TB Genome Annotation Portal

Rv1493 (mutB)

• Current annotations:
  • TBCAP: (community-based annotations - see table at bottom of page)
  • TBDB: methylmalonyl-CoA mutase domain-containing protein
  • REFSEQ: methylmalonyl-CoA mutase
  • PATRIC: Methylmalonyl-CoA mutase (EC 5.4.99.2)
  • TUBERCULIST: Probable methylmalonyl-CoA mutase large subunit MutB (MCM)
  • NCBI: Probable methylmalonyl-CoA mutase large subunit MutB (MCM)
  • updated information (H37Rv4):
    • gene name: mutB
    • function:
    • reference:
• Type: Not Target
• Start: 1684005
• End: 1686257
• Operon:


• Trans-membrane region:
  
• Role: I.A.3 - Fatty acids
• GO terms:
  • GO:0046872 - metal ion binding (Uniprot)
  • GO:0031419 - cobalamin binding (Uniprot)
  • GO:0019678 - propionate metabolic process, methylmalonyl pathway (Uniprot)
  • GO:0016866 - intramolecular transferase activity (Uniprot)
  • GO:0016853 - isomerase activity (Uniprot)
  • GO:0008152 - metabolic process (Uniprot)
  • GO:0005886 - plasma membrane (Uniprot)
  • GO:0004494 - methylmalonyl-CoA mutase activity (Uniprot)
  • GO:0003824 - catalytic activity (Uniprot)
• Reaction(s) (based on iSM810 metabolic model):
  • SUCCOA[c] + 0.001 COB_III[c] -> RMMALONYLCOA[c]
  • RMMALONYLCOA[c] + 0.001 COB_III[c] -> SUCCOA[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 Homologs in PDB
• Top 10 Homologs in PDB (as of Nov 2020):
  

  PDB	aa ident	species	PDB title
  6OXD	100%	Mycobacterium tuberculosis	Structure of Mycobacterium tuberculosis methylmalonyl-CoA mutase with adenosyl cobalamin
  6OXC	100%	Mycobacterium tuberculosis	Structure of Mycobacterium tuberculosis methylmalonyl-CoA mutase with adenosyl cobalamin
  7REQ	74%	Propionibacterium freudenreichii subsp. shermanii	METHYLMALONYL-COA MUTASE, 2-CARBOXYPROPYL-COA INHIBITOR COMPLEX
  6REQ	74%	Propionibacterium freudenreichii subsp. shermanii	METHYLMALONYL-COA MUTASE, 3-CARBOXYPROPYL-COA INHIBITOR COMPLEX
  4REQ	74%	Propionibacterium freudenreichii subsp. shermanii	Methylmalonyl-COA Mutase substrate complex
  3REQ	74%	Propionibacterium freudenreichii subsp. shermanii	METHYLMALONYL-COA MUTASE, SUBSTRATE-FREE STATE (POOR QUALITY STRUCTURE)
  2REQ	74%	Propionibacterium freudenreichii subsp. shermanii	METHYLMALONYL-COA MUTASE, NON-PRODUCTIVE COA COMPLEX, IN OPEN CONFORMATION REPRESENTING SUBSTRATE-FREE STATE
  1REQ	74%	Propionibacterium freudenreichii subsp. shermanii	METHYLMALONYL-COA MUTASE
  5REQ	74%	Propionibacterium freudenreichii subsp. shermanii	Methylmalonyl-COA MUTASE, Y89F Mutant, substrate complex
  1E1C	74%	PROPIONIBACTERIUM FREUDENREICHII SUBSP. SHERMANII	METHYLMALONYL-COA MUTASE H244A Mutant

• Links to additional information on mutB:
  • TBDB (updated)
  • Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
  • UniProt
  • AlphaFold model
  • Vulnerability = 0.665 (from Jeremy Rock's lab)
  • KEGG - nucleotide and amino acid sequences of gene
  • Mycobrowser
  • PATRIC
  • BioCyc
  • Systems Biology

Amino Acid Sequence

MTTKTPVIGSFAGVPLHSERAAQSPTEAAVHTHVAAAAAAHGYTPEQLVWHTPEGIDVTPVYIAADRAAAEAEGYPLHSFPGEPPFVRGPYPTMYVNQPW
TIRQYAGFSTAADSNAFYRRNLAAGQKGLSVAFDLATHRGYDSDHPRVQGDVGMAGVAIDSILDMRQLFDGIDLSTVSVSMTMNGAVLPILALYVVAAEE
QGVAPEQLAGTIQNDILKEFMVRNTYIYPPKPSMRIISDIFAYTSAKMPKFNSISISGYHIQEAGATADLELAYTLADGVDYIRAGLNAGLDIDSFAPRL
SFFWGIGMNFFMEVAKLRAGRLLWSELVAQFAPKSAKSLSLRTHSQTSGWSLTAQDVFNNVARTCIEAMAATQGHTQSLHTNALDEALALPTDFSARIAR
NTQLVLQQESGTTRPIDPWGGSYYVEWLTHRLARRARAHIAEVAEHGGMAQAISDGIPKLRIEEAAARTQARIDSGQQPVVGVNKYQVPEDHEIEVLKVE
NSRVRAEQLAKLQRLRAGRDEPAVRAALAELTRAAAEQGRAGADGLGNNLLALAIDAARAQATVGEISEALEKVYGRHRAEIRTISGVYRDEVGKAPNIA
AATELVEKFAEADGRRPRILIAKMGQDGHDRGQKVIATAFADIGFDVDVGSLFSTPEEVARQAADNDVHVIGVSSLAAGHLTLVPALRDALAQVGRPDIM
IVVGGVIPPGDFDELYAAGATAIFPPGTVIADAAIDLLHRLAERLGYTLD

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)	1.59 (0.28)	1.53 (0.77)
codons under selection
omega plots
genetic variants*	link	link
statistics at each codon	link	link