papA4 Resolved · medium auto-curated

H37Rv Rv1528c · MTBC0 mtbc0_001635 · 165 aa · 1738762–1739259 (-) · RefSeq NP_216044.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)polyketide synthase associated protein PapA
MTBC0 PGAP re-annotationpolyketide synthase
Revised (this work)Polyketide synthase.

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

Curated reference (UniProt)

UniProt O53902 TrEMBL · unreviewed · Predicted
UniProt nameProbable conserved polyketide synthase associated protein PapA4

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category Q Secondary metabolites biosynthesis, transport and catabolism
Preferred namepapA4
eggNOG descriptionD-alanine [D-alanyl carrier protein] ligase activity
Orthologous groupCOG1020

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 n/a
Polymorphic sites (≥ 0.1% of strains) 0 synonymous, 1 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)

No Pfam-A domain above the gathering threshold (or not yet scanned).

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

PartnerProductScoreNo text-miningChannels (≥400)
Rv3800c pks13 polyketide synthase 855 827 coexpression:648 experimental:465
Rv1527c pks5 polyketide synthase 967 821 coexpression:453 experimental:642 textmining:827
Rv2933 ppsC phthiocerol synthesis polyketide synthase type I PpsC 870 821 coexpression:456 experimental:642
Rv2940c mas multifunctional mycocerosic acid synthase 845 821 coexpression:456 experimental:642
Rv3825c pks2 phthioceranic/hydroxyphthioceranic acid synthase 844 821 coexpression:455 experimental:642
Rv2048c pks12 polyketide synthase 844 821 coexpression:454 experimental:642
Rv3177 peroxidase 732 733 coexpression:732
Rv2946c pks1 polyketide synthase 759 720 coexpression:429 experimental:465
Rv1661 pks7 polyketide synthase 740 713 coexpression:435 experimental:465
Rv1181 pks4 polyketide beta-ketoacyl synthase 738 710 coexpression:430 experimental:465
Rv2932 ppsB phthiocerol synthesis polyketide synthase type I PpsB 735 706 coexpression:429 experimental:465
Rv2383c mbtB phenyloxazoline synthase 740 699 coexpression:664
Rv2931 ppsA phthiocerol synthesis polyketide synthase type I PpsA 709 694 coexpression:432 experimental:465
Rv0405 pks6 membrane bound polyketide synthase 708 693 coexpression:430 experimental:465
Rv2377c mbtH hyp hypothetical protein 710 692 coexpression:419 experimental:475

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 associated protein PapA
  • MTBC0 PGAP product: polyketide synthase
  • (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_216044.1)
  • Domains: Pfam-A via hmmscan --cut_ga — none above threshold
  • 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 COG1020
  • Curated reference: UniProt O53902 (TrEMBL, unreviewed; Predicted)
  • 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 — 43 functional partner(s)
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001635|Rv1528c|papA4
MTQLPQPTWRWWQQRETEQVQSSHIDGEIVGALIPDLAVLHSEDASRAAVGREKHRCSLDPLGGGFRSRRASMPAGALLLSAVIAIQLDRMNARVFGDGWIGAQACMWVNKFHEESTVTALSPSSPIAQGSIARHPETMQSAYVRIAEGGSRDVAPAAQLQRRRP