Rv2015c Resolved · high auto-curated
H37Rv Rv2015c · MTBC0 mtbc0_001879 ·
418 aa · 2015252–2016508 (-) ·
RefSeq NP_216531.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | HNH endonuclease signature motif containing protein |
| Revised (this work) | HNH endonuclease signature motif containing protein. Pfam: DUF222 (PF02720.23), HNH (PF01844.30). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53461
TrEMBL · unreviewed
· Inferred from homology
|
|---|---|
| UniProt name | HNH nuclease domain-containing protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
V Defense mechanisms
|
|---|---|
| eggNOG description | PFAM HNH 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 | 0.0 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 0 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 |
|---|---|---|---|---|
DUF222 | PF02720.23 | 1.1e-75 | 23–306 | Domain of unknown function (DUF222) |
HNH | PF01844.30 | 2.1e-07 | 314–352 | HNH endonuclease |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv1401 (membrane protein), medium confidence from genomic context alone (score 617 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) |
|---|---|---|---|---|
Rv0336 hyp |
hypothetical protein | 815 | 816 ctx | cooccurence:766 |
Rv0515 hyp |
hypothetical protein | 777 | 778 ctx | cooccurence:766 |
Rv3776 hyp |
hypothetical protein | 773 | 773 ctx | cooccurence:764 |
Rv2100 hyp |
hypothetical protein | 769 | 770 ctx | cooccurence:761 |
Rv0393 hyp |
hypothetical protein | 742 | 742 ctx | cooccurence:740 |
Rv2721c hyp |
hypothetical protein | 728 | 729 ctx | cooccurence:727 |
Rv0441c hyp |
hypothetical protein | 669 | 670 ctx | cooccurence:668 |
Rv1148c hyp |
hypothetical protein | 651 | 652 ctx | cooccurence:586 |
Rv1587c hyp |
hypothetical protein | 645 | 645 ctx | cooccurence:642 |
Rv1128c hyp |
hypothetical protein | 642 | 642 ctx | cooccurence:640 |
Rv1702c hyp |
hypothetical protein | 637 | 638 ctx | cooccurence:625 |
Rv3467 hyp |
hypothetical protein | 631 | 631 ctx | cooccurence:626 |
Rv0094c hyp |
hypothetical protein | 630 | 630 ctx | cooccurence:626 |
Rv1401 |
membrane protein | 617 | 617 ctx | cooccurence:615 |
Rv1945 hyp |
hypothetical protein | 615 | 615 ctx | cooccurence:603 |
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 signature motif containing protein
- Pfam (hmmscan --cut_ga): DUF222 PF02720.23 (E=1e-75), HNH PF01844.30 (E=2e-07)
- (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_216531.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF222 (PF02720.23), HNH (PF01844.30)
- 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 O53461 (TrEMBL, unreviewed; Inferred from homology)
- 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 —
54 functional partner(s); context anchor
Rv1401 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001879|Rv2015c| MSSTATSGAAVVSPAERVEVLFEELAELAGQRNAIDGRIVEIVAELDRDGLWGVTGARSVAGLVAWKMGCSSGNAHTIATVARRLPEFPRCARGMREGRLSLDQVGVIAGRAGEGSDAHYAQLAGVATVNQLRTALKLEPRPEPEPDFRPEPRPSITRSADEQFSCWRIKLPHVEAAKFDAALQSHLDALIAEYKRDHDNSDGVSDQRPPLPGNVEAFLRLVEAGWDAEVARRPHGQHTTVVMHLDVQERAAGLHLGPLLSESERRYLLCDATFEAWFERDGQVIGCGRTTRQINRRLRRALEHRDRTCVVPGCGATRGLHAHHIRHWQDGGATELANLVLVCPYHHRAHHRGLITITGPADNLTVADSAGRPLSAGSLARASTKPPPAVAPWPGPTGERADWWWYEPFQPQPPPISN