Rv3706c Family assigned · medium
H37Rv Rv3706c · MTBC0 mtbc0_003929 ·
106 aa · 4173539–4173859 (-) ·
RefSeq NP_218223.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | Effector of the TcrXY acid-sensing two-component system regulon, required for persistent infection. RefSeq leaves it of unknown function. Rv3706c, with Rv3705A, is a characterised member of the TcrXY regulon implicated in Mtb survival in vivo by mitigating redox stress at acidic pH (Stupar 2024). Molecular function unfixed. |
Curated reference (UniProt)
| UniProt |
I6X849
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | Conserved hypothetical proline rich protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 2AY2R |
|---|
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 65.6 (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 |
|---|---|---|---|---|
7ak5-assembly1_p |
0.05 | 0.39 | 7.2e+00 | 7ak5-assembly1_p Cryo-EM structure of respiratory complex I in the deactive state from Mus musculus at 3.2 A |
6hiv-assembly1_CR |
0.01 | 0.21 | 9.6e+00 | 6hiv-assembly1_CR Cryo-EM structure of the Trypanosoma brucei mitochondrial ribosome - This entry contains the complete mitoribosome |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: asd (aspartate-semialdehyde dehydrogenase), medium confidence from genomic context alone (score 523 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) |
|---|---|---|---|---|
Rv3705A hyp |
hypothetical protein | 644 | 645 ctx | neighborhood:555 |
Rv3707c hyp |
hypothetical protein | 524 | 523 ctx | neighborhood:522 |
Rv3708c asd |
aspartate-semialdehyde dehydrogenase | 524 | 523 ctx | neighborhood:522 |
Rv3709c ask |
aspartokinase | 523 | 522 ctx | neighborhood:522 |
Rv3705c hyp |
hypothetical protein | 434 | 433 ctx | neighborhood:430 |
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
- TcrXY two-component regulon effector; redox-stress survival at acidic pH (Stupar 2024, PMID 38388565)
- Curated from the literature crible (project 'Still unknown gene function', 2026-06-09)
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_218223.1)
- 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
2AY2R - Curated reference: UniProt I6X849 (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 65.6, low)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
5 functional partner(s); context anchor
asd - Primary literature: Stupar M, Tan L, Kerr ED, De Voss CJ, Forde BM, Schulz BL, West NP (2024). TcrXY is an acid-sensing two-component transcriptional regulator of Mycobacterium tuberculosis required for persistent infection Nat Commun 15(1):1615. doi:10.1038/s41467-024-45343-7 PMID:38388565
Ancestral MTBC0 protein sequence
>mtbc0_003929|Rv3706c| MRHMSETSETPTPPPHQTPKVFKAAAWVAIAAGTVFIVAVIFFTGYILGKHAGHGGFHHRQHHQHPAMMLRPGSPHGGPAAVRPGPGPGGPGQVPSSVSPPATPAP