vapC18 Family assigned · medium auto-curated
H37Rv Rv2546 · MTBC0 mtbc0_002713 ·
137 aa · 2891699–2892112 (+) ·
RefSeq NP_217062.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | ribonuclease VapC18 |
|---|---|
| MTBC0 PGAP re-annotation | PIN domain nuclease |
| Revised (this work) | PIN domain nuclease. 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 |
P95007
SwissProt · reviewed
· Inferred from homology
|
|---|---|
| UniProt name | Ribonuclease VapC18 |
| EC (curated) |
EC 3.1.-.-
|
| Curated function | Toxic component of a type II toxin-antitoxin (TA) system. An RNase. The cognate antitoxin is VapB18 (By similarity). |
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 |
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 | 1.302 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 4 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 | 1.2e-14 | 4–122 | PIN domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: vapB18 (antitoxin VapB18), high confidence from genomic context alone (score 817 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2545 vapB18 |
antitoxin VapB18 | 816 | 817 ctx | neighborhood:768 |
Rv2548 vapC19 |
ribonuclease VapC19 | 740 | 740 ctx | neighborhood:739 |
Rv2547 vapB19 |
antitoxin VapB19 | 740 | 740 ctx | neighborhood:739 |
Rv0582 vapC26 |
ribonuclease VapC26 | 568 | 568 ctx | cooccurence:561 |
Rv2544 lppB |
lipoprotein LppB | 555 | 555 ctx | neighborhood:551 |
Rv2543 lppA |
lipoprotein LppA | 546 | 546 ctx | neighborhood:543 |
Rv3347c PPE55 |
PPE family protein PPE55 | 443 | 443 ctx | cooccurence:436 |
Rv2542 hyp |
hypothetical protein | 442 | 442 | |
Rv0355c PPE8 |
PPE family protein PPE8 | 438 | 438 ctx | cooccurence:430 |
Rv1770 hyp |
hypothetical protein | 432 | 433 ctx | cooccurence:431 |
Rv3350c PPE56 |
PPE family protein PPE56 | 431 | 431 ctx | cooccurence:424 |
Rv0300 vapB2 |
antitoxin VapB2 | 430 | 430 | experimental:412 |
Rv3407 vapB47 |
antitoxin VapB47 | 426 | 426 | |
Rv0304c PPE5 |
PPE family protein PPE5 | 417 | 417 ctx | cooccurence:408 |
Rv1004c |
membrane protein | 411 | 412 ctx | cooccurence:403 |
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 VapC18
- MTBC0 PGAP product: PIN domain nuclease
- Pfam (hmmscan --cut_ga): PIN PF01850.28 (E=1e-14)
- (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_217062.1)
- 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 P95007 (SwissProt, reviewed; Inferred from homology)
- 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
vapB18 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002713|Rv2546|vapC18 MVFCVDTSAWHHAARPEVARRWLAALSADQIGICDHVRLEILYSANSATDYDALADELDGLARIPVGAETFTRACQVQRELAHVAGLHHRSVKIADLVIAAAAELSGTIVWHYDENYDRVAAITGQPTEWIVPRGTL