TB Genome Annotation Portal

Rv0642c (mmaA4)

• Current annotations:
  • TBCAP: (community-based annotations - see table at bottom of page)
  • TBDB: hydroxymycolate synthase MmaA4
  • REFSEQ: methoxy mycolic acid synthase
  • PATRIC: Cyclopropane-fatty-acyl-phospholipid synthase (EC 2.1.1.79)
  • TUBERCULIST: Methoxy mycolic acid synthase 4 MmaA4 (methyl mycolic acid synthase 4) (MMA4) (hydroxy mycolic acid synthase)
  • NCBI: Methoxy mycolic acid synthase 4 MmaA4 (methyl mycolic acid synthase 4) (MMA4) (hydroxy mycolic acid synthase)
  • updated information (H37Rv4):
    • gene name: mmaA4
    • function:
    • reference:
• Coordinates in H37Rv: 736298 - 737203
• Gene length: 906 bp (with stop codon), 301 aa (without stop codon)
• Operon:


• Trans-membrane region:
  
• Role: I.H.2 - Modification of fatty and mycolic acids
• GO terms:
  • GO:0071768 - mycolic acid biosynthetic process (Uniprot)
  • GO:0032259 - methylation (Uniprot)
  • GO:0016740 - transferase activity (Uniprot)
  • GO:0008757 - S-adenosylmethionine-dependent methyltransferase 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:0005618 - cell wall (Uniprot)
  • GO:0005515 - protein binding (Uniprot)
• Reaction(s) (based on iSM810 metabolic model):
  • SAM[c] + CIS_DELTA_2_19_44_37_ENOYL_C56_ACYL_ACP[c] -> SAH[c] + CIS_DELTA_37_ENOYL_METHY_HYDROXY_C56_ACYL_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: 3ha5, 2fk8, 2fk7, 3ha3, 3ha7
• Search for Homologs in PDB
• Top 10 Homologs in PDB (as of Nov 2020):
  

  PDB	aa ident	species	PDB title
  3HA7	100%	Mycobacterium tuberculosis	Crystal structure of HMA (MMAA4) from mycobacterium tuberculosis complexed with S-adenosyl-N-decyl-aminoethyl (SADAE)
  3HA5	100%	Mycobacterium tuberculosis	Crystal structure of HMA (MMAA4) from mycobacterium tuberculosis complexed with sinefungin
  3HA3	100%	Mycobacterium tuberculosis	Crystal structure of HMA (MMAA4) from mycobacterium tuberculosis complexed with S-adenosylhomocysteine
  2FK8	100%	Mycobacterium tuberculosis	Crystal structure of Hma (MmaA4) from Mycobacterium tuberculosis complexed with S-adenosylmethionine
  2FK7	100%	Mycobacterium tuberculosis	Crystal structure of Hma (MmaA4) from Mycobacterium tuberculosis, apo-form
  1KPH	58%	Mycobacterium tuberculosis	Crystal Structure of mycolic acid cyclopropane synthase CmaA1 complexed with SAH and DDDMAB
  1KPG	58%	Mycobacterium tuberculosis	Crystal Structure of mycolic acid cyclopropane synthase CmaA1 complexed with SAH and CTAB
  1KP9	58%	Mycobacterium tuberculosis	Crystal structure of mycolic acid cyclopropane synthase CmaA1, apo-form
  1TPY	56%	Mycobacterium tuberculosis	Structure of the cyclopropane synthase MmaA2 from Mycobacterium tuberculosis
  1L1E	55%	Mycobacterium tuberculosis	Crystal Structure of Mycolic Acid Cyclopropane Synthase PcaA Complexed with S-adenosyl-L-homocysteine

• Links to additional information on mmaA4:
  • KEGG - nucleotide and amino acid sequences of gene
  • TBDB (updated)
  • Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
  • UniProt
  • AlphaFold model
  • Vulnerability = 0.91 (from Jeremy Rock's lab)
  • Mycobrowser
  • PATRIC
  • BioCyc
  • Systems Biology

Amino Acid Sequence

MTRMAEKPISPTKTRTRFEDIQAHYDVSDDFFALFQDPTRTYSCAYFEPPELTLEEAQYAKVDLNLDKLDLKPGMTLLDIGCGWGTTMRRAVERFDVNVI
GLTLSKNQHARCEQVLASIDTNRSRQVLLQGWEDFAEPVDRIVSIEAFEHFGHENYDDFFKRCFNIMPADGRMTVQSSVSYHPYEMAARGKKLSFETARF
IKFIVTEIFPGGRLPSTEMMVEHGEKAGFTVPEPLSLRPHYIKTLRIWGDTLQSNKDKAIEVTSEEVYNRYMKYLRGCEHYFTDEMLDCSLVTYLKPGAA
A

Additional Information

Analysis of Positive Selection in Clinical Isolates *new*

• data from Culviner et al (2025) (55,259 Mtb clinical isolates)
  • overall pN/pS for Rv0642c: 0.514726433
  • lineage-specific pN/pS in L1: 0.413999641
  • lineage-specific pN/pS in L2: 0.835960813
  • lineage-specific pN/pS in L3: 0.624184074
  • lineage-specific pN/pS in L4: 0.468138055

• 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)	1.64 (0.38)	1.74 (0.67)
codons under selection
omega plots
genetic variants*	link	link
statistics at each codon	link	link