Rv0034 Family assigned · medium
H37Rv Rv0034 · MTBC0 mtbc0_000039 ·
131 aa · 36853–37248 (+) ·
RefSeq NP_214548.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | nuclear transport factor 2 family protein |
| Revised (this work) | NTF2-like / SnoaL-like superfamily protein (Pfam SnoaL_2, PF12680). This alpha+beta cone fold occurs in polyketide cyclases, ketosteroid isomerases and NTF2 domains, often binding a hydrophobic ligand in a deep cavity. The precise physiological role in M. tuberculosis is not established. |
Curated reference (UniProt)
| UniProt |
P9WM93
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized protein Rv0034 |
UniProt still lists this protein as Uncharacterized protein Rv0034; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | SnoaL-like domain |
| Orthologous group | COG3631 |
| KEGG orthology |
K06893
|
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 | 0.226 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 2 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.12% of strains (176) · clonal |
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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
SnoaL_2 | PF12680.14 | 2.2e-13 | 10–115 | SnoaL-like domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: acpA (acyl carrier protein AcpA), high confidence from genomic context alone (score 983 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) |
|---|---|---|---|---|
Rv0033 acpA |
acyl carrier protein AcpA | 983 | 983 ctx | neighborhood:882 coexpression:863 |
Rv0035 fadD34 |
fatty-acid--CoA ligase FadD34 | 982 | 983 ctx | neighborhood:882 coexpression:860 |
Rv0032 bioF2 |
8-amino-7-oxononanoate synthase | 971 | 972 ctx | neighborhood:781 coexpression:860 |
Rv2305 hyp |
hypothetical protein | 714 | 714 ctx | cooccurence:701 |
Rv1907c hyp |
hypothetical protein | 605 | 606 ctx | cooccurence:600 |
Rv2490c PE_PGRS43 |
PE-PGRS family protein PE_PGRS43 | 578 | 578 ctx | cooccurence:578 |
Rv2098c PE_PGRS36 |
PE-PGRS family protein PE_PGRS36; Rv2098c, (MTCY49.38c), len: 434 aa. PE_PGRS36,Member of the Mycobacterium tuberculosis PE family, PGRS sub | 547 | 547 ctx | cooccurence:547 |
Rv2337c hyp |
hypothetical protein | 535 | 536 ctx | cooccurence:526 |
Rv0330c hyp |
hypothetical protein | 528 | 528 ctx | cooccurence:523 |
Rv2487c PE_PGRS42 |
PE-PGRS family protein PE_PGRS42 | 515 | 515 ctx | cooccurence:515 |
Rv0341 iniB |
isoniazid inducible protein IniB | 498 | 499 ctx | cooccurence:498 |
Rv0355c PPE8 |
PPE family protein PPE8 | 458 | 458 ctx | cooccurence:455 |
Rv2209 |
integral membrane protein | 454 | 454 ctx | cooccurence:454 |
Rv1917c PPE34 |
PPE family protein PPE34 | 454 | 454 ctx | cooccurence:429 |
Rv3347c PPE55 |
PPE family protein PPE55 | 451 | 451 ctx | cooccurence:449 |
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: 'nuclear transport factor 2 family protein'
- Pfam: SnoaL_2 PF12680 (E=2.2e-13) -- NTF2-like / SnoaL-like superfamily (polyketide-cyclase / ketosteroid-isomerase-like cavity fold)
- No Mtb-specific functional study found in tbmonitor (2021-2026)
ESM Atlas signal (exploratory)
Ancestral protein hash 845846715164c4453e40c8b61a9c874e ·
10 ESM-space neighbours (max similarity 0.930).
SAE features are orienting indices, not validated domains.
| # | Index | Activation | Interpretation |
|---|---|---|---|
| 1 | 3816 |
1.13 | Acidic amphipathic surface helix |
| 2 | 690 |
1.09 | C-terminal tail/linker activation |
| 3 | 2719 |
1.01 | Beta-edge helix cap |
| 4 | 2936 |
0.93 | Charged surface beta/loop patches |
| 5 | 3387 |
0.91 | N-terminal low-complexity IDR |
| 6 | 13932 |
0.87 | Acidic-aromatic helix capping motif |
| 7 | 6934 |
0.81 | Active-site gating loop |
| 8 | 12646 |
0.73 | Secondary-structure capping loops |
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_214548.1)
- Domains: Pfam-A via hmmscan --cut_ga — SnoaL_2 (PF12680.14)
- 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
COG3631 - Curated reference: UniProt P9WM93 (SwissProt, reviewed; 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)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
30 functional partner(s); context anchor
acpA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000039|Rv0034| MTDDADLDLVRRTFAAFARGDLAELTQCFAPDVEQFVPGKHALAGVFRGVDNVVACLGDTAAAADGTMTVTLEDVLSNTDGQVIAVYRLRASRAGKVLDQREAILVTVAGGRITRLSEFYADPAATESFWA