Rv3705A Family assigned · medium
H37Rv Rv3705A · MTBC0 - ·
129 aa · 4149091–4149480 (-) ·
RefSeq YP_178006.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Effector of the TcrXY acid-sensing two-component system regulon, required for persistent infection. RefSeq leaves it of unknown function. Rv3705A is one of two characterised members of the ~70-gene TcrXY regulon implicated as a key determinant of Mtb survival in vivo by mitigating redox stress at acidic pH (Stupar 2024). Molecular function unfixed. |
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
I6YGY9
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | Conserved hypothetical proline rich protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 2BJN6 |
|---|
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 | 0.753 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 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).
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3706c hyp |
hypothetical protein | 644 | 645 ctx | neighborhood:555 |
Rv3705c hyp |
hypothetical protein | 536 | 536 ctx | neighborhood:531 |
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 YP_178006.1)
- 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
2BJN6 - Curated reference: UniProt I6YGY9 (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 82.2, confident)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 2 functional partner(s)
- 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
>H37Rv|Rv3705A| MTETPQPAAPPPSAATTSPPPSPQQEKPPRLYRAAAWVVIVAGIVFTVAVIFFSGALVLGQGKCPYHRYYHHGMFRPVGPVAPGPGMGWVFGFPGGPPPPGMGPGFPGGPGGPAVGPTGPGPTTAPARP