Rv0463 Still unknown · low auto-curated

H37Rv Rv0463 · MTBC0 mtbc0_000487 · 97 aa · 557381–557674 (+) · RefSeq NP_214977.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)membrane protein
MTBC0 PGAP re-annotationhypothetical protein
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.

Curated reference (UniProt)

UniProt O53748 TrEMBL · unreviewed · Predicted
UniProt nameProbable conserved membrane protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

Orthologous group2B0XH

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 0.0 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 2 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: lpdC (dihydrolipoamide dehydrogenase), high confidence from genomic context alone (score 889 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0462 lpdC dihydrolipoamide dehydrogenase 889 889 ctx neighborhood:882
Rv0461 transmembrane protein 800 800 ctx neighborhood:797
Rv0460 hyp hypothetical protein 763 763 ctx neighborhood:759
Rv0459 hyp hypothetical protein 713 713 ctx neighborhood:711
Rv0458 aldehyde dehydrogenase 711 711 ctx neighborhood:711
Rv0457c peptidase 488 489 ctx neighborhood:487

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: membrane protein
  • MTBC0 PGAP product: 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_214977.1)
  • 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 2B0XH
  • Curated reference: UniProt O53748 (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 — 6 functional partner(s); context anchor lpdC
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000487|Rv0463|
MTRRASTDTPQIIMGAIGGVVTGYILWLAAISVGDGLTTVSQWSRVVLLLSVLVAVCGAAGGLRLRSRGKLAWSAFAFSLPIPPVVLTVAVLADIYL