Rv2076c Family assigned · low
H37Rv Rv2076c · MTBC0 - ·
83 aa · 2333037–2333288 (-) ·
RefSeq NP_216592.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Polytopic integral membrane protein with 3 predicted transmembrane helices (DeepTMHMM). RefSeq leaves it 'hypothetical protein'. A topological feature consistent with a membrane transporter/permease or membrane-embedded enzyme; the transported substrate and molecular function are undetermined. |
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 |
P9WLL3
SwissProt · reviewed
· Predicted
|
|---|---|
| UniProt name | Uncharacterized protein Rv2076c |
UniProt still lists this protein as Uncharacterized protein Rv2076c; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 2B3FH |
|---|
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, 1 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 50.9 (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 |
|---|---|---|---|---|
8e0m-assembly3_I |
0.13 | 0.59 | 6.3e+00 | 8e0m-assembly3_I Homotrimeric variant of tcTRP9, BGL15 |
8e0m-assembly4_J |
0.13 | 0.60 | 6.7e+00 | 8e0m-assembly4_J Homotrimeric variant of tcTRP9, BGL15 |
7tj9-assembly1_A |
0.13 | 0.60 | 7.2e+00 | 7tj9-assembly1_A Cryo-EM structure of the human Nax channel in complex with beta3 solved in GDN |
8f0r-assembly1_A |
0.13 | 0.60 | 7.2e+00 | 8f0r-assembly1_A Structure of VSD4-NaV1.7-NaVPas channel chimera bound to the arylsulfonamide inhibitor GNE-3565 |
8f0p-assembly1_A |
0.13 | 0.55 | 5.2e+00 | 8f0p-assembly1_A Structure of VSD4-NaV1.7-NaVPas channel chimera bound to the hybrid inhibitor GNE-1305 |
6xr2-assembly1_C |
0.10 | 0.58 | 8.7e+00 | 6xr2-assembly1_C Computationally designed right-handed alpha/alpha homotrimeric toroid with 3 repeats per subunit |
8f0s-assembly1_A |
0.10 | 0.54 | 7.2e+00 | 8f0s-assembly1_A Structure of VSD4-NaV1.7-NaVPas channel chimera bound to the hybrid inhibitor GNE-9296 |
8e0m-assembly1_B |
0.09 | 0.62 | 9.9e+00 | 8e0m-assembly1_B Homotrimeric variant of tcTRP9, BGL15 |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv2077c (transmembrane protein), high confidence from genomic context alone (score 767 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) |
|---|---|---|---|---|
Rv2077c |
transmembrane protein | 767 | 767 ctx | neighborhood:756 |
Rv2077A hyp |
hypothetical protein | 676 | 677 ctx | neighborhood:675 |
Rv2075c hyp |
hypothetical protein | 478 | 478 ctx | neighborhood:475 |
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
- DeepTMHMM: 3 transmembrane helices (type TM)
- Integral membrane topology (localisation feature, not a function)
- DeepTMHMM topology prediction (project 'Still unknown gene function', phase8, 2026-06-10). A topological feature, not a demonstrated molecular function.
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_216592.1)
- 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
2B3FH - Curated reference: UniProt P9WLL3 (SwissProt, reviewed; 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 50.9, low)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
3 functional partner(s); context anchor
Rv2077c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2076c| MVVCLIGGVAGSLWPRPAGRLRGGCYFAFMGVAWVLLAISAIANAVKGSLWWDIWSLGLLVLIPAVVYGKMRRSRRISSDQDR