TB Genome Annotation Portal

Rv1662 (pks8)

• Current annotations:
  • TBCAP: (community-based annotations - see table at bottom of page)
  • TBDB: polyketide synthase 8
  • REFSEQ: polyketide synthase pks8
  • PATRIC: Probable polyketide synthase pks7
  • TUBERCULIST: Probable polyketide synthase Pks8
  • NCBI: Probable polyketide synthase Pks8
  • updated information (H37Rv4):
    • gene name: pks8
    • function:
    • reference:
• Type: Not Target
• Start: 1881704
• End: 1886512
• Operon:


• Trans-membrane region:
  
• Role: I.I - Polyketide and non-ribosomal peptide synthesis
• GO terms:
  • GO:0055114 - oxidation-reduction process (Uniprot)
  • GO:0048037 - cofactor binding (Uniprot)
  • GO:0040007 - growth (Uniprot)
  • GO:0016740 - transferase activity (Uniprot)
  • GO:0016491 - oxidoreductase activity (Uniprot)
  • GO:0008270 - zinc ion binding (Uniprot)
  • GO:0008152 - metabolic process (Uniprot)
  • GO:0006636 - unsaturated fatty acid biosynthetic process (Uniprot)
  • GO:0003824 - catalytic activity (Uniprot)
• Reaction(s) (based on iSM810 metabolic model):
  • H[c] + 2 NADPH[c] + SMMALONYLCOA[c] + HEXADECANOATE[c] -> NADP[c] + CO2[c] + COA[c] + METHYL_OCTADECANOATE[c]
  • 15 H[c] + 10 NADPH[c] + SMMALONYLCOA[c] + 4 MALCOA[c] + OCTANOATE[c] -> 10 NADP[c] + 5 CO2[c] + 5 COA[c] + TUBERCULOSTEROYL_ACP... <Preview truncated at 128 characters>
  • 3 H[c] + 2 NADPH[c] + SMMALONYLCOA[c] + METHYL_OCTADECANOATE[c] -> 2 NADP[c] + CO2[c] + COA[c] + DMARACH[c]
  • H[c] + 2 NADPH[c] + SMMALONYLCOA[c] + DMARACH[c] -> 2 NADP[c] + CO2[c] + COA[c] + TMBHN[c]
  • 3 H[c] + 2 NADPH[c] + SMMALONYLCOA[c] + OCTADECANOATE[c] -> 2 NADP[c] + CO2[c] + COA[c] + MARACH[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
  3SLK	54%	Saccharopolyspora spinosa	Structure of ketoreductase and enoylreductase didomain from modular polyketide synthase
  2HG4	50%	Saccharopolyspora erythraea	Structure of the ketosynthase-acyltransferase didomain of module 5 from DEBS.
  2QO3	48%	Saccharopolyspora erythraea	Crystal Structure of [KS3][AT3] didomain from module 3 of 6-deoxyerthronolide B synthase
  6C9U	48%	Saccharopolyspora erythraea	Crystal structure of [KS3][AT3] didomain from module 3 of 6-deoxyerthronolide B synthase in complex with antibody fragment (Fab)
  6IYO	46%	Streptomyces albus subsp. albus	Crystal Structure of the acyltransferase domain from the second module of the salinomycin polyketide synthase
  6OBV	45%	Actinomadura vulgaris	Structural insights into dehydratase substrate selection for the borrelidin and fluvirucin polyketide synthases
  5DP1	45%	Moorea producens 3L	Crystal structure of CurK enoyl reductase
  5O16	44%	Sorangium cellulosum	Crystal structure of bifunctional dehydratase-cyclase domain in ambruticin biosynthesis
  5O15	44%	Sorangium cellulosum	Crystal structure of bifunctional dehydratase-cyclase domain in ambruticin biosynthesis
  4OKI	43%	Mycobacterium tuberculosis	X-ray structure of the nucleotide-binding subdomain of the enoylreductase domain of PpsC from Mycobacterium tuberculosis

• Links to additional information on pks8:
  • TBDB (updated)
  • Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
  • UniProt
  • AlphaFold model
  • Vulnerability = 0.468 (from Jeremy Rock's lab)
  • KEGG - nucleotide and amino acid sequences of gene
  • Mycobrowser
  • PATRIC
  • BioCyc
  • Systems Biology

Amino Acid Sequence

MSGTTTHVDYLKRLTADLRRTRRRLSDLEAKLSEPVAVVGMGCRYPGGVDSPETLWELVAQGRDAVSDFPADRGWDVDGLFDPDPDACGKMYTRRGTFLE
HAGDFDAGFFGIGPSEALAMDPQQRLLLEVSWEALERTGIDPTKLRGSATGVFAGVIHAGYGGQLSGELEGYGLTGSTLSVASGRVAYVLGLEGPAVSVD
TACSSSLVALHLAVQSLRSGECDLALAGGVTVMATPAAFVEFSRQRALARDGRCKVYAGAADGTAWSEGAGVLVVERLVDARRLGHPVLALVRGSAVNQD
GASNGLTAPNGPSQQRVIRAALASARLRAVEVDVVEGHGTGTMLGDPIEAQALLATYGQDRVEPLWLGSIKSNIGHTSAAAGVAGVIKMVQAMRHGVMPK
TLHVDVPTPHVDWSVGAVSLLTQPRAWSVHGRPRRAGVSSFGISGTNAHVILEQAPVVESVVPEVASPTAASAVPWVLSARSEQALAGQAQRLLAFVAAN
PDLDPIDVGWSLVKTRAMFEHRAVVVGADRGALLAGLAALAAGESGAGVAVGRARSVGKTVFVFPGQGAQWVGMGAQLYAELPLFALAFDAVAEELDRHL
RLPLRNVLWEGDEALLTSTEFAQPALFAIEVALATLLQHWGISPDFLIGHSVGEIAAAHLAGVLSLTDAAGLVAARGRLMAELPAGGVMVVVAASEEEVL
PVLVDGANLAAVNAPHSVVVSGCEAAVSDIADHFARRGRRVHRLAVSHAFHSLLMEPMLAEFTRIAAGISVSKPRIPLVSNVTGQMAGAGYGDGQYWVEH
ARRPVRFAEGVQLLNAVGATRFVEVGPGGGLTALVEQSLPLGEALSVAMMRREHPEVSSVLGAVATLFTAGAQMDWPAVFGSPGRRIELPTYAFQRQRYW
LPPTSAGSADISGVGLLAARHGLLGAVVEQPDSDVVVLTGRLSVGEQRWLADHVIAGVVLLAGAAFVELALRAADQVDCGVVEELTVVTPLVLPTVGGVQ
LQVVVGVGEMGQRPVSIYSRNAESDSGWVLHARGVLGAKAVAPAADLSVWPPLGAAPVDVDGAYQRFAELGYEYGRAFQGLTAMWRRESELFADVAVPDD
VDVTLSGFGIHPLVLDAALHAMGMVGEQAATMLPFSWQGVSLHAAGASRVRARIAPAGDGTVSVELADQAGLPVLSVQALVMRSVSSQLLSAAVAAADAA
GRGLLEVAWLPVELAHNDISADLVVWELESFQDGVGPVYSATHRVLVALQSWLAQERAGRLVVLTQGSVGQDATNLAGAAVWGLVRSAQAEHPGRVMLVD
SDGSMDVGDVIGCGEEQLMIRNGTAYAARLAQLRPQPILQLPDTNSGWRLVAGGAGALEDLTLASCPAKELAPGQVRIEVRALGVNFRDVLVALGIYPGA
AELGAEGAGVVTEVGPGVTGLAVGDPVMGLLGVAGSEAVVDARLVVKLPNRWPLTDAAGVPVVFLTAYYALRVLAQVQPGESVLVHAAAGGVGMAAVQLA
RLWGLEVFATASRGKWDTLHTMGCDNTHVADSRTLAFEETFWLTTEGRGVDVVLNSLAGEFTDASLRLLPRGGRFIEMGKTEFGTPRSLPRTILGWPTGL
ST

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	YES
omega peak height (95%CI lower bound)	2.53 (0.89)	1.93 (1.1)
codons under selection		780, 781, 782, 783, 784, 785, 786
omega plots
genetic variants*	link	link
statistics at each codon	link	link