Rv3691 Still unknown · low auto-curated
H37Rv Rv3691 · MTBC0 - ·
333 aa · 4132518–4133519 (+) ·
RefSeq NP_218208.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Conserved hypothetical protein; DUF domain(s) DUF4350. Function unknown. Foldseek best (non-significant) hit: 8hx9-assembly1_B Crystal structure of 4-amino-4-deoxychorismate syntha (prob 0.77, TM 0.44). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
O69659
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized membrane protein Rv3691 |
UniProt still lists this protein as Uncharacterized membrane protein Rv3691; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 29B69 |
|---|---|
| Gene Ontology (6) |
GO:0005575, GO:0005623, GO:0005886, GO:0016020, 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 | 0.627 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 5 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 |
|---|---|---|---|---|
DUF4350 | PF14258.13 | 6.4e-29 | 3–170 | Domain of unknown function (DUF4350) |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 93.7 (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 |
|---|---|---|---|---|
8hx9-assembly1_B |
0.77 | 0.44 | 3.4e-02 | 8hx9-assembly1_B Crystal structure of 4-amino-4-deoxychorismate synthase from Streptomyces venezuelae with chorismate |
3kxa-assembly2_D |
0.33 | 0.23 | 9.2e-02 | 3kxa-assembly2_D Crystal Structure of NGO0477 from Neisseria gonorrhoeae |
4pon-assembly1_B |
0.04 | 0.48 | 8.4e+00 | 4pon-assembly1_B The crystal structure of a putative SAM-dependent methyltransferase, YtqB, from Bacillus subtilis |
4poo-assembly1_A |
0.04 | 0.39 | 4.7e+00 | 4poo-assembly1_A The crystal structure of Bacillus subtilis YtqB in complex with SAM |
1cnt-assembly1_1 |
0.02 | 0.27 | 7.0e+00 | 1cnt-assembly1_1 CILIARY NEUROTROPHIC FACTOR |
2vou-assembly1_A |
0.02 | 0.15 | 3.9e-01 | 2vou-assembly1_A Structure of 2,6-dihydroxypyridine-3-hydroxylase from Arthrobacter nicotinovorans |
3eey-assembly4_I |
0.02 | 0.39 | 9.4e+00 | 3eey-assembly4_I CRYSTAL STRUCTURE OF PUTATIVE RRNA-METHYLASE FROM Clostridium thermocellum |
4eit-assembly2_E-2 |
0.02 | 0.33 | 7.5e+00 | 4eit-assembly2_E-2 Crystal structure of an enoyl-(acyl carrier protein) reductase from Bartonella henselae |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv3690 (membrane protein), high confidence from genomic context alone (score 986 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) |
|---|---|---|---|---|
Rv3690 |
membrane protein | 986 | 986 ctx | neighborhood:760 cooccurence:774 coexpression:767 |
Rv3693 |
membrane protein | 978 | 977 ctx | neighborhood:756 cooccurence:774 coexpression:621 |
Rv3689 |
transmembrane protein | 938 | 938 ctx | neighborhood:737 cooccurence:765 |
Rv3692 moxR2 |
methanol dehydrogenase transcriptional regulator MoxR | 910 | 910 ctx | neighborhood:881 |
Rv3694c |
transmembrane protein | 791 | 792 ctx | cooccurence:774 |
Rv3695 |
membrane protein | 786 | 787 ctx | cooccurence:774 |
Rv3688c hyp |
hypothetical protein | 693 | 693 ctx | neighborhood:690 |
Rv2226 hyp |
hypothetical protein | 453 | 432 ctx | cooccurence:401 |
Rv2332 mez |
malate oxidoreductase | 466 | 427 | coexpression:417 |
Rv2531c |
amino acid decarboxylase | 447 | 423 | experimental:405 |
Rv0518 hyp |
hypothetical protein | 402 | 403 | |
Rv0886 fprB |
ferredoxin/ferredoxin--NADP reductase | 602 | 165 | textmining:543 |
Rv0255c cobQ1 |
cobyric acid synthase | 667 | 66 | textmining:659 |
Rv2057c rpmG1 |
50S ribosomal protein L33 | 553 | 48 | textmining:550 |
Rv2943 |
insertion sequence element IS1533 transposase | 768 | 47 | textmining:767 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): hypothetical protein
- Pfam (hmmscan --cut_ga): DUF4350 PF14258.13 (E=6e-29)
- Foldseek best: 8hx9-assembly1_B Crystal structure of 4-amino-4-deoxychorismate synthase from St (prob 0.77, E=3e-02, TM=0.44)
- (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_218208.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF4350 (PF14258.13)
- 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
29B69 - Curated reference: UniProt O69659 (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)
- Model confidence: ESMFold per-residue pLDDT (mean 93.7, very high)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
18 functional partner(s); context anchor
Rv3690 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3691| MAPASTSSTGGHALATLLGNHGVEVVVADSIADVEAAARPDSLLLVAQTQYLVDNALLDRLAKAPGDLLLVAPTSRTRTALTPQLRIAAASPFNSQPNCTLREANRAGSVQWGPSDTYQATGDLVLTSCYGGALVRFRAEGRTITVVGSSNFMTNGGLLPAGNAALAMNLAGNRPRLVWYAPDHIEGEMSSPSSLSDLIPENVHWTIWQLWLVVLLVALWKGRRIGPLVAEELPVVIRASETVEGRGRLYRSRRARDRAADALRTATLQRLRPRLGVGAGAPAPAVVTTIAQRSKADPPFVAYHLFGPAPATDNDLLQLARALDDIERQVTHS