Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | integral membrane protein |
|---|
| MTBC0 PGAP re-annotation | DUF4407 domain-containing protein |
|---|
| Revised (this work) | Conserved hypothetical protein; DUF domain(s) DUF4407. 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 |
O53930
TrEMBL · unreviewed
· Evidence at protein level
|
|---|
| UniProt name | Possible integral membrane protein |
|---|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|
| eggNOG description | Domain of unknown function (DUF4407) |
|---|
| Orthologous group | 2ANPG |
|---|
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 |
0.668 · relaxed/neutral
|
|---|
| Polymorphic sites (≥ 0.1% of strains) |
5 synonymous, 8 missense, 1 nonsense, 0 frameshift
|
|---|
| Disruption |
1 distinct premature-stop/frameshift site(s); most common in
0.50% of strains
(732) · 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 |
|---|
DUF4407 | PF14362.12 |
2.8e-66 | 34–318 |
Domain of unknown function (DUF4407) |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|
Rv1778c hyp |
hypothetical protein |
540 |
540 ctx |
neighborhood:540 |
Rv1780 hyp |
hypothetical protein |
496 |
495 ctx |
neighborhood:495 |
Rv1592c hyp |
hypothetical protein |
440 |
46 |
textmining:438 |
Rv0180c |
transmembrane protein |
755 |
44 |
textmining:755 |
Rv0546c hyp |
hypothetical protein |
806 |
41 |
textmining:806 |
Rv2564 glnQ |
glutamine ABC transporter ATP-binding protein |
803 |
41 |
textmining:803 |
Rv2961 |
transposase |
803 |
41 |
textmining:803 |
Rv1086 |
(2Z,6E)-farnesyl diphosphate synthase |
578 |
41 |
textmining:578 |
Rv3274c fadE25 |
acyl-CoA dehydrogenase |
545 |
41 |
textmining:545 |
Rv1080c greA |
transcription elongation factor GreA |
531 |
41 |
textmining:531 |
Rv1419 hyp |
hypothetical protein |
511 |
41 |
textmining:511 |
Rv0863 hyp |
hypothetical protein |
446 |
41 |
textmining:446 |
Rv0108c hyp |
hypothetical protein |
446 |
41 |
textmining:446 |
Rv1159 pimE |
polyprenol-phosphate-mannose-dependent alpha-(1-2)-phosphatidylinositol pentamannoside mannosyltransferase |
437 |
41 |
textmining:437 |
Rv2224c caeA |
carboxylesterase A |
434 |
41 |
textmining:434 |
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: integral membrane protein
- MTBC0 PGAP product: DUF4407 domain-containing protein
- Pfam (hmmscan --cut_ga): DUF4407 PF14362.12 (E=3e-66)
- (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_216295.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF4407 (PF14362.12)
- 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
2ANPG
- Curated reference: UniProt
O53930
(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 —
15 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001893|Rv1779c|
MCAHEYAEQRSAVSGIEGLLTWLGGGHWRELGERHERSTHAVAGVIVAVGAALAGLLASLAVSEAAQGPISSPIGAASLALVLGLLVGAVTRGTASGPARGRAGVTGRASVAVAVGFVVGELAALVMFSGAIDRRLDEQAMHSADATPAAVQASASLQQARNARTALDSAVERARGRLDDALVVARCEYHPTPACPQTRITGVPGRGPETRTANQLLADAQRELDNALAARDHQAPALDAKMAHDEQALAEVRQAVVADAGRGLGSRWVAMNDLTLASAGALTARMLAIAFFALLYLLPLILRLWRGDTTHDRHAAARAERERAELEADTAIAIKRAEVRRAAEIMWAEHQLTQTRLAIEAQAEIDREQQRRRVVEALEGPVRASSERTLQPVEDEVYLPIAAETEAASRTVAQLPAGAAHHRPGIAKNLPAQVQPEGAVEPREKRATPVIRSIPDATKAAARWIRPLVPPFVARMLDNTTAPLRTARQVFEEVEEIAFSFKRTHKVTVNAEGSDPNDQPPLESHSPAAPAESNPIASSDSARRSRLATNDDHPPLAQVPPRDLASLSVGSTGELTQREGPHELRSPDGPRQLPPPR
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