TB Genome Annotation Portal

Rv1266c (pknH)

• Current annotations:
  • TBCAP: (community-based annotations - see table at bottom of page)
  • TBDB: serine/threonine protein kinase
  • REFSEQ: transmembrane serine/threonine-protein kinase H
  • PATRIC: Serine/threonine protein kinase (EC 2.7.11.1)
  • TUBERCULIST: Probable transmembrane serine/threonine-protein kinase H PknH (protein kinase H) (STPK H)
  • NCBI: Probable transmembrane serine/threonine-protein kinase H PknH (protein kinase H) (STPK H)
  • updated information (H37Rv4):
    • gene name: pknH
    • function:
    • reference:
• Type: Not Target
• Start: 1413960
• End: 1415840
• Operon:


• Trans-membrane region:
  
• Role: I.J.3 - Serine-Threonine protein kinases and phosphoprotein phosphatases
• GO terms:
  • GO:0052572 - response to host immune response (Uniprot)
  • GO:0046890 - regulation of lipid biosynthetic process (Uniprot)
  • GO:0046777 - protein autophosphorylation (Uniprot)
  • GO:0045926 - negative regulation of growth (Uniprot)
  • GO:0045893 - positive regulation of transcription, DNA-templated (Uniprot)
  • GO:0043388 - positive regulation of DNA binding (Uniprot)
  • GO:0043086 - negative regulation of catalytic activity (Uniprot)
  • GO:0043085 - positive regulation of catalytic activity (Uniprot)
  • GO:0016740 - transferase activity (Uniprot)
  • GO:0016310 - phosphorylation (Uniprot)
  • GO:0016301 - kinase activity (Uniprot)
  • GO:0016021 - integral component of membrane (Uniprot)
  • GO:0016020 - membrane (Uniprot)
  • GO:0006468 - protein phosphorylation (Uniprot)
  • GO:0005887 - integral component of plasma membrane (Uniprot)
  • GO:0005886 - plasma membrane (Uniprot)
  • GO:0005618 - cell wall (Uniprot)
  • GO:0005524 - ATP binding (Uniprot)
  • GO:0004674 - protein serine/threonine kinase activity (Uniprot)
  • GO:0004672 - protein kinase activity (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: 4esq
• Search for Homologs in PDB
• Top 10 Homologs in PDB (as of Nov 2020):
  

  PDB	aa ident	species	PDB title
  4ESQ	99%	Mycobacterium tuberculosis	Crystal structure of the extracellular domain of PknH from Mycobacterium tuberculosis
  2H34	68%	Mycobacterium tuberculosis	Apoenzyme crystal structure of the tuberculosis serine/threonine kinase, PknE
  3F69	40%	Mycobacterium tuberculosis	Crystal structure of the Mycobacterium tuberculosis PknB mutant kinase domain in complex with KT5720
  6I2P	40%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of the Mycobacterium tuberculosis PknB kinase domain (L33E mutant) in complex with its substrate GarA
  6B2P	40%	Mycobacterium tuberculosis	Dual Inhibition of the Essential Protein Kinases A and B in Mycobacterium tuberculosis
  3ORT	40%	Mycobacterium tuberculosis	Mycobacterium tuberculosis PknB kinase domain L33D mutant (crystal form 6)
  3ORP	40%	Mycobacterium tuberculosis	Mycobacterium tuberculosis PknB kinase domain L33D mutant (crystal form 5)
  3ORO	40%	Mycobacterium tuberculosis	Mycobacterium tuberculosis PknB kinase domain L33D mutant (crystal form 4)
  3ORL	40%	Mycobacterium tuberculosis	Mycobacterium tuberculosis PknB kinase domain L33D mutant (crystal form 3)
  3ORK	40%	Mycobacterium tuberculosis	Mycobacterium tuberculosis PknB kinase domain L33D mutant (crystal form 2)

• Links to additional information on pknH:
  • TBDB (updated)
  • Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
  • UniProt
  • AlphaFold model
  • Vulnerability = 0.745 (from Jeremy Rock's lab)
  • KEGG - nucleotide and amino acid sequences of gene
  • Mycobrowser
  • PATRIC
  • BioCyc
  • Systems Biology

Amino Acid Sequence

MSDAQDSRVGSMFGPYHLKRLLGRGGMGEVYEAEHTVKEWTVAVKLMTAEFSKDPVFRERMKREARIAGRLQEPHVVPIHDYGEVDGQMFLEMRLVEGTD
LDSVLKRFGPLTPPRAVAIITQIASALDAAHADGVMHRDVKPQNILITRDDFAYLVDFGIASATTDEKLTQLGTAVGTWKYMAPERFSNDEVTYRADIYA
LACVLHECLTGAPPYRADSAGTLVSSHLMGPIPQPSAIRPGIPKAFDAVVARGMAKKPEDRYASAGDLALAAHEALSDPDQDHAADILRRSQESTLPAPP
KPVPPPTMPATAMAPRQPPAPPVTPPGVQPAPKPSYTPPAQPGPAGQRPGPTGQPSWAPNSGPMPASGPTPTPQYYQGGGWGAPPSGGPSPWAQTPRKTN
PWPLVAGAAAVVLVLVLGAIGIWIAIRPKPVQPPQPVAEERLSALLLNSSEVNAVMGSSSMQPGKPITSMDSSPVTVSLPDCQGALYTSQDPVYAGTGYT
AINGLISSEPGDNYEHWVNQAVVAFPTADKARAFVQTSADKWKNCAGKTVTVTNKAKTYRWTFADVKGSPPTITVIDTQEGAEGWECQRAMSVANNVVVD
VNACGYRITNQAGQIAAKIVDKVNKE

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)	2.83 (0.81)	1.97 (0.87)
codons under selection
omega plots
genetic variants*	link	link
statistics at each codon	link	link