Rv0201c Family assigned · low
H37Rv Rv0201c · MTBC0 mtbc0_000215 ·
167 aa · 238244–238747 (-) ·
RefSeq NP_214715.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | XRE family transcriptional regulator |
| Revised (this work) | XRE/Cro-family helix-turn-helix transcriptional regulator (PGAP). No Pfam domain above threshold, but Foldseek strongly matches DNA-binding folds (prob 1.00, TM=0.81). Putative DNA-binding regulator. |
Curated reference (UniProt)
| UniProt |
O53652
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Conserved protein |
UniProt still lists this protein as Conserved protein; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 2E42V |
|---|
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 | 0.09 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 8 synonymous, 2 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 94.9 (very high). A confident model makes the fold comparison meaningful.
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 |
|---|---|---|---|---|
8tac-assembly2_B |
1.00 | 0.81 | 3.0e-01 | 8tac-assembly2_B Designed DNA binding protein |
1y7y-assembly1_A |
1.00 | 0.78 | 3.0e-01 | 1y7y-assembly1_A High-resolution crystal structure of the restriction-modification controller protein C.AhdI from Aeromonas hydrophila |
3f52-assembly1_E |
1.00 | 0.86 | 5.3e-01 | 3f52-assembly1_E Crystal structure of the clp gene regulator ClgR from C. glutamicum |
1y9q-assembly1_A-2 |
1.00 | 0.83 | 5.6e-01 | 1y9q-assembly1_A-2 Crystal Structure of HTH_3 family Transcriptional Regulator from Vibrio cholerae |
3vk0-assembly2_B |
1.00 | 0.83 | 4.8e-01 | 3vk0-assembly2_B Crystal Structure of hypothetical transcription factor NHTF from Neisseria |
6jq1-assembly1_A |
1.00 | 0.84 | 5.6e-01 | 6jq1-assembly1_A Crystal Structure of DdrO from Deinococcus geothermalis |
2b5a-assembly1_A |
1.00 | 0.77 | 3.9e-01 | 2b5a-assembly1_A C.BclI, Control Element of the BclI Restriction-Modification System |
2ef8-assembly1_B |
1.00 | 0.86 | 6.8e-01 | 2ef8-assembly1_B Crystal structure of C.EcoT38IS |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mmpL11 (transmembrane transport protein MmpL11), high confidence from genomic context alone (score 883 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) |
|---|---|---|---|---|
Rv0202c mmpL11 |
transmembrane transport protein MmpL11 | 931 | 883 ctx | neighborhood:881 textmining:438 |
Rv0203 hyp |
hypothetical protein | 713 | 513 ctx | neighborhood:506 textmining:435 |
Rv0204c |
transmembrane protein | 496 | 66 | textmining:483 |
Rv0205 |
transmembrane protein | 807 | 64 | textmining:803 |
Rv0200 |
transmembrane protein | 658 | 55 | textmining:653 |
Rv0199 |
membrane protein | 483 | 49 | textmining:479 |
Rv0208c trmB |
tRNA (guanine-N(7)-)-methyltransferase | 657 | 47 | textmining:655 |
Rv3444c esxT |
ESAT-6 like protein EsxT | 520 | 47 | textmining:517 |
Rv1972 |
Mce associated membrane protein | 758 | 44 | textmining:758 |
Rv0177 |
Mce associated protein | 650 | 41 | textmining:650 |
Rv3812 PE_PGRS62 |
PE-PGRS family protein PE_PGRS62 | 431 | 41 | textmining:431 |
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: 'XRE family transcriptional regulator'
- Pfam: none above threshold
- Foldseek on the ESMFold model: strong match to DNA-binding domains (TM=0.81)
ESM Atlas signal (exploratory)
Ancestral protein hash a7da9e0403c5b1957104e25e4e1b4a76 ·
10 ESM-space neighbours (max similarity 0.948).
SAE features are orienting indices, not validated domains.
| # | Index | Activation | Interpretation |
|---|---|---|---|
| 1 | 4744 |
0.98 | Regulatory and DNA-contact interfaces |
| 2 | 4410 |
0.80 | Basic HTH/winged-helix hairpin |
| 3 | 6264 |
0.79 | N-terminal basic tails |
| 4 | 13912 |
0.78 | HTH DNA recognition helices |
| 5 | 10141 |
0.65 | DNA/RNA-binding regulatory modules |
| 6 | 2405 |
0.65 | HTH/homeodomain recognition helix |
| 7 | 8295 |
0.64 | HTH/homeodomain recognition helix |
| 8 | 2674 |
0.64 | Short basic helix–loop motif |
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_214715.1)
- 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
2E42V - Curated reference: UniProt O53652 (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 94.9, very high)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
11 functional partner(s); context anchor
mmpL11 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000215|Rv0201c| MTLAAEPHPAPPQQPTVAWSEPDVDRRVEFWPTVAIRSALESGDIATWQRIAAALKRDPYGRTARQVEEVLEGIPATGIANAFWEVLDRARTHLDANERAEVARQVGLLLDRSGLQRQEFASRIGVTAQDLTAYLDGIVSPSASLMIRMRRLSDRFVRAKSVRAADS