Rv3195 Resolved · high auto-curated
H37Rv Rv3195 · MTBC0 mtbc0_003396 ·
472 aa · 3586496–3587914 (+) ·
RefSeq NP_217711.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | zinc-dependent metalloprotease |
| Revised (this work) | Zinc-dependent metalloprotease. Pfam: Zincin_2 (PF10103.16). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53341
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | Hydrolase |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | hydrolase |
| Orthologous group | COG5282 |
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 | 0.633 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 9 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.45% of strains (654) · clonal |
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 |
|---|---|---|---|---|
Zincin_2 | PF10103.16 | 1.2e-125 | 85–433 | Zincin-like metallopeptidase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv1830 (HTH-type transcriptional regulator), high confidence from genomic context alone (score 718 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) |
|---|---|---|---|---|
Rv3194c hyp |
hypothetical protein | 837 | 838 ctx | neighborhood:784 |
Rv3196 hyp |
hypothetical protein | 803 | 803 ctx | neighborhood:802 |
Rv2460c clpP2 |
ATP-dependent CLP protease proteolytic subunit 2 | 807 | 776 | coexpression:776 |
Rv1998c hyp |
hypothetical protein | 767 | 768 | coexpression:768 |
Rv1830 |
HTH-type transcriptional regulator | 717 | 718 ctx | cooccurence:717 |
Rv2413c hyp |
hypothetical protein | 717 | 717 ctx | cooccurence:716 |
Rv2219 |
transmembrane protein | 709 | 709 ctx | cooccurence:709 |
Rv2699c hyp |
hypothetical protein | 701 | 701 ctx | cooccurence:701 |
Rv3219 whiB1 |
transcriptional regulator WhiB1 | 701 | 701 ctx | cooccurence:701 |
Rv2050 rbpA |
RNA polymerase-binding protein RbpA | 687 | 687 ctx | cooccurence:687 |
Rv1440 secG |
protein-export membrane protein SecG | 683 | 683 ctx | cooccurence:683 |
Rv2693c |
integral membrane protein | 677 | 677 ctx | cooccurence:676 |
Rv1321 nucS |
endonuclease NucS | 658 | 659 ctx | cooccurence:657 |
Rv2708c hyp |
hypothetical protein | 655 | 655 ctx | cooccurence:655 |
Rv1390 rpoZ |
DNA-directed RNA polymerase subunit omega | 644 | 644 ctx | cooccurence:638 |
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: zinc-dependent metalloprotease
- Pfam (hmmscan --cut_ga): Zincin_2 PF10103.16 (E=1e-125)
- (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_217711.1)
- Domains: Pfam-A via hmmscan --cut_ga — Zincin_2 (PF10103.16)
- 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
COG5282 - Curated reference: UniProt O53341 (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 —
50 functional partner(s); context anchor
Rv1830 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003396|Rv3195| MSTGEVMGDLPFGFSSGDDPPEDPSGRDKRGKDGADSGSGANPLGAFGIGGEFNMADLGQIFTRLGEMFGGVGTAMAAGKTSGPVNYDLARQVASSSIGFIAPIPAATNSAIADAVHLADTWLDGATSLPAGATKAVGWSPTDWVDNTLATWKRLCDPMAQQISTVWASSLPEEAKSMAGPLLSIMSQMGGIAFGSQLGQALGRLSREVLTSTDIGLPLGPKGVAAILPGAVESFAAGLEQPRSEILTFLATREAAHHRLFSHVPWLASQLLGAVEAYAMGMKIDMTGIEELARDINPTSLADPAAMEQLLSQGVFEPKATPAQTQALERLETLLALIEGWVQTVVTAALGERIPGEAALSETLRRRRASGGPAEQTFATLVGLELRPRKLREAGALWERLTRAVGMDARDAVWQHPDLLPATDDLDDPAAFIDRVIGGDTSGIDEAIAELERDQQARGADDSGHDGGPVDN