Rv3440c Family assigned · low auto-curated · to review
H37Rv Rv3440c · MTBC0 mtbc0_003659 ·
103 aa · 3885551–3885862 (-) ·
RefSeq NP_217957.1
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 5los-assembly1_A Piriformospora indica PIIN_05872 (prob 0.96, TM 0.86). 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 |
O06257
TrEMBL · unreviewed
· Predicted
|
|---|---|
| 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 | 2BI3A |
|---|
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 | 0.0 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 0 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 67.4 (low). Low-confidence model: the fold may be unreliable, so treat these structural hits with caution.
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 |
|---|---|---|---|---|
5los-assembly1_A |
0.96 | 0.86 | 1.3e+00 | 5los-assembly1_A Piriformospora indica PIIN_05872 |
6tz5-assembly1_AA |
0.63 | 0.73 | 2.8e+00 | 6tz5-assembly1_AA CryoEM reconstruction of membrane-bound ESCRT-III filament composed of CHMP1B+IST1 (left-handed) |
7zch-assembly1_B |
0.35 | 0.66 | 5.0e+00 | 7zch-assembly1_B CHMP2A-CHMP3 heterodimer (410 Angstrom diameter) |
8v2q-assembly1_A-1 |
0.35 | 0.72 | 5.7e+00 | 8v2q-assembly1_A-1 CHMP1B/IST1 ssRNA bound copolymer |
6zw6-assembly1_A |
0.08 | 0.44 | 9.8e+00 | 6zw6-assembly1_A C16 symmetry: Bacterial Vipp1 and PspA are members of the ancient ESCRT-III membrane-remodeling superfamily. |
6zw5-assembly1_A |
0.07 | 0.44 | 9.2e+00 | 6zw5-assembly1_A C15 symmetry: Bacterial Vipp1 and PspA are members of the ancient ESCRT-III membrane-remodeling superfamily. |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mrsA (phosphoglucosamine mutase), high confidence from genomic context alone (score 826 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) |
|---|---|---|---|---|
Rv3439c hyp |
hypothetical protein | 932 | 932 ctx | neighborhood:882 coexpression:449 |
Rv3441c mrsA |
phosphoglucosamine mutase | 826 | 826 ctx | neighborhood:816 |
Rv3442c rpsI |
30S ribosomal protein S9 | 725 | 726 ctx | neighborhood:722 |
Rv3443c rplM |
50S ribosomal protein L13 | 526 | 526 ctx | neighborhood:523 |
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: 5los-assembly1_A Piriformospora indica PIIN_05872 (prob 0.96, E=1e+00, TM=0.86)
- (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_217957.1)
- 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
2BI3A - Curated reference: UniProt O06257 (TrEMBL, unreviewed; Predicted)
- 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 67.4, low)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
4 functional partner(s); context anchor
mrsA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003659|Rv3440c| MRPDSVNSAGIDIAAVYAVADRFSAAAELIDDAIGNHLTRLAFGGACAGRGHASRGDALRCRLDRLAGELSVWSRAAVQIAFALRAGANRYAEADLCAAARIG