Rv0459 Still unknown · low auto-curated
H37Rv Rv0459 · MTBC0 mtbc0_000483 ·
163 aa · 554563–555054 (+) ·
RefSeq NP_214973.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | DUF779 domain-containing protein |
| Revised (this work) | Conserved hypothetical protein; DUF domain(s) DUF779. Function unknown. Foldseek best (non-significant) hit: 1x0g-assembly1_C Crystal Structure of IscA with the [2Fe-2S] cluster (prob 0.93, TM 0.49). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53744
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | DUF779 domain-containing protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Protein of unknown function (DUF779) |
| Orthologous group | COG3564 |
| KEGG orthology |
K09959
|
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 | 0.686 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 4 missense, 2 nonsense, 0 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 0.25% of strains (361) · 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 |
|---|---|---|---|---|
DUF779 | PF05610.17 | 4.9e-43 | 16–113 | Protein of unknown function (DUF779) |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 89.8 (confident). 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 |
|---|---|---|---|---|
1x0g-assembly1_C |
0.93 | 0.49 | 1.5e-02 | 1x0g-assembly1_C Crystal Structure of IscA with the [2Fe-2S] cluster |
2apn-assembly1_A |
0.87 | 0.39 | 3.9e-03 sig | 2apn-assembly1_A hi1723 solution structure |
1x0g-assembly1_A |
0.82 | 0.48 | 3.2e-02 | 1x0g-assembly1_A Crystal Structure of IscA with the [2Fe-2S] cluster |
7xq3-assembly1_D |
0.02 | 0.36 | 4.6e+00 | 7xq3-assembly1_D Crystal structure of the tetramer of thioredoxin domain containing-protein of Oncomelania hupensis(OhTRP14) |
5gan-assembly1_A |
0.01 | 0.30 | 7.1e+00 | 5gan-assembly1_A The overall structure of the yeast spliceosomal U4/U6.U5 tri-snRNP at 3.7 Angstrom |
5nyo-assembly1_A |
0.01 | 0.26 | 7.1e+00 | 5nyo-assembly1_A Crystal structure of an atypical poplar thioredoxin-like2.1 variant in dimeric form |
7jw2-assembly1_B |
0.01 | 0.23 | 6.6e+00 | 7jw2-assembly1_B Crystal structure of Aedes aegypti Nibbler EXO domain |
1yt3-assembly1_A |
0.01 | 0.22 | 6.6e+00 | 1yt3-assembly1_A Crystal Structure of Escherichia coli RNase D, an exoribonuclease involved in structured RNA processing |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0458 (aldehyde dehydrogenase), high confidence from genomic context alone (score 995 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) |
|---|---|---|---|---|
Rv0458 |
aldehyde dehydrogenase | 994 | 995 ctx | neighborhood:882 cooccurence:770 coexpression:827 |
Rv0460 hyp |
hypothetical protein | 793 | 793 ctx | neighborhood:792 |
Rv0457c |
peptidase | 772 | 772 ctx | neighborhood:772 |
Rv0461 |
transmembrane protein | 750 | 751 ctx | neighborhood:749 |
Rv0463 |
membrane protein | 713 | 713 ctx | neighborhood:711 |
Rv0462 lpdC |
dihydrolipoamide dehydrogenase | 712 | 712 ctx | neighborhood:711 |
Rv0456c echA2 |
enoyl-CoA hydratase EchA2 | 650 | 650 ctx | neighborhood:649 |
Rv0456B mazE1 |
antitoxin MazE1 | 426 | 426 ctx | neighborhood:426 |
Rv0456A mazF1 |
toxin MazF1 | 426 | 426 ctx | neighborhood:426 |
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: DUF779 domain-containing protein
- Pfam (hmmscan --cut_ga): DUF779 PF05610.17 (E=5e-43)
- Foldseek best: 1x0g-assembly1_C Crystal Structure of IscA with the [2Fe-2S] cluster (prob 0.93, E=2e-02, TM=0.49)
- (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_214973.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF779 (PF05610.17)
- 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
COG3564 - Curated reference: UniProt O53744 (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)
- Model confidence: ESMFold per-residue pLDDT (mean 89.8, confident)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
9 functional partner(s); context anchor
Rv0458 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000483|Rv0459| MNAPAGVLITAEAAALLAGLQDRHGPVMFHQSGGCCDGSAPMCYPRADFLVGDRDILLGVLDVGEDGVPVWISGPQYQAWKHTQLIIDVVPGRGGGFSLEAPEGVRFLSRGRVFSDAEKAMREAAPVITGAAYECGERPLVRGLVVDLDDPDATPGVCRASRR