Rv2798c Family assigned · medium
H37Rv Rv2798c · MTBC0 mtbc0_002977 ·
108 aa · 3129726–3130052 (-) ·
RefSeq NP_217314.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | ESAT-6-like (WXG100) / ESX-secretion family protein (EsxF-like, four-helical bundle). RefSeq leaves it 'hypothetical protein'. |
Curated reference (UniProt)
| UniProt |
P71653
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | WXG100 family type VII secretion target |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Belongs to the WXG100 family |
| Orthologous group | 2AYPW |
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 | 0.956 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 6 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 83.3 (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 |
|---|---|---|---|---|
3zbh-assembly1_B |
1.00 | 0.83 | 1.4e-02 | 3zbh-assembly1_B Geobacillus thermodenitrificans EsxA crystal form I |
4j11-assembly1_B |
1.00 | 0.91 | 2.7e-02 | 4j11-assembly1_B The crystal structure of a secreted protein ESXB (wild-type, in P21 space group) from Bacillus anthracis str. sterne |
4j7k-assembly1_B |
1.00 | 0.91 | 2.7e-02 | 4j7k-assembly1_B The crystal structure of a secreted protein EsxB (Mutant E54Q) from Bacillus anthracis str. Sterne |
3zbh-assembly2_G |
1.00 | 0.82 | 2.2e-02 | 3zbh-assembly2_G Geobacillus thermodenitrificans EsxA crystal form I |
3zbh-assembly4_E |
1.00 | 0.83 | 3.3e-02 | 3zbh-assembly4_E Geobacillus thermodenitrificans EsxA crystal form I |
4j41-assembly2_D |
1.00 | 0.86 | 4.0e-02 | 4j41-assembly2_D The crystal structure of a secreted protein EsxB (Mutant P67A) from Bacillus anthracis str. Sterne |
4j10-assembly1_A |
1.00 | 0.86 | 4.3e-02 | 4j10-assembly1_A The crystal structure of a secreted protein ESXB (SeMet-labeled) from Bacillus anthracis str. Sterne |
4j11-assembly1_A |
1.00 | 0.87 | 4.5e-02 | 4j11-assembly1_A The crystal structure of a secreted protein ESXB (wild-type, in P21 space group) from Bacillus anthracis str. sterne |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: lppV (lipoprotein LppV), high confidence from genomic context alone (score 883 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) |
|---|---|---|---|---|
Rv2797c hyp |
hypothetical protein | 883 | 883 ctx | neighborhood:882 |
Rv2796c lppV |
lipoprotein LppV | 883 | 883 ctx | neighborhood:882 |
Rv2799 |
membrane protein | 658 | 658 ctx | neighborhood:653 |
Rv2800 |
hydrolase | 565 | 565 ctx | neighborhood:562 |
Rv2795c hyp |
hypothetical protein | 546 | 546 ctx | neighborhood:542 |
Rv2794c pptT |
4'-phosphopantetheinyl transferase | 545 | 545 ctx | neighborhood:542 |
Rv2793c truB |
tRNA pseudouridine synthase B | 545 | 544 ctx | neighborhood:542 |
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: ESAT-6-like protein EsxF, TM 0.90, E 5e-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.
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_217314.1)
- 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
2AYPW - Curated reference: UniProt P71653 (TrEMBL, unreviewed; 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 83.3, 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
lppV - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002977|Rv2798c| MFQISPEQWMHSAAQVTTQGEGLAVGHLSSDYRMQAAQFGWQGASAMALNAKMDDWLDASRALLTRIGDHAFGLQEAAIQHAAAEAERAQALAQVGVSADVVAGPRGV