TB Genome Annotation Portal

Rv2780 (ald)

• Current annotations:
  • TBCAP: (community-based annotations - see table at bottom of page)
  • TBDB: alanine dehydrogenase
  • REFSEQ: secreted L-alanine dehydrogenase ALD (40 kDa antigen) (TB43)
  • PATRIC: Alanine dehydrogenase (EC 1.4.1.1)
  • TUBERCULIST: Secreted L-alanine dehydrogenase Ald (40 kDa antigen) (TB43)
  • NCBI: Secreted L-alanine dehydrogenase Ald (40 kDa antigen) (TB43)
  • updated information (H37Rv4):
    • gene name: ald
    • function:
    • reference:
• Type: Not Target
• Start: 3086820
• End: 3087935
• Operon:


• Trans-membrane region:
  
• Role: I.A.2 - Amino acids and amines
• GO terms:
  • GO:0055114 - oxidation-reduction process (Uniprot)
  • GO:0046872 - metal ion binding (Uniprot)
  • GO:0042853 - L-alanine catabolic process (Uniprot)
  • GO:0016491 - oxidoreductase activity (Uniprot)
  • GO:0006524 - alanine catabolic process (Uniprot)
  • GO:0005886 - plasma membrane (Uniprot)
  • GO:0005829 - cytosol (Uniprot)
  • GO:0005618 - cell wall (Uniprot)
  • GO:0005576 - extracellular region (Uniprot)
  • GO:0001666 - response to hypoxia (Uniprot)
  • GO:0000286 - alanine dehydrogenase activity (Uniprot)
  • GO:0000166 - nucleotide binding (Uniprot)
• Reaction(s) (based on iSM810 metabolic model):
  • NADH[c] + PYR[c] + NH3[c] <=> NAD[c] + ALA[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: 2voe, 2vhw, 2vhv, 2vhz, 2vhy, 2vhx, 2voj
• Search for Homologs in PDB
• Top 10 Homologs in PDB (as of Nov 2020):
  

  PDB	aa ident	species	PDB title
  6O7F	100%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Mycobacterium tuberculosis L-alanine dehydrogenase x-ray structure in complex with N6-isobutyl adenosine
  4LMP	100%	Mycobacterium tuberculosis	Mycobacterium tuberculosis L-alanine dehydrogenase x-ray structure in complex with N6-methyl adenosine
  2VOJ	100%	MYCOBACTERIUM TUBERCULOSIS	Ternary complex of M. tuberculosis Rv2780 with NAD and pyruvate
  2VOE	100%	MYCOBACTERIUM TUBERCULOSIS	Crystal structure of Rv2780 from M. tuberculosis H37Rv
  2VHZ	100%	MYCOBACTERIUM TUBERCULOSIS	Crystal structure of holo L-alanine dehydrogenase from Mycobacterium tuberculosis in the closed conformation
  2VHY	100%	MYCOBACTERIUM TUBERCULOSIS	Crystal structure of apo L-alanine dehydrogenase from Mycobacterium tuberculosis
  2VHX	100%	MYCOBACTERIUM TUBERCULOSIS	Crystal structure of the ternary complex of L-alanine dehydrogenase from Mycobacterium tuberculosis with NAD+ and pyruvate
  2VHW	100%	MYCOBACTERIUM TUBERCULOSIS	Crystal structure of holo L-alanine dehydrogenase from Mycobacterium tuberculosis in the open and closed conformation
  2VHV	99%	MYCOBACTERIUM TUBERCULOSIS	Crystal structure of the D270A mutant of L-alanine dehydrogenase from Mycobacterium tuberculosis in complex with NADH.
  2EEZ	56%	Thermus thermophilus	Crystal structure of alanine dehydrogenase from themus thermophilus

• Links to additional information on ald:
  • KEGG - nucleotide and amino acid sequences of gene
  • Mycobrowser
  • PATRIC
  • BioCyc
  • Systems Biology
  • TBDB (updated)
  • Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
  • UniProt
  • AlphaFold model
  • Vulnerability = 1.363 (from Jeremy Rock's lab)

Amino Acid Sequence

MRVGIPTETKNNEFRVAITPAGVAELTRRGHEVLIQAGAGEGSAITDADFKAAGAQLVGTADQVWADADLLLKVKEPIAAEYGRLRHGQILFTFLHLAAS
RACTDALLDSGTTSIAYETVQTADGALPLLAPMSEVAGRLAAQVGAYHLMRTQGGRGVLMGGVPGVEPADVVVIGAGTAGYNAARIANGMGATVTVLDIN
IDKLRQLDAEFCGRIHTRYSSAYELEGAVKRADLVIGAVLVPGAKAPKLVSNSLVAHMKPGAVLVDIAIDQGGCFEGSRPTTYDHPTFAVHDTLFYCVAN
MPASVPKTSTYALTNATMPYVLELADHGWRAACRSNPALAKGLSTHEGALLSERVATDLGVPFTEPASVLA

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)	1.95 (0.49)	1.45 (0.76)
codons under selection
omega plots
genetic variants*	link	link
statistics at each codon	link	link