Rv3126c Still unknown · low auto-curated

H37Rv Rv3126c · MTBC0 - · 104 aa · 3491808–3492122 (-) · RefSeq NP_217642.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotation
Revised (this work)Conserved hypothetical protein; no recognised domain. Function unknown.

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 P9WL09 SwissProt · reviewed · Evidence at transcript level
UniProt nameUncharacterized protein Rv3126c

UniProt still lists this protein as Uncharacterized protein Rv3126c; the revised annotation above is ahead of the current UniProt record.

Conservation & selection (intra-MTBC, 145 209 strains)

pN/pS 0.0 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 0 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)

No Pfam-A domain above the gathering threshold (or not yet scanned).

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

Closest characterised functional partner: PPE49 (PPE family protein PPE49), medium confidence from genomic context alone (score 585 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3127 hyp hypothetical protein 806 621 ctx neighborhood:617 textmining:511
Rv3125c PPE49 PPE family protein PPE49 585 585 ctx neighborhood:501
Rv1735c membrane protein 737 70 textmining:729
Rv1734c hyp hypothetical protein 525 68 textmining:512
Rv1813c hyp hypothetical protein 440 53 textmining:433
Rv0572c hyp hypothetical protein 805 51 textmining:803
Rv1812c dehydrogenase 519 47 textmining:516
Rv0085 hycP hydrogenase HycP 549 44 textmining:548
Rv0086 hycQ hydrogenase HycQ 630 42 textmining:630
Rv1519 hyp hypothetical protein 803 41 textmining:803
Rv0087 hycE formate hydrogenase HycE 511 41 textmining:511

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
  • (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_217642.1)
  • Domains: Pfam-A via hmmscan --cut_ga — none above threshold
  • Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
  • Curated reference: UniProt P9WL09 (SwissProt, reviewed; Evidence at transcript 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)
  • Model confidence: ESMFold per-residue pLDDT (mean 49.5, very low)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 11 functional partner(s); context anchor PPE49
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3126c|
MVIRFDQIGSLVLSMKSLASLSFQRCLRENSSLVAALDRLDAAVDELSALSFDALTTPERDRARRDRDHHPWSRSRSQLSPRMAHGAVHQCQWPKAVWAVIDNP