vapC4 Resolved · high auto-curated
H37Rv Rv0595c · MTBC0 mtbc0_000625 ·
130 aa · 698391–698783 (-) ·
RefSeq NP_215109.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | ribonuclease VapC4 |
|---|---|
| MTBC0 PGAP re-annotation | type II toxin-antitoxin system toxin ribonuclease C4 |
| Revised (this work) | Type II toxin-antitoxin system toxin ribonuclease C4. Pfam: PIN (PF01850.28). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O07783
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Ribonuclease VapC4 |
| EC (curated) |
EC 3.1.-.-
|
| Curated function | Toxic component of a type II toxin-antitoxin (TA) system. Probably exerts its toxic effect by binding to mRNA, inhibiting translation. Binds to, recognizes and cleaves ssRNA at ACGC and AC(A/U)GC sequences, usually between the G and C; cleavage is not very efficient, nor is cleavage required to inhibit protein synthesis. Upon expression in situ, in M.smegmatis or E.coli inhibits cell growth and colony formation; in at least E.coli also causes increased levels of cellular RNA. Its toxic effect is neutralized by coexpression with cognate antitoxin VapB4. |
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 | COG1487 |
| Gene Ontology (8) |
GO:0005575, GO:0005576, GO:0008150, GO:0040008, GO:0045926, GO:0048519, GO:0050789, GO:0065007
|
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 | 1.439 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 3 missense, 1 nonsense, 0 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.34% of strains (500) · 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 |
|---|---|---|---|---|
PIN | PF01850.28 | 4.7e-17 | 7–123 | PIN domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: vapB5 (antitoxin VapB5), high confidence from genomic context alone (score 977 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0626 vapB5 |
antitoxin VapB5 | 977 | 977 ctx | cooccurence:771 experimental:891 |
Rv0596c vapB4 |
antitoxin VapB4 | 985 | 956 ctx | neighborhood:801 experimental:784 textmining:672 |
Rv0749 vapC31 |
ribonuclease VapC31 | 807 | 558 ctx | cooccurence:550 textmining:581 |
Rv0597c hyp |
hypothetical protein | 555 | 555 ctx | neighborhood:473 |
Rv3479 |
transmembrane protein | 529 | 529 ctx | cooccurence:529 |
Rv3697c vapC48 |
ribonuclease VapC48 | 527 | 528 ctx | cooccurence:523 |
Rv2872 vapC43 |
ribonuclease VapC43 | 760 | 527 ctx | cooccurence:517 textmining:514 |
Rv0277c vapC25 |
ribonuclease VapC25 | 879 | 518 ctx | cooccurence:509 textmining:761 |
Rv3407 vapB47 |
antitoxin VapB47 | 503 | 503 | |
Rv2103c vapC37 |
ribonuclease VapC37 | 754 | 498 ctx | cooccurence:493 textmining:531 |
Rv1242 vapC33 |
ribonuclease VapC33 | 815 | 493 ctx | cooccurence:488 textmining:651 |
Rv0659c mazF2 |
toxin MazF2 | 476 | 475 ctx | cooccurence:470 |
Rv3408 vapC47 |
ribonuclease VapC47 | 698 | 465 ctx | cooccurence:457 textmining:459 |
Rv3180c vapC49 |
ribonuclease VapC45 | 675 | 451 ctx | cooccurence:445 textmining:434 |
Rv1720c vapC12 |
ribonuclease VapC12 | 459 | 447 ctx | cooccurence:442 |
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: ribonuclease VapC4
- MTBC0 PGAP product: type II toxin-antitoxin system toxin ribonuclease C4
- Pfam (hmmscan --cut_ga): PIN PF01850.28 (E=5e-17)
- (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_215109.1)
- Domains: Pfam-A via hmmscan --cut_ga — PIN (PF01850.28)
- 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
COG1487 - Curated reference: UniProt O07783 (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 —
56 functional partner(s); context anchor
vapB5 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000625|Rv0595c|vapC4 MNVRRALADTSVFIGIEATRFDPDRFAGYEWGVSVVTLGELRLGVLQASGPEAAARRLSTYQLAQRFEPLGIDEAVSEAWALLVSKLRAAKLRVPINDSWIAATAVAHGIAILTQDNDYAAMPDVEVITI