TB Genome Annotation Portal

Rv1181 (pks4)

• Current annotations:
  • TBCAP: (community-based annotations - see table at bottom of page)
  • TBDB: polyketide beta-ketoacyl synthase pks4
  • REFSEQ: polyketide beta-ketoacyl synthase PKS4
  • PATRIC: Polyketide synthase
  • TUBERCULIST: Probable polyketide beta-ketoacyl synthase Pks4
  • NCBI: Probable polyketide beta-ketoacyl synthase Pks4
  • updated information (H37Rv4):
    • gene name: pks4
    • function:
    • reference:
• Type: Not Target
• Start: 1315234
• End: 1319982
• Operon:


• Trans-membrane region:
  
• Role: I.I - Polyketide and non-ribosomal peptide synthesis
• GO terms:
  • GO:1902321 - methyl-branched fatty acid biosynthetic process (Uniprot)
  • GO:0055114 - oxidation-reduction process (Uniprot)
  • GO:0034081 - polyketide synthase complex (Uniprot)
  • GO:0031177 - phosphopantetheine binding (Uniprot)
  • GO:0016746 - transferase activity, transferring acyl groups (Uniprot)
  • GO:0016740 - transferase activity (Uniprot)
  • GO:0016491 - oxidoreductase activity (Uniprot)
  • GO:0016020 - membrane (Uniprot)
  • GO:0008152 - metabolic process (Uniprot)
  • GO:0006633 - fatty acid biosynthetic process (Uniprot)
  • GO:0005886 - plasma membrane (Uniprot)
  • GO:0003824 - catalytic activity (Uniprot)
• Reaction(s) (based on iSM810 metabolic model):
  • 6 NADPH[c] + OCTADECANOYL_COA[c] + 3 RMMALONYLACP[c] -> 6 NADP[c] + 3 CO2[c] + COA[c] + 2 ACP[c] + MYCOLIPANOIC_ACP[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
  5BP1	69%	Mycobacterium smegmatis (strain ATCC 700084 / mc(2)155)	Condensing di-domain (KS-AT) of a mycocerosic acid synthase-like (MAS-like) PKS
  5BP4	60%	Mycobacterium smegmatis	Modifying region (DH-ER-KR) of a mycocerosic acid synthase-like (MAS-like) PKS
  5BP3	51%	Mycobacterium smegmatis	Dehydratase domain (DH) of a mycocerosic acid synthase-like (MAS-like) PKS, crystal form 2
  5BP2	51%	Mycobacterium smegmatis	Dehydratase domain (DH) of a mycocerosic acid synthase-like (MAS-like) PKS, crystal form 1
  4OKI	47%	Mycobacterium tuberculosis	X-ray structure of the nucleotide-binding subdomain of the enoylreductase domain of PpsC from Mycobacterium tuberculosis
  1PQW	46%	Mycobacterium tuberculosis	Putative enoyl reductase domain of polyketide synthase
  5XUO	44%	Mycobacterium tuberculosis H37Rv	Pks13 AT domain fragment from Mycobacterium tuberculosis
  4IMP	41%	Saccharopolyspora spinosa	The missing linker: a dimerization motif located within polyketide synthase modules
  6WH9	41%	Saccharopolyspora erythraea	Ketoreductase from module 1 of the 6-deoxyerythronolide B synthase (KR1) in complex with antibody fragment (Fab) 1D10
  6W7S	41%	Saccharopolyspora erythraea	Ketoreductase from module 1 of the 6-deoxyerythronolide B synthase (KR1) in complex with antibody fragment (Fab) 2G10

• Links to additional information on pks4:
  • TBDB (updated)
  • Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
  • UniProt
  • AlphaFold model
  • Vulnerability = 1.768 (from Jeremy Rock's lab)
  • KEGG - nucleotide and amino acid sequences of gene
  • BioCyc
  • Systems Biology
  • Mycobrowser
  • PATRIC

Amino Acid Sequence

VTASSFDELSAALRDVAGDQIPYQPAVGHDDRGPVWVFSGQGSQWPGMGTELLVAEPVFAATVAAMEPVIARESGFSVTEAMSAPQTVSGIDRVQPTIFA
VQVALAAALKSYGVRPGAIIGHSLGEAAAAVVAGALSLHDGLRVICRRSRLMSRIAGSGAMASVELPGQQVLSELAIRGISDVVLSVVASPTSTVVGGAT
QSIRDLVAAWEQQDVLAREVAVDVASHTPQVDPILDELLEVLAEVDPTAPEIPYYSATLWDPRERPSFTGEYWVENLRYTVRFAAAVQAALKDGYRVFGE
LAPHPLLTYAVEQNAASLDMPIATLAAMRRGEQLPFGLRGFVADVHNAGAKVDFSVQYPDGRLVDAPLPSWTHRTLMLSREDSHRSHTGAVQAVHPLLGA
HVHLLEEPERHVWQAGVGTGAHPWLGDHRIHNVAAFPGAAYCEMALAAARTTLGELSEVRDIKFEQTLLLDEQTVVSSAATIAAPGILQFAVESHQEGEP
ARRASAMLHALEEMPQPPGYDTNALTAAHESSMSGEELRKMFNSLGIQYGPAFSGLVAVHTARGDVTTVLAEVALPGAIRSQQSAYASHPALLDACFQSV
LVHPEVQKATVGGLMLPVGVRRLRNYHSTRSAHYCLARVTSSSRAGECEADLDVFDQAGTVLLTVEGLRLAAGISEHERANRVFDERLLTIEWERGELPE
VPQIDAGSWLLLSASEADPLTAQLADALNAVGAQSTSVASASDVAQLRSLLGGRLTGVVVVTGPPTGGLTQCGRDYVSQLVGIARELAELPGEPPRLFVV
TRSAASVLPSDLANLEQAGLRGLMRVIDSEHPHLGATAIDVDNDETVAALVASQLQSGSQEDETAWRNGIWYTARLRPGPLRPAERRTAVVEYRRDGMRL
QIRTPGDLESLEFVTFDRVAPGPGEIEVAVTASSVNFADVLVAFGRYPTFEGYRQQLGIDFAGVVTAVGPDVTEHRIGDHVGGMSANGCWSTFVRCDARL
AVTLPPELPVAAAAAVPTASATAWYALHDLARICSDDKVLIHSGTGGVGQAAIAIARAAGCEIFATAGSAQRRQLLHDMGVEHVYDSRSTEFAEQIRGDT
DGYGVDVVLNSLPGAAQRAGIELLAFGGRFVEIGKRDIYGDTRLGLFPFRRNLSLYAVDLALLTHSHPHTVRRLLKTVYQHTVEGTLPVPQTTHYPIHDA
AVAIRLVGGAGHTGKVVLDVPRTGEGVAVVPPEQVRTSRPDGAYLVTGGLGGLGLFLAGELAAAGCGRIVLNSRSTPSPHATRVIERLRAAGADIQVECG
DIADAATAHRVVAVATASGLPVRGVLHAAAVVEDATLANVTDELIDRCWAPKVHGAWNIHRATAAQPLEWFCLFSSAAALVGSPGQGAYAAANSWLDAFA
HWRRAQGLPATSIAWGAWAEIGRATALAEGTGAAIAPAEGARAFQTLLRYGRAYSGYAPIMGTPWLTAFAQRSRFAEAFHATGQNQPATGKFLAELGSLP
REEWPRTVRRLVSDQISLLLRRTIDPDRPLSDYGLDSLGNLELRTRIETETGIRVSPTKITTVRGLAEHVCDELAAAQSAPV

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)	2.72 (0.85)	1.52 (0.66)
codons under selection
omega plots
genetic variants*	link	link
statistics at each codon	link	link