Rv0325 Still unknown · low auto-curated
H37Rv Rv0325 · MTBC0 - ·
74 aa · 392039–392263 (+) ·
RefSeq NP_214839.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Conserved hypothetical protein; no recognised domain. Function unknown. Foldseek best (non-significant) hit: 5u0p-assembly1_V Cryo-EM structure of the transcriptional Mediator (prob 0.02, TM 0.31). |
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 |
O07250
TrEMBL · unreviewed
· Predicted
|
|---|---|
| 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)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| eggNOG description | methyltransferase |
| Orthologous group | COG0500 |
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, 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)
No Pfam-A domain above the gathering threshold (or not yet scanned).
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 81.4 (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 |
|---|---|---|---|---|
5u0p-assembly1_V |
0.02 | 0.31 | 9.8e+00 | 5u0p-assembly1_V Cryo-EM structure of the transcriptional Mediator |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0324 (transcriptional regulator), high confidence from genomic context alone (score 791 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) |
|---|---|---|---|---|
Rv0326 hyp |
hypothetical protein | 952 | 913 ctx | neighborhood:762 fusion:628 textmining:480 |
Rv0324 |
transcriptional regulator | 799 | 791 ctx | neighborhood:786 |
Rv0323c hyp |
hypothetical protein | 569 | 570 ctx | neighborhood:559 |
Rv0327c cyp135A1 |
cytochrome P450 Cyp135A1 | 449 | 222 | |
Rv2292c hyp |
hypothetical protein | 706 | 161 | textmining:665 |
Rv3433c nnr |
bifunctional ADP-dependent (S)-NAD(P)H-hydrate dehydratase/NAD(P)H-hydrate epimerase | 465 | 102 | textmining:430 |
Rv2139 pyrD |
dihydroorotate dehydrogenase | 470 | 77 | textmining:450 |
Rv0213c |
methyltransferase | 545 | 76 | textmining:529 |
Rv1767 hyp |
hypothetical protein | 527 | 69 | textmining:513 |
Rv0245 |
oxidoreductase | 535 | 56 | textmining:528 |
Rv0134 ephF |
epoxide hydrolase EphF | 437 | 54 | textmining:430 |
Rv1829 hyp |
hypothetical protein | 446 | 52 | textmining:440 |
Rv2528c mrr |
restriction system protein | 417 | 52 | textmining:411 |
Rv1833c dhmA2 |
haloalkane dehalogenase | 443 | 51 | textmining:438 |
Rv2534c efp |
elongation factor P | 481 | 50 | textmining:477 |
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
- Foldseek best: 5u0p-assembly1_V Cryo-EM structure of the transcriptional Mediator (prob 0.02, E=1e+01, TM=0.31)
- (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_214839.1)
- 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
COG0500 - Curated reference: UniProt O07250 (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 81.4, confident)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
21 functional partner(s); context anchor
Rv0324 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0325| MGPKGSLRLVKRQPELLVAQHEHWQDTYRAHPVLYGTRPSEPGVYAAEVFNADGVQRVLELAAGHGRDTLYFAG