Rv2660c Still unknown · low auto-curated

H37Rv Rv2660c · MTBC0 mtbc0_002834 · 75 aa · 3003166–3003393 (-) · RefSeq NP_217176.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationhypothetical protein
Revised (this work)Conserved hypothetical protein; no recognised domain. Function unknown. Foldseek best (non-significant) hit: 8pui-assembly1_A human PHOX2B C-terminal domain including the polyA fr (prob 0.02, TM 0.30).

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

Curated reference (UniProt)

UniProt I6Y1F5 TrEMBL · unreviewed · Predicted
UniProt nameUncharacterized protein

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

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

pN/pS n/a
Polymorphic sites (≥ 0.1% of strains) 0 synonymous, 3 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).

Structural neighbours (Foldseek on the ESMFold model, exploratory)

ESMFold model confidence: mean pLDDT 40.3 (very low). Low-confidence model: the fold may be unreliable, so treat these structural hits with caution.

Best matches against the PDB, ranked by Foldseek homology probability. A high probability / TM-score suggests a shared fold; unless flagged sig (E < 0.01) these are fold hypotheses, not assignments.

TargetProbTME-valueDescription
8pui-assembly1_A 0.02 0.30 8.2e+00 8pui-assembly1_A human PHOX2B C-terminal domain including the polyA fragment at 298K

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

Closest characterised functional partner: Rv2659c (prophage integrase), medium confidence from genomic context alone (score 486 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2661c hyp hypothetical protein 776 775 ctx neighborhood:773
Rv2662 hyp hypothetical protein 577 577 ctx neighborhood:572
Rv2659c prophage integrase 486 486 ctx neighborhood:481
Rv2658c prophage protein 485 484 ctx neighborhood:481
Rv2656c prophage protein 476 476 ctx neighborhood:461
Rv2654c antitoxin 476 476 ctx neighborhood:461
Rv2655c prophage protein 469 469 ctx neighborhood:461
Rv2657c prophage protein 511 464 ctx neighborhood:461
Rv2663 hyp hypothetical protein 406 406 ctx neighborhood:403
Rv1954c hyp hypothetical protein 641 70 textmining:630
Rv3288c usfY hyp hypothetical protein 664 53 textmining:660
Rv1374c hyp hypothetical protein 562 50 textmining:558
Rv1168c PPE17 PPE family protein PPE17 514 50 textmining:510
Rv2558 hyp hypothetical protein 731 47 textmining:730
Rv2557 hyp hypothetical protein 515 47 textmining:512

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: hypothetical protein
  • Foldseek best: 8pui-assembly1_A human PHOX2B C-terminal domain including the polyA fragment at (prob 0.02, E=8e+00, TM=0.30)
  • (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_217176.1)
  • Domains: Pfam-A via hmmscan --cut_ga — none above threshold
  • Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
  • Curated reference: UniProt I6Y1F5 (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)
  • Model confidence: ESMFold per-residue pLDDT (mean 40.3, very low)
  • 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 Rv2659c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002834|Rv2660c|
MIAGVDQALAATGQASQRAAGASGGVTVGVGVGTEQRNLSVVAPSQFTFSSRSPDFVDETAGQSWCAILGLNQFH