Rv0645c (mmaA1)
Current annotations:
TBCAP: (community-based annotations - see table at bottom of page )
TBDB: mycolic acid methyltransferase MmaA1
REFSEQ: methoxy mycolic acid synthase
PATRIC: Methoxy mycolic acid synthase 1 MmaA1 (EC 2.1.1.-)
TUBERCULIST: Methoxy mycolic acid synthase 1 MmaA1 (methyl mycolic acid synthase 1) (MMA1) (hydroxy mycolic acid synthase)
NCBI: Methoxy mycolic acid synthase 1 MmaA1 (methyl mycolic acid synthase 1) (MMA1) (hydroxy mycolic acid synthase)
updated information (H37Rv4):
gene name: mmaA1
function:
reference:
Type: Not Target
Start: 739327
End: 740187
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:
Search for Homologs in PDB
Top 10 Homologs in PDB (as of Nov 2020): PDB aa ident species PDB title 1KPH 56% Mycobacterium tuberculosis Crystal Structure of mycolic acid cyclopropane synthase CmaA1 complexed with SAH and DDDMAB 1KPG 56% Mycobacterium tuberculosis Crystal Structure of mycolic acid cyclopropane synthase CmaA1 complexed with SAH and CTAB 1KP9 56% Mycobacterium tuberculosis Crystal structure of mycolic acid cyclopropane synthase CmaA1, apo-form 1L1E 54% Mycobacterium tuberculosis Crystal Structure of Mycolic Acid Cyclopropane Synthase PcaA Complexed with S-adenosyl-L-homocysteine 1TPY 53% Mycobacterium tuberculosis Structure of the cyclopropane synthase MmaA2 from Mycobacterium tuberculosis 3HA7 51% Mycobacterium tuberculosis Crystal structure of HMA (MMAA4) from mycobacterium tuberculosis complexed with S-adenosyl-N-decyl-aminoethyl (SADAE) 3HA5 51% Mycobacterium tuberculosis Crystal structure of HMA (MMAA4) from mycobacterium tuberculosis complexed with sinefungin 3HA3 51% Mycobacterium tuberculosis Crystal structure of HMA (MMAA4) from mycobacterium tuberculosis complexed with S-adenosylhomocysteine 2FK8 51% Mycobacterium tuberculosis Crystal structure of Hma (MmaA4) from Mycobacterium tuberculosis complexed with S-adenosylmethionine 2FK7 51% Mycobacterium tuberculosis Crystal structure of Hma (MmaA4) from Mycobacterium tuberculosis, apo-form
Links to additional information on mmaA1:
Amino Acid Sequence
MAKLRPYYEESQSAYDISDDFFALFLDPTWVYTCAYFERDDMTLEEAQLAKVDLALDKLNLEPGMTLLDVGCGWGGALVRAVEKYDVNVIGLTLSRNHYE
RSKDRLAAIGTQRRAEARLQGWEEFEENVDRIVSFEAFDAFKKERYLTFFERSYDILPDDGRMLLHSLFTYDRRWLHEQGIALTMSDLRFLKFLRESIFP
GGELPSEPDIVDNAQAAGFTIEHVQLLQQHYARTLDAWAANLQAARERAIAVQSEEVYNNFMHYLTGCAERFRRGLINVAQFTMTK
(
Nucleotide sequence available on
KEGG )
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) 1.29 (0.23) 0.73 (0.25)
codons under selection
omega plots
genetic variants* link link
statistics at each codon link link
* example format for variants: "D27 (GAC): D27H (CAC,11)" means "Asp27 (native codon GAC) mutated to His (codon CAC) in 11 isolates"
MtbTnDB - interactive tool for exploring a database of published TnSeq datasets for Mtb
TnSeqCorr - genes with correlated TnSeq profiles across ~100 conditions
Rv0645c/mmaA1,
gene len: 860 bp, num TA sites: 21
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 non-essential 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 non-essential M9 minimal+cholesterol Gumbel 3 replicates; Padj<0.05
differentially essential in cholesterol Griffin 2011 PPath NO (LFC=-0.5) 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 advantage 7H9 HMM 6 replicates (raw data in Subramaniam 2017, PMID 31752678)
in-vivo (mice) Smith 2022 eLife growth advantage BL6 mice HMM 6 replicates (raw data in Subramaniam 2017, PMID 31752678)
differentially essential in mice Smith 2022 eLife NO (LFC=0.489) 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 advantage minimal medium HMM
in-vitro (YM rich medium) Minato 2019 mSys growth advantage YM rich medium HMM 7H9 supplemented with ~20 metabolites (amino acids, vitamins)
differentially essential in YM rich medium Minato 2019 mSys NO (LFC=0.26) YM rich vs minimal medium resampling
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
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:
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
Name MmaA1 METHOXY MYCOLIC ACID SYNTHASE; trans cyclopropanation of methoxy- and ketomycolates mjackson IMP S-adenosyl-methionine-dependent mycolic acid methyltransferases
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
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 MMAS-1, the branch point between cis- and trans-cyclopropane-containing oxygenated mycolates in Mycobacterium tuberculosis. authors,Y. Yuan,DC. Crane,JM. Musser,S. Sreevatsan,CE. Barry J. Biol. Chem. 1997 extern:JZUCKER 9092547 Inferred from experiment
Term EC:2.1.1.- Transferases. Transferring one-carbon groups. Methyltransferases. - NR extern:JZUCKER NR Inferred from experimentauthors,Y. Yuan,DC. Crane,JM. Musser,S. Sreevatsan,CE. Barry MMAS-1, the branch point between cis- and trans-cyclopropane-containing oxygenated mycolates in Mycobacterium tuberculosis. J. Biol. Chem. 1997
Term EC:2.1.1.79 Cyclopropane-fatty-acyl-phospholipid synthase. - NR extern:JZUCKER NR Inferred from experimentauthors,Y. Yuan,DC. Crane,JM. Musser,S. Sreevatsan,CE. Barry MMAS-1, the branch point between cis- and trans-cyclopropane-containing oxygenated mycolates in Mycobacterium tuberculosis. J. Biol. Chem. 1997