TB18.5 Family assigned · medium auto-curated

H37Rv Rv0164 · MTBC0 - · 161 aa · 193626–194111 (+) · RefSeq YP_177617.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotation
Revised (this work)Contains Polyketide_cyc2 (PF10604.16), Polyketide_cyc (PF03364.26) domain(s); putative function inferred from the domain architecture.

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 L7N657 TrEMBL · unreviewed · Evidence at protein level
UniProt nameConserved protein TB18.5

UniProt still lists this protein as Conserved protein TB18.5; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
eggNOG descriptionCyclase dehydrase
Orthologous groupCOG2867

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 1.221 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 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 5.6e-0717–156 Polyketide cyclase / dehydrase and lipid transport
Polyketide_cycPF03364.26 7.9e-1125–152 Polyketide cyclase / dehydrase and lipid transport

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

Closest characterised functional partner: adhE1 (zinc-type alcohol dehydrogenase subunit E), high confidence from genomic context alone (score 742 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0163 hyp hypothetical protein 809 809 ctx neighborhood:807
Rv0162c adhE1 zinc-type alcohol dehydrogenase subunit E 742 742 ctx neighborhood:742
Rv0854 hyp hypothetical protein 658 659 ctx cooccurence:655
Rv3810 pirG cell surface protein 642 643 ctx cooccurence:636
Rv3287c rsbW anti-sigma factor RsbW 622 622 ctx cooccurence:621
Rv0273c transcriptional regulator 605 605 ctx cooccurence:604
Rv0518 hyp hypothetical protein 527 527 ctx cooccurence:515
Rv3058c TetR family transcriptional regulator 507 508 ctx cooccurence:502
Rv0857 hyp hypothetical protein 487 488 ctx cooccurence:486
Rv3446c hyp hypothetical protein 487 487 ctx cooccurence:480
Rv0856 hyp hypothetical protein 477 478 ctx cooccurence:476
Rv0009 ppiA iron-regulated peptidyl-prolyl cis-trans isomerase PpiA 474 474 coexpression:474
Rv0138 hyp hypothetical protein 463 464 ctx cooccurence:461
Rv0227c membrane protein 453 453 ctx cooccurence:425
Rv2905 lppW lipoprotein LppW 451 451 ctx cooccurence:448

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): hypothetical protein
  • Pfam (hmmscan --cut_ga): Polyketide_cyc2 PF10604.16 (E=6e-07), Polyketide_cyc PF03364.26 (E=8e-11)
  • (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_177617.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Polyketide_cyc2 (PF10604.16), Polyketide_cyc (PF03364.26)
  • 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 COG2867
  • Curated reference: UniProt L7N657 (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 — 22 functional partner(s); context anchor adhE1
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv0164|TB18.5
MTAISCSPRPRYASRMPVLSKTVEVTADAASIMAIVADIERYPEWNEGVKGAWVLARYDDGRPSQVRLDTAVQGIEGTYIHAVYYPGENQIQTVMQQGELFAKQEQLFSVVATGAASLLTVDMDVQVTMPVPEPMVKMLLNNVLEHLAENLKQRAEQLAAS