Rv2663 Family assigned · low auto-curated · to review
H37Rv Rv2663 · MTBC0 mtbc0_002837 ·
77 aa · 3004056–3004289 (+) ·
RefSeq NP_217179.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | No Pfam domain above threshold; Foldseek indicates a fold similar to 7vd7-assembly1_A Toxin - Antitoxin complex from Salmonella enterica serovar Typh (prob 1.00, TM 0.66). Structure-based, putative. |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed (flagged for human review).
Curated reference (UniProt)
| UniProt |
I6X520
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | Toxin |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Ribonuclease toxin, BrnT, of type II toxin-antitoxin system |
| Orthologous group | COG2929 |
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 | 0.161 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 1 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)
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 92.8 (very high). A confident model makes the fold comparison meaningful.
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 |
|---|---|---|---|---|
7vd7-assembly1_A |
1.00 | 0.66 | 3.8e-03 sig | 7vd7-assembly1_A Toxin - Antitoxin complex from Salmonella enterica serovar Typhimurium |
2gu3-assembly1_A |
0.89 | 0.59 | 2.7e-01 | 2gu3-assembly1_A YpmB protein from Bacillus subtilis |
3cfi-assembly3_G |
0.41 | 0.58 | 1.2e+00 | 3cfi-assembly3_G Nanobody-aided structure determination of the EPSI:EPSJ pseudopilin heterdimer from Vibrio Vulnificus |
4hzb-assembly1_F |
0.35 | 0.46 | 4.4e-01 | 4hzb-assembly1_F Crystal structure of the type VI SeMet effector-immunity complex Tae3-Tai3 from Ralstonia pickettii |
4hzb-assembly1_C |
0.30 | 0.43 | 4.4e-01 | 4hzb-assembly1_C Crystal structure of the type VI SeMet effector-immunity complex Tae3-Tai3 from Ralstonia pickettii |
2oxb-assembly1_A |
0.23 | 0.70 | 3.8e+00 | 2oxb-assembly1_A Crystal structure of a cell-wall invertase (E203Q) from Arabidopsis thaliana in complex with sucrose |
8xpo-assembly1_L |
0.23 | 0.67 | 4.3e+00 | 8xpo-assembly1_L Cryo-EM structure of Lassa virus RdRP elongation complex with the NTP form of compound HNC-1664 bound in the active site |
7fhr-assembly1_A |
0.21 | 0.56 | 2.4e+00 | 7fhr-assembly1_A Crystal Structure of a Rieske Oxygenase from Cupriavidus metallidurans |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2664 hyp |
hypothetical protein | 971 | 971 ctx | neighborhood:874 coexpression:780 |
Rv2662 hyp |
hypothetical protein | 577 | 577 ctx | neighborhood:572 |
Rv2665 hyp |
hypothetical protein | 411 | 411 ctx | neighborhood:407 |
Rv2661c hyp |
hypothetical protein | 406 | 406 ctx | neighborhood:403 |
Rv2660c hyp |
hypothetical protein | 406 | 406 ctx | neighborhood:403 |
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: hypothetical protein
- Foldseek best: 7vd7-assembly1_A Toxin - Antitoxin complex from Salmonella enterica serovar Typh (prob 1.00, E=4e-03, TM=0.66)
- (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_217179.1)
- 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
COG2929 - Curated reference: UniProt I6X520 (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)
- Model confidence: ESMFold per-residue pLDDT (mean 92.8, very high)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 5 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002837|Rv2663| MEVRASARKHGINDDAMLHAYRNALRYVELEYHGEVQLLVIGPDQTGRLLELVIPADEPPRIIHANVLRPKFYDYLR