Rv2742c Resolved · medium
H37Rv Rv2742c · MTBC0 - ·
277 aa · 3055515–3056348 (-) ·
RefSeq NP_217258.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Component of the mycobacterial Psp-like (phage-shock-protein) envelope-stress system. RefSeq leaves it 'hypothetical'. Rv2742c belongs to a four-gene module (clgR-pspA[Rv2744c]-rv2743c-rv2742c) regulated by ClgR and required for envelope integrity, surface-stress tolerance, MprAB-sigmaE stress signalling and intramacrophage growth; the module is restricted to tuberculous mycobacteria (Datta 2015). |
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 |
O33285
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Putative envelope-preserving system protein Rv2742c |
| Curated function | Involved in preservation of envelope integrity and tolerance to surface stress. Reverses the inhibitory effect of PspA on ClgR activity. Facilitates intracellular growth of M.tuberculosis. |
UniProt still lists this protein as Putative envelope-preserving system protein Rv2742c; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 2B8YK |
|---|
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) pseudogene candidate
| pN/pS | 1.788 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 5 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 6.72% of strains (9764) · 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 |
|---|---|---|---|---|
DUF3046 | PF11248.14 | 4.0e-12 | 228–268 | Protein of unknown function (DUF3046) |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2743c hyp |
hypothetical protein | 955 | 668 ctx | neighborhood:572 textmining:870 |
Rv2744c 35kd_ag hyp |
hypothetical protein | 789 | 554 ctx | neighborhood:540 textmining:547 |
Rv2745c clgR |
transcriptional regulator ClgR | 909 | 372 | textmining:861 |
Rv0983 pepD |
serine protease PepD | 894 | 222 | textmining:870 |
Rv2461c clpP1 |
ATP-dependent CLP protease proteolytic subunit 1 | 433 | 46 | textmining:431 |
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
- Member of the clgR-pspA-rv2743c-rv2742c Psp-like envelope-stress module (Datta 2015, PMID 25899163)
- Required for envelope integrity, surface-stress tolerance and intramacrophage growth
- Curated from the literature crible (project 'Still unknown gene function', 2026-06-09)
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_217258.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF3046 (PF11248.14)
- 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
2B8YK - Curated reference: UniProt O33285 (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 45.4, very low)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 5 functional partner(s)
- Primary literature: Datta P, Ravi J, Guerrini V, Chauhan R, Neiditch MB, Shell SS, Fortune SM, Hancioglu B, Igoshin OA, Gennaro ML (2015). The Psp system of Mycobacterium tuberculosis integrates envelope stress-sensing and envelope-preserving functions Mol Microbiol 97(3):408-22. doi:10.1111/mmi.13037 PMID:25899163
Ancestral MTBC0 protein sequence
>H37Rv|Rv2742c| MLVDELGVKIVHAQHVPAPYLVQRMREIHERDENRQRHAQVDVQRRRDQPERGQHQHRRNRDADHHPDGRTLAGQIVAHPVSHRVRQPRPVAIADVLPRVGPRADCVVAHSLQGSPRRRERRRGQTAHQRLGRRSGNAIACPLYLENAAGPEPDTKRAEGRRFGAFGGGDLRWMADRVPRQGSGRRGLGSRSGAGVPQGADARGWRHTADGVPRVGQPAIRRGVPGFWCWLDHVLTGFGGRNAICAIEDGVEPRVAWWALCTDFDVPRSMGRRTPGG