Rv0964c Still unknown · low auto-curated
H37Rv Rv0964c · MTBC0 - ·
160 aa · 1076196–1076678 (-) ·
RefSeq NP_215479.1
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: 7b9v-assembly1_y Yeast C complex spliceosome at 2.8 Angstrom resolutio (prob 0.02, TM 0.27). |
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 |
P9WKM5
SwissProt · reviewed
· Predicted
|
|---|---|
| UniProt name | Uncharacterized protein Rv0964c |
UniProt still lists this protein as Uncharacterized protein Rv0964c; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| eggNOG description | Alpha/beta hydrolase |
| Orthologous group | COG1071 |
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 | 0.703 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 2 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.12% of strains (171) · 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)
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 59.9 (low). Low-confidence model: the fold may be unreliable, so treat these structural hits with caution.
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 |
|---|---|---|---|---|
7b9v-assembly1_y |
0.02 | 0.27 | 7.2e+00 | 7b9v-assembly1_y Yeast C complex spliceosome at 2.8 Angstrom resolution with Prp18/Slu7 bound |
6zhe-assembly1_C |
0.01 | 0.21 | 8.8e+00 | 6zhe-assembly1_C Cryo-EM structure of DNA-PK dimer |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0963c hyp |
hypothetical protein | 627 | 627 ctx | neighborhood:621 |
Rv0965c hyp |
hypothetical protein | 588 | 588 ctx | neighborhood:587 |
Rv0966c hyp |
hypothetical protein | 490 | 490 ctx | neighborhood:488 |
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: 7b9v-assembly1_y Yeast C complex spliceosome at 2.8 Angstrom resolution with Prp (prob 0.02, E=7e+00, TM=0.27)
- (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_215479.1)
- 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
COG1071 - Curated reference: UniProt P9WKM5 (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)
- Model confidence: ESMFold per-residue pLDDT (mean 59.9, low)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 3 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0964c| MGLLGFGGAAAEAAQVATHHTTVLLDHHAGACEAVARAAEKAAEEVAAIKMRLQVIRDAAREHHLTIAYATGTALPPPDLSSYSPADQQAILNTAIRRASNVCWPTPRPPMRIWPRRFDAPPGPCRASRSMPNSAMRHPQCRRCRRRTATLRRSSGGGIR