vapC22 Family assigned · medium auto-curated
H37Rv Rv2829c · MTBC0 mtbc0_003008 ·
130 aa · 3157286–3157678 (-) ·
RefSeq NP_217345.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | ribonuclease VapC22 |
|---|---|
| MTBC0 PGAP re-annotation | PIN domain-containing protein |
| Revised (this work) | PIN domain-containing protein. 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 |
P71623
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Ribonuclease VapC22 |
| EC (curated) |
EC 3.1.-.-
|
| Curated function | Toxic component of a type II toxin-antitoxin (TA) system. An RNase (By similarity). Upon expression in M.smegmatis inhibits translation and colony formation. Its toxic effect on colony formation is neutralized by coexpression with cognate antitoxin VapB22; the effect on translation has not been tested but is probably neutralized also. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | ribonuclease activity |
| Orthologous group | COG3744 |
| Gene Ontology (36) |
GO:0005575, GO:0005576, GO:0006417, GO:0008150, GO:0009889, GO:0009890, GO:0009892, GO:0010468, GO:0010556, GO:0010558, GO:0010605, GO:0010608 +24 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 | 0.116 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 1 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.40% of strains (577) · 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 | 8.1e-21 | 4–120 | PIN domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: vapB22 (antitoxin VapB22), high confidence from genomic context alone (score 889 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2830c vapB22 |
antitoxin VapB22 | 921 | 889 ctx | neighborhood:882 |
Rv2828A hyp |
hypothetical protein | 786 | 787 ctx | neighborhood:787 |
Rv2828c hyp |
hypothetical protein | 755 | 754 ctx | neighborhood:751 |
Rv2831 echA16 |
enoyl-CoA hydratase EchA16 | 822 | 652 ctx | neighborhood:647 textmining:511 |
Rv2827c hyp |
hypothetical protein | 434 | 417 | |
Rv2826c hyp |
hypothetical protein | 416 | 403 | |
Rv2494 vapC38 |
ribonuclease VapC38 | 485 | 313 | |
Rv2548 vapC19 |
ribonuclease VapC19 | 511 | 308 | |
Rv1561 vapC11 |
ribonuclease VapC11 | 544 | 304 | |
Rv2010 vapC15 |
ribonuclease VapC15 | 482 | 301 | |
Rv2530c vapC39 |
ribonuclease VapC39 | 485 | 288 | |
Rv3320c vapC44 |
ribonuclease VapC44 | 501 | 277 | |
Rv2801c mazF9 |
mRNA interferase MazF9 | 508 | 245 | |
Rv1102c mazF3 |
mRNA interferase MazF3 | 402 | 191 | |
Rv0609 vapC28 |
ribonuclease VapC28 | 514 | 185 | textmining:429 |
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 VapC22
- MTBC0 PGAP product: PIN domain-containing protein
- Pfam (hmmscan --cut_ga): PIN PF01850.28 (E=8e-21)
- (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_217345.1)
- 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
COG3744 - Curated reference: UniProt P71623 (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 —
21 functional partner(s); context anchor
vapB22 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003008|Rv2829c|vapC22 MTTVLLDSHVAYWWSAEPQRLSMAASQAIEHADELAVAAISWFELAWLAEQERIQLAIPVLSWLQQLAEHVRTVGITPSVAATAVALPSSFPGDPADRLIYATAIEHGWRLVTKDRRLRSHRHPRPVTVW