Rv0963c Family assigned · medium auto-curated
H37Rv Rv0963c · MTBC0 - ·
266 aa · 1075297–1076097 (-) ·
RefSeq NP_215478.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Contains Abhydrolase_8 (PF06259.19) domain(s); putative function inferred from the domain architecture. |
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 |
P9WKM7
SwissProt · reviewed
· Predicted
|
|---|---|
| UniProt name | Uncharacterized protein Rv0963c |
UniProt still lists this protein as Uncharacterized protein Rv0963c; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| eggNOG description | Alpha/beta hydrolase |
| Orthologous group | COG1506 |
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 | 2.376 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 7 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 |
|---|---|---|---|---|
Abhydrolase_8 | PF06259.19 | 5.9e-72 | 53–230 | Alpha/beta hydrolase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: lprP (lipoprotein LprP), medium confidence from genomic context alone (score 620 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) |
|---|---|---|---|---|
Rv0964c hyp |
hypothetical protein | 627 | 627 ctx | neighborhood:621 |
Rv0962c lprP |
lipoprotein LprP | 620 | 620 ctx | neighborhood:605 |
Rv0965c hyp |
hypothetical protein | 592 | 592 ctx | neighborhood:592 |
Rv2490c PE_PGRS43 |
PE-PGRS family protein PE_PGRS43 | 499 | 499 ctx | cooccurence:499 |
Rv2098c PE_PGRS36 |
PE-PGRS family protein PE_PGRS36; Rv2098c, (MTCY49.38c), len: 434 aa. PE_PGRS36,Member of the Mycobacterium tuberculosis PE family, PGRS sub | 497 | 498 ctx | cooccurence:496 |
Rv2305 hyp |
hypothetical protein | 493 | 494 ctx | cooccurence:481 |
Rv2159c hyp |
hypothetical protein | 484 | 485 ctx | cooccurence:483 |
Rv3347c PPE55 |
PPE family protein PPE55 | 472 | 473 ctx | cooccurence:470 |
Rv3879c espK |
ESX-1 secretion-associated protein EspK | 472 | 472 ctx | cooccurence:472 |
Rv2945c lppX |
lipoprotein LppX | 459 | 459 ctx | cooccurence:456 |
Rv3350c PPE56 |
PPE family protein PPE56 | 458 | 459 ctx | cooccurence:456 |
Rv3343c PPE54 |
PPE family protein PPE54 | 447 | 447 ctx | cooccurence:442 |
Rv1004c |
membrane protein | 447 | 447 ctx | cooccurence:447 |
Rv3871 eccCb1 |
ESX-1 secretion system protein EccCb | 441 | 442 ctx | cooccurence:437 |
Rv0341 iniB |
isoniazid inducible protein IniB | 427 | 427 ctx | cooccurence:424 |
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
- Pfam (hmmscan --cut_ga): Abhydrolase_8 PF06259.19 (E=6e-72)
- (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_215478.1)
- Domains: Pfam-A via hmmscan --cut_ga — Abhydrolase_8 (PF06259.19)
- 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
COG1506 - Curated reference: UniProt P9WKM7 (SwissProt, reviewed; 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 —
36 functional partner(s); context anchor
lprP - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0963c| MLQRELTRLQNGWLSRDGVWHTDTDKLADLRALRDTLAAHPGTSLILLDTASDPRKVLAAVGVGDVDNAERVGVTMGGLNTRVSSSVGDMVKEAGIQRAKAAELRERAGWPNYDAVASIAWLGYDAPDGLKDVMHDWSARDAAGPLNRFDKGLAATTNVSDQHITAFGHSYGSLVTSLALQQGAPVSDVVLYGSPGTELTHASQLGVEPGHAFYMIGVNDHVANTIPEFGAFGSAPQDVPGMTQLSVNTGLAPGPLLGDGQLHERA