Rv2468A Still unknown · low auto-curated

H37Rv Rv2468A · MTBC0 - · 77 aa · 2772098–2772331 (-) · RefSeq YP_007411168.1

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 I6YDH3 TrEMBL · unreviewed · Evidence at protein level
UniProt nameConserved protein

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

Functional vocabulary (eggNOG-mapper, orthology transfer)

Orthologous group2APNU

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 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).

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

Closest characterised functional partner: aglA (alpha-glucosidase AglA), 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)
Rv3043c ctaD cytochrome C oxidase cytochrome 1 997 997 experimental:997
Rv2468c hyp hypothetical protein 936 937 ctx neighborhood:882 experimental:484
Rv2196 qcrB ubiquinol-cytochrome C reductase cytochrome subunit B 870 870 experimental:870
Rv2195 qcrA ubiquinol-cytochrome C reductase rieske iron-sulfur subunit 870 870 experimental:870
Rv2193 ctaE cytochrome C oxidase subunit III 870 870 experimental:870
Rv2200c ctaC cytochrome C oxidase subunit II 870 870 experimental:870
Rv2199c ctaF cytochrome c oxidase polypeptide 4 870 870 experimental:870
Rv2194 qcrC ubiquinol-cytochrome C reductase cytochrome subunit C 870 870 experimental:870
Rv2469c hyp hypothetical protein 831 832 ctx neighborhood:832
Rv2471 aglA alpha-glucosidase AglA 742 742 ctx neighborhood:742
Rv2470 glbO hemoglobin GlbO 563 563 ctx neighborhood:563
Rv3367 PE_PGRS51 PE-PGRS family protein PE_PGRS51 502 502 experimental:484
Rv2345 transmembrane protein 502 502 experimental:484

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 YP_007411168.1)
  • Domains: Pfam-A via hmmscan --cut_ga — none above threshold
  • 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 2APNU
  • Curated reference: UniProt I6YDH3 (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)
  • Model confidence: ESMFold per-residue pLDDT (mean 59.5, low)
  • 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 aglA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv2468A|
MEIHLFFVGIPLLLVVVLSVLIWSRKGPHPATYKLSEPWTHPPILWAATDEVVGSAHGGHGHDASEFTVGGGASGTW