Rv0461 Resolved · high auto-curated
H37Rv Rv0461 · MTBC0 - ·
174 aa · 552026–552550 (+) ·
RefSeq NP_214975.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | transmembrane protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Transmembrane protein. Pfam: Rv0461 (PF27066.1). |
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 |
I6X961
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Protein Rv0461 |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 2ATNP |
|---|
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 | 0.071 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 1 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.46% of strains (661) · clonal |
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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
Rv0461 | PF27066.1 | 3.7e-41 | 48–122 | Rv0461-like membrane protein |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: lpdC (dihydrolipoamide dehydrogenase), high confidence from genomic context alone (score 800 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0460 hyp |
hypothetical protein | 849 | 849 ctx | neighborhood:826 |
Rv0462 lpdC |
dihydrolipoamide dehydrogenase | 800 | 800 ctx | neighborhood:798 |
Rv0463 |
membrane protein | 800 | 800 ctx | neighborhood:797 |
Rv0459 hyp |
hypothetical protein | 750 | 751 ctx | neighborhood:749 |
Rv0458 |
aldehyde dehydrogenase | 740 | 740 ctx | neighborhood:739 |
Rv0457c |
peptidase | 681 | 681 ctx | neighborhood:680 |
Rv0299 |
toxin | 653 | 47 | textmining:651 |
Rv3119 moaE1 |
molybdopterin synthase catalytic subunit 1 | 649 | 47 | textmining:647 |
Rv2781c |
oxidoreductase | 437 | 47 | textmining:434 |
Rv0424c hyp |
hypothetical protein | 870 | 44 | textmining:870 |
Rv0291 mycP3 |
membrane-anchored mycosin MycP | 413 | 44 | textmining:412 |
Rv0560c |
benzoquinone methyltransferase | 520 | 41 | textmining:520 |
Rv1772 hyp |
hypothetical protein | 511 | 41 | textmining:511 |
Rv3016 lpqA |
lipoprotein LpqA | 431 | 41 | textmining:431 |
Rv2846c efpA |
MFS-type transporter EfpA | 410 | 41 | textmining:411 |
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): Rv0461 PF27066.1 (E=4e-41)
- (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_214975.1)
- Domains: Pfam-A via hmmscan --cut_ga — Rv0461 (PF27066.1)
- 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
2ATNP - Curated reference: UniProt I6X961 (SwissProt, reviewed; 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)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
15 functional partner(s); context anchor
lpdC - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0461| MPDFDTGAHSQRFLSLAGQQDRAGKSWPGSTPKPQEDPVGVAPSASVEVLGSEPAATLAHSVTVPGRYTYLKWWKFVLVVLGVWIGAGEVGLSLFYWWYHTLDKTAAVFVVLVYVVACTVGGLILALVPGRPLITALSLGVMSGPFASVAAAAPLYGYYYCERMSHCLVGVIPY