TB Genome Annotation Portal

Rv0350 (dnaK)

• Current annotations:
  • TBCAP: (community-based annotations - see table at bottom of page)
  • TBDB: chaperone dnaK
  • REFSEQ: molecular chaperone DnaK
  • PATRIC: Chaperone protein DnaK
  • TUBERCULIST: Probable chaperone protein DnaK (heat shock protein 70) (heat shock 70 kDa protein) (HSP70)
  • NCBI: Probable chaperone protein DnaK (heat shock protein 70) (heat shock 70 kDa protein) (HSP70)
  • updated information (H37Rv4):
    • gene name: dnaK
    • function:
    • reference:
• Type: Not Target
• Start: 419835
• End: 421712
• Operon:


• Trans-membrane region:
  
• Role: III.B - Chaperones/Heat shock
• GO terms:
  • GO:2000679 - positive regulation of transcription regulatory region DNA binding (Uniprot)
  • GO:0097691 - bacterial extracellular vesicle (Uniprot)
  • GO:0071451 - cellular response to superoxide (Uniprot)
  • GO:0051082 - unfolded protein binding (Uniprot)
  • GO:0046777 - protein autophosphorylation (Uniprot)
  • GO:0046688 - response to copper ion (Uniprot)
  • GO:0046677 - response to antibiotic (Uniprot)
  • GO:0044044 - interaction with host via substance in symbiont surface (Uniprot)
  • GO:0042603 - capsule (Uniprot)
  • GO:0040007 - growth (Uniprot)
  • GO:0035375 - zymogen binding (Uniprot)
  • GO:0010756 - positive regulation of plasminogen activation (Uniprot)
  • GO:0009986 - cell surface (Uniprot)
  • GO:0009408 - response to heat (Uniprot)
  • GO:0006457 - protein folding (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:0005524 - ATP binding (Uniprot)
  • GO:0001968 - fibronectin binding (Uniprot)
  • GO:0000166 - nucleotide binding (Uniprot)
• Reaction(s) (based on iSM810 metabolic model):
• 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
  4RTF	100%	Mycobacterium tuberculosis H37Rv	Crystal structure of molecular chaperone DnaK from Mycobacterium tuberculosis H37Rv
  1DG4	70%	Escherichia coli	NMR STRUCTURE OF THE SUBSTRATE BINDING DOMAIN OF DNAK IN THE APO FORM
  1Q5L	69%	Escherichia coli	NMR structure of the substrate binding domain of DnaK bound to the peptide NRLLLTG
  3DQG	68%	Caenorhabditis elegans	Peptide-binding domain of heat shock 70 kDa protein F, mitochondrial precursor, from Caenorhabditis elegans.
  7HSC	67%	Rattus norvegicus	HIGH RESOLUTION SOLUTION STRUCTURE OF THE HEAT SHOCK COGNATE-70 KD SUBSTRATE BINDING DOMAIN OBTAINED BY MULTIDIMENSIONAL NMR TECHNIQUES
  1CKR	67%	Rattus norvegicus	HIGH RESOLUTION SOLUTION STRUCTURE OF THE HEAT SHOCK COGNATE-70 KD SUBSTRATE BINDING DOMAIN OBTAINED BY MULTIDIMENSIONAL NMR TECHNIQUES
  3N8E	66%	Homo sapiens	Substrate binding domain of the human Heat Shock 70kDa protein 9 (mortalin)
  4ANI	66%	GEOBACILLUS KAUSTOPHILUS	Structural basis for the intermolecular communication between DnaK and GrpE in the DnaK chaperone system from Geobacillus kaustophilus HTA426
  2V7Y	66%	GEOBACILLUS KAUSTOPHILUS HTA426	Crystal structure of the molecular chaperone DnaK from Geobacillus kaustophilus HTA426 in post-ATP hydrolysis state
  6JPV	65%	Homo sapiens	Structural analysis of AIMP2-DX2 and HSP70 interaction

• Links to additional information on dnaK:
  • KEGG - nucleotide and amino acid sequences of gene
  • Mycobrowser
  • PATRIC
  • TBDB (updated)
  • Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
  • UniProt
  • AlphaFold model
  • Vulnerability = -7.119 (from Jeremy Rock's lab)
  • BioCyc
  • Systems Biology
  • Photo of spot titer

Amino Acid Sequence

MARAVGIDLGTTNSVVSVLEGGDPVVVANSEGSRTTPSIVAFARNGEVLVGQPAKNQAVTNVDRTVRSVKRHMGSDWSIEIDGKKYTAPEISARILMKLK
RDAEAYLGEDITDAVITTPAYFNDAQRQATKDAGQIAGLNVLRIVNEPTAAALAYGLDKGEKEQRILVFDLGGGTFDVSLLEIGEGVVEVRATSGDNHLG
GDDWDQRVVDWLVDKFKGTSGIDLTKDKMAMQRLREAAEKAKIELSSSQSTSINLPYITVDADKNPLFLDEQLTRAEFQRITQDLLDRTRKPFQSVIADT
GISVSEIDHVVLVGGSTRMPAVTDLVKELTGGKEPNKGVNPDEVVAVGAALQAGVLKGEVKDVLLLDVTPLSLGIETKGGVMTRLIERNTTIPTKRSETF
TTADDNQPSVQIQVYQGEREIAAHNKLLGSFELTGIPPAPRGIPQIEVTFDIDANGIVHVTAKDKGTGKENTIRIQEGSGLSKEDIDRMIKDAEAHAEED
RKRREEADVRNQAETLVYQTEKFVKEQREAEGGSKVPEDTLNKVDAAVAEAKAALGGSDISAIKSAMEKLGQESQALGQAIYEAAQAASQATGAAHPGGE
PGGAHPGSADDVVDAEVVDDGREAK

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)	1.74 (0.27)	1.92 (0.68)
codons under selection
omega plots
genetic variants*	link	link
statistics at each codon	link	link