Rv1874 Family assigned · low auto-curated · to review
H37Rv Rv1874 · MTBC0 - ·
228 aa · 2123684–2124370 (+) ·
RefSeq NP_216390.3
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | No Pfam domain above threshold; Foldseek indicates a fold similar to 2ftr-assembly1_B Crystal structure of an ethyl tert-butyl ether d (ethd) family (prob 1.00, TM 0.62). Structure-based, putative. |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed (flagged for human review).
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 |
O07755
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized protein |
UniProt still lists this protein as Uncharacterized protein; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | EthD domain |
| Orthologous group | 28KNT |
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 | 3.187 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 9 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)
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 92.4 (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 |
|---|---|---|---|---|
2ftr-assembly1_B |
1.00 | 0.62 | 4.6e-03 sig | 2ftr-assembly1_B Crystal structure of an ethyl tert-butyl ether d (ethd) family protein (bh0200) from bacillus halodurans c-125 at 1.40 A resolution |
3f44-assembly1_A |
1.00 | 0.48 | 4.4e-04 sig | 3f44-assembly1_A Crystal structure of putative monooxygenase (YP_193413.1) from Lactobacillus acidophilus NCFM at 1.55 A resolution |
5f9p-assembly2_B |
0.98 | 0.48 | 3.2e-03 sig | 5f9p-assembly2_B Crystal structure study of anthrone oxidase-like protein |
3bgu-assembly1_A |
0.96 | 0.54 | 1.4e-02 | 3bgu-assembly1_A Crystal structure of a dimeric ferredoxin-like protein of unknown function (tfu_0763) from thermobifida fusca yx at 1.50 A resolution |
1r6y-assembly1_A |
0.95 | 0.52 | 1.5e-02 | 1r6y-assembly1_A Crystal structure of YgiN from Escherichia coli |
2qyc-assembly1_A |
0.93 | 0.54 | 3.1e-02 | 2qyc-assembly1_A Crystal structure of a dimeric ferredoxin-like protein (bb1511) from bordetella bronchiseptica rb50 at 1.90 A resolution |
4d4f-assembly1_C |
0.93 | 0.40 | 3.8e-03 sig | 4d4f-assembly1_C Mutant P250A of bacterial chalcone isomerase from Eubacterium ramulus |
4d4f-assembly1_F |
0.92 | 0.41 | 7.9e-03 sig | 4d4f-assembly1_F Mutant P250A of bacterial chalcone isomerase from Eubacterium ramulus |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0273c (transcriptional regulator), medium confidence from genomic context alone (score 629 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) |
|---|---|---|---|---|
Rv1875 hyp |
hypothetical protein | 877 | 878 ctx | neighborhood:874 |
Rv0138 hyp |
hypothetical protein | 755 | 755 ctx | cooccurence:755 |
Rv2910c hyp |
hypothetical protein | 753 | 754 ctx | cooccurence:753 |
Rv0293c hyp |
hypothetical protein | 697 | 698 ctx | cooccurence:696 |
Rv0310c hyp |
hypothetical protein | 650 | 650 ctx | cooccurence:646 |
Rv3577 hyp |
hypothetical protein | 645 | 645 ctx | cooccurence:645 |
Rv0273c |
transcriptional regulator | 629 | 629 ctx | cooccurence:624 |
Rv1873 hyp |
hypothetical protein | 596 | 596 ctx | neighborhood:593 |
Rv3810 pirG |
cell surface protein | 595 | 595 ctx | cooccurence:594 |
Rv2627c hyp |
hypothetical protein | 593 | 593 ctx | cooccurence:591 |
Rv1817 |
flavoprotein | 583 | 583 ctx | cooccurence:582 |
Rv3169 hyp |
hypothetical protein | 567 | 568 ctx | cooccurence:563 |
Rv0272c hyp |
hypothetical protein | 555 | 555 ctx | cooccurence:550 |
Rv3906c hyp |
hypothetical protein | 552 | 553 ctx | cooccurence:550 |
Rv1191 hyp |
hypothetical protein | 552 | 553 ctx | cooccurence:550 |
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
- Foldseek best: 2ftr-assembly1_B Crystal structure of an ethyl tert-butyl ether d (ethd) family (prob 1.00, E=5e-03, TM=0.62)
- (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_216390.3)
- 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
28KNT - Curated reference: UniProt O07755 (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 92.4, very high)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
33 functional partner(s); context anchor
Rv0273c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv1874| MLMRPEPDDDWCARQRAQVADALLGLGVAGLSINVRDSTVRDSLMTLTTLYPPVAAVVSLWTQQCYGEQVAAALRLLAQECDELGAYLVTESVPLTFPSLVESGSRTPGLANIALLRRPDGLDQATWLTRWQRDHTQVAIEAQATFGYTQNWVVRALTPEAPGIAGIVEELFPVAATTDLKAFFGAADDNDLRNRISRMVASTSAFGANQNIDTVPTSRYVFRTPFKD