Rv0057 Still unknown · low
H37Rv Rv0057 · MTBC0 mtbc0_000062 ·
173 aa · 60004–60525 (+) ·
RefSeq NP_214571.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | Conserved hypothetical protein. No Pfam-A domain above the gathering threshold and no Foldseek structural hit on the ESMFold model: genuinely uncharacterised at both the sequence and the structure level. |
Curated reference (UniProt)
| UniProt |
P9WM77
SwissProt · reviewed
· Inferred from homology
|
|---|---|
| UniProt name | Uncharacterized protein Rv0057 |
UniProt still lists this protein as Uncharacterized protein Rv0057; the revised annotation above is ahead of the current UniProt record.
Conservation & selection (intra-MTBC, 145 209 strains) pseudogene candidate
| pN/pS | 0.511 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 6 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 5.96% of strains (8649) · 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)
No Pfam-A domain above the gathering threshold (or not yet scanned).
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: dnaB (replicative DNA helicase), high confidence from genomic context alone (score 889 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0058 dnaB |
replicative DNA helicase | 943 | 889 ctx | neighborhood:882 textmining:511 |
Rv0056 rplI |
50S ribosomal protein L9 | 743 | 743 ctx | neighborhood:731 |
Rv0055 rpsR1 |
30S ribosomal protein S18 | 645 | 644 ctx | neighborhood:634 |
Rv0054 ssb |
single-strand DNA-binding protein | 546 | 547 ctx | neighborhood:523 |
Rv0059 darT hyp |
hypothetical protein | 497 | 497 ctx | neighborhood:473 |
Rv0060 darG hyp |
hypothetical protein | 463 | 464 ctx | neighborhood:450 |
Rv0053 rpsF |
30S ribosomal protein S6 | 406 | 407 | |
Rv0010c |
membrane protein | 868 | 57 | textmining:866 |
Rv0001 dnaA |
chromosomal replication initiator protein DnaA | 437 | 50 | textmining:432 |
Rv3843c |
transmembrane protein | 870 | 47 | textmining:870 |
Rv0011c crgA |
cell division protein CrgA | 804 | 47 | textmining:803 |
Rv3924c rpmH |
50S ribosomal protein L34 | 655 | 41 | textmining:655 |
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
- MTBC0 PGAP product: 'hypothetical protein' (PGAP itself leaves it unannotated)
- Pfam (hmmscan --cut_ga): no domain above threshold
- Foldseek on the ESMFold model: no structural hit -- one of the few truly dark genes of the set
ESM Atlas signal (exploratory)
Ancestral protein hash be9ce41de1497f9ff42715afc4b5a900 ·
10 ESM-space neighbours (max similarity 0.607).
SAE features are orienting indices, not validated domains.
| # | Index | Activation | Interpretation |
|---|---|---|---|
| 1 | 10621 |
1.33 | Outer-membrane β-barrel initiation |
| 2 | 972 |
0.80 | Ser/Thr/Gly-rich disordered regions |
| 3 | 7187 |
0.77 | Exposed polar low-structure patches |
| 4 | 1738 |
0.77 | Autotransporter passenger-translocator junction linker |
| 5 | 3332 |
0.74 | Mature N-terminal interaction region |
| 6 | 4761 |
0.66 | Arg/Ser/Thr-rich targeting leaders |
| 7 | 2268 |
0.54 | Transmembrane beta-barrel strands |
| 8 | 11694 |
0.53 | Secreted disordered acidic motifs |
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_214571.1)
- Domains: Pfam-A via hmmscan --cut_ga — none above threshold
- Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
- Curated reference: UniProt P9WM77 (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)
- Model confidence: ESMFold per-residue pLDDT (mean 32.1, very low)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
12 functional partner(s); context anchor
dnaB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000062|Rv0057| MPVVTAVGRRRGFAMPWVSTARSGAVMLANYSAGVCGRVSSPGLNVRKMCLKANTPGAVTWLDTPKRFLSTQTASRCMAVNSSDVVTGRIDPQVLHTPLNTDVDGYAHAMHSSINSGPLEYLPATFSVFPALGDVGDLGGGVGAATYALDRLSNMRSGACVGGGESPWRSLMT