Rv3749c Family assigned · medium auto-curated
H37Rv Rv3749c · MTBC0 - ·
169 aa · 4197628–4198137 (-) ·
RefSeq NP_218266.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Contains VapC50_C (PF26343.1) domain(s); putative function inferred from the domain architecture. |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
L0TGF0
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Putative ribonuclease VapC50 |
| EC (curated) |
EC 3.1.-.-
|
| Curated function | Toxic component of a type II toxin-antitoxin (TA) system. An RNase. The cognate antitoxin is VapB50. |
UniProt still lists this protein as Putative ribonuclease VapC50; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | PIN domain |
| Orthologous group | COG1569 |
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 | 0.165 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 1 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 |
|---|---|---|---|---|
VapC50_C | PF26343.1 | 1.0e-14 | 98–151 | VapC50 C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: vapB50 (excisionase), high confidence from genomic context alone (score 962 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3750c vapB50 |
excisionase | 994 | 962 ctx | neighborhood:786 cooccurence:774 textmining:853 |
Rv2310 |
excisionase | 800 | 801 ctx | cooccurence:774 |
Rv0330c hyp |
hypothetical protein | 459 | 459 ctx | cooccurence:456 |
Rv2018 vapB45 hyp |
hypothetical protein | 695 | 379 | textmining:529 |
Rv1045 hyp |
hypothetical protein | 409 | 369 | |
Rv0837c hyp |
hypothetical protein | 413 | 343 | |
Rv1246c relE |
toxin RelE | 492 | 314 | |
Rv3181c vapB49 |
antitoxin VapB45 | 588 | 194 | textmining:511 |
Rv2022c higB2 hyp |
hypothetical protein | 693 | 157 | textmining:651 |
Rv3357 relJ |
antitoxin RelJ | 655 | 73 | textmining:644 |
Rv2021c higA2 |
transcriptional regulator | 656 | 57 | textmining:651 |
Rv0624 vapC30 |
ribonuclease VapC30 | 519 | 55 | textmining:512 |
Rv0065 vapC1 |
ribonuclease VapC1 | 669 | 53 | textmining:665 |
Rv3183 higA3 |
transcriptional regulator | 654 | 52 | textmining:650 |
Rv0299 |
toxin | 810 | 50 | textmining:809 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): hypothetical protein
- Pfam (hmmscan --cut_ga): VapC50_C PF26343.1 (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_218266.1)
- Domains: Pfam-A via hmmscan --cut_ga — VapC50_C (PF26343.1)
- 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
COG1569 - Curated reference: UniProt L0TGF0 (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 —
22 functional partner(s); context anchor
vapB50 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3749c| MPCCGSLTRAPIGLCGRRTSWPRLGEPWSTASTSAPNGLTTAFAFGYNDLIAAMNNHYKDRHVLAAAVRERAEVIVTTNLKHFPDDALKPYQIKALHPDDFLLDQLDLYEEATKAVILGMVDAYIDPPFTPHSLLDALGEQVPQFAAKARRLFPSGSPFGLGVLLPFDQ