papA2 Resolved · high auto-curated

H37Rv Rv3820c · MTBC0 - · 468 aa · 4284419–4285825 (-) · RefSeq YP_178020.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)trehalose-2-sulfate acyltransferase
MTBC0 PGAP re-annotation
Revised (this work)Trehalose-2-sulfate acyltransferase. Pfam: Condensation (PF00668.26).

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

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt P9WIK7 SwissProt · reviewed · Evidence at protein level
UniProt nameTrehalose-2-sulfate acyltransferase PapA2
EC (curated) EC 2.3.1.288
Curated functionRequired for the biosynthesis of sulfolipid-1 (SL-1), a major mycobacterial cell wall lipid. Catalyzes the acylation of trehalose-2-sulfate by adding the palmitoyl group at the 2'-position to yield the intermediate trehalose-2-sulfate-2'-palmitate (SL659).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category Q Secondary metabolites biosynthesis, transport and catabolism
Preferred namepapA2
eggNOG descriptionCOG1020 Non-ribosomal peptide synthetase modules and related proteins
Orthologous groupCOG1020
Gene Ontology (24) GO:0003674, GO:0003824, GO:0006082, GO:0006629, GO:0006790, GO:0008150, GO:0008152, GO:0008610, GO:0009058, GO:0009987, GO:0016740, GO:0016746 +12 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 3.442 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 11 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
CondensationPF00668.26 1.2e-1470–362 Condensation domain

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

Closest characterised functional partner: Rv0128 (transmembrane protein), medium confidence from genomic context alone (score 691 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1527c pks5 polyketide synthase 900 884 coexpression:471 experimental:721
Rv3825c pks2 phthioceranic/hydroxyphthioceranic acid synthase 953 883 coexpression:466 experimental:721 textmining:619
Rv2940c mas multifunctional mycocerosic acid synthase 914 882 coexpression:468 experimental:721
Rv2933 ppsC phthiocerol synthesis polyketide synthase type I PpsC 898 864 coexpression:467 experimental:721
Rv2048c pks12 polyketide synthase 883 864 coexpression:469 experimental:721
Rv3800c pks13 polyketide synthase 888 854 coexpression:658 experimental:473
Rv1181 pks4 polyketide beta-ketoacyl synthase 877 807 coexpression:438 experimental:473
Rv2377c mbtH hyp hypothetical protein 760 746 coexpression:422 experimental:564
Rv2946c pks1 polyketide synthase 775 732 coexpression:443 experimental:473
Rv1661 pks7 polyketide synthase 751 723 coexpression:438 experimental:473
Rv2932 ppsB phthiocerol synthesis polyketide synthase type I PpsB 749 721 coexpression:442 experimental:473
Rv2383c mbtB phenyloxazoline synthase 781 715 coexpression:678
Rv0405 pks6 membrane bound polyketide synthase 720 704 coexpression:442 experimental:473
Rv2931 ppsA phthiocerol synthesis polyketide synthase type I PpsA 755 703 coexpression:440 experimental:473
Rv0128 transmembrane protein 690 691 ctx cooccurence:686

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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): trehalose-2-sulfate acyltransferase
  • Pfam (hmmscan --cut_ga): Condensation PF00668.26 (E=1e-14)
  • (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 YP_178020.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Condensation (PF00668.26)
  • 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 P9WIK7 (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 — 109 functional partner(s); context anchor Rv0128
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3820c|papA2
MFSITTLRDWTPDPGSIICWHASPTAKAKARQAPISEVPPSYQQAQHLRRYRDHVARGLDMSRLMIFTWDLPGRCNIRAMNYAINAHLRRHDTYHSWFEFDNAEHIVRHTIADPADIEVVQAEHQNMTSAELRHHIATPQPLQWDCFLFGIIQSDDHFTFYASIAHLCVDPMIVGVLFIEIHMMYSALVGGDPPIELPPAGRYDDHCVRQYADTAALTLDSARVRRWVEFAANNDGTLPHFPLPLGDLSVPHTGKLLTETLMDEQQGERFEAACVAAGARFSGGVFACAALAERELTNCETFDVVTTTDTRRTPTELRTTGWFTGLVPITVPVASGLFDSAARVAQISFDSGKDLATVPFDRVLELARPETGLRPPRPGNFVMSFLDASIAPLSTVANSDLNFRIYDEGRVSHQVSMWVNRYQHQTTVTVLFPDNPIASESVANYIAAMKSIYIRTADGTLATLKPGT