TB Genome Annotation Portal

Rv1436 (gap)

• Current annotations:
  • TBCAP: (community-based annotations - see table at bottom of page)
  • TBDB: glyceraldehyde-3-phosphate dehydrogenase
  • REFSEQ: glyceraldehyde-3-phosphate dehydrogenase
  • PATRIC: NAD-dependent glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.12)
  • TUBERCULIST: Probable glyceraldehyde 3-phosphate dehydrogenase Gap (GAPDH)
  • NCBI: Probable glyceraldehyde 3-phosphate dehydrogenase Gap (GAPDH)
  • updated information (H37Rv4):
    • gene name: gap
    • function: shifts core carbon metablism in response to acidic stress (low pH)
    • reference: Gouzy (2021) PMID 34341117
• Type: Not Target
• Start: 1613307
• End: 1614326
• Operon:


• Trans-membrane region:
  
• Role: I.B.1 - Glycolysis
• GO terms:
  • GO:0055114 - oxidation-reduction process (Uniprot)
  • GO:0051287 - NAD binding (Uniprot)
  • GO:0050661 - NADP binding (Uniprot)
  • GO:0040007 - growth (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:0006096 - glycolytic process (Uniprot)
  • GO:0006006 - glucose metabolic process (Uniprot)
  • GO:0005886 - plasma membrane (Uniprot)
  • GO:0005829 - cytosol (Uniprot)
  • GO:0005737 - cytoplasm (Uniprot)
  • GO:0005618 - cell wall (Uniprot)
  • GO:0005576 - extracellular region (Uniprot)
  • GO:0004365 - glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity (Uniprot)
  • GO:0000166 - nucleotide binding (Uniprot)
• Reaction(s) (based on iSM810 metabolic model):
  • NAD[c] + PI[c] + G3P[c] <=> NADH[c] + 13PDG[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
  1VC2	61%	Thermus thermophilus	Crystal structure of Glyceraldehyde 3-Phosphate Dehydrogenase from Thermus thermophilus HB8
  3CMC	60%	Bacillus stearothermophilus	Thioacylenzyme intermediate of Bacillus stearothermophilus phosphorylating GAPDH
  2GD1	60%	Geobacillus stearothermophilus	COENZYME-INDUCED CONFORMATIONAL CHANGES IN GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE FROM BACILLUS STEAROTHERMOPHILLUS
  1GD1	60%	Geobacillus stearothermophilus	STRUCTURE OF HOLO-GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE FROM BACILLUS STEAROTHERMOPHILUS AT 1.8 ANGSTROMS RESOLUTION
  2G82	60%	Thermus aquaticus	High Resolution Structures of Thermus aquaticus Glyceraldehyde-3-Phosphate Dehydrogenase: Role of 220's Loop Motion in Catalysis
  1CER	60%	Thermus aquaticus	DETERMINANTS OF ENZYME THERMOSTABILITY OBSERVED IN THE MOLECULAR STRUCTURE OF THERMUS AQUATICUS D-GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE AT 2.5 ANGSTROMS RESOLUTION
  1NQO	60%	Geobacillus stearothermophilus	Glyceraldehyde-3-Phosphate Dehydrogenase Mutant With Cys 149 Replaced By Ser Complexed With Nad+ and D-Glyceraldehyde-3-Phosphate
  1NQA	60%	Geobacillus stearothermophilus	Glyceraldehyde-3-Phosphate Dehydrogenase Mutant With Cys 149 Replaced By Ala Complexed With Nad+ and D-Glyceraldehyde-3-Phosphate
  1NQ5	60%	Geobacillus stearothermophilus	Glyceraldehyde-3-Phosphate Dehydrogenase Mutant With Cys 149 Replaced By Ser Complexed With Nad+
  1NPT	60%	Geobacillus stearothermophilus	Glyceraldehyde-3-Phosphate Dehydrogenase Mutant With Cys 149 replaced by Ala complexed with NAD+

• Links to additional information on gap:
  • TBDB (updated)
  • Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
  • UniProt
  • AlphaFold model
  • Vulnerability = -8.621 (from Jeremy Rock's lab)
  • KEGG - nucleotide and amino acid sequences of gene
  • Mycobrowser
  • PATRIC
  • BioCyc
  • Systems Biology

Amino Acid Sequence

VTVRVGINGFGRIGRNFYRALLAQQEQGTADVEVVAANDITDNSTLAHLLKFDSILGRLPCDVGLEGDDTIVVGRAKIKALAVREGPAALPWGDLGVDVV
VESTGLFTNAAKAKGHLDAGAKKVIISAPATDEDITIVLGVNDDKYDGSQNIISNASCTTNCLAPLAKVLDDEFGIVKGLMTTIHAYTQDQNLQDGPHKD
LRRARAAALNIVPTSTGAAKAIGLVMPQLKGKLDGYALRVPIPTGSVTDLTVDLSTRASVDEINAAFKAAAEGRLKGILKYYDAPIVSSDIVTDPHSSIF
DSGLTKVIDDQAKVVSWYDNEWGYSNRLVDLVTLVGKSL

Additional Information

Gouzy A, Healy C, Black KA, Rhee KY, Ehrt S. Growth of Mycobacterium
tuberculosis at acidic pH depends on lipid assimilation and is
accompanied by reduced GAPDH activity. Proc Natl Acad Sci U S A. 2021
Aug 10;118(32):e2024571118. doi: 10.1073/pnas.2024571118. PMID:
34341117; PMCID: PMC8364206.

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)	1.04 (0.11)	0.66 (0.19)
codons under selection
omega plots
genetic variants*	link	link
statistics at each codon	link	link