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:
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: 3ha5 , 2fk8 , 2fk7 , 3ha3 , 3ha7
Search for Latest Homologs in PDB
Top 10 Homologs in PDB (as of Apr 2026): PDB aa ident species PDB title 7Q2H 100% Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) mycolic acid methyltransferase Hma (MmaA4) from Mycobac-terium tuberculosis in complex with ZT275 7Q2G 100% Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) mycolic acid methyltransferase Hma (MmaA4) from Mycobac-terium tuberculosis in complex with ZT726 7Q2F 100% Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) mycolic acid methyltransferase Hma (MmaA4) from Mycobac-terium tuberculosis in complex with ZT585 7Q2E 100% Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) mycolic acid methyltransferase Hma (MmaA4) from Mycobac-terium tuberculosis in complex with ZT424 7Q2D 100% Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) mycolic acid methyltransferase Hma (MmaA4) from Mycobac-terium tuberculosis in complex with ZT320 7Q2C 100% Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) mycolic acid methyltransferase Hma (MmaA4) from Mycobac-terium tuberculosis in complex with ZT260 7Q2B 100% Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) mycolic acid methyltransferase Hma (MmaA4) from Mycobac-terium tuberculosis in complex with ZT218 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
Links to additional information on mmaA4:
Amino Acid Sequence
MTRMAEKPISPTKTRTRFEDIQAHYDVSDDFFALFQDPTRTYSCAYFEPPELTLEEAQYAKVDLNLDKLDLKPGMTLLDIGCGWGTTMRRAVERFDVNVI
GLTLSKNQHARCEQVLASIDTNRSRQVLLQGWEDFAEPVDRIVSIEAFEHFGHENYDDFFKRCFNIMPADGRMTVQSSVSYHPYEMAARGKKLSFETARF
IKFIVTEIFPGGRLPSTEMMVEHGEKAGFTVPEPLSLRPHYIKTLRIWGDTLQSNKDKAIEVTSEEVYNRYMKYLRGCEHYFTDEMLDCSLVTYLKPGAA
A
(
Nucleotide sequence available on
KEGG )
Additional Information
MtbTnDB - interactive tool for exploring a database of published TnSeq datasets for Mtb
TnSeqCorr - genes with correlated TnSeq profiles across ~100 conditions
Rv0642c/mmaA4,
gene len: 905 bp, num TA sites: 19
condition dataset call medium method notes
in-vitro DeJesus 2017 mBio growth advantage 7H9 HMM fully saturated, 14 TnSeq libraries combined
in-vitro Sassetti 2003 Mol Micro non-essential 7H9 TRASH essential if hybridization ratio<0.2
in-vivo (mice) Sassetti 2003 PNAS no data BL6 mice TRASH essential if hybridization ratio<0.4, min over 4 timepoints (1-8 weeks)
in-vitro (glycerol) Griffin 2011 PPath non-essential M9 minimal+glycerol Gumbel 2 replicates; Padj<0.05
in-vitro (cholesterol) Griffin 2011 PPath essential M9 minimal+cholesterol Gumbel 3 replicates; Padj<0.05
differentially essential in cholesterol Griffin 2011 PPath NO (LFC=-2.9) cholesterol vs glycerol resampling-SR YES if Padj<0.05, else not significant; LFC<0 means less insertions/more essential in cholesterol
in-vitro Smith 2022 eLife growth defect 7H9 HMM 6 replicates (raw data in Subramaniam 2017, PMID 31752678)
in-vivo (mice) Smith 2022 eLife growth defect BL6 mice HMM 6 replicates (raw data in Subramaniam 2017, PMID 31752678)
differentially essential in mice Smith 2022 eLife NO (LFC=0.443) in-vivo vs in-vitro ZINB YES if Padj<0.05, else not significant; LFC<0 means less insertions/more essential in mice
in-vitro (minimal) Minato 2019 mSys growth defect minimal medium HMM
in-vitro (YM rich medium) Minato 2019 mSys growth advantage YM rich medium HMM 7H9 supplemented with ~20 metabolites (amino acids, cofactors)
differentially essential in YM rich medium Minato 2019 mSys YES (LFC=6.87) YM rich vs minimal medium resampling
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 a global collection of 10k Mtb clinical isolates using GenomegaMap (Window model)
clinical isolates collection: global set of 10,626 Mtb genomes
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.
global set of 10,626 Mtb clinical isolates
under significant positive selection? NO
omega peak height (95%CI lower bound) 1.53 (0.68)
codons under selection
omega plots
genetic variants* link
* example format for variants: "D27 (GAC): D27H (CAC,11)" means "Asp27 (native codon GAC) mutated to His (codon CAC) in 11 isolates"
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:
see table of TFOE interactions below
Interactions based on ChIPSeq data
RNA processing and modification
Energy production and conversion
Chromatin structure and dynamics
Amino acid transport and metabolism
Cell cycle control, cell division, chromosome partitioning
Carbohydrate transport and metabolism
Nucleotide transport and metabolism
Lipid transport and metabolism
Coenzyme transport and metabolism
Translation, ribosomal structure and biogenesis
Cell wall/membrane/envelope biogenesis
Replication, recombination and repair
Posttranslational modification, protein turnover, chaperones
Secondary metabolites biosynthesis, transport and catabolism
Inorganic ion transport and metabolism
General function prediction only
Intracellular trafficking, secretion, and vesicular transport
Signal transduction mechanisms
Differentially expressed as result of RNASeq in glycerol environment (Only top 20 genes shown sorted by log fold change with p_adj 0.05).
Conditionally essential as result of TNSeq (Only top 20 genes shown sorted by log fold change with p_adj 0.05).
Binds To:
No bindings to other targets were found.
Bound By:
No bindings from other targets were found.
Binds To:
No bindings to other targets were found.
Bound By:
TFOE = Transcription Factor Over-Expression study
significance criteria used in paper: greater than 2-fold change (|LFC|>=1.0) and Padj<0.01
no significant interactions found
Upregulates:
Does not upregulate other genes.
Upregulated by:
Not upregulated by other genes.
Downregulates:
Does not downregulate other genes.
Downregulated by:
Not downregulated by other genes.
Property Value Creator Evidence PMID Comment
Term TBRXN:MYC1M2 Mycolic Acid Methyl Hydroxyl Addition - IDA njamshidi IDA 16356931 PMID: 16356931F. 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:MYC1M2 Mycolic Acid Methyl Hydroxyl Addition - ISS njamshidi ISS 16356931 PMID: 16356931F. 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
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:MYC1M1 Mycolic Acid Methyl Hydroxyl Addition - IDA njamshidi IDA 16356931 PMID: 16356931F. 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:MYC1M1 Mycolic Acid Methyl Hydroxyl Addition - ISS njamshidi ISS 16356931 PMID: 16356931F. 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 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
Name MmaA4 METHOXY MYCOLIC ACID SYNTHASE 4; synthesis of oxygenated mycolates mjackson IMP S-adenosyl-methionine-dependent mycolic acid methyltransferases
Term EC:2.1.1.- Transferases. Transferring one-carbon groups. Methyltransferases. - NR jjmcfadden NR Inferred from direct assayK. Takayama, C. Wang et al. Pathway to synthesis and processing of mycolic acids in Mycobacterium tuberculosis. Clin. Microbiol. Rev. 2005
Citation Pathway to synthesis and processing of mycolic acids in Mycobacterium tuberculosis. K. Takayama, C. Wang et al. Clin. Microbiol. Rev. 2005 jjmcfadden 15653820 Inferred from direct assay
Citation Tracking the putative biosynthetic precursors of oxygenated mycolates of Mycobacterium tuberculosis. Structural analysis of fatty acids of a mutant strain deviod of methoxy- and ketomycolates. authors,P. Dinadayala,F. Laval,C. Raynaud,A. Lemassu,MA. Laneelle,G. Laneelle,M. Daffe J. Biol. Chem. 2003 extern:JZUCKER 12473649 Reaction blocked in mutant
Term EC:2.1.1.- Transferases. Transferring one-carbon groups. Methyltransferases. - NR extern:JZUCKER NR Reaction blocked in mutantauthors,P. Dinadayala,F. Laval,C. Raynaud,A. Lemassu,MA. Laneelle,G. Laneelle,M. Daffe Tracking the putative biosynthetic precursors of oxygenated mycolates of Mycobacterium tuberculosis. Structural analysis of fatty acids of a mutant strain deviod of methoxy- and ketomycolates. J. Biol. Chem. 2003
Term EC:2.1.1.79 Cyclopropane-fatty-acyl-phospholipid synthase. - NR extern:JZUCKER NR Reaction blocked in mutantauthors,P. Dinadayala,F. Laval,C. Raynaud,A. Lemassu,MA. Laneelle,G. Laneelle,M. Daffe Tracking the putative biosynthetic precursors of oxygenated mycolates of Mycobacterium tuberculosis. Structural analysis of fatty acids of a mutant strain deviod of methoxy- and ketomycolates. J. Biol. Chem. 2003