Rv0349 Family assigned · low
H37Rv Rv0349 · MTBC0 - ·
219 aa · 418949–419608 (+) ·
RefSeq NP_214863.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | MazF/PemK-family ribonuclease fold (candidate toxin of a type II toxin-antitoxin system). RefSeq leaves it 'hypothetical protein'. The AlphaFold model superposes on MazF (PDB 9g2g; Foldseek prob 1.0, TM 0.72). A distinct locus from the named M. tuberculosis MazF paralogues. Fold-level TA-toxin assignment; the cognate antitoxin and cleavage specificity are undemonstrated. |
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 |
O06300
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized protein |
UniProt still lists this protein as Uncharacterized protein; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 2D5EC |
|---|
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 | n/a |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 0 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)
No Pfam-A domain above the gathering threshold (or not yet scanned).
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0347 (membrane protein), high confidence from genomic context alone (score 833 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) |
|---|---|---|---|---|
Rv0347 |
membrane protein | 834 | 833 ctx | neighborhood:801 |
Rv0348 mosR |
transcriptional regulator | 810 | 810 ctx | neighborhood:809 |
Rv0350 dnaK |
chaperone protein DnaK | 465 | 465 ctx | neighborhood:462 |
Rv0351 grpE |
stress response protein GrpE | 465 | 465 ctx | neighborhood:462 |
Rv0353 hspR |
heat shock protein transcriptional repressor HspR | 400 | 400 | |
Rv0352 dnaJ1 |
chaperone protein DnaJ | 400 | 400 |
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
- Foldseek -> MazF ribonuclease (9g2g), prob 1.0, TM 0.72
- Distinct from named mazF paralogues
- Structural homology: AlphaFold DB model + Foldseek vs PDB (project 'Still unknown gene function', phase5-7, 2026-06-10). A fold-level family assignment, not a demonstrated activity.
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_214863.1)
- Domains: Pfam-A via hmmscan --cut_ga — none above threshold
- 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
2D5EC - Curated reference: UniProt O06300 (TrEMBL, unreviewed; 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 —
6 functional partner(s); context anchor
Rv0347 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0349| MPELETPDDPESIYLARLEDVGEHRPTFTGDIYRLGDGRMVMILQHPCALRHGVDLHPRLLVAPVRPDSLRSNWARAPFGTMPLPKLIDGQDHSADFINLELIDSPTLPTCERIAVLSQSGVNLVMQRWVYHSTRLAVPTHTYSDSTVGPFDEADLIEEWVTDRVDDGADPQAAEHECASWLDERISGRTRRALLSDRQHASSIRREARSHRKSVKLAD