TB Genome Annotation Portal

Rv1552 (frdA)

• Current annotations:
  • TBCAP: (community-based annotations - see table at bottom of page)
  • TBDB: fumarate reductase flavoprotein subunit
  • REFSEQ: fumarate reductase flavoprotein subunit
  • PATRIC: Succinate dehydrogenase flavoprotein subunit (EC 1.3.99.1)
  • TUBERCULIST: Probable fumarate reductase [flavoprotein subunit] FrdA (fumarate dehydrogenase) (fumaric hydrogenase)
  • NCBI: Probable fumarate reductase [flavoprotein subunit] FrdA (fumarate dehydrogenase) (fumaric hydrogenase)
  • updated information (H37Rv4):
    • gene name: frdA
    • function:
    • reference:
• Type: Not Target
• Start: 1757681
• End: 1759432
• Operon:


• Trans-membrane region:
  
• Role: I.B.6.b - anaerobic
• GO terms:
  • GO:0102040 - fumarate reductase (menaquinone) (Uniprot)
  • GO:0055114 - oxidation-reduction process (Uniprot)
  • GO:0050660 - flavin adenine dinucleotide binding (Uniprot)
  • GO:0045284 - plasma membrane fumarate reductase complex (Uniprot)
  • GO:0022900 - electron transport chain (Uniprot)
  • GO:0016627 - oxidoreductase activity, acting on the CH-CH group of donors (Uniprot)
  • GO:0016491 - oxidoreductase activity (Uniprot)
  • GO:0009061 - anaerobic respiration (Uniprot)
  • GO:0009055 - electron transfer activity (Uniprot)
  • GO:0006113 - fermentation (Uniprot)
  • GO:0005886 - plasma membrane (Uniprot)
  • GO:0000104 - succinate dehydrogenase activity (Uniprot)
• Reaction(s) (based on iSM810 metabolic model):
  • SUCC[c] + FAD[c] <=> FUM[c] + FADH2[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
  6AWF	54%	Escherichia coli (strain K12)	Escherichia coli quinol:fumarate reductase crystallized without dicarboxylate
  1L0V	54%	Escherichia coli	Quinol-Fumarate Reductase with Menaquinol Molecules
  1KFY	54%	Escherichia coli	QUINOL-FUMARATE REDUCTASE WITH QUINOL INHIBITOR 2-[1-(4-CHLORO-PHENYL)-ETHYL]-4,6-DINITRO-PHENOL
  1KF6	54%	Escherichia coli	E. coli Quinol-Fumarate Reductase with Bound Inhibitor HQNO
  6B58	54%	Escherichia coli	FrdA-SdhE assembly intermediate
  5VPN	54%	Escherichia coli (strain K12)	E. coli Quinol fumarate reductase FrdA E245Q mutation
  4KX6	54%	Escherichia coli	Plasticity of the quinone-binding site of the complex II homolog quinol:fumarate reductase
  3P4S	54%	Escherichia coli 042	Crystal structure of Menaquinol:fumarate oxidoreductase in complex with a 3-nitropropionate adduct
  3P4R	54%	Escherichia coli 042	Crystal structure of Menaquinol:fumarate oxidoreductase in complex with glutarate
  3P4Q	54%	Escherichia coli 042	Crystal structure of Menaquinol:oxidoreductase in complex with oxaloacetate

• Links to additional information on frdA:
  • TBDB (updated)
  • Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
  • UniProt
  • AlphaFold model
  • Vulnerability = 0.984 (from Jeremy Rock's lab)
  • KEGG - nucleotide and amino acid sequences of gene
  • Mycobrowser
  • PATRIC
  • BioCyc
  • Systems Biology

Amino Acid Sequence

MTAQHNIVVIGGGGAGLRAAIAIAETNPHLDVAIVSKVYPMRSHTVSAEGGAAAVTGDDDSLDEHAHDTVSGGDWLCDQDAVEAFVAEAPKELVQLEHWG
CPWSRKPDGRVAVRPFGGMKKLRTWFAADKTGFHLLHTLFQRLLTYSDVMRYDEWFATTLLVDDGRVCGLVAIELATGRIETILADAVILCTGGCGRVFP
FTTNANIKTGDGMALAFRAGAPLKDMEFVQYHPTGLPFTGILITEAARAEGGWLLNKDGYRYLQDYDLGKPTPEPRLRSMELGPRDRLSQAFVHEHNKGR
TVDTPYGPVVYLDLRHLGADLIDAKLPFVRELCRDYQHIDPVVELVPVRPVVHYMMGGVHTDINGATTLPGLYAAGETACVSINGANRLGSNSLPELLVF
GARAGRAAADYAARHQKSDRGPSSAVRAQARTEALRLERELSRHGQGGERIADIRADMQATLESAAGIYRDGPTLTKAVEEIRVLQERFATAGIDDHSRT
FNTELTALLELSGMLDVALAIVESGLRREESRGAHQRTDFPNRDDEHFLAHTLVHRESDGTLRVGYLPVTITRWPPGERVYGR

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)	1.8 (0.29)	1.1 (0.6)
codons under selection
omega plots
genetic variants*	link	link
statistics at each codon	link	link