Rv2469c Resolved · high auto-curated
H37Rv Rv2469c · MTBC0 mtbc0_002631 ·
222 aa · 2796615–2797283 (-) ·
RefSeq NP_216985.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | HNH endonuclease |
| Revised (this work) | HNH endonuclease. Pfam: HNH (PF01844.30), HNH_5 (PF14279.13). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53196
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | HNH nuclease domain-containing protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
L Replication, recombination and repair
|
|---|---|
| eggNOG description | endonuclease |
| Orthologous group | COG1403 |
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 | 0.358 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
HNH | PF01844.30 | 1.2e-11 | 138–179 | HNH endonuclease |
HNH_5 | PF14279.13 | 1.0e-11 | 138–184 | HNH endonuclease |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: aglA (alpha-glucosidase AglA), high confidence from genomic context alone (score 774 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) |
|---|---|---|---|---|
Rv2468A hyp |
hypothetical protein | 831 | 832 ctx | neighborhood:832 |
Rv2468c hyp |
hypothetical protein | 811 | 812 ctx | neighborhood:811 |
Rv2471 aglA |
alpha-glucosidase AglA | 774 | 774 ctx | neighborhood:773 |
Rv2470 glbO |
hemoglobin GlbO | 774 | 774 ctx | neighborhood:773 |
Rv2472 hyp |
hypothetical protein | 457 | 458 ctx | neighborhood:451 |
Rv2473 hyp |
hypothetical protein | 412 | 413 ctx | neighborhood:407 |
Rv0423c thiC |
phosphomethylpyrimidine synthase | 532 | 71 | textmining:517 |
Rv2594c ruvC |
crossover junction endodeoxyribonuclease RuvC | 515 | 50 | textmining:511 |
Rv1014c pth |
peptidyl-tRNA hydrolase | 431 | 41 | textmining:431 |
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
- Legacy H37Rv annotation: hypothetical protein
- MTBC0 PGAP product: HNH endonuclease
- Pfam (hmmscan --cut_ga): HNH PF01844.30 (E=1e-11), HNH_5 PF14279.13 (E=1e-11)
- (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_216985.1)
- Domains: Pfam-A via hmmscan --cut_ga — HNH (PF01844.30), HNH_5 (PF14279.13)
- 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
COG1403 - Curated reference: UniProt O53196 (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)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
9 functional partner(s); context anchor
aglA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002631|Rv2469c| MAHGKKRRGHRSSGVAAGVTGPASCLHSVHSHRLASGVETHPPNRHESASIWNRRRVLLLNSTYEPLTALSMRRAIVMVICGKADVVHEDPSGPVIHSATRSILVPSVIQLRSYVRVPYRARVPMTRAALMHRDRFCCAYCGGKADTVDHVVPRSRGGAHSWENCVACCSPCNHRKGDRLLTELGWALRRAPLPPTGPHWRLLSAVKELDPSWARYLGEGAA