Rv0690c Still unknown · low auto-curated
H37Rv Rv0690c · MTBC0 mtbc0_000730 ·
349 aa · 794110–795159 (-) ·
RefSeq NP_215204.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | DUF2332 domain-containing protein |
| Revised (this work) | Conserved hypothetical protein; DUF domain(s) DUF2332. Function unknown. Foldseek best (non-significant) hit: 8rpr-assembly1_A Crystal Structure of SgvM methyltransferase in comple (prob 0.47, TM 0.27). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6Y4G1
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | DUF2332 domain-containing protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Uncharacterized protein conserved in bacteria (DUF2332) |
| Orthologous group | COG4427 |
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 | 1.045 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 3 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 |
|---|---|---|---|---|
DUF2332 | PF10094.15 | 5.5e-121 | 9–348 | Uncharacterized protein conserved in bacteria (DUF2332) |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 97.0 (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 |
|---|---|---|---|---|
8rpr-assembly1_A |
0.47 | 0.27 | 2.2e-02 | 8rpr-assembly1_A Crystal Structure of SgvM methyltransferase in complex with alpha-ketoleucine and Zn2+ ion |
6o6x-assembly1_B |
0.25 | 0.27 | 8.7e-02 | 6o6x-assembly1_B Crystal structure of Csm6 W14A/E337A mutant in complex with cA4 by cocrystallization |
1ixm-assembly1_A |
0.18 | 0.26 | 1.8e-01 | 1ixm-assembly1_A CRYSTAL STRUCTURE OF SPOOB FROM BACILLUS SUBTILIS |
5ms2-assembly1_A |
0.18 | 0.46 | 1.2e+00 | 5ms2-assembly1_A Crystal structure of the Legionella pneumophila effector protein RavZ in complex with human LC3B |
4bro-assembly1_B |
0.10 | 0.45 | 2.9e+00 | 4bro-assembly1_B Legionella pneumophila NTPDase1 crystal form IV (part-open) |
4bra-assembly1_B |
0.10 | 0.48 | 3.4e+00 | 4bra-assembly1_B Legionella pneumophila NTPDase1 crystal form II, closed, Mg AMPPNP complex |
2c1i-assembly1_A |
0.08 | 0.39 | 3.1e+00 | 2c1i-assembly1_A Structure of Streptococcus pneumoniae peptidoglycan deacetylase (SpPgdA) D 275 N Mutant. |
8xih-assembly1_A |
0.08 | 0.28 | 7.0e-01 | 8xih-assembly1_A protein-DNA complex |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mftR (mycofactocin biosynthesis transcriptional regulator MftR), high confidence from genomic context alone (score 882 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) |
|---|---|---|---|---|
Rv0691c mftR |
mycofactocin biosynthesis transcriptional regulator MftR | 882 | 882 ctx | neighborhood:882 |
Rv0696 mftF |
mycofactocin biosynthesis glycosyltransferase MftF | 638 | 638 ctx | neighborhood:630 |
Rv0693 mftC |
mycofactocin radical SAM maturase MftC | 621 | 621 ctx | neighborhood:596 |
Rv0694 mftD |
mycofactocin system heme/flavin oxidoreductase MftD | 616 | 616 ctx | neighborhood:592 |
Rv0692 mftB |
mycofactocin system protein MftB | 608 | 607 ctx | neighborhood:595 |
Rv1014c pth |
peptidyl-tRNA hydrolase | 574 | 573 ctx | fusion:538 |
Rv0691A mftA |
mycofactocin precursor | 573 | 573 ctx | neighborhood:573 |
Rv1006 hyp |
hypothetical protein | 557 | 558 ctx | cooccurence:551 |
Rv1868 hyp |
hypothetical protein | 556 | 557 ctx | cooccurence:554 |
Rv0695 mftE |
mycofactocin system creatinine amidohydrolase family protein MftE | 545 | 545 ctx | neighborhood:529 |
Rv0697 mftG |
dehydrogenase | 491 | 491 ctx | neighborhood:479 |
Rv2047c hyp |
hypothetical protein | 436 | 436 ctx | cooccurence:431 |
Rv1435c hyp |
hypothetical protein | 402 | 403 |
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: DUF2332 domain-containing protein
- Pfam (hmmscan --cut_ga): DUF2332 PF10094.15 (E=6e-121)
- Foldseek best: 8rpr-assembly1_A Crystal Structure of SgvM methyltransferase in complex with alp (prob 0.47, E=2e-02, TM=0.27)
- (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_215204.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF2332 (PF10094.15)
- 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
COG4427 - Curated reference: UniProt I6Y4G1 (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 97.0, very high)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
13 functional partner(s); context anchor
mftR - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000730|Rv0690c| MTGTEHLVHTLRSQGRVCTSSGSPMYRELLELVAADVESGGVFASILADQKGAPEGQAVPLRLLGGLHRMVLDGRAPVLRRWYPSTGGTWQAEAAWPDIVRTATDQPESLRAALDRPPQTNEVGRSAALIGGLLIACLQFDLPIRLFEIGSSAGLNLRPDRYRYRYLGGEWGLADSPVRIDNAWLGELPPTATVRIVERHGYDIAPIDVTSPDGELNALSYIWPDQTDRLERLRGAIAVARNIPADLHRQAAHAAVAGMTLTDDALTVLWHSITWQYLPADERAAIRAGIDALAAQADAHCPFVHLTLEPAHQRPGAQIKYLVRMRSWPGGHARVLGECHPHGPPVTWQ