Rv3748 Family assigned · low auto-curated · to review
H37Rv Rv3748 · MTBC0 mtbc0_003971 ·
119 aa · 4221358–4221717 (+) ·
RefSeq NP_218265.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | No Pfam domain above threshold; Foldseek indicates a fold similar to 1qvy-assembly3_C Crystal structure of RhoGDI K(199,200)R double mutant (prob 1.00, TM 0.60). 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).
Curated reference (UniProt)
| UniProt |
O69715
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)
| Orthologous group | 2AU2R |
|---|
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 | n/a |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 0 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)
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 77.6 (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 |
|---|---|---|---|---|
1qvy-assembly3_C |
1.00 | 0.60 | 2.7e-03 sig | 1qvy-assembly3_C Crystal structure of RhoGDI K(199,200)R double mutant |
7k2t-assembly1_C |
1.00 | 0.55 | 1.7e-03 sig | 7k2t-assembly1_C Mg2+/ATP-bound structure of the full-length WzmWzt O antigen ABC transporter in lipid nanodiscs |
8dnc-assembly1_C |
1.00 | 0.59 | 5.4e-03 sig | 8dnc-assembly1_C CryoEM structure of the A. aeolicus WzmWzt transporter bound to the native O antigen and ADP |
8dne-assembly1_C |
1.00 | 0.54 | 1.7e-03 sig | 8dne-assembly1_C CryoEM structure of the A.aeolicus WzmWzt transporter bound to ATP |
2jhw-assembly2_B |
1.00 | 0.51 | 1.9e-03 sig | 2jhw-assembly2_B CRYSTAL STRUCTURE OF RHOGDI E155A, E157A MUTANT |
2jht-assembly2_B |
1.00 | 0.58 | 1.2e-02 | 2jht-assembly2_B CRYSTAL STRUCTURE OF RHOGDI K135T,K138T,K141T MUTANT |
6kn9-assembly2_B |
1.00 | 0.54 | 5.6e-03 sig | 6kn9-assembly2_B Crystal structure of human interleukin 18 receptor beta extracellular domain in complex with an antagonistic scFv |
5fr2-assembly1_B |
1.00 | 0.53 | 6.3e-03 sig | 5fr2-assembly1_B Farnesylated RhoA-GDP in complex with RhoGDI-alpha, lysine acetylated at K178 |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3747 hyp |
hypothetical protein | 578 | 579 ctx | neighborhood:554 |
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: hypothetical protein
- Foldseek best: 1qvy-assembly3_C Crystal structure of RhoGDI K(199,200)R double mutant (prob 1.00, E=3e-03, TM=0.60)
- (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_218265.1)
- 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
2AU2R - Curated reference: UniProt O69715 (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 77.6, confident)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 1 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003971|Rv3748| MIVGAFLAEAASVVDNKLNVSGGVLYRFAVDPDRSAQFLLVVLTQAETDDPDRRVDVEVWPPTGDDAHHIEFELPEAAVAAEVGFAIFRIEVNLPVDGRWVLVVTGGAGTISLPLIVTG