Rv2969c Resolved · high auto-curated
H37Rv Rv2969c · MTBC0 mtbc0_003153 ·
255 aa · 3344884–3345651 (-) ·
RefSeq NP_217485.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | mycothiol-dependent reductase |
| Revised (this work) | Mycothiol-dependent reductase. Pfam: Thioredoxin_4 (PF13462.13). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O33272
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Possible conserved membrane or secreted protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
O Post-translational modification, protein turnover, chaperones
|
|---|---|
| eggNOG description | Thioredoxin |
| Orthologous group | COG1651 |
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 | 2.019 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 6 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 |
|---|---|---|---|---|
Thioredoxin_4 | PF13462.13 | 2.1e-15 | 73–237 | Thioredoxin |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv2968c (integral membrane protein), high confidence from genomic context alone (score 938 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) |
|---|---|---|---|---|
Rv2968c |
integral membrane protein | 991 | 938 ctx | neighborhood:881 textmining:870 |
Rv2967c pca |
pyruvate carboxylase | 842 | 842 ctx | neighborhood:840 |
Rv2970c lipN |
lipase/esterase LipN | 785 | 785 ctx | neighborhood:775 |
Rv2971 |
oxidoreductase | 704 | 705 ctx | neighborhood:525 coexpression:404 |
Rv2966c rsmD |
methyltransferase | 694 | 682 ctx | neighborhood:680 |
Rv2970A hyp |
hypothetical protein | 660 | 660 ctx | neighborhood:652 |
Rv1275 lprC |
lipoprotein LprC | 485 | 485 | |
Rv1274 lprB |
lipoprotein LprB | 483 | 484 | |
Rv2199c ctaF |
cytochrome c oxidase polypeptide 4 | 451 | 451 ctx | cooccurence:431 |
Rv0479c |
membrane protein | 428 | 429 | |
Rv0786c hyp |
hypothetical protein | 418 | 419 ctx | cooccurence:417 |
Rv1280c oppA |
oligopeptide ABC transporter substrate-binding lipoprotein OppA | 411 | 394 | |
Rv2878c mpt53 |
soluble secreted antigen Mpt53 | 653 | 390 | textmining:455 |
Rv1677 dsbF |
lipoprotein DsbF | 674 | 322 | textmining:539 |
Rv3673c |
membrane-anchored thioredoxin-like protein | 654 | 310 | textmining:519 |
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: mycothiol-dependent reductase
- Pfam (hmmscan --cut_ga): Thioredoxin_4 PF13462.13 (E=2e-15)
- (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_217485.1)
- Domains: Pfam-A via hmmscan --cut_ga — Thioredoxin_4 (PF13462.13)
- 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
COG1651 - Curated reference: UniProt O33272 (TrEMBL, unreviewed; 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 —
19 functional partner(s); context anchor
Rv2968c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003153|Rv2969c| MADKSKRPPRFDLKSADGSFGRLVQIGGTTIVVVFAVVLVFYIVTSRDDKKDGVAGPGDAVRVTSSKLVTQPGTSNPKAVVSFYEDFLCPACGIFERGFGPTVSKLVDIGAVAADYTMVAILDSASNQHYSSRAAAAAYCVADESIEAFRRFHAALFSKDIQPAELGKDFPDNARLIELAREAGVVGKVPDCINSGKYIEKVDGLAAAVNVHATPTVRVNGTEYEWSTPAALVAKIKEIVGDVPGIDSAAATATS