Rv0356c Family assigned · medium auto-curated

H37Rv Rv0356c · MTBC0 mtbc0_000376 · 214 aa · 438192–438836 (-) · RefSeq NP_214870.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationPaaI family thioesterase
Revised (this work)PaaI family thioesterase. Pfam: 4HBT (PF03061.29).

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

Curated reference (UniProt)

UniProt O06307 TrEMBL · unreviewed · Evidence at protein level
UniProt nameAcyl-coenzyme A thioesterase THEM4
EC (curated) EC 3.1.2.2

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category Q Secondary metabolites biosynthesis, transport and catabolism
eggNOG descriptionthioesterase
Orthologous groupCOG2050

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 0.19 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 11 synonymous, 6 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
4HBTPF03061.29 3.2e-10126–199 Thioesterase superfamily

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

Closest characterised functional partner: purA (adenylosuccinate synthetase), high confidence from genomic context alone (score 945 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0357c purA adenylosuccinate synthetase 944 945 ctx neighborhood:801 coexpression:733
Rv2383c mbtB phenyloxazoline synthase 707 664 coexpression:431 experimental:402
Rv1125 hyp hypothetical protein 647 641 ctx cooccurence:542
Rv2042c hyp hypothetical protein 638 638 ctx cooccurence:637
Rv3035 hyp hypothetical protein 624 624 ctx cooccurence:609
Rv0358 hyp hypothetical protein 623 623 ctx neighborhood:563
Rv2524c fas fatty acid synthase 731 620 coexpression:412
Rv3531c hyp hypothetical protein 599 599 ctx cooccurence:599
Rv1780 hyp hypothetical protein 589 589 ctx cooccurence:589
Rv3529c hyp hypothetical protein 588 588 ctx cooccurence:544
Rv2876 transmembrane protein 563 563 ctx cooccurence:559
Rv0359 rip2 zinc metalloprotease 561 560 ctx neighborhood:551
Rv2342 hyp hypothetical protein 557 557 ctx cooccurence:557
Rv0310c hyp hypothetical protein 562 536 ctx cooccurence:499
Rv3792 aftA arabinofuranosyltransferase 534 535 ctx cooccurence:529

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: hypothetical protein
  • MTBC0 PGAP product: PaaI family thioesterase
  • Pfam (hmmscan --cut_ga): 4HBT PF03061.29 (E=3e-10)
  • (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_214870.1)
  • Domains: Pfam-A via hmmscan --cut_ga — 4HBT (PF03061.29)
  • 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 COG2050
  • Curated reference: UniProt O06307 (TrEMBL, unreviewed; 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 — 32 functional partner(s); context anchor purA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000376|Rv0356c|
MTDASVHPDELDPEYHHHGGFPEYGPASPGAGFGQFVATMRRLQDLAVAADPGDAVWDEAAERAAALVELLSPFEADEGKAPAGRTPGLPGMGSLLLPPWTVTRYGTDGVEMRGSFSRFHVGGNSAVHGGVLPLLFDHMFGMISHAAGRPISRTAFLHVDYRRITPIDVPLIVRGRVTNTEGRKAFVCAELFDSDETLLAEGNGLMVRLLPGQP