Rv2541 Still unknown · low auto-curated
H37Rv Rv2541 · MTBC0 - ·
135 aa · 2864427–2864834 (+) ·
RefSeq NP_217057.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Conserved hypothetical protein; no recognised domain. Function unknown. Foldseek best (non-significant) hit: 3zbh-assembly1_B Geobacillus thermodenitrificans EsxA crystal form I (prob 1.00, TM 0.78). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
P95012
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | Hypothetical alanine rich protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 2B1B8 |
|---|
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 | 0.976 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 7 missense, 0 nonsense, 2 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 0.27% of strains (398) · 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)
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 69.3 (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 |
|---|---|---|---|---|
3zbh-assembly1_B |
1.00 | 0.78 | 1.2e-01 | 3zbh-assembly1_B Geobacillus thermodenitrificans EsxA crystal form I |
3zbh-assembly4_E |
1.00 | 0.79 | 1.7e-01 | 3zbh-assembly4_E Geobacillus thermodenitrificans EsxA crystal form I |
3zbh-assembly3_C |
1.00 | 0.78 | 3.8e-01 | 3zbh-assembly3_C Geobacillus thermodenitrificans EsxA crystal form I |
6uuj-assembly3_H |
0.95 | 0.74 | 7.6e-01 | 6uuj-assembly3_H Structure of PE5-PPE4-EspG3 complex from the type VII (ESX-3) secretion system, space group P212121 |
3ogi-assembly1_B |
0.87 | 0.67 | 1.1e+00 | 3ogi-assembly1_B Crystal structure of the Mycobacterium tuberculosis H37Rv EsxOP complex (Rv2346c-Rv2347c) |
8qae-assembly2_C-2 |
0.69 | 0.67 | 2.0e+00 | 8qae-assembly2_C-2 X-ray crystal structure of a de novo designed single-chain antiparallel 6-helix alpha-helical barrel, sc-apCC-6-SLLA |
2gl2-assembly2_B |
0.28 | 0.56 | 3.1e+00 | 2gl2-assembly2_B Crystal structure of the tetra mutant (T66G,R67G,F68G,Y69G) of bacterial adhesin FadA |
3etx-assembly2_B |
0.10 | 0.50 | 7.5e+00 | 3etx-assembly2_B Crystal structure of bacterial adhesin FadA L14A mutant |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: aroF (chorismate synthase), medium confidence from genomic context alone (score 575 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) |
|---|---|---|---|---|
Rv2540c aroF |
chorismate synthase | 575 | 575 ctx | neighborhood:569 |
Rv2539c aroK |
shikimate kinase | 573 | 573 ctx | neighborhood:569 |
Rv2538c aroB |
3-dehydroquinate synthase | 570 | 570 ctx | neighborhood:569 |
Rv2537c aroD |
3-dehydroquinate dehydratase | 570 | 570 ctx | neighborhood:569 |
Rv2542 hyp |
hypothetical protein | 429 | 430 ctx | neighborhood:426 |
Rv3224 |
iron-regulated short-chain dehydrogenase/reductase | 434 | 46 | textmining:432 |
Rv0991c hyp |
hypothetical protein | 642 | 44 | textmining:641 |
Rv3729 |
transferase | 870 | 42 | textmining:870 |
Rv2012 hyp |
hypothetical protein | 803 | 41 | textmining:803 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): hypothetical protein
- Foldseek best: 3zbh-assembly1_B Geobacillus thermodenitrificans EsxA crystal form I (prob 1.00, E=1e-01, TM=0.78)
- (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_217057.1)
- 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
2B1B8 - Curated reference: UniProt P95012 (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 69.3, low)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
9 functional partner(s); context anchor
aroF - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2541| MRRRRPPHVNAPTPCDRGDVRPPGCPASIPGVEVAGGTRARLRVTADGLQALAGRCATLAGELSAAVAPSGAVLSWQANAVAVNAAHARAGAAAAAVSARMRATAAALGQAARRYAGQDTAAAAALGAVRPWGTH