Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|
| MTBC0 PGAP re-annotation | DUF222 domain-containing protein |
|---|
| Revised (this work) | Conserved hypothetical protein; DUF domain(s) DUF222. Function unknown. |
|---|
Auto-curated: this verdict and function were generated by rules from
PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6XG38
TrEMBL · unreviewed
· Predicted
|
|---|
| UniProt name | HNH nuclease domain-containing protein |
|---|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
V Defense mechanisms
|
|---|
| eggNOG description | endonuclease |
|---|
| Orthologous group | COG1403 |
|---|
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 |
1.122 · relaxed/neutral
|
|---|
| Polymorphic sites (≥ 0.1% of strains) |
3 synonymous, 9 missense, 0 nonsense, 1 frameshift
|
|---|
| Disruption |
1 distinct premature-stop/frameshift site(s); most common in
0.19% of strains
(271) · 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 |
|---|
DUF222 | PF02720.23 |
7.3e-10 | 32–323 |
Domain of unknown function (DUF222) |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|
Rv3776 hyp |
hypothetical protein |
971 |
862 |
coexpression:798 textmining:803 |
Rv1378c hyp |
hypothetical protein |
806 |
804 |
coexpression:801 |
Rv2100 hyp |
hypothetical protein |
927 |
800 |
coexpression:730 textmining:652 |
Rv2633c hyp |
hypothetical protein |
672 |
673 ctx |
cooccurence:670 |
Rv1128c hyp |
hypothetical protein |
692 |
627 ctx |
cooccurence:615 |
Rv1702c hyp |
hypothetical protein |
859 |
612 ctx |
cooccurence:593 textmining:653 |
Rv1978 hyp |
hypothetical protein |
602 |
602 ctx |
cooccurence:602 |
Rv3073c hyp |
hypothetical protein |
599 |
599 ctx |
neighborhood:598 |
Rv3072c hyp |
hypothetical protein |
584 |
584 ctx |
neighborhood:580 |
Rv1587c hyp |
hypothetical protein |
580 |
581 ctx |
cooccurence:570 |
Rv3467 hyp |
hypothetical protein |
547 |
548 ctx |
cooccurence:532 |
Rv1945 hyp |
hypothetical protein |
625 |
546 ctx |
cooccurence:524 |
Rv0094c hyp |
hypothetical protein |
546 |
546 ctx |
cooccurence:532 |
Rv1148c hyp |
hypothetical protein |
612 |
531 ctx |
cooccurence:500 |
Rv0393 hyp |
hypothetical protein |
497 |
498 ctx |
cooccurence:492 |
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
- Legacy H37Rv annotation: hypothetical protein
- MTBC0 PGAP product: DUF222 domain-containing protein
- Pfam (hmmscan --cut_ga): DUF222 PF02720.23 (E=7e-10)
- (auto-curated by rules from PGAP + Pfam + Foldseek; not hand-reviewed)
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_217590.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF222 (PF02720.23)
- 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
COG1403
- Curated reference: UniProt
I6XG38
(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)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
32 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003268|Rv3074|
MFETLTAIDPDAEEAALIERIAELERLKSAAAAGQARAAAAVDAARRAAEGAAGVPAARRGRGLASEIALARRDSPARGSRHLGFAKALVYEMPHTLAALDCGALSEWRATLIVRESACLDVADRRALDAELCGDPGDLEGMGDARVVAAARAIAYRLDPQAVVDRAANAENDRTVTIRPAPDTMTYLTALLPVAQGVSVYAALTRAADTRCDGRSRGQVMADTLVERVTGRDAAVPTPIAVNLVMSDETLLGAANTPAQLCGYGPIPAAVARTMVASAVTDQRSRATLRRLYAHPQAGALVSMESRARLFPRGLAAFIELRDQRCRTPYCDAPIRHRDHAHPWADGGPTSAHNGLGTCERCNYAKQAPGWRVSTSVDENHTHTAEFITPTGSRHRSGAPPHLPAVTVSELEVRIGIALARYAA
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