Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|
| MTBC0 PGAP re-annotation | pyridoxamine 5'-phosphate oxidase family protein |
|---|
| Revised (this work) | Pyridoxamine-5'-phosphate-oxidase (PNPOx) family protein / FMN-binding split-barrel (Pfam Pyridox_ox_2 PF12900). Putative FMN-dependent oxidoreductase; specific reaction not established. |
|---|
Curated reference (UniProt)
| UniProt |
P9WMA5
SwissProt · reviewed
· Evidence at protein level
|
|---|
| UniProt name | Uncharacterized protein Rv0080 |
|---|
UniProt still lists this protein as Uncharacterized protein Rv0080; the revised
annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K Transcription
|
|---|
| eggNOG description | pyridoxamine 5-phosphate |
|---|
| Orthologous group | COG3467 |
|---|
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 |
5.511 · diversifying/relaxed
|
|---|
| Polymorphic sites (≥ 0.1% of strains) |
1 synonymous, 15 missense, 0 nonsense, 3 frameshift
|
|---|
| Disruption |
3 distinct premature-stop/frameshift site(s); most common in
0.46% of strains
(671) · 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 |
|---|
Pyridox_ox_2 | PF12900.14 |
8.9e-25 | 20–144 |
Pyridoxamine 5'-phosphate oxidase |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|
Rv0079 hyp |
hypothetical protein |
989 |
983 ctx |
neighborhood:882 coexpression:860 textmining:435 |
Rv3134c |
universal stress protein |
915 |
891 |
coexpression:823 |
Rv1996 |
universal stress protein |
887 |
883 |
coexpression:854 |
Rv3127 hyp |
hypothetical protein |
883 |
883 |
coexpression:845 |
Rv2623 TB31.7 |
universal stress protein |
912 |
877 |
coexpression:845 |
Rv1738 hyp |
hypothetical protein |
895 |
867 |
coexpression:804 |
Rv2032 acg |
NAD(P)H nitroreductase |
906 |
839 |
coexpression:808 textmining:439 |
Rv2031c hspX |
alpha-crystallin |
872 |
833 |
coexpression:829 |
Rv1733c |
transmembrane protein |
826 |
827 |
coexpression:733 |
Rv2007c fdxA |
ferredoxin |
868 |
824 |
coexpression:819 |
Rv3131 |
NAD(P)H nitroreductase |
916 |
811 |
coexpression:807 textmining:579 |
Rv2626c hrp1 |
hypoxic response protein |
872 |
811 |
coexpression:805 |
Rv3130c tgs1 |
diacyglycerol O-acyltransferase |
852 |
803 |
coexpression:803 |
Rv1737c narK2 |
nitrate/nitrite transporter |
797 |
774 |
coexpression:730 |
Rv2030c hyp |
hypothetical protein |
912 |
759 |
coexpression:751 textmining:652 |
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: 'pyridoxamine 5'-phosphate oxidase family protein'
- Pfam: Pyridox_ox_2 PF12900 (E=8.9e-25) -- FMN-binding split-barrel
ESM Atlas signal (exploratory)
Ancestral protein hash 20522aa6b5630a7a0a096cf5b84cc4e1 ·
10 ESM-space neighbours (max similarity 0.926).
SAE features are orienting indices, not validated domains.
| # | Index | Activation | Interpretation |
|---|
| 1 | 8276 |
0.94 |
Acidic/His catalytic loops |
| 2 | 3114 |
0.91 |
Active-site rim β-loop elements |
| 3 | 733 |
0.87 |
Aromatic cofactor-binding glycine loop |
| 4 | 7714 |
0.74 |
C-terminal cofactor-binding tails |
| 5 | 9248 |
0.70 |
Beta-sheet strand-turn motif |
| 6 | 5217 |
0.65 |
Ligand-binding cleft rim module |
| 7 | 7803 |
0.48 |
N-terminal domain-cap scaffold |
| 8 | 5515 |
0.48 |
Trp/Pro-rich beta-strand motif |
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_214594.1)
- Domains: Pfam-A via hmmscan --cut_ga — Pyridox_ox_2 (PF12900.14)
- 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
COG3467
- Curated reference: UniProt
P9WMA5
(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 —
47 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000090|Rv0080|
MSPGSRRASPQSAREVVELDRDEAMRLLASVDHGRVVFTRAALPAIRPVNHLVVDGRVIVRTRLTAKVSVAVRSSADAGVVVAYEADDLDPRRRTGWSVVVTGLATEVSDPEQVARYQRLLHPWVNMAMDTVVAIEPEIVTGIRIVADSRTP
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