Rv0857 Family assigned · medium auto-curated

H37Rv Rv0857 · MTBC0 - · 157 aa · 953257–953730 (+) · RefSeq NP_215372.2

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 I6Y4Z9 TrEMBL · unreviewed · Predicted
UniProt nameCyclase

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptioncyclase dehydrase
Orthologous groupCOG3832

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 1.346 · 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 4.2e-1110–145 Polyketide cyclase / dehydrase and lipid transport
Polyketide_cycPF03364.26 5.5e-0718–142 Polyketide cyclase / dehydrase and lipid transport

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

Closest characterised functional partner: Rv0474 (HTH-type transcriptional regulator), high confidence from genomic context alone (score 753 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0856 hyp hypothetical protein 846 846 ctx neighborhood:841
Rv0474 HTH-type transcriptional regulator 752 753 ctx cooccurence:749
Rv0855 far fatty-acid-CoA racemase 741 741 ctx neighborhood:741
Rv3679 anion transporter ATPase 715 716 ctx cooccurence:715
Rv0487 hyp hypothetical protein 709 709 ctx cooccurence:696
Rv3197 ABC transporter ATP-binding protein 674 675 ctx cooccurence:670
Rv0502 hyp hypothetical protein 668 668 ctx cooccurence:667
Rv3916c hyp hypothetical protein 587 587 ctx cooccurence:576
Rv3680 anion transporter ATPase 584 585 ctx cooccurence:582
Rv0854 hyp hypothetical protein 561 560 ctx neighborhood:516
Rv0501 galE2 UDP-glucose 4-epimerase GalE 556 557 ctx cooccurence:554
Rv3662c hyp hypothetical protein 536 536 ctx cooccurence:534
Rv2974c hyp hypothetical protein 499 499 ctx cooccurence:496
Rv3698 hyp hypothetical protein 498 498 ctx cooccurence:486
Rv2712c hyp hypothetical protein 495 496 ctx cooccurence:493

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=4e-11), Polyketide_cyc PF03364.26 (E=6e-07)
  • (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_215372.2)
  • 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 COG3832
  • Curated reference: UniProt I6Y4Z9 (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 — 22 functional partner(s); context anchor Rv0474
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv0857|
MIANLVAVAIRASREVVIEAPPEVIVEALADMDAVPSWSSVHKRVEVVDTYSDGRPHHVKVTIKVAGIVDTELLEYHWGPDWVVWDAAKTAQQHGQHGEYNLRREDNDKTRVRFTLTVEPSAPLPAFWVNIARKKILHAATEGLRKQVVGRRRFTSG