Rv0028 Family assigned · low
H37Rv Rv0028 · MTBC0 mtbc0_000033 ·
101 aa · 31500–31805 (+) ·
RefSeq NP_214542.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | DUF2694 domain-containing protein |
| Revised (this work) | ESX-1 secretion-associated protein (EspH-like). RefSeq leaves it 'hypothetical protein'. |
Curated reference (UniProt)
| UniProt |
P9WM97
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized protein Rv0028 |
UniProt still lists this protein as Uncharacterized protein Rv0028; 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 (DUF2694) |
| Orthologous group | 2AUU9 |
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 | 0.255 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 3 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.19% of strains (278) · 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
DUF2694 | PF10904.14 | 5.8e-61 | 1–97 | Protein of unknown function (DUF2694) |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 76.7 (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 |
|---|---|---|---|---|
7aor-assembly1_an |
1.00 | 0.75 | 5.0e-02 | 7aor-assembly1_an mt-SSU from Trypanosoma cruzi in complex with mt-IF-3. |
3f42-assembly1_A-2 |
0.98 | 0.75 | 1.4e-01 | 3f42-assembly1_A-2 Crystal structure of uncharacterized protein HP0035 from Helicobacter pylori |
1j8b-assembly1_A-2 |
0.97 | 0.76 | 2.0e-01 | 1j8b-assembly1_A-2 Structure of YbaB from Haemophilus influenzae (HI0442), a protein of unknown function |
3f42-assembly1_B-2 |
0.96 | 0.76 | 2.0e-01 | 3f42-assembly1_B-2 Crystal structure of uncharacterized protein HP0035 from Helicobacter pylori |
1ybx-assembly1_A |
0.90 | 0.71 | 2.7e-01 | 1ybx-assembly1_A Conserved hypothetical protein Cth-383 from Clostridium thermocellum |
1pug-assembly1_A |
0.87 | 0.60 | 1.5e-01 | 1pug-assembly1_A Structure of E. coli Ybab |
1pug-assembly1_B |
0.85 | 0.68 | 2.6e-01 | 1pug-assembly1_B Structure of E. coli Ybab |
1pug-assembly2_D |
0.75 | 0.69 | 5.1e-01 | 1pug-assembly2_D Structure of E. coli Ybab |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0023 (transcriptional regulator), medium confidence from genomic context alone (score 670 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) |
|---|---|---|---|---|
Rv0027 hyp |
hypothetical protein | 932 | 933 ctx | neighborhood:881 coexpression:458 |
Rv0029 hyp |
hypothetical protein | 730 | 731 ctx | neighborhood:728 |
Rv0023 |
transcriptional regulator | 670 | 670 ctx | neighborhood:670 |
Rv0025 hyp |
hypothetical protein | 661 | 661 ctx | neighborhood:660 |
Rv0022c whiB5 |
transcriptional regulator WhiB5 | 641 | 641 ctx | neighborhood:638 |
Rv0026 hyp |
hypothetical protein | 535 | 534 ctx | neighborhood:528 |
Rv0030 hyp |
hypothetical protein | 443 | 443 ctx | neighborhood:439 |
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
- Foldseek vs AFDB-SwissProt: ESX-1 secretion-associated protein EspH, TM 0.61, E 1e-3
- Structural homology vs AlphaFold-Swiss-Prot (Foldseek; 542k curated SwissProt structures), project 'Still unknown gene function' phase13, 2026-06-10. Fold/family-level, not a demonstrated function.
ESM Atlas signal (exploratory)
Ancestral protein hash 7d0c86be9dfc224ecfe16be7a29e515d ·
3 ESM-space neighbours (max similarity 0.720).
SAE features are orienting indices, not validated domains.
| # | Index | Activation | Interpretation |
|---|---|---|---|
| 1 | 16353 |
0.71 | Acidic catalytic motifs and coiled-coils |
| 2 | 407 |
0.64 | Disordered pre-sequences and tails |
| 3 | 8645 |
0.61 | Charged C-terminal helical tails |
| 4 | 8723 |
0.56 | Cofactor-anchoring helix-loop caps |
| 5 | 7936 |
0.53 | Cofactor-binding beta-loop patches |
| 6 | 12593 |
0.47 | Disordered low-complexity regulatory tails |
| 7 | 4679 |
0.47 | Active-site gating segments |
| 8 | 9873 |
0.46 | Cys/Sec-centered redox/cofactor loops |
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_214542.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF2694 (PF10904.14)
- 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
2AUU9 - Curated reference: UniProt P9WM97 (SwissProt, reviewed; 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 76.7, confident)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
7 functional partner(s); context anchor
Rv0023 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000033|Rv0028| MTDANPAFDTVHPSGHILVRSCRGGYMHSVSLSEAAMETDAETLAEAILLTADVSCLKALLEVRNEIVAAGHTPSAQVPTTDDLNVAIEKLLAHQLRRRNR