Rv2405 Family assigned · medium auto-curated
H37Rv Rv2405 · MTBC0 - ·
189 aa · 2703269–2703838 (+) ·
RefSeq NP_216921.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Contains PemK_toxin (PF02452.24) domain(s); putative function inferred from the domain architecture. |
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 |
P71738
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Conserved protein |
UniProt still lists this protein as Conserved protein; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
T Signal transduction mechanisms
|
|---|---|
| eggNOG description | PemK-like, MazF-like toxin of type II toxin-antitoxin system |
| Orthologous group | COG2337 |
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 | 0.235 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 2 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 |
|---|---|---|---|---|
PemK_toxin | PF02452.24 | 5.8e-12 | 84–183 | PemK-like, MazF-like toxin of type II toxin-antitoxin system |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: lepA (GTP-binding protein LepA), medium confidence from genomic context alone (score 653 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) |
|---|---|---|---|---|
Rv2404c lepA |
GTP-binding protein LepA | 653 | 653 ctx | neighborhood:651 |
Rv2403c lppR |
lipoprotein LppR | 621 | 622 ctx | neighborhood:620 |
Rv1991A mazE6 |
antitoxin MazE6 | 623 | 600 | experimental:430 |
Rv3095 |
HTH-type transcriptional regulator | 555 | 555 | coexpression:554 |
Rv1725c hyp |
hypothetical protein | 555 | 555 | coexpression:555 |
Rv1204c hyp |
hypothetical protein | 538 | 539 ctx | cooccurence:536 |
Rv0315 |
beta-1,3-glucanase | 414 | 414 | |
Rv1632c hyp |
hypothetical protein | 408 | 408 | coexpression:408 |
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
- Pfam (hmmscan --cut_ga): PemK_toxin PF02452.24 (E=6e-12)
- (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_216921.1)
- Domains: Pfam-A via hmmscan --cut_ga — PemK_toxin (PF02452.24)
- 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
COG2337 - Curated reference: UniProt P71738 (TrEMBL, unreviewed; 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)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
8 functional partner(s); context anchor
lepA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2405| MQRFAENLVFTEAPKLVRHLQNTQETLRTIRQAVKITANIMTTAVPSPPAEIAAGRPVTSTSCPTAARARRLVYAPDLDGRADPGEIVWTWVAYEQDPTRGKDRPVLVVGRDRSVLLGLLVSSQERHAADRDWVGIGSGAWDYEGRESWVRLDRVLDVPEESIRREGAILEREVFDVVAARLRADYAWR