vapC20 Resolved · high auto-curated
H37Rv Rv2549c · MTBC0 mtbc0_002717 ·
131 aa · 2893272–2893667 (-) ·
RefSeq NP_217065.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | ribonuclease VapC20 |
|---|---|
| MTBC0 PGAP re-annotation | type II toxin-antitoxin system toxin 23S rRNA-specific endonuclease VapC20 |
| Revised (this work) | Type II toxin-antitoxin system toxin 23S rRNA-specific endonuclease VapC20. 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 |
P95004
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | 23S rRNA-specific endonuclease VapC20 |
| EC (curated) |
EC 3.1.-.-
|
| Curated function | Toxic component of a type II toxin-antitoxin (TA) system. An endoribonuclease that cleaves both E.coli and M.smegmatis 23S rRNA between G2661 and A2662 in the sarcin-ricin loop (SRL, E.coli 23S rRNA numbering). The SRL sequence is highly conserved and is implicated in GTP hydrolysis by EF-Tu and EF-G. Acts on purified ribosomes but not on isolated RNA in E.coli, nor on a shortened artificial substrate. Upon expression in E.coli inhibits cell growth, colony formation and translation. Its toxic effect is neutralized by coexpression, or subsequent expression (tested over 2 hours) with cognate ant. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | toxic component of a |
| Orthologous group | COG2402 |
| KEGG orthology |
K07065
|
| Gene Ontology (48) |
GO:0003674, GO:0003824, GO:0004518, GO:0004519, GO:0004521, GO:0004540, GO:0006139, GO:0006401, GO:0006725, GO:0006807, GO:0008150, GO:0008152 +36 more
|
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 | 0.231 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 3 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 |
|---|---|---|---|---|
PIN | PF01850.28 | 2.4e-18 | 2–125 | PIN domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: vapB20 (antitoxin VapB20), high confidence from genomic context alone (score 888 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2550c vapB20 |
antitoxin VapB20 | 917 | 888 ctx | neighborhood:882 |
Rv0581 vapB26 |
antitoxin VapB26 | 682 | 668 | experimental:652 |
Rv2548A hyp |
hypothetical protein | 592 | 592 ctx | neighborhood:592 |
Rv0582 vapC26 |
ribonuclease VapC26 | 910 | 565 ctx | cooccurence:562 textmining:803 |
Rv0240 vapC24 |
ribonuclease VapC24 | 531 | 532 ctx | cooccurence:529 |
Rv0611c hyp |
hypothetical protein | 517 | 518 ctx | cooccurence:515 |
Rv1397c vapC10 |
ribonuclease VapC10 | 680 | 484 ctx | cooccurence:475 textmining:406 |
Rv1034c |
Probable transposase (fragment); Rv1034c, (MTCY10G2.15), len: 129 aa. Probable IS1560 transposase fragment, similar to part of Rv3387|E12023 | 479 | 479 ctx | cooccurence:479 |
Rv3386 |
transposase | 465 | 465 ctx | cooccurence:465 |
Rv2961 |
transposase | 460 | 460 ctx | cooccurence:460 |
Rv3387 |
transposase | 439 | 439 ctx | cooccurence:439 |
Rv2548 vapC19 |
ribonuclease VapC19 | 718 | 420 ctx | cooccurence:408 textmining:534 |
Rv0659c mazF2 |
toxin MazF2 | 452 | 408 ctx | cooccurence:406 |
Rv2949c |
chorismate pyruvate-lyase | 408 | 408 ctx | cooccurence:406 |
Rv2010 vapC15 |
ribonuclease VapC15 | 784 | 395 | textmining:658 |
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 VapC20
- MTBC0 PGAP product: type II toxin-antitoxin system toxin 23S rRNA-specific endonuclease VapC20
- Pfam (hmmscan --cut_ga): PIN PF01850.28 (E=2e-18)
- (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_217065.1)
- 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
COG2402 - Curated reference: UniProt P95004 (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 —
50 functional partner(s); context anchor
vapB20 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002717|Rv2549c|vapC20 MIFVDTSFWAALGNAGDARHGTAKRLWASKPPVVMTSNHVLGETWTLLNRRCGHRAAVAAAAIRLSTVVRVEHVTADLEEQAWEWLVRHDEREYSFVDATSFAVMRKKGIQNAYAFDGDFSAAGFVEVRPE