Rv0476 Resolved · medium auto-curated

H37Rv Rv0476 · MTBC0 - · 87 aa · 566508–566771 (+) · RefSeq NP_214990.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)transmembrane protein
MTBC0 PGAP re-annotation
Revised (this work)Transmembrane protein.

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 P9WKW1 SwissProt · reviewed · Inferred from homology
UniProt nameUncharacterized protein Rv0476

UniProt still lists this protein as Uncharacterized protein Rv0476; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionProtein of unknown function (DUF2516)
Orthologous group2EHMU

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) 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)

PfamAccessioni-EvalueResiduesDescription
DUF2516PF10724.15 6.2e-261–84 Protein of unknown function (DUF2516)

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

Closest characterised functional partner: deoC (2-deoxyribose-5-phosphate aldolase), high confidence from genomic context alone (score 884 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0478 deoC 2-deoxyribose-5-phosphate aldolase 884 884 ctx neighborhood:882
Rv0477 hyp hypothetical protein 882 882 ctx neighborhood:882
Rv0475 hbhA heparin binding hemagglutinin HbhA 827 827 ctx neighborhood:766
Rv0474 HTH-type transcriptional regulator 709 709 ctx neighborhood:661
Rv0473 transmembrane protein 696 697 ctx neighborhood:622
Rv0472c HTH-type transcriptional regulator 584 584
Rv2700 cei hyp hypothetical protein 475 475 ctx cooccurence:475
Rv3050c AsnC family transcriptional regulator 472 472
Rv2360c hyp hypothetical protein 454 455 ctx cooccurence:452
Rv0556 transmembrane protein 451 452 ctx cooccurence:449
Rv2772c transmembrane protein 436 437 ctx cooccurence:434
Rv1382 hyp hypothetical protein 431 431 ctx cooccurence:431
Rv3212 hyp hypothetical protein 422 423 ctx cooccurence:416
Rv3438 hyp hypothetical protein 422 422 ctx cooccurence:422
Rv1486c hyp hypothetical protein 421 422 ctx cooccurence:418

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): transmembrane protein
  • Pfam (hmmscan --cut_ga): DUF2516 PF10724.15 (E=6e-26)
  • (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_214990.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF2516 (PF10724.15)
  • 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 2EHMU
  • Curated reference: UniProt P9WKW1 (SwissProt, reviewed; Inferred from homology)
  • 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 — 17 functional partner(s); context anchor deoC
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv0476|
MLVLLVAVLVTAVYAFVHAALQRPDAYTAADKLTKPVWLVILGAAVALASILYPVLGVLGMAMSACASGVYLVDVRPKLLEIQGKSR