Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
|---|
| Revised (this work) | TetR/AcrR-family transcriptional regulator (Pfam TetR_C_16 PF17920). PGAP left it 'hypothetical', but the TetR C-terminal ligand-binding/regulatory domain identifies it as a one-component transcriptional regulator. |
|---|
Curated reference (UniProt)
| UniProt |
P95215
TrEMBL · unreviewed
· Predicted
|
|---|
| UniProt name | Tetracyclin repressor-like C-terminal domain-containing protein |
|---|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K Transcription
|
|---|
| eggNOG description | transcriptional regulator |
|---|
| Orthologous group | COG1309 |
|---|
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 |
0.46 · purifying
|
|---|
| Polymorphic sites (≥ 0.1% of strains) |
3 synonymous, 4 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 |
|---|
TetR_C_16 | PF17920.7 |
2.3e-25 | 39–144 |
Tetracyclin repressor-like, C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner:
Rv0260c (transcriptional regulator),
high confidence from genomic context alone
(score 761 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) |
|---|
Rv0259c hyp |
hypothetical protein |
761 |
762 ctx |
neighborhood:760 |
Rv0260c |
transcriptional regulator |
771 |
761 ctx |
neighborhood:760 |
Rv3687c rsfB |
anti-anti-sigma factor RsfB |
623 |
623 ctx |
cooccurence:623 |
Rv0419 lpqM |
lipoprotein peptidase LpqM |
610 |
610 ctx |
cooccurence:610 |
Rv0941c hyp |
hypothetical protein |
562 |
562 ctx |
cooccurence:561 |
Rv1006 hyp |
hypothetical protein |
535 |
535 ctx |
cooccurence:535 |
Rv1868 hyp |
hypothetical protein |
507 |
507 ctx |
cooccurence:502 |
Rv0261c narK3 |
nitrate/nitrite transporter |
501 |
502 ctx |
neighborhood:501 |
Rv2079 hyp |
hypothetical protein |
490 |
490 ctx |
cooccurence:490 |
Rv2695 hyp |
hypothetical protein |
456 |
456 ctx |
cooccurence:447 |
Rv2114 hyp |
hypothetical protein |
451 |
451 ctx |
cooccurence:451 |
Rv2047c hyp |
hypothetical protein |
446 |
426 ctx |
cooccurence:413 |
Rv1364c |
sigma factor regulatory protein |
453 |
420 ctx |
cooccurence:418 |
Rv3886c mycP2 |
membrane-anchored mycosin |
408 |
408 |
|
Rv0541c |
integral membrane protein |
404 |
404 ctx |
cooccurence:404 |
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
- MTBC0 PGAP product: 'hypothetical protein'
- Pfam: TetR_C_16 PF17920 (E=2.3e-25) -- TetR/AcrR-family regulatory domain
ESM Atlas signal (exploratory)
Ancestral protein hash 5e66cb9e21b9ba9c1df61fbde35aeaf7 ·
10 ESM-space neighbours (max similarity 0.943).
SAE features are orienting indices, not validated domains.
| # | Index | Activation | Interpretation |
|---|
| 1 | 1844 |
1.05 |
C-terminal helical interface hotspots |
| 2 | 5096 |
0.90 |
C-terminal helix-coil linkers |
| 3 | 12534 |
0.86 |
TetR post-HTH hinge helix |
| 4 | 4887 |
0.85 |
C-terminal amphipathic packing helices |
| 5 | 3077 |
0.82 |
Hydrophobic helical ligand pockets |
| 6 | 2118 |
0.77 |
C-terminal hydrophobic pocket helices |
| 7 | 6381 |
0.74 |
Amphipathic hinge linker helices |
| 8 | 10672 |
0.73 |
Helical hydrophobic ligand-binding pocket |
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_214772.1)
- Domains: Pfam-A via hmmscan --cut_ga — TetR_C_16 (PF17920.7)
- 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
COG1309
- Curated reference: UniProt
P95215
(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)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
18 functional partner(s); context anchor
Rv0260c
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000274|Rv0258c|
MARSQEPSRGLLDPVAKMLRLPFGTPDFIEKIVTGSVNQVGRRTLYVLITTWDAAGGGPFAASAIATTGLAKTAEIVQSMFIGPVFNPLLKMLGADKIAIRASLCAAQLVGLGIMRYGVRSEPLHSMSVEMLVDAIGPTMQRYLVGDIGRG
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