolic acid synthase 2) (mycolic acid trans-cyclopropane synthetase)
  • updated information (H37Rv4):
    • gene name: cmaA2
    • function:
    • reference:
• Type: Not Target
• Start: 593871
• End: 594779
• Operon:


• Trans-membrane region:
  
• Role: I.H.2 - Modification of fatty and mycolic acids
• GO terms:
  • GO:0071769 - mycolate cell wall layer assembly (Uniprot)
  • GO:0071768 - mycolic acid biosynthetic process (Uniprot)
  • GO:0071766 - Actinobacterium-type cell wall biogenesis (Uniprot)
  • GO:0052167 - modulation by symbiont of host innate immune response (Uniprot)
  • GO:0046500 - S-adenosylmethionine metabolic process (Uniprot)
  • GO:0032259 - methylation (Uniprot)
  • GO:0016740 - transferase activity (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:0005886 - plasma membrane (Uniprot)
  • GO:0005829 - cytosol (Uniprot)
  • GO:0005737 - cytoplasm (Uniprot)
  • GO:0001666 - response to hypoxia (Uniprot)
• Reaction(s) (based on iSM810 metabolic model):
  • 2 NADP[c] + 2 SAM[c] + CIS_DELTA_2_19_44_31_ENOYL_C50_ACYL_ACP[c] -> 2 NADPH[c] + 2 SAH[c] + CYCLOPROPYL_MEROACYL_ACP[c]
  • 2 NADP[c] + 2 SAM[c] + CIS_DELTA_37_ENOYL_DIMETHY_HYDROXY_C56_ACYL_ACP[c] -> 2 NADPH[c] + 2 SAH[c] + TRANS_METHOXY_MEROACYL_ACP... <Preview truncated at 128 characters>
  • 2 NADP[c] + SAM[c] + CIS_DELTA_37_ENOYL_DIMETHY_HYDROXY_C56_ACYL_ACP[c] -> 2 NADPH[c] + SAH[c] + TRANS_KETO_MEROACYL_ACP[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: 1kpi, 3hem
• Search for Homologs in PDB
• Top 10 Homologs in PDB (as of Nov 2020):
  

  PDB	aa ident	species	PDB title
  3HEM	99%	Mycobacterium tuberculosis	Structure of Mycobacterium tuberculosis Mycolic Acid Cyclopropane Synthase CmaA2 in Complex with Dioctylamine
  1KPI	99%	Mycobacterium tuberculosis	Crystal Structure of mycolic acid cyclopropane synthase CmaA2 complexed with SAH and DDDMAB
  1L1E	58%	Mycobacterium tuberculosis	Crystal Structure of Mycolic Acid Cyclopropane Synthase PcaA Complexed with S-adenosyl-L-homocysteine
  1TPY	55%	Mycobacterium tuberculosis	Structure of the cyclopropane synthase MmaA2 from Mycobacterium tuberculosis
  1KPH	55%	Mycobacterium tuberculosis	Crystal Structure of mycolic acid cyclopropane synthase CmaA1 complexed with SAH and DDDMAB
  1KPG	55%	Mycobacterium tuberculosis	Crystal Structure of mycolic acid cyclopropane synthase CmaA1 complexed with SAH and CTAB
  1KP9	55%	Mycobacterium tuberculosis	Crystal structure of mycolic acid cyclopropane synthase CmaA1, apo-form
  3HA7	50%	Mycobacterium tuberculosis	Crystal structure of HMA (MMAA4) from mycobacterium tuberculosis complexed with S-adenosyl-N-decyl-aminoethyl (SADAE)
  3HA5	50%	Mycobacterium tuberculosis	Crystal structure of HMA (MMAA4) from mycobacterium tuberculosis complexed with sinefungin
  3HA3	50%	Mycobacterium tuberculosis	Crystal structure of HMA (MMAA4) from mycobacterium tuberculosis complexed with S-adenosylhomocysteine

• Links to additional information on cmaA2:
  • KEGG - nucleotide and amino acid sequences of gene
  • Mycobrowser
  • PATRIC
  • TBDB (updated)
  • Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
  • UniProt
  • AlphaFold model
  • Vulnerability = 1.424 (from Jeremy Rock's lab)
  • BioCyc
  • Systems Biology

Amino Acid Sequence

MTSQGDTTSGTQLKPPVEAVRSHYDKSNEFFKLWLDPSMTYSCAYFERPDMTLEEAQYAKRKLALDKLNLEPGMTLLDIGCGWGSTMRHAVAEYDVNVIG
LTLSENQYAHDKAMFDEVDSPRRKEVRIQGWEEFDEPVDRIVSLGAFEHFADGAGDAGFERYDTFFKKFYNLTPDDGRMLLHTITIPDKEEAQELGLTSP
MSLLRFIKFILTEIFPGGRLPRISQVDYYSSNAGWKVERYHRIGANYVPTLNAWADALQAHKDEAIALKGQETYDIYMHYLRGCSDLFRDKYTDVCQFTL
VK

Additional Information

Analysis of Positive Selection in Clinical Isolates *new*

• Analysis of dN/dS (omega) in two collections of Mtb clinical isolates using GenomegaMap (Window model) (see description of methods)
  • Moldova: 2,057 clinical isolates
  • global set: 5,195 clinical isolates from 15 other countries
• In the omega plots, the black line shows the mean estimate of omega (dN/dS) at each codon, and the blue lines are the bounds for the 95% credible interval (95%CI, from MCMC sampling).
• A gene is under significant positive selection if the lower-bound of the 95%CI of omega (lower blue line) exceeds 1.0 at any codon.

	Moldova (2,057)	global set (5,195)
under significant positive selection?	NO	NO
omega peak height (95%CI lower bound)	1.26 (0.17)	1.21 (0.29)
codons under selection
omega plots
genetic variants*	link	link
statistics at each codon	link	link