TB Genome Annotation Portal

Rv3339c (icd1)

• Current annotations:
  • TBCAP: (community-based annotations - see table at bottom of page)
  • TBDB: isocitrate dehydrogenase [NADP]
  • REFSEQ: isocitrate dehydrogenase
  • PATRIC: Isocitrate dehydrogenase [NADP] (EC 1.1.1.42)
  • TUBERCULIST: Probable isocitrate dehydrogenase [NADP] Icd1 (oxalosuccinate decarboxylase) (IDH) (NADP+-specific ICDH) (IDP)
  • NCBI: Probable isocitrate dehydrogenase [NADP] Icd1 (oxalosuccinate decarboxylase) (IDH) (NADP+-specific ICDH) (IDP)
  • updated information (H37Rv4):
    • gene name: icd1
    • function:
    • reference:
• Type: Not Target
• Start: 3724615
• End: 3725844
• Operon:


• Trans-membrane region:
  
• Role: I.B.3 - TCA cycle
• GO terms:
  • GO:0055114 - oxidation-reduction process (Uniprot)
  • GO:0051287 - NAD binding (Uniprot)
  • GO:0046872 - metal ion binding (Uniprot)
  • GO:0016616 - oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor (Uniprot)
  • GO:0016491 - oxidoreductase activity (Uniprot)
  • GO:0008270 - zinc ion binding (Uniprot)
  • GO:0006102 - isocitrate metabolic process (Uniprot)
  • GO:0006099 - tricarboxylic acid cycle (Uniprot)
  • GO:0006097 - glyoxylate cycle (Uniprot)
  • GO:0005886 - plasma membrane (Uniprot)
  • GO:0005515 - protein binding (Uniprot)
  • GO:0004450 - isocitrate dehydrogenase (NADP+) activity (Uniprot)
  • GO:0000287 - magnesium ion binding (Uniprot)
• Reaction(s) (based on iSM810 metabolic model):
  • NADP[c] + ICIT[c] -> NADPH[c] + CO2[c] + AKG[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: 4hcx
• Search for Homologs in PDB
• Top 10 Homologs in PDB (as of Nov 2020):
  

  PDB	aa ident	species	PDB title
  4HCX	100%	Mycobacterium tuberculosis	Structure of ICDH-1 from M.tuberculosis complexed with NADPH & Mn2+
  3US8	73%	Sinorhizobium meliloti	Crystal Structure of an isocitrate dehydrogenase from Sinorhizobium meliloti 1021
  6AJC	67%	Trypanosoma cruzi (strain CL Brener)	Crystal structure of Trypanosoma cruzi cytosolic isocitrate dehydrogenase in complex with NADP+, isocitrate and ca2+
  6PAY	65%	Homo sapiens	Structure of HsICDH1:Mg(II):ICT:NADPH(50%) complex reveals structural basis for observation of half-sites reactivity
  6BL2	65%	Homo sapiens	Novel Modes of Inhibition of Wild-Type IDH1: Direct Covalent Modification of His315 with Cmpd15
  6BL1	65%	Homo sapiens	Novel Modes of Inhibition of Wild-Type IDH1: Direct Covalent Modification of His315 with Cmpd13
  6BL0	65%	Homo sapiens	Novel Modes of Inhibition of Wild-Type IDH1:Direct Covalent Modification of His315 with Cmpd11
  6BKZ	65%	Homo sapiens	Novel Modes of Inhibition of Wild-Type IDH1: Non-equivalent Allosteric Inhibition with Cmpd3
  6BKY	65%	Homo sapiens	Novel Binding Modes of Inhibition of Wild-Type IDH1: Allosteric Inhibition with Cmpd2
  6BKX	65%	Homo sapiens	Novel Modes of Inhibition of Wild-Type IDH1: Direct Covalent Modification of His315 with Cmpd1

• Links to additional information on icd1:
  • TBDB (updated)
  • Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
  • UniProt
  • AlphaFold model
  • Vulnerability = 0.58 (from Jeremy Rock's lab)
  • KEGG - nucleotide and amino acid sequences of gene
  • Mycobrowser
  • PATRIC
  • BioCyc
  • Systems Biology

Amino Acid Sequence

MSNAPKIKVSGPVVELDGDEMTRVIWKLIKDMLILPYLDIRLDYYDLGIEHRDATDDQVTIDAAYAIKKHGVGVKCATITPDEARVEEFNLKKMWLSPNG
TIRNILGGTIFREPIVISNVPRLVPGWTKPIVIGRHAFGDQYRATNFKVDQPGTVTLTFTPADGSAPIVHEMVSIPEDGGVVLGMYNFKESIRDFARASF
SYGLNAKWPVYLSTKNTILKAYDGMFKDEFERVYEEEFKAQFEAAGLTYEHRLIDDMVAACLKWEGGYVWACKNYDGDVQSDTVAQGYGSLGLMTSVLMT
ADGKTVEAEAAHGTVTRHYRQYQAGKPTSTNPIASIFAWTRGLQHRGKLDGTPEVIDFAHKLESVVIATVESGKMTKDLAILIGPEQDWLNSEEFLDAIA
DNLEKELAN

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)	1.69 (0.17)	1.84 (0.82)
codons under selection
omega plots
genetic variants*	link	link
statistics at each codon	link	link