Rv2308a Family assigned · medium
H37Rv Rv2308a · MTBC0 - ·
110 aa · 2581145–2581477 (+) ·
RefSeq YP_009030038.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | 3'-5' exonuclease of the DEDDh / RNase-T superfamily (Mut-7-like exoribonuclease fold); nuclease activity RefSeq leaves this locus uncharacterised. |
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 2CC52 |
|---|
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 | 0.19 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 1 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 44.1 (very 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 |
|---|---|---|---|---|
1zud-assembly3_1 |
0.08 | 0.55 | 2.6e+00 | 1zud-assembly3_1 Structure of ThiS-ThiF protein complex |
2i22-assembly1_A |
0.08 | 0.50 | 5.9e+00 | 2i22-assembly1_A Crystal structure of Escherichia coli phosphoheptose isomerase in complex with reaction substrate sedoheptulose 7-phosphate |
6yub-assembly1_A |
0.05 | 0.45 | 4.6e+00 | 6yub-assembly1_A Crystal structure of Uba4 from Chaetomium thermophilum |
7u58-assembly1_B |
0.05 | 0.48 | 4.0e+00 | 7u58-assembly1_B YcaO-mediated ATP-dependent peptidase activity in ribosomal peptide biosynthesis |
7u58-assembly1_A |
0.05 | 0.49 | 4.0e+00 | 7u58-assembly1_A YcaO-mediated ATP-dependent peptidase activity in ribosomal peptide biosynthesis |
5gaj-assembly1_A |
0.04 | 0.35 | 4.0e+00 | 5gaj-assembly1_A Solution NMR structure of De novo designed PLOOP2X3_50 fold protein, Northeast Structural Genomics Consortium (NESG) target OR258 |
1prx-assembly1_B |
0.02 | 0.41 | 9.8e+00 | 1prx-assembly1_B HORF6 A NOVEL HUMAN PEROXIDASE ENZYME |
8oif-assembly1_A |
0.02 | 0.41 | 8.6e+00 | 8oif-assembly1_A Structure of the UBE1L activating enzyme bound to ISG15 and UBE2L6 |
Evidence
- HHpred (Neff 9.09): top hit 8Q66_A Mut-7 exonuclease Prob 98.8%, E 1.7e-8, 93 aligned cols; corroborated by RNase P (PRORP metallonuclease) and PIN-domain nuclease hits; strong purifying
- HHpred web (MPI Bioinformatics Toolkit, profile-profile remote homology), interpreted in project 'Still unknown gene function', 2026-06-10. A fold/family-level assignment, not a demonstrated function.
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_009030038.1)
- 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
2CC52 - 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 44.1, very low)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2308a| MLEVDKVTHVVDENLLRLGVALSPSEKTRPGLAARPSTTCYRKASSTPTGSPSSGVGWVVISNDRHLRTRPVEAELAVAHKLKVVHLHGRVGGLVRVGTADAAGCAVAGH