Rv2516c Still unknown · low auto-curated
H37Rv Rv2516c · MTBC0 mtbc0_002679 ·
267 aa · 2855600–2856403 (-) ·
RefSeq NP_217032.2
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | Conserved hypothetical protein; no recognised domain. Function unknown. Foldseek best (non-significant) hit: 7b90-assembly1_E Circular permutant of ribosomal protein S6, P54-55 tr (prob 0.99, TM 0.64). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6YDM0
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Helix-turn-helix domain-containing protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 2ENST |
|---|
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 | 1.113 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 7 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).
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 86.2 (confident). A confident model makes the fold comparison meaningful.
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 |
|---|---|---|---|---|
7b90-assembly1_E |
0.99 | 0.64 | 1.2e-01 | 7b90-assembly1_E Circular permutant of ribosomal protein S6, P54-55 truncated, I8A mutant |
7bff-assembly1_E |
0.99 | 0.65 | 1.4e-01 | 7bff-assembly1_E Circular permutant of ribosomal protein S6, P54-55 truncated, I25A mutant. |
7bfd-assembly1_K |
0.98 | 0.66 | 2.4e-01 | 7bfd-assembly1_K Circular permutant of ribosomal protein S6, P54-55 truncated, Y4A mutant. |
7lwr-assembly1_A |
0.97 | 0.73 | 4.9e-01 | 7lwr-assembly1_A Structural and Biochemical Insight into Assembly of Molecular Motors Involved in Viral DNA Packaging |
5d90-assembly2_C |
0.96 | 0.68 | 4.6e-01 | 5d90-assembly2_C Crystal structure of HiNmlR, a MerR family regulator lacking the sensor domain, bound to promoter DNA |
7bfe-assembly1_E |
0.95 | 0.66 | 4.6e-01 | 7bfe-assembly1_E Circular permutant of ribosomal protein S6, P54-55 truncated, L21A mutant. |
7lxs-assembly1_A |
0.94 | 0.71 | 6.4e-01 | 7lxs-assembly1_A Structural and Biochemical Insight into Assembly of Molecular Motors Involved in Viral DNA Packaging |
5d8c-assembly1_A |
0.94 | 0.71 | 6.4e-01 | 5d8c-assembly1_A Crystal structure of HiNmlR, a MerR family regulator lacking the sensor domain, bound to promoter DNA |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2517c hyp |
hypothetical protein | 904 | 904 ctx | neighborhood:882 |
Rv2515c hyp |
hypothetical protein | 578 | 578 ctx | neighborhood:566 |
Rv2514c hyp |
hypothetical protein | 514 | 515 ctx | neighborhood:513 |
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: hypothetical protein
- MTBC0 PGAP product: hypothetical protein
- Foldseek best: 7b90-assembly1_E Circular permutant of ribosomal protein S6, P54-55 truncated, I (prob 0.99, E=1e-01, 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 NP_217032.2)
- 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
2ENST - Curated reference: UniProt I6YDM0 (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 86.2, confident)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 3 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002679|Rv2516c| MTADWVVTFTFDADPSMETMDAWETQLEGFDALVSRVPGHGIDVTVYAPGDWSVFDALAKMAGEVMPVVQAKSPIAVQIISEPEHRLRAEAFTTPELMSAAEIADELGVSRQRVHQLRSTAGFPAPLADLRGGAVWDAAAVRRFAETWERKPGRPHTGTAKFAYSWAVGPAVGRSGKAPNVRWRVENPDKIRFVLRNIGDDIAEDVEIDLSRIDAITRNVPKKTVIRPGEGLNMVLIAAWGHPLPNQLYVRWAGQDEWAAVPLHPAH