Rv2308 Family assigned · low auto-curated · to review
H37Rv Rv2308 · MTBC0 mtbc0_002452 ·
238 aa · 2605168–2605884 (+) ·
RefSeq NP_216824.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | DUF433 domain-containing protein |
| Revised (this work) | DUF433 domain-containing protein. |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed (flagged for human review).
Curated reference (UniProt)
| UniProt |
P9WLC5
SwissProt · reviewed
· Predicted
|
|---|---|
| UniProt name | Uncharacterized protein Rv2308 |
UniProt still lists this protein as Uncharacterized protein Rv2308; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Protein of unknown function (DUF433) |
| Orthologous group | COG2442 |
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 | 1.718 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 5 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
DUF433 | PF04255.21 | 1.8e-11 | 173–226 | Protein of unknown function (DUF433) |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 89.2 (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 |
|---|---|---|---|---|
5af3-assembly1_A |
1.00 | 0.65 | 5.6e-08 sig | 5af3-assembly1_A X-RAY CRYSTAL STRUCTURE OF RV2018 FROM MYCOBACTERIUM TUBERCULOSIS |
5af3-assembly1_B |
1.00 | 0.64 | 7.1e-08 sig | 5af3-assembly1_B X-RAY CRYSTAL STRUCTURE OF RV2018 FROM MYCOBACTERIUM TUBERCULOSIS |
2ga1-assembly1_B |
1.00 | 0.74 | 5.3e-02 | 2ga1-assembly1_B Crystal structure of a duf433 member protein (ava_0674) from anabaena variabilis atcc 29413 at 2.00 A resolution |
7vim-assembly1_A |
0.87 | 0.79 | 1.2e+00 | 7vim-assembly1_A The C-terminal DNA binding domain of EsrB from Edwardsiella piscicida |
7vim-assembly1_B-2 |
0.77 | 0.82 | 2.0e+00 | 7vim-assembly1_B-2 The C-terminal DNA binding domain of EsrB from Edwardsiella piscicida |
1fse-assembly1_A |
0.60 | 0.78 | 2.7e+00 | 1fse-assembly1_A CRYSTAL STRUCTURE OF THE BACILLUS SUBTILIS REGULATORY PROTEIN GERE |
5hev-assembly1_A |
0.60 | 0.74 | 2.4e+00 | 5hev-assembly1_A Crystal Structure of the beryllofluoride-activated LiaR from Enterococcus faecium |
5cy2-assembly2_E |
0.57 | 0.80 | 3.6e+00 | 5cy2-assembly2_E Tn3 resolvase - site III complex crystal form II |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: vapC16 (ribonuclease VapC16), high confidence from genomic context alone (score 791 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) |
|---|---|---|---|---|
Rv2231A vapC16 |
ribonuclease VapC16 | 791 | 791 ctx | cooccurence:742 |
Rv2082 hyp |
hypothetical protein | 783 | 772 ctx | cooccurence:745 |
Rv2209 |
integral membrane protein | 778 | 769 ctx | cooccurence:763 |
Rv1004c |
membrane protein | 765 | 765 ctx | cooccurence:764 |
Rv0355c PPE8 |
PPE family protein PPE8 | 765 | 765 ctx | cooccurence:764 |
Rv3347c PPE55 |
PPE family protein PPE55 | 765 | 765 ctx | cooccurence:764 |
Rv3350c PPE56 |
PPE family protein PPE56 | 764 | 765 ctx | cooccurence:764 |
Rv2490c PE_PGRS43 |
PE-PGRS family protein PE_PGRS43 | 762 | 762 ctx | cooccurence:762 |
Rv0304c PPE5 |
PPE family protein PPE5 | 761 | 762 ctx | cooccurence:760 |
Rv1452c PE_PGRS28 |
PE-PGRS family protein PE_PGRS28 | 760 | 761 ctx | cooccurence:760 |
Rv1917c PPE34 |
PPE family protein PPE34 | 760 | 761 ctx | cooccurence:759 |
Rv3343c PPE54 |
PPE family protein PPE54 | 757 | 757 ctx | cooccurence:756 |
Rv1651c PE_PGRS30 |
PE-PGRS family protein PE_PGRS30 | 754 | 755 ctx | cooccurence:754 |
Rv0872c PE_PGRS15 |
PE-PGRS family protein PE_PGRS15 | 745 | 746 ctx | cooccurence:745 |
Rv2819c csm5 |
CRISPR type III-associated RAMP protein Csm5 | 743 | 744 ctx | cooccurence:742 |
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: DUF433 domain-containing protein
- Pfam (hmmscan --cut_ga): DUF433 PF04255.21 (E=2e-11)
- Foldseek best: 5af3-assembly1_A X-RAY CRYSTAL STRUCTURE OF RV2018 FROM MYCOBACTERIUM TUBERCULOS (prob 1.00, E=6e-08, TM=0.65)
- (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_216824.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF433 (PF04255.21)
- 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
COG2442 - Curated reference: UniProt P9WLC5 (SwissProt, reviewed; Predicted)
- 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 89.2, confident)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
113 functional partner(s); context anchor
vapC16 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002452|Rv2308| MRADMSVTSMLDREVYVYAEVDKLIGLPAGTAKRWINGYERGGKDHPPILRVTPGATPWVTWGEFVETRMLAEYRDRRKVPIVRQRAAIEELRARFNLRYPLAHLRPFLSTHERDLTMGGEEIGLPDAEVTIRTGQALLGDARWLASIATPGRDEVGEAVIVELPVDKAFPEIVINPSRYSGQPTFVGRRVSPVTIAQMVDGGEEREDLAADYGLSLKQIQDAIDYTKKYRLARLVAA