Rv0123 Family assigned · low
H37Rv Rv0123 · MTBC0 mtbc0_000134 ·
122 aa · 149022–149390 (+) ·
RefSeq NP_214637.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | DNA-binding protein |
| Revised (this work) | Putative DNA-binding protein. No Pfam domain above threshold, but Foldseek matches antitoxin DNA-binding domains strongly and consistently (CopASO antitoxin prob 0.99 / TM 0.83; ParDE antitoxin; PutA HTH), pointing to a ribbon-helix-helix / antitoxin-type DNA-binding fold. Structure-based, consistent with the PGAP 'DNA-binding protein' call. |
Curated reference (UniProt)
| UniProt |
O07173
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 | 28Z1X |
|---|
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 57.6 (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 |
|---|---|---|---|---|
6iya-assembly2_C |
0.99 | 0.83 | 1.6e-01 | 6iya-assembly2_C Structure of the DNA binding domain of antitoxin CopASO |
6xrw-assembly1_B-2 |
0.96 | 0.80 | 3.7e-01 | 6xrw-assembly1_B-2 Chromosomal ParDE TA system from P. aeruginosa |
3ft7-assembly1_A |
0.94 | 0.79 | 4.3e-01 | 3ft7-assembly1_A Crystal structure of an extremely stable dimeric protein from sulfolobus islandicus |
2gpe-assembly1_A |
0.72 | 0.77 | 1.5e+00 | 2gpe-assembly1_A Structure of the DNA-binding domain of E. Coli Proline Utilization A (PUTA) |
8ypj-assembly1_A |
0.66 | 0.66 | 1.0e+00 | 8ypj-assembly1_A Cyrstal structure of the MazE-mt10 Antitoxin from Mycobacterium tuberculosis |
2k5j-assembly1_B |
0.57 | 0.65 | 7.4e-01 | 2k5j-assembly1_B Solution structure of protein yiiF from Shigella flexneri serotype 5b (strain 8401) . Northeast Structural Genomics Consortium target sft1 |
8u12-assembly1_A |
0.51 | 0.67 | 1.7e+00 | 8u12-assembly1_A Crystal Structure of Antitoxin Protein Rv0298 of Type II Toxin-antitoxin Systems from Mycobacterium tuberculosis |
6sbw-assembly1_A |
0.35 | 0.72 | 3.6e+00 | 6sbw-assembly1_A CdbA Form One |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: PE_PGRS2 (PE-PGRS family protein PE_PGRS2), medium confidence from genomic context alone (score 405 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) |
|---|---|---|---|---|
Rv0122 hyp |
hypothetical protein | 887 | 887 ctx | neighborhood:882 |
Rv0121c hyp |
hypothetical protein | 533 | 533 ctx | neighborhood:532 |
Rv0124 PE_PGRS2 |
PE-PGRS family protein PE_PGRS2 | 406 | 405 ctx | neighborhood:405 |
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: 'DNA-binding protein'
- Pfam: no domain above threshold
- Foldseek on the ESMFold model: consistent hits to antitoxin DNA-binding domains (6IYA CopASO prob 0.99 TM 0.83; ParDE; PutA HTH) -- a DNA-binding fold
ESM Atlas signal (exploratory)
Ancestral protein hash 6d93c8d3df3504116923c5bb3be78ee0 ·
10 ESM-space neighbours (max similarity 0.956).
SAE features are orienting indices, not validated domains.
| # | Index | Activation | Interpretation |
|---|---|---|---|
| 1 | 8116 |
1.42 | Terminal disorder and cap motifs |
| 2 | 14869 |
1.11 | N-terminal basic DNA-binding patch |
| 3 | 6413 |
0.93 | Basic amphipathic interface patches |
| 4 | 952 |
0.91 | Basic phosphate-binding DNA/RNA/CoA patches |
| 5 | 13077 |
0.89 | Short basic amphipathic recognition helices |
| 6 | 9286 |
0.89 | Short amphipathic alpha-helix motif |
| 7 | 5762 |
0.84 | Charged low-complexity terminal/linker IDRs |
| 8 | 9860 |
0.76 | Amphipathic helix N-cap motifs |
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_214637.1)
- 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
28Z1X - Curated reference: UniProt O07173 (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 57.6, 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
PE_PGRS2 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000134|Rv0123| MTKKPRNPADYVIGDDVEVSDVDLKQEEVYVDGERLTDERVEQMASESLRLAREREANLIPGGKSLSGGSAHSPAVQVVVSKATHAKLKELARSRKMSVSKLLRPVLDEFVQRETGRILPRR