Rv3169 Family assigned · medium
H37Rv Rv3169 · MTBC0 mtbc0_003368 ·
374 aa · 3562086–3563210 (+) ·
RefSeq NP_217685.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | NTF2-like / SnoaL-like superfamily enzyme (polyketide cyclase / steroid-lyase / [4+2]-Diels-Alderase fold). RefSeq leaves it 'hypothetical protein'. Strongest match to 25-phosphosteroid lyase (steroid/cholesterol degradation); a candidate steroid/lipid-processing lyase-cyclase, though the precise substrate within this functionally diverse superfamily is undetermined. RefSeq leaves this locus uncharacterised. |
Curated reference (UniProt)
| UniProt |
O53319
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)
| Orthologous group | 2BYTM |
|---|
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 | 0.274 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 synonymous, 4 missense, 1 nonsense, 0 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.12% of strains (167) · 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)
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 94.9 (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 |
|---|---|---|---|---|
8j1g-assembly1_A |
0.30 | 0.77 | 2.0e+00 | 8j1g-assembly1_A Structure of amino acid dehydrogenase in complex with NADPH |
3hdj-assembly1_B |
0.20 | 0.75 | 3.1e+00 | 3hdj-assembly1_B The crystal structure of probable ornithine cyclodeaminase from Bordetella pertussis Tohama I |
8j1c-assembly1_A |
0.16 | 0.75 | 4.3e+00 | 8j1c-assembly1_A Structure of amino acid dehydrogenase in complex with NADP |
8j1g-assembly2_C |
0.15 | 0.61 | 2.7e+00 | 8j1g-assembly2_C Structure of amino acid dehydrogenase in complex with NADPH |
4egd-assembly1_A |
0.14 | 0.29 | 3.3e-01 | 4egd-assembly1_A 1.85 Angstrom crystal structure of native hypothetical protein SAOUHSC_02783 from Staphylococcus aureus |
7red-assembly1_A |
0.14 | 0.21 | 8.6e-02 | 7red-assembly1_A Holo Hemophilin from A. baumannii |
2wvp-assembly1_A |
0.13 | 0.18 | 1.7e-02 | 2wvp-assembly1_A Synthetically modified OmpG |
4bih-assembly1_A |
0.12 | 0.54 | 1.9e+00 | 4bih-assembly1_A Crystal structure of the conserved staphylococcal antigen 1A, Csa1A |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv3168 (aminoglycoside phosphotransferase), high confidence from genomic context alone (score 992 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) |
|---|---|---|---|---|
Rv3168 |
aminoglycoside phosphotransferase | 997 | 992 ctx | neighborhood:881 cooccurence:765 coexpression:746 textmining:629 |
Rv3167c |
TetR family transcriptional regulator | 900 | 804 ctx | neighborhood:743 textmining:511 |
Rv0311 hyp |
hypothetical protein | 718 | 718 ctx | cooccurence:717 |
Rv0310c hyp |
hypothetical protein | 689 | 690 ctx | cooccurence:688 |
Rv3170 aofH |
flavin-containing monoamine oxidase | 664 | 663 ctx | neighborhood:617 |
Rv0138 hyp |
hypothetical protein | 648 | 648 ctx | cooccurence:648 |
Rv0272c hyp |
hypothetical protein | 643 | 644 ctx | cooccurence:639 |
Rv1132 hyp |
hypothetical protein | 637 | 637 ctx | cooccurence:636 |
Rv0767c |
HTH-type transcriptional regulator | 618 | 618 ctx | cooccurence:617 |
Rv1874 hyp |
hypothetical protein | 567 | 568 ctx | cooccurence:563 |
Rv3359 |
oxidoreductase | 564 | 565 ctx | cooccurence:561 |
Rv0762c hyp |
hypothetical protein | 541 | 541 ctx | cooccurence:535 |
Rv2574 hyp |
hypothetical protein | 523 | 523 ctx | cooccurence:521 |
Rv0692 mftB |
mycofactocin system protein MftB | 521 | 522 ctx | cooccurence:520 |
Rv2740 ephG |
epoxide hydrolase | 504 | 505 ctx | cooccurence:499 |
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
- HHpred: top hit 9FZN 25-phosphosteroid lyase Prob 100%, E 2.4e-47, 354 cols; followed by kievitone hydratase (CrtC) and multiple Diels-Alderases ([4+2]-cyclases) at 99.8%
- HHpred web (MPI Bioinformatics Toolkit, profile-profile remote homology), interpreted in project 'Still unknown gene function', 2026-06-10. A fold/family-level assignment, not a demonstrated function.
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_217685.1)
- 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
2BYTM - Curated reference: UniProt O53319 (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 94.9, very high)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
35 functional partner(s); context anchor
Rv3168 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003368|Rv3169| MPQMLGPLDEYPLHQLPQPIAWPGSSDRNFYDRSYFNAHDRTGNIFLITGIGYYPNLGVKDAFVLIRRADIQTAVHLSDAIDSDRLHQHVNGYRVEVVEPLRKLRIVLDETEGVAADLTWEGLFDVVQEQPHVLRSGNRVTLDAQRFAQLGTWSGRIVVDGERIAVDPATWLGSRDRSWGIRPVGEPEPAGRPADPPFEGMWWLYVPLAFDDFAVVLIIQEEPDGFRSLNDCTRIWRDGHVEQLGWPRVRIHYRSGTRIPTGATIEASTPDGAPVHFDVESKLAVPTHVGGGYGGDSDWSHGMWKGEKFVERRTYDMTDPTIIARAGFGVIDHVGRALCRDGDGNPVQGWGLFEHGALGRHDPSGFADWSTLAP