vapB4 Resolved · high auto-curated
H37Rv Rv0596c · MTBC0 mtbc0_000626 ·
85 aa · 698780–699037 (-) ·
RefSeq NP_215110.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | antitoxin VapB4 |
|---|---|
| MTBC0 PGAP re-annotation | type II toxin-antitoxin system antitoxin VapB4 |
| Revised (this work) | Type II toxin-antitoxin system antitoxin VapB4. Pfam: PhdYeFM_antitox (PF02604.27). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WF21
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Antitoxin VapB4 |
| Curated function | Antitoxin component of a type II toxin-antitoxin (TA) system. Antitoxin that counteracts the effect of its cognate VapC4 toxin. Upon expression in situ, in M.smegmatis or E.coli neutralizes the effect of cognate toxin VapC4. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
D Cell cycle control, cell division, chromosome partitioning
|
|---|---|
| eggNOG description | Antitoxin component of a toxin-antitoxin (TA) module |
| Orthologous group | COG4118 |
| Gene Ontology (10) |
GO:0003674, GO:0005488, GO:0005515, GO:0008150, GO:0040008, GO:0045927, GO:0048518, GO:0050789, GO:0065007, GO:0097351
|
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 | 0.365 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 0 missense, 1 nonsense, 0 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.32% of strains (458) · 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 |
|---|---|---|---|---|
PhdYeFM_antitox | PF02604.27 | 2.1e-09 | 3–49 | Antitoxin Phd_YefM, type II toxin-antitoxin system |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: vapC4 (ribonuclease VapC4), high confidence from genomic context alone (score 956 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0595c vapC4 |
ribonuclease VapC4 | 985 | 956 ctx | neighborhood:801 experimental:784 textmining:672 |
Rv0627 vapC5 |
ribonuclease VapC5 | 805 | 797 | experimental:784 |
Rv0665 vapC8 |
ribonuclease VapC8 | 804 | 796 | experimental:784 |
Rv1953 vapC14 |
ribonuclease VapC14 | 529 | 529 | experimental:513 |
Rv0597c hyp |
hypothetical protein | 487 | 488 ctx | neighborhood:485 |
Rv0598c vapC27 |
ribonuclease VapC27 | 514 | 306 | |
Rv0549c vapC3 |
ribonuclease VapC3 | 449 | 72 | textmining:431 |
Rv0624 vapC30 |
ribonuclease VapC30 | 428 | 69 | textmining:411 |
Rv3180c vapC49 |
ribonuclease VapC45 | 528 | 64 | textmining:517 |
Rv3408 vapC47 |
ribonuclease VapC47 | 522 | 62 | textmining:512 |
Rv0661c vapC7 |
ribonuclease VapC7 | 444 | 61 | textmining:433 |
Rv1838c vapC13 |
ribonuclease VapC13 | 449 | 59 | textmining:439 |
Rv2863 vapC23 |
ribonuclease VapC23 | 631 | 58 | textmining:625 |
Rv2494 vapC38 |
ribonuclease VapC38 | 448 | 58 | textmining:439 |
Rv2871 vapB43 |
antitoxin VapB43 | 445 | 49 | textmining:441 |
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
- Legacy H37Rv annotation: antitoxin VapB4
- MTBC0 PGAP product: type II toxin-antitoxin system antitoxin VapB4
- Pfam (hmmscan --cut_ga): PhdYeFM_antitox PF02604.27 (E=2e-09)
- (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_215110.1)
- Domains: Pfam-A via hmmscan --cut_ga — PhdYeFM_antitox (PF02604.27)
- 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
COG4118 - Curated reference: UniProt P9WF21 (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)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
20 functional partner(s); context anchor
vapC4 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000626|Rv0596c|vapB4 MSATIPARDLRNHTAEVLRRVAAGEEIEVLKDNRPVARIVPLKRRRQWLPAAEVIGELVRLGPDTTNLGEELRETLTQTTDDVRW