TB Genome Annotation Portal

Rv0753c (mmsA)

• Current annotations:
  • TBCAP: (community-based annotations - see table at bottom of page)
  • TBDB: methylmalonate-semialdehyde dehydrogenase (acylating)
  • REFSEQ: methylmalonate-semialdehyde dehydrogenase
  • PATRIC: Methylmalonate-semialdehyde dehydrogenase (EC 1.2.1.27)
  • TUBERCULIST: Probable methylmalonate-semialdehyde dehydrogenase MmsA (methylmalonic acid semialdehyde dehydrogenase) (MMSDH)
  • NCBI: Probable methylmalonate-semialdehyde dehydrogenase MmsA (methylmalonic acid semialdehyde dehydrogenase) (MMSDH)
  • updated information (H37Rv4):
    • gene name: mmsA
    • function:
    • reference:
• Coordinates in H37Rv: 844421 - 845953
• Gene length: 1533 bp (with stop codon), 510 aa (without stop codon)
• Operon:


• Trans-membrane region:
  
• Role: I.A.2 - Amino acids and amines
• GO terms:
  • GO:0055114 - oxidation-reduction process (Uniprot)
  • GO:0016620 - oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor (Uniprot)
  • GO:0016491 - oxidoreductase activity (Uniprot)
  • GO:0008152 - metabolic process (Uniprot)
  • GO:0005886 - plasma membrane (Uniprot)
  • GO:0004491 - methylmalonate-semialdehyde dehydrogenase (acylating) activity (Uniprot)
• Reaction(s) (based on iSM810 metabolic model):
  • NAD[c] + COA[c] + METHYMALONATE[c] -> NADH[c] + CO2[c] + PROPIONYLCOA[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:
• Search for Latest Homologs in PDB
• Top 10 Homologs in PDB (as of Apr 2026):
  

  PDB	aa ident	species	PDB title
  4IYM	67%	Sinorhizobium meliloti	Crystal structure of putative methylmalonate-semialdehyde dehydrogenase from Sinorhizobium meliloti 1021 complexed with NAD, target 011934
  4E4G	67%	Sinorhizobium meliloti	Crystal structure of putative Methylmalonate-semialdehyde dehydrogenase from Sinorhizobium meliloti 1021
  9Q0D	55%	Burkholderia cenocepacia	CryoEM structure of methylmalonic acid semialdehyde dehydrogenase from Burkholderia cenocepacia at 2.38A resolution
  5TJR	55%	Pseudomonas sp. AAC	X-ray Crystal structure of a methylmalonate semialdehyde dehydrogenase from Pseudomonas sp. AAC
  4ZZ7	53%	Oceanimonas doudoroffii	Crystal structure of methylmalonate-semialdehyde dehydrogenase (DddC) from Oceanimonas doudoroffii
  9IZV	43%	Homo sapiens	Cryo-EM structure of ALDH6A1-Y172H & R535C
  8XXQ	43%	Homo sapiens	Structural of methylmalonate semialdehyde dehydrogenase ALDH6A1
  9IZX	43%	Homo sapiens	Cryo-EM structure of ALDH6A1-G446R
  9IZW	43%	Homo sapiens	Cryo-EM structure of ALDH6A1-S262Y
  9IZU	43%	Homo sapiens	Cryo-EM structure of ALDH6A1-P62S

• Links to additional information on mmsA:
  • TBDB (updated)
  • Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
  • UniProt
  • AlphaFold model
  • Vulnerability = 1.16 (from Jeremy Rock's lab)
  • KEGG - nucleotide and amino acid sequences of gene
  • Mycobrowser
  • PATRIC
  • BioCyc
  • Systems Biology

Amino Acid Sequence

MTTQISHFIDGQRTAGQSTRSADVFDPNTGQIQAKVPMAGKSDIDAAVASAVEAQKGWAAWNPQRRARVLMRFIELVNDTIDELAELLSREHGKTLADAR
GDVQRGIEVIEFCLGIPHLLKGEYTEGAGPGIDVYSLRQPLGVVAGITPFNFPAMIPLWKAGPALACGNAFVLKPSERDPSVPVRLAELFIEAGLPAGVF
QVVHGDKEAVDAILHHPDIKAVGFVGSSDIAQYIYAGAAATGKRAQCFGGAKNHMIVMPDADLDQAVDALIGAGYGSAGERCMAISVAVPVGDQTAERLR
ARLIERINNLRVGHSLDPKADYGPLVTGAALARVRDYIGQGVAAGAELVVDGRDRASDDLTFGLPEGDANLEGGFFIGPTLFDHVAAHMSIYTDEIFGPV
LCMVRARDYEEALRLPSEHEYGNGVAIFTRDGDAARDFVSRVQVGMVGVNVPIPVPVAYHTFGGWKRSGFGDLNQHGPAAIQFYTKVKTVTSRWPSGIKD
GAEFVIPTMS

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 Rv0753c: 0.671766983
  • lineage-specific pN/pS in L1: 0.669630999
  • lineage-specific pN/pS in L2: 0.64354148
  • lineage-specific pN/pS in L3: 0.56846164
  • lineage-specific pN/pS in L4: 0.721600678

• 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)	1.26 (0.63)
codons under selection
omega plots
genetic variants*	link