Rv2466c Family assigned · medium auto-curated
H37Rv Rv2466c · MTBC0 mtbc0_002627 ·
207 aa · 2792509–2793132 (-) ·
RefSeq NP_216982.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | Rv2466c family mycothiol-dependent reductase |
| Revised (this work) | Rv2466c family mycothiol-dependent reductase. Pfam: DSBA (PF01323.27), Rv2466c-like (PF22234.3). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53193
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Thioredoxin-like reductase Rv2466c |
| Curated function | In vitro, the reduced form of Rv2466c catalyzes the reduction and activation of TP053, which is a thienopyrimidine derivative drug that can kill both replicating and non-replicating M.tuberculosis. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| eggNOG description | DSBA-like thioredoxin domain |
| Orthologous group | COG2761 |
| Gene Ontology (6) |
GO:0005575, GO:0005618, GO:0005623, GO:0030312, GO:0044464, GO:0071944
|
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 | n/a |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 0 synonymous, 2 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.14% of strains (205) · 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 |
|---|---|---|---|---|
DSBA | PF01323.27 | 1.2e-11 | 12–165 | DSBA-like thioredoxin domain |
Rv2466c-like | PF22234.3 | 1.4e-92 | 18–198 | Mycothiol-dependent nitroreductase Rv2466c |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: rpiB (ribose-5-phosphate isomerase B), high confidence from genomic context alone (score 818 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) |
|---|---|---|---|---|
Rv2465c rpiB |
ribose-5-phosphate isomerase B | 817 | 818 ctx | neighborhood:773 |
Rv3463 hyp |
hypothetical protein | 806 | 807 | coexpression:806 |
Rv2464c nei1 |
DNA glycosylase | 801 | 802 ctx | neighborhood:773 |
Rv0819 mshD |
mycothiol acetyltransferase | 798 | 799 ctx | cooccurence:769 |
Rv1082 mca |
mycothiol S-conjugate amidase | 789 | 789 ctx | cooccurence:773 |
Rv1170 mshB |
1D-myo-inositol 2-acetamido-2-deoxy-alpha-D-glucopyranoside deacetylase | 752 | 752 ctx | cooccurence:740 |
Rv3054c hyp |
hypothetical protein | 745 | 745 | coexpression:729 |
Rv0360c hyp |
hypothetical protein | 747 | 738 ctx | cooccurence:738 |
Rv2130c mshC |
cysteine:1D-myo-inosityl 2-amino-2-deoxy--D-glucopyranoside ligase | 694 | 683 ctx | cooccurence:666 |
Rv2467 pepN |
aminopeptidase PepN | 638 | 638 ctx | neighborhood:633 |
Rv0486 mshA |
D-inositol 3-phosphate glycosyltransferase | 628 | 552 ctx | cooccurence:552 |
Rv2470 glbO |
hemoglobin GlbO | 576 | 533 | coexpression:419 |
Rv0443 hyp |
hypothetical protein | 525 | 525 ctx | cooccurence:521 |
Rv0323c hyp |
hypothetical protein | 467 | 467 ctx | cooccurence:440 |
Rv2389c rpfD |
resuscitation-promoting factor RpfD | 466 | 466 ctx | cooccurence:466 |
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: Rv2466c family mycothiol-dependent reductase
- Pfam (hmmscan --cut_ga): DSBA PF01323.27 (E=1e-11), Rv2466c-like PF22234.3 (E=1e-92)
- (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_216982.1)
- Domains: Pfam-A via hmmscan --cut_ga — DSBA (PF01323.27), Rv2466c-like (PF22234.3)
- 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
COG2761 - Curated reference: UniProt O53193 (SwissProt, reviewed; Evidence at protein level)
- 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 —
48 functional partner(s); context anchor
rpiB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002627|Rv2466c| MLEKAPQKSVADFWFDPLCPWCWITSRWILEVAKVRDIEVNFHVMSLAILNENRDDLPEQYREGMARAWGPVRVAIAAEQAHGAKVLDPLYTAMGNRIHNQGNHELDEVITQSLADAGLPAELAKAATSDAYDNALRKSHHAGMDAVGEDVGTPTIHVNGVAFFGPVLSKIPRGEEAGKLWDASVTFASYPHFFELKRTRTEPPQFD