pks16 Resolved · high auto-curated

H37Rv Rv1013 · MTBC0 mtbc0_001088 · 544 aa · 1138962–1140596 (+) · RefSeq NP_215529.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)polyketide synthase
MTBC0 PGAP re-annotationfatty acyl-AMP ligase
Revised (this work)Fatty acyl-AMP ligase. Pfam: AMP-binding (PF00501.35).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt O05598 SwissProt · reviewed · Evidence at protein level
UniProt namePutative ligase Rv1013
EC (curated) EC 6.2.1.-

UniProt still lists this protein as Putative ligase Rv1013; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
Q Secondary metabolites biosynthesis, transport and catabolism
Preferred namepks16
eggNOG descriptionActivates fatty acids by binding to coenzyme A
Orthologous groupCOG0318
KEGG orthology K00666
Gene Ontology (37) GO:0003674, GO:0003824, GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0006082, GO:0006629, GO:0006631, GO:0006633, GO:0008150, GO:0008152 +25 more

Orthology-based transfer (eggNOG 5.0.2, diamond). EC/KO/GO/CAZy are computed annotations, not manual curation; cross-check against the primary literature before treating a specific reaction as established.

Conservation & selection (intra-MTBC, 145 209 strains)

pN/pS 0.172 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 6 synonymous, 3 missense, 0 nonsense, 0 frameshift

pN/pS from segregating SNPs (singletons removed) normalised by possible sites. Low pN/pS = purifying selection (a strong signal that a "hypothetical" is a real, constrained gene). A high pN/pS is ambiguous: relaxed constraint or positive selection (drug resistance, antigenic variation) inflate it; e.g. rpoB/katG/pncA score high here for resistance, not loss of function. A clonal disruption (one allele over a clade) suggests lineage pseudogenisation; a convergent one (many independent alleles) is typical of resistance loss-of-function.

Domains (Pfam, hmmscan --cut_ga)

PfamAccessioni-EvalueResiduesDescription
AMP-bindingPF00501.35 4.7e-5627–401 AMP-binding enzyme

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: mbtE (peptide synthetase), high confidence from genomic context alone (score 864 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2380c mbtE peptide synthetase 869 864 ctx cooccurence:528 experimental:465
Rv2379c mbtF peptide synthetase 769 767 ctx cooccurence:540
Rv1592c hyp hypothetical protein 737 737 coexpression:736
Rv1011 ispE 4-diphosphocytidyl-2C-methyl-D-erythritol kinase 739 726 ctx neighborhood:724
Rv0719 rplF 50S ribosomal protein L6 696 696 experimental:402 database:510
Rv1527c pks5 polyketide synthase 706 682
Rv2048c pks12 polyketide synthase 706 680
Rv2940c mas multifunctional mycocerosic acid synthase 706 680
Rv3825c pks2 phthioceranic/hydroxyphthioceranic acid synthase 705 680
Rv2933 ppsC phthiocerol synthesis polyketide synthase type I PpsC 704 679
Rv3800c pks13 polyketide synthase 682 650
Rv0101 nrp peptide synthetase Nrp 652 634 ctx cooccurence:428
Rv0542c menE 2-succinylbenzoic acid--CoA ligase 633 633 ctx cooccurence:633
Rv2946c pks1 polyketide synthase 730 632
Rv2932 ppsB phthiocerol synthesis polyketide synthase type I PpsB 647 626

STRING combines evidence channels (neighborhood, fusion, cooccurrence, coexpression, experimental, database, text-mining) into a 0–1000 score. The ctx badge marks edges carried by the genomic-context channels (conserved neighborhood, fusion, phylogenetic co-occurrence), which are independent of orthology and structure and the strongest signal for an unknown gene. The no text-mining column recomputes the score from data alone, so a link that does not depend on the literature is visible. Association is a function hypothesis, not proof: corroborate with the operon context and the primary literature before assigning a function.

Evidence

  • Legacy H37Rv annotation: polyketide synthase
  • MTBC0 PGAP product: fatty acyl-AMP ligase
  • Pfam (hmmscan --cut_ga): AMP-binding PF00501.35 (E=5e-56)
  • (auto-curated by rules from PGAP + Pfam + Foldseek; not hand-reviewed)

Sources

  • Ancestral sequence & coordinates: Harrison LB et al. (2024), An imputed ancestral reference genome for the MTBC, doi:10.1101/2023.09.07.556366
  • Product annotation: NCBI PGAP on MTBC0; legacy from H37Rv NC_000962.3 (RefSeq NP_215529.1)
  • Domains: Pfam-A via hmmscan --cut_ga — AMP-binding (PF00501.35)
  • Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
  • Controlled vocabulary: eggNOG-mapper 2.1.12 (Cantalapiedra et al. 2021, doi:10.1093/molbev/msab293), eggNOG 5.0 DB (Huerta-Cepas et al. 2019) — OG COG0318
  • Curated reference: UniProt O05598 (SwissProt, reviewed; Evidence at protein level)
  • Intra-MTBC selection: pN/pS and disruption from SPDI variants of 145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 81 functional partner(s); context anchor mbtE
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001088|Rv1013|pks16
MSRFTEKMFHNARTATTGMVTGEPHMPVRHTWGEVHERARCIAGGLAAAGVGLGDVVGVLAGFPVEIAPTAQALWMRGASLTMLHQPTPRTDLAVWAEDTMTVIGMIEAKAVIVSEPFLVAIPILEQKGMQVLTVADLLASDPIGPIEVGEDDLALMQLTSGSTGSPKAVQITHRNIYSNAEAMFVGAQYDVDKDVMVSWLPCFHDMGMVGFLTIPMFFGAELVKVTPMDFLRDTLLWAKLIDKYQGTMTAAPNFAYALLAKRLRRQAKPGDFDLSTLRFALSGAEPVEPADVEDLLDAGKPFGLRPSAILPAYGMAETTLAVSFSECNAGLVVDEVDADLLAALRRAVPATKGNTRRLATLGPLLQDLEARIIDEQGDVMPARGVGVIELRGESLTPGYLTMGGFIPAQDEHGWYDTGDLGYLTEEGHVVVCGRVKDVIIMAGRNIYPTDIERAAGRVDGVRPGCAVAVRLDAGHSRESFAVAVESNAFEDPAEVRRIEHQVAHEVVAEVDVRPRNVVVLGPGTIPKTPSGKLRRANSVTLVT