Rv3294c Still unknown · low
H37Rv Rv3294c · MTBC0 - ·
269 aa · 3675186–3675995 (-) ·
RefSeq YP_177954.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Conserved hypothetical; function unknown. Structure-based hint rejected: mismatch endonuclease NucS/EndoMS is Rv1321; this gene is a DUF4143 protein (paralogue-of-fold). |
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 |
L7N658
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | DUF4143 domain-containing protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
J Translation, ribosomal structure and biogenesis
|
|---|---|
| eggNOG description | Domain of unknown function (DUF4143) |
| Orthologous group | COG1373 |
| KEGG orthology |
K07133
|
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 | 1.116 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 3 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 |
|---|---|---|---|---|
DUF4143 | PF13635.13 | 1.8e-41 | 53–214 | Domain of unknown function (DUF4143) |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 87.0 (confident). A confident model makes the fold comparison meaningful.
Best matches against the PDB, ranked by Foldseek homology probability. A high probability / TM-score suggests a shared fold; unless flagged sig (E < 0.01) these are fold hypotheses, not assignments.
| Target | Prob | TM | E-value | Description |
|---|---|---|---|---|
2dk5-assembly1_A |
0.99 | 0.71 | 5.4e-02 | 2dk5-assembly1_A Solution structure of Winged-Helix domain in RNA polymerase III 39KDa polypeptide |
5gkh-assembly1_B |
0.97 | 0.55 | 2.1e-02 | 5gkh-assembly1_B Structure of EndoMS-dsDNA2 complex |
1r1u-assembly1_B |
0.97 | 0.55 | 3.0e-02 | 1r1u-assembly1_B Crystal structure of the metal-sensing transcriptional repressor CzrA from Staphylococcus aureus in the apo-form |
5f6f-assembly1_B |
0.97 | 0.45 | 2.4e-02 | 5f6f-assembly1_B S. aureus MepR G34R Mutant |
5fb2-assembly1_A |
0.96 | 0.41 | 1.3e-02 | 5fb2-assembly1_A S. aureus MepR F27L Mutant bound to oligodeoxyribonucleotide |
5ffx-assembly2_D |
0.95 | 0.43 | 2.2e-02 | 5ffx-assembly2_D S. aureus MepR G34K Mutant |
5ffz-assembly1_A-2 |
0.95 | 0.46 | 3.8e-02 | 5ffz-assembly1_A-2 S. aureus MepR bound to ethidium bromide |
2vld-assembly1_B |
0.93 | 0.50 | 1.7e-02 | 2vld-assembly1_B crystal structure of a repair endonuclease from Pyrococcus abyssi |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv3295 (TetR family transcriptional regulator), medium confidence from genomic context alone (score 609 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) |
|---|---|---|---|---|
Rv2810c |
Probable transposase; Rv2810c, (MTCY16B7.33), len: 133 aa. Probable transposase for IS1555, similar to C-terminal domain of transposases for | 733 | 733 | coexpression:733 |
Rv3295 |
TetR family transcriptional regulator | 610 | 609 ctx | neighborhood:605 |
Rv0962c lprP |
lipoprotein LprP | 553 | 553 | coexpression:553 |
Rv3297 nei |
endonuclease VIII | 493 | 494 ctx | neighborhood:491 |
Rv3296 lhr |
ATP-dependent helicase | 469 | 469 ctx | neighborhood:464 |
Rv0919 |
GCN5-like N-acetyltransferase | 443 | 443 ctx | cooccurence:436 |
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
- Structural Foldseek hit not propagated -- mismatch endonuclease NucS/EndoMS is Rv1321; this gene is a DUF4143 protein (paralogue-of-fold)
- Reviewed against literature (extended structural cross-check, 2026-06-02)
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 YP_177954.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF4143 (PF13635.13)
- 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
COG1373 - Curated reference: UniProt L7N658 (TrEMBL, unreviewed; 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)
- Model confidence: ESMFold per-residue pLDDT (mean 87.0, confident)
- 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
Rv3295 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3294c| MGLPRRPCCDTTGSARYRESVRRYPRIGEDSAAYRRRLCRESAKARNVDRVVKRDAADVSNLQRIADLPRLIRLLAARSASELNLSSLATDAEIPVRTLPPYLDLLETLYLIDRIPAWSTNLSKRVVDRPKVLLLDSGLAARLVNVSPTGAGPHANPNAAGAIIETFVIAELRRQLGWSQQAPRLFHYRDRDGAEVDLILETADGLIAAIEIKSAATLRGRDTRSISRLRDKVGARFAGGVILHTGPQAQPFGDRLAAVPIDILWSPSG