Rv2664 Family assigned · medium
H37Rv Rv2664 · MTBC0 mtbc0_002838 ·
84 aa · 3004300–3004554 (+) ·
RefSeq NP_217180.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | DNA-binding transcriptional regulator (winged-HTH / ECF-sigma-factor-like fold), structural homolog of the mycobacterial transcription factor Rv2667/CymA (ClpC2/CymA system) RefSeq leaves this locus uncharacterised. |
Curated reference (UniProt)
| UniProt |
I6Y9Z5
TrEMBL · unreviewed
· Predicted
|
|---|---|
| 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 | 2EIKQ |
|---|
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 | 0.328 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 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 84.9 (confident). 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 |
|---|---|---|---|---|
8dtq-assembly1_B |
0.16 | 0.64 | 5.0e+00 | 8dtq-assembly1_B Crystal Structure of Staphylococcus aureus pSK41 Cop |
7tz1-assembly1_A |
0.14 | 0.49 | 2.4e+00 | 7tz1-assembly1_A Crystal Structure of a Mycobacteriophage Cluster A2 Immunity Repressor:DNA Complex |
6vmh-assembly1_C |
0.13 | 0.57 | 4.7e+00 | 6vmh-assembly1_C Crystal structure of transcriptional regulator from bacteriophage 186 |
8b4h-assembly1_D |
0.12 | 0.65 | 9.1e+00 | 8b4h-assembly1_D IstA transposase cleaved donor complex |
3ikt-assembly1_A |
0.04 | 0.38 | 8.6e+00 | 3ikt-assembly1_A Crystal structure of a Rex-family repressor/DNA/NAD+ complex from Thermus aquaticus |
7pan-assembly1_p |
0.04 | 0.31 | 6.2e+00 | 7pan-assembly1_p 70S ribosome with A/P- and P/E-site tRNAs in Mycoplasma pneumoniae cells |
7nrd-assembly1_Sh |
0.04 | 0.32 | 9.1e+00 | 7nrd-assembly1_Sh Structure of the yeast Gcn1 bound to a colliding stalled 80S ribosome with MBF1, A/P-tRNA and P/E-tRNA |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2663 hyp |
hypothetical protein | 971 | 971 ctx | neighborhood:874 coexpression:780 |
Rv2662 hyp |
hypothetical protein | 564 | 564 ctx | neighborhood:558 |
Rv2665 hyp |
hypothetical protein | 418 | 418 ctx | neighborhood:414 |
Rv2661c hyp |
hypothetical protein | 400 | 400 |
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
- HHpred: top hit 8ADA Rv2667 CymA DNA-binding TF 99.05%, E 3.9e-9, 64 cols; corroborated by ECF sigma factor, SpoIIID, sigma-H, TrfB HTH repressor (all ~95%)
- HHpred web (MPI Bioinformatics Toolkit, profile-profile remote homology), interpreted in project 'Still unknown gene function', 2026-06-10. A fold/family-level assignment, not a demonstrated 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_217180.1)
- 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
2EIKQ - Curated reference: UniProt I6Y9Z5 (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)
- Model confidence: ESMFold per-residue pLDDT (mean 84.9, confident)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 4 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002838|Rv2664| MKHKTDIDEWLDTIEPNPADAHDASHLRRIIAAKEAVQTAESELRAAVNAARAAGDTWAAIGVALGITRQAAFQRFGPHSTASP