Rv0061c Still unknown · low auto-curated
H37Rv Rv0061c · MTBC0 - ·
112 aa · 65012–65350 (-) ·
RefSeq YP_007408697.1
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. Foldseek best (non-significant) hit: 5oun-assembly1_A NMR solution structure of the external DII domain of (prob 0.15, TM 0.64). |
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 |
I6X8E6
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Secreted protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 2A57W |
|---|
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) pseudogene candidate
| pN/pS | 0.301 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 3 missense, 1 nonsense, 0 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 25.80% of strains (37464) · 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).
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 52.4 (low). Low-confidence model: the fold may be unreliable, so treat these structural hits with caution.
Best matches against the PDB, ranked by Foldseek homology probability. A high probability / TM-score suggests a shared fold; unless flagged sig (E < 0.01) these are fold hypotheses, not assignments.
| Target | Prob | TM | E-value | Description |
|---|---|---|---|---|
5oun-assembly1_A |
0.15 | 0.64 | 3.7e+00 | 5oun-assembly1_A NMR solution structure of the external DII domain of Rvb2 from Saccharomyces cerevisiae |
5jr8-assembly2_B |
0.15 | 0.66 | 3.2e+00 | 5jr8-assembly2_B Disposal of Iron by a Mutant form of Siderocalin NGAL |
2fgg-assembly1_A |
0.14 | 0.57 | 3.2e+00 | 2fgg-assembly1_A Crystal Structure of Rv2632c |
6cib-assembly1_A |
0.12 | 0.69 | 6.1e+00 | 6cib-assembly1_A The structure of YcaO from Methanopyrus kandleri bound with AMPPCP and Mg2+ |
2ys3-assembly1_A |
0.09 | 0.62 | 5.7e+00 | 2ys3-assembly1_A Solution structure of the PH domain of Kindlin-3 from human |
4qae-assembly6_F |
0.09 | 0.69 | 8.3e+00 | 4qae-assembly6_F Crystal structure of an engineered lipocalin (Anticalin) in complex with human hepcidin |
4qae-assembly1_A |
0.09 | 0.61 | 5.7e+00 | 4qae-assembly1_A Crystal structure of an engineered lipocalin (Anticalin) in complex with human hepcidin |
3tdh-assembly1_B |
0.08 | 0.57 | 5.7e+00 | 3tdh-assembly1_B Structure of the regulatory fragment of sccharomyces cerevisiae AMPK in complex with AMP |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: celA1 (cellulase CelA), medium confidence from genomic context alone (score 520 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) |
|---|---|---|---|---|
Rv0062 celA1 |
cellulase CelA | 520 | 520 ctx | neighborhood:520 |
Rv0157A hyp |
hypothetical protein | 870 | 41 | textmining:870 |
Rv0500A |
DNA-binding protein | 803 | 41 | textmining:803 |
Rv2310 |
excisionase | 803 | 41 | textmining:803 |
Rv2660c hyp |
hypothetical protein | 660 | 41 | textmining:660 |
Rv0842 |
integral membrane protein | 655 | 41 | textmining:655 |
Rv1584c |
phage protein | 652 | 41 | textmining:652 |
Rv1954c hyp |
hypothetical protein | 652 | 41 | textmining:652 |
Rv1374c hyp |
hypothetical protein | 651 | 41 | textmining:651 |
Rv1954A |
Rv1954A, len: 100 aa. Hypothetical unknown protein. | 651 | 41 | textmining:651 |
Rv3750c vapB50 |
excisionase | 516 | 41 | textmining:516 |
Rv2657c |
prophage protein | 515 | 41 | textmining:515 |
Rv1734c hyp |
hypothetical protein | 510 | 41 | textmining:510 |
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
- Foldseek best: 5oun-assembly1_A NMR solution structure of the external DII domain of Rvb2 from (prob 0.15, E=4e+00, TM=0.64)
- (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_007408697.1)
- 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
2A57W - Curated reference: UniProt I6X8E6 (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 52.4, 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
celA1 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0061c| MKLKFARLSTAILGCAAALVFPASVASADPPDPHQPDMTKGYCPGGRWGFGDLAVCDGEKYPDGSFWHQWMQTWFTGPQFYFDCVSGGEPLPGPPPPGGCGGAIPSEQPNAP