TB Genome Annotation Portal

Rv3025c (iscS)

• Current annotations:
  • TBCAP: (community-based annotations - see table at bottom of page)
  • TBDB: cysteine desulfurase
  • REFSEQ: cysteine desulfurase IscS
  • PATRIC: Cysteine desulfurase (EC 2.8.1.7)
  • TUBERCULIST: Cysteine desulfurase IscS (NIFS protein homolog) (nitrogenase metalloclusters biosynthesis protein NIFS)
  • NCBI: Cysteine desulfurase IscS (NIFS protein homolog) (nitrogenase metalloclusters biosynthesis protein NIFS)
  • updated information (H37Rv4):
    • gene name: iscS
    • function: iron-sulfur cluster biogenesis; oxidative stress response
    • reference: Rybniker (2014) PMID: 24548275
• Type: Not Target
• Start: 3383885
• End: 3385066
• Operon:


• Trans-membrane region:
  
• Role: IV.H - Miscellaneous transferases
• GO terms:
  • GO:0051536 - iron-sulfur cluster binding (Uniprot)
  • GO:0046872 - metal ion binding (Uniprot)
  • GO:0040007 - growth (Uniprot)
  • GO:0031071 - cysteine desulfurase activity (Uniprot)
  • GO:0016740 - transferase activity (Uniprot)
  • GO:0016226 - iron-sulfur cluster assembly (Uniprot)
  • GO:0008483 - transaminase activity (Uniprot)
  • GO:0003824 - catalytic activity (Uniprot)
• Reaction(s) (based on iSM810 metabolic model):
  • ATP[c] + CYS[c] + MOAD_COOH[c] -> PPI[c] + AMP[c] + SER[c] + MOAD_COSH[c]
  • FE2[c] + CYS[c] -> FERO[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:
• Search for Homologs in PDB
• Top 10 Homologs in PDB (as of Nov 2020):
  

  PDB	aa ident	species	PDB title
  4ISY	100%	Mycobacterium tuberculosis	Crystal structure of IscS from Mycobacterium tuberculosis
  3LVM	40%	Escherichia coli	Crystal Structure of E.coli IscS
  3LVL	40%	Escherichia coli	Crystal Structure of E.coli IscS-IscU complex
  3LVK	40%	Escherichia coli	Crystal Structure of E.coli IscS-TusA complex (form 2)
  3LVJ	40%	Escherichia coli	Crystal Structure of E.coli IscS-TusA complex (form 1)
  1P3W	40%	Escherichia coli	X-ray crystal structure of E. coli IscS
  6WIH	39%	Homo sapiens	N-terminal mutation of ISCU2 (L35H36) traps Nfs1 Cys loop in the active site of ISCU2 without metal present. Structure of human mitochondrial complex Nfs1-ISCU2(L35H36)-ISD11 with E.coli ACP1 at 1.9 A resolution (NIAU)2.
  6WI2	39%	Homo sapiens	Structure of human mitochondrial complex Nfs1-ISCU2-ISD11 with E.coli ACP1 at 1.95 A resolution (NIAU)2. N-terminal mutation of ISCU2 (L35) traps Nfs1 Cys loop in the active site of ISCU2 without metal present.
  6W1D	39%	Homo sapiens	Structure of human mitochondrial complex Nfs1-ISCU2 (WT)-ISD11 with E.coli ACP1 at 1.8 A resolution (NIAU)2
  6UXE	39%	Homo sapiens	Structure of the human mitochondrial desulfurase complex Nfs1-ISCU2(M140I)-ISD11 with E.coli ACP1 at 1.57 A resolution showing flexibility of N terminal end of ISCU2

• Links to additional information on iscS:
  • TBDB (updated)
  • Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
  • UniProt
  • AlphaFold model
  • Vulnerability = -1.315 (from Jeremy Rock's lab)
  • KEGG - nucleotide and amino acid sequences of gene
  • Mycobrowser
  • PATRIC
  • BioCyc
  • Systems Biology

Amino Acid Sequence

MAYLDHAATTPMHPAAIEAMAAVQRTIGNASSLHTSGRSARRRIEEARELIADKLGARPSEVIFTAGGTESDNLAVKGIYWARRDAEPHRRRIVTTEVEH
HAVLDSVNWLVEHEGAHVTWLPTAADGSVSATALREALQSHDDVALVSVMWANNEVGTILPIAEMSVVAMEFGVPMHSDAIQAVGQLPLDFGASGLSAMS
VAGHKFGGPPGVGALLLRRDVTCVPLMHGGGQERDIRSGTPDVASAVGMATAAQIAVDGLEENSARLRLLRDRLVEGVLAEIDDVCLNGADDPMRLAGNA
HFTFRGCEGDALLMLLDANGIECSTGSACTAGVAQPSHVLIAMGVDAASARGSLRLSLGHTSVEADVDAALEVLPGAVARARRAALAAAGASR

Additional Information

Rybniker J, Pojer F, Marienhagen J, Kolly GS, Chen JM, van Gumpel E,
Hartmann P, Cole ST. The cysteine desulfurase IscS of Mycobacterium
tuberculosis is involved in iron-sulfur cluster biogenesis and
oxidative stress defence. Biochem J. 2014 May 1;459(3):467-78. doi:
10.1042/BJ20130732. PMID: 24548275.

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)	1.65 (0.35)	1.19 (0.5)
codons under selection
omega plots
genetic variants*	link	link
statistics at each codon	link	link