Rv3463 Resolved · high auto-curated
H37Rv Rv3463 · MTBC0 mtbc0_003681 ·
285 aa · 3906847–3907704 (+) ·
RefSeq NP_217980.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | LLM class F420-dependent oxidoreductase |
| Revised (this work) | LLM class F420-dependent oxidoreductase. Pfam: Bac_luciferase (PF00296.27). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6X7D4
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Conserved protein |
UniProt still lists this protein as Conserved protein; 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 | F420-dependent oxidoreductase |
| Orthologous group | COG2141 |
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 | 0.863 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 7 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.23% of strains (328) · 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 |
|---|---|---|---|---|
Bac_luciferase | PF00296.27 | 4.3e-12 | 28–123 | Luciferase-like monooxygenase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: rmlB (dTDP-glucose 4,6-dehydratase), high confidence from genomic context alone (score 792 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) |
|---|---|---|---|---|
Rv2466c hyp |
hypothetical protein | 806 | 807 | coexpression:806 |
Rv3464 rmlB |
dTDP-glucose 4,6-dehydratase | 792 | 792 ctx | neighborhood:790 |
Rv3465 rmlC |
dTDP-4-dehydrorhamnose 3,5-epimerase | 791 | 791 ctx | neighborhood:790 |
Rv1471 trxB1 |
thioredoxin | 746 | 746 | coexpression:746 |
Rv3462c infA |
translation initiation factor IF-1 | 739 | 739 ctx | neighborhood:738 |
Rv3054c hyp |
hypothetical protein | 960 | 696 | coexpression:639 textmining:875 |
Rv1875 hyp |
hypothetical protein | 605 | 606 ctx | cooccurence:546 |
Rv3368c |
oxidoreductase | 616 | 602 ctx | cooccurence:571 |
Rv1155 |
pyridoxine/pyridoxamine 5'-phosphate oxidase | 586 | 587 ctx | cooccurence:585 |
Rv2693c |
integral membrane protein | 533 | 512 | |
Rv0121c hyp |
hypothetical protein | 470 | 451 ctx | cooccurence:448 |
Rv3461c rpmJ |
50S ribosomal protein L36 | 453 | 450 ctx | neighborhood:419 |
Rv3916c hyp |
hypothetical protein | 447 | 448 ctx | cooccurence:446 |
Rv3466 hyp |
hypothetical protein | 442 | 441 ctx | neighborhood:433 |
Rv3467 hyp |
hypothetical protein | 420 | 420 ctx | neighborhood:415 |
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: LLM class F420-dependent oxidoreductase
- Pfam (hmmscan --cut_ga): Bac_luciferase PF00296.27 (E=4e-12)
- (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_217980.1)
- Domains: Pfam-A via hmmscan --cut_ga — Bac_luciferase (PF00296.27)
- 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
COG2141 - Curated reference: UniProt I6X7D4 (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 —
20 functional partner(s); context anchor
rmlB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003681|Rv3463| MTNCAAGKPSSGPNLGRFGSFGRGVTPQQATEIEALGYGAVWVGGSPPAALSWVEPILQATTTLCVATGIVNIWSAPAQRVAESFHRIEAAYPGRFLLGIGVGHAEMISEYRKPYNALVEYLDRLDDYGVPANRRVVAALGPRVLGLSARRSAGAHPYLTTPEHTARARELIGPSAFLAPEHKVVLTTDSARARTVGRQALDMYFNLANYRNNWKRLGFTDDEVSRPGSDRLVDAVVAYGTPDAIAARLNEHLLAGADHVPIQVLTEDDNLVSALTELAKPLRLT