Rv0088 Resolved · high auto-curated

H37Rv Rv0088 · MTBC0 - · 224 aa · 96927–97601 (+) · RefSeq NP_214602.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)polyketide cyclase/dehydrase
MTBC0 PGAP re-annotation
Revised (this work)Polyketide cyclase/dehydrase. Pfam: Polyketide_cyc2 (PF10604.16).

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 P9WM73 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized protein Rv0088

UniProt still lists this protein as Uncharacterized protein Rv0088; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionPolyketide cyclase / dehydrase and lipid transport
Orthologous groupCOG3832
Gene Ontology (8) GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0016020, GO:0030312, GO:0044464, GO:0071944

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 0.456 · purifying
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 4 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
Polyketide_cyc2PF10604.16 1.8e-0877–215 Polyketide cyclase / dehydrase and lipid transport

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

Closest characterised functional partner: hycE (formate hydrogenase HycE), medium confidence from genomic context alone (score 673 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0087 hycE formate hydrogenase HycE 673 673 ctx neighborhood:658
Rv0086 hycQ hydrogenase HycQ 667 668 ctx neighborhood:658
Rv0081 HTH-type transcriptional regulator 751 667 ctx neighborhood:651
Rv0085 hycP hydrogenase HycP 666 666 ctx neighborhood:658
Rv0084 hycD formate hydrogenlyase HycD 657 657 ctx neighborhood:644
Rv0082 oxidoreductase 656 656 ctx neighborhood:644
Rv0083 oxidoreductase 653 653 ctx neighborhood:644
Rv0089 methyltransferase 564 564 ctx neighborhood:499
Rv0080 hyp hypothetical protein 456 457 ctx neighborhood:455
Rv0079 hyp hypothetical protein 452 452 ctx neighborhood:452
Rv0090 membrane protein 429 429
Rv2529 hyp hypothetical protein 406 407 ctx cooccurence:403
Rv1117 hyp hypothetical protein 406 406 ctx cooccurence:406

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): polyketide cyclase/dehydrase
  • Pfam (hmmscan --cut_ga): Polyketide_cyc2 PF10604.16 (E=2e-08)
  • (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_214602.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Polyketide_cyc2 (PF10604.16)
  • 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 COG3832
  • Curated reference: UniProt P9WM73 (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 — 13 functional partner(s); context anchor hycE
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv0088|
MSVYKHAPSRVRLRQTRSTVVKGRSGSLSWRRVRTGDLGLAVWGGREEYRAVKPGTPGIQPKGDMMTVTVVDAGPGRVSRSVEVAAPAAELFAIVADPRRHRELDGSGTVRGNIKVPAKLVVGSKFSTKMKLFGLPYRITSRVTALKPNELVEWSHPLGHRWRWEFESLSPTLTRVTETFDYHAAGAIKNGLKFYEMTGFAKSNAAGIEATLAKLSDQYARGRA