Rv3750c Resolved · high auto-curated
H37Rv Rv3750c · MTBC0 - ·
130 aa · 4198205–4198597 (-) ·
RefSeq NP_218267.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | excisionase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Excisionase. Pfam: HTH_17 (PF12728.14). |
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 |
O69717
SwissProt · reviewed
· Predicted
|
|---|---|
| UniProt name | Putative antitoxin VapB50 |
| Curated function | Possibly the antitoxin component of a type II toxin-antitoxin (TA) system. Its cognate toxin is VapC50. |
UniProt still lists this protein as Putative antitoxin VapB50; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K Transcription
|
|---|---|
| eggNOG description | Helix-turn-helix domain |
| Orthologous group | COG3311 |
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 | 0.354 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 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 |
|---|---|---|---|---|
HTH_17 | PF12728.14 | 8.6e-15 | 55–103 | Helix-turn-helix domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv3751 (Rv3751, (MTV025.099), len: 71 aa. Probable integrase (fragment), similar to part of many e.g. Q48908 integrase (fragment) from Mycobacterium), medium confidence from genomic context alone (score 448 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3749c vapC50 hyp |
hypothetical protein | 994 | 962 ctx | neighborhood:786 cooccurence:774 textmining:853 |
Rv3751 |
Rv3751, (MTV025.099), len: 71 aa. Probable integrase (fragment), similar to part of many e.g. Q48908 integrase (fragment) from Mycobacterium | 476 | 448 ctx | neighborhood:446 |
Rv2018 vapB45 hyp |
hypothetical protein | 573 | 281 | textmining:431 |
Rv1246c relE |
toxin RelE | 452 | 264 | |
Rv2022c higB2 hyp |
hypothetical protein | 607 | 170 | textmining:547 |
Rv3182 higB3 hyp |
hypothetical protein | 679 | 169 | textmining:630 |
Rv0065 vapC1 |
ribonuclease VapC1 | 407 | 162 | |
Rv2021c higA2 |
transcriptional regulator | 595 | 110 | textmining:564 |
Rv3183 higA3 |
transcriptional regulator | 589 | 105 | textmining:560 |
Rv1765c hyp |
hypothetical protein | 493 | 63 | textmining:481 |
Rv0299 |
toxin | 804 | 50 | textmining:803 |
Rv0298 |
antitoxin | 806 | 47 | textmining:805 |
Rv3181c vapB49 |
antitoxin VapB45 | 437 | 47 | textmining:434 |
Rv1584c |
phage protein | 698 | 46 | textmining:697 |
Rv3697c vapC48 |
ribonuclease VapC48 | 523 | 45 | textmining:522 |
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): excisionase
- Pfam (hmmscan --cut_ga): HTH_17 PF12728.14 (E=9e-15)
- (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_218267.1)
- Domains: Pfam-A via hmmscan --cut_ga — HTH_17 (PF12728.14)
- 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
COG3311 - Curated reference: UniProt O69717 (SwissProt, reviewed; Predicted)
- 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 —
23 functional partner(s); context anchor
Rv3751 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3750c| MTSLLEVLGAPEVSVCGNAGQPMTLPEPVRDALYNVVLALSQGKGISLVPRHLKLTTQEAADLLNISRPTLVRLLEDGRIPFEKPGRHRRVSLDALLEYQQETRSNRRAALGELSRDALGELQAALAEKK