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_4 PF13577 + SnoaL_2 PF12680). A cone fold often acting as a polyketide cyclase or hydrophobic-ligand-binding domain; the specific role is not established. |
|---|
Curated reference (UniProt)
| UniProt |
P96815
TrEMBL · unreviewed
· Evidence at protein level
|
|---|
| UniProt name | SnoaL-like domain-containing protein |
|---|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|
| eggNOG description | SnoaL-like domain |
|---|
| Orthologous group | 2F5RB |
|---|
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 |
0.468 · purifying
|
|---|
| Polymorphic sites (≥ 0.1% of strains) |
5 synonymous, 8 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|
SnoaL_4 | PF13577.13 |
2.9e-05 | 20–106 |
SnoaL-like domain |
SnoaL_2 | PF12680.14 |
7.2e-07 | 24–75 |
SnoaL-like domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner:
Rv0139 (oxidoreductase),
high confidence from genomic context alone
(score 914 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) |
|---|
Rv0139 |
oxidoreductase |
914 |
914 ctx |
neighborhood:882 |
Rv0140 hyp |
hypothetical protein |
800 |
800 ctx |
neighborhood:800 |
Rv0137c msrA |
peptide methionine sulfoxide reductase MsrA |
780 |
780 ctx |
neighborhood:779 |
Rv1874 hyp |
hypothetical protein |
755 |
755 ctx |
cooccurence:755 |
Rv0272c hyp |
hypothetical protein |
701 |
701 ctx |
cooccurence:701 |
Rv3906c hyp |
hypothetical protein |
688 |
689 ctx |
cooccurence:688 |
Rv0273c |
transcriptional regulator |
686 |
686 ctx |
cooccurence:686 |
Rv0311 hyp |
hypothetical protein |
663 |
663 ctx |
cooccurence:663 |
Rv0767c |
HTH-type transcriptional regulator |
650 |
650 ctx |
cooccurence:650 |
Rv3169 hyp |
hypothetical protein |
648 |
648 ctx |
cooccurence:648 |
Rv3168 |
aminoglycoside phosphotransferase |
626 |
626 ctx |
cooccurence:626 |
Rv1191 hyp |
hypothetical protein |
609 |
609 ctx |
cooccurence:609 |
Rv1776c |
transcriptional regulator |
606 |
606 ctx |
cooccurence:606 |
Rv0310c hyp |
hypothetical protein |
592 |
592 ctx |
cooccurence:591 |
Rv1786 |
ferredoxin |
583 |
584 ctx |
cooccurence:580 |
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_4 PF13577 (E=2.9e-05), SnoaL_2 PF12680 (E=7.2e-07)
ESM Atlas signal (exploratory)
Ancestral protein hash e30e130713569e5a62a06f6ba90324d4 ·
10 ESM-space neighbours (max similarity 0.954).
SAE features are orienting indices, not validated domains.
| # | Index | Activation | Interpretation |
|---|
| 1 | 3816 |
1.19 |
Acidic amphipathic surface helix |
| 2 | 2719 |
1.11 |
Beta-edge helix cap |
| 3 | 690 |
1.07 |
C-terminal tail/linker activation |
| 4 | 3387 |
1.05 |
N-terminal low-complexity IDR |
| 5 | 2936 |
1.02 |
Charged surface beta/loop patches |
| 6 | 6934 |
0.95 |
Active-site gating loop |
| 7 | 4441 |
0.89 |
Short acidic-aromatic motifs |
| 8 | 12646 |
0.85 |
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_214652.1)
- Domains: Pfam-A via hmmscan --cut_ga — SnoaL_4 (PF13577.13), 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
2F5RB
- Curated reference: UniProt
P96815
(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)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
41 functional partner(s); context anchor
Rv0139
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000149|Rv0138|
MSASEFSRAELAAAFEKFEKTVARAAATRDWDCWVQHYTPDVEYIEHAAGIMRGRQRVRAWIQETMTTFPGSHMVAFPSLWSVIDESTGRIICELDNPMLDPGDGSVISATNISIITYAGNGQWCRQEDIYNPLRFLRAAMKWCRKAQELGTLDEDAARWMRRHGGP
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