TB9.4 Family assigned · low
H37Rv Rv3208A · MTBC0 - ·
90 aa · 3585677–3585949 (-) ·
RefSeq YP_177943.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Structurally characterized DUF3107 protein (Pfam) of unknown biochemical function. RefSeq leaves it 'hypothetical protein'. A crystal structure of the hexadecameric form of this family was solved (PDB 7rur; Foldseek prob 1.0, E 3e-11, TM 0.95). STRING context links it to the cytochrome bcc subunit qcrC (Rv2194). Family/structure assigned; molecular function unfixed. |
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 |
Q6MWZ8
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Conserved protein TB9.4 |
UniProt still lists this protein as Conserved protein TB9.4; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Protein of unknown function (DUF3107) |
| Orthologous group | 2E3M2 |
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) | 2 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
DUF3107 | PF11305.14 | 3.6e-31 | 1–73 | Protein of unknown function (DUF3107) |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 69.8 (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 |
|---|---|---|---|---|
7rur-assembly1_A |
1.00 | 0.93 | 3.5e-10 sig | 7rur-assembly1_A Crystal structure of the hexadecameric form of Rv3208A |
7rur-assembly1_B |
1.00 | 0.93 | 3.5e-10 sig | 7rur-assembly1_B Crystal structure of the hexadecameric form of Rv3208A |
7rus-assembly1_A |
1.00 | 0.90 | 2.0e-10 sig | 7rus-assembly1_A Crystal structure of the octameric form of Rv3208A |
7rur-assembly1_C |
1.00 | 0.92 | 3.7e-10 sig | 7rur-assembly1_C Crystal structure of the hexadecameric form of Rv3208A |
2rd1-assembly2_B |
0.97 | 0.60 | 8.6e-02 | 2rd1-assembly2_B X-Ray structure of the protein Q7CQI7. Northeast Structural Genomics Consortium target StR87A |
1zq1-assembly1_B |
0.96 | 0.52 | 4.1e-02 | 1zq1-assembly1_B Structure of GatDE tRNA-Dependent Amidotransferase from Pyrococcus abyssi |
3hfo-assembly1_B |
0.94 | 0.55 | 1.1e-01 | 3hfo-assembly1_B Crystal Structure of an Hfq protein from Synechocystis sp. |
2rb6-assembly3_B-2 |
0.91 | 0.58 | 1.0e-01 | 2rb6-assembly3_B-2 X-Ray structure of the protein Q8EI81. Northeast Structural Genomics Consortium target SoR78A |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: qcrC (ubiquinol-cytochrome C reductase cytochrome subunit C), high confidence from genomic context alone (score 717 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) |
|---|---|---|---|---|
Rv2194 qcrC |
ubiquinol-cytochrome C reductase cytochrome subunit C | 716 | 717 ctx | cooccurence:714 |
Rv3209 hyp |
hypothetical protein | 705 | 706 ctx | neighborhood:704 |
Rv2199c ctaF |
cytochrome c oxidase polypeptide 4 | 675 | 676 ctx | cooccurence:662 |
Rv2195 qcrA |
ubiquinol-cytochrome C reductase rieske iron-sulfur subunit | 613 | 614 ctx | cooccurence:608 |
Rv2169c |
transmembrane protein | 514 | 515 ctx | cooccurence:513 |
Rv2698 |
transmembrane protein | 511 | 511 ctx | cooccurence:504 |
Rv2196 qcrB |
ubiquinol-cytochrome C reductase cytochrome subunit B | 496 | 497 ctx | cooccurence:482 |
Rv3013 hyp |
hypothetical protein | 487 | 488 ctx | cooccurence:482 |
Rv1828 |
HTH-type transcriptional regulator | 482 | 482 ctx | cooccurence:479 |
Rv0528 |
transmembrane protein | 453 | 454 ctx | cooccurence:451 |
Rv0004 hyp |
hypothetical protein | 449 | 449 ctx | cooccurence:449 |
Rv2680 hyp |
hypothetical protein | 446 | 447 ctx | cooccurence:444 |
Rv2229c hyp |
hypothetical protein | 445 | 445 ctx | cooccurence:442 |
Rv1234 |
transmembrane protein | 428 | 428 ctx | cooccurence:423 |
Rv2219A |
membrane protein | 408 | 409 |
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
- Pfam DUF3107
- Foldseek -> 7rur (hexadecameric Rv3208 family), prob 1.0, E 3e-11, TM 0.95
- STRING anchor qcrC/Rv2194 (respiratory chain)
- Structural homology: AlphaFold DB model + Foldseek vs PDB (project 'Still unknown gene function', phase5-7, 2026-06-10). A fold-level family assignment, not a demonstrated activity.
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 YP_177943.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF3107 (PF11305.14)
- 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
2E3M2 - Curated reference: UniProt Q6MWZ8 (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 69.8, low)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
15 functional partner(s); context anchor
qcrC - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3208A|TB9.4 MEVKIGITDSPRELVFSSAQTPSEVEELVSNALRDDSGLLTLTDERGRRFLIHTARIAYVEIGVADARRVGFGVGVDAAAGSAGKVATSG