Rv2422 Family assigned · low
H37Rv Rv2422 · MTBC0 mtbc0_002579 ·
90 aa · 2743351–2743623 (+) ·
RefSeq NP_216938.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | Predicted toxin of a type II toxin-antitoxin (TA) system (eggNOG COG1848). RefSeq leaves it 'hypothetical protein'. Note: the Rv2421c-Rv2422 region also harbours a cryptic beta-lactam-binding ORF (Kumar 2017); the eggNOG orthology points to a TA-toxin fold for Rv2422 itself. Family-level; the cognate antitoxin and activity are undetermined. |
Curated reference (UniProt)
| UniProt |
P71926
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | Uncharacterized protein |
UniProt still lists this protein as Uncharacterized protein; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Toxic component of a toxin-antitoxin (TA) module. An RNase |
| Orthologous group | COG1848 |
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 | 0.376 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 1 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).
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: gpgP (glucosyl-3-phosphoglycerate phosphatase), medium confidence from genomic context alone (score 477 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) |
|---|---|---|---|---|
Rv2419c gpgP |
glucosyl-3-phosphoglycerate phosphatase | 477 | 477 ctx | neighborhood:477 |
Rv0620 galK |
galactokinase | 457 | 458 | coexpression:458 |
Rv2421c nadD |
nicotinate-nucleotide adenylyltransferase | 787 | 449 ctx | neighborhood:449 textmining:630 |
Rv2418c octT hyp |
hypothetical protein | 449 | 449 ctx | neighborhood:449 |
Rv2420c rsfS hyp |
hypothetical protein | 449 | 449 ctx | neighborhood:449 |
Rv2423 hyp |
hypothetical protein | 428 | 428 ctx | neighborhood:425 |
Rv0449c hyp |
hypothetical protein | 441 | 47 | textmining:438 |
Rv3160c |
TetR family transcriptional regulator | 517 | 44 | textmining:516 |
Rv3240c secA1 |
protein translocase subunit SecA | 413 | 44 | textmining:412 |
Rv2068c blaC |
beta-lactamase | 543 | 41 | textmining:543 |
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
- eggNOG COG1848 = toxic component of a toxin-antitoxin system
- eggNOG-mapper orthology (COG functional assignment, under-propagated by the auto-curation). A family/activity-level assignment from orthology, not a substrate demonstrated in M. tuberculosis.
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_216938.1)
- 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
COG1848 - Curated reference: UniProt P71926 (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)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
10 functional partner(s); context anchor
gpgP - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002579|Rv2422| MPASVSTVLVDTSVAVAPVVADHDHHEDTFQALRGRTLGLAGHAAFERRTLATVAKLLAHTFPATRFLGAGAAMSLLPELAPAEIAGGAV