Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | oxidoreductase |
|---|
| MTBC0 PGAP re-annotation | FAD-binding oxidoreductase |
|---|
| Revised (this work) | FAD-binding oxidoreductase. Pfam: FAD_binding_4 (PF01565.29), BBE (PF08031.18). |
|---|
Auto-curated: this verdict and function were generated by rules from
PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P71984
TrEMBL · unreviewed
· Inferred from homology
|
|---|
| UniProt name | Probable oxidoreductase |
|---|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|
| eggNOG description | PFAM FAD linked oxidase domain protein |
|---|
| Orthologous group | COG0277 |
|---|
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 |
0.852 · relaxed/neutral
|
|---|
| Polymorphic sites (≥ 0.1% of strains) |
5 synonymous, 12 missense, 0 nonsense, 2 frameshift
|
|---|
| Disruption |
2 distinct premature-stop/frameshift site(s); most common in
0.47% of strains
(686) · 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 |
|---|
FAD_binding_4 | PF01565.29 |
1.4e-28 | 42–175 |
FAD binding domain |
BBE | PF08031.18 |
9.2e-14 | 413–458 |
Berberine and berberine like |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|
Rv1727 hyp |
hypothetical protein |
767 |
767 ctx |
neighborhood:712 |
Rv3177 |
peroxidase |
767 |
767 |
coexpression:767 |
Rv1725c hyp |
hypothetical protein |
712 |
712 ctx |
neighborhood:596 |
Rv2810c |
Probable transposase; Rv2810c, (MTCY16B7.33), len: 133 aa. Probable transposase for IS1555, similar to C-terminal domain of transposases for |
615 |
615 |
coexpression:615 |
Rv1758 cut1 |
cutinase |
615 |
615 |
coexpression:615 |
Rv1551 plsB1 |
acyltransferase PlsB |
621 |
605 |
database:549 |
Rv2482c plsB2 |
glycerol-3-phosphate acyltransferase |
619 |
603 |
database:549 |
Rv1724c hyp |
hypothetical protein |
595 |
596 ctx |
neighborhood:596 |
Rv3806c ubiA |
decaprenyl-phosphate phosphoribosyltransferase |
592 |
571 |
database:552 |
Rv1310 atpD |
ATP synthase subunit beta |
573 |
558 |
database:538 |
Rv1135A |
Rv1135A, len: 80 aa. Possible acetyl-CoA acetyltransferase (possible gene fragment), highly similar to other acetyl-CoA acetyltransferases e |
550 |
546 |
|
Rv1305 atpE |
ATP synthase subunit C |
539 |
539 |
database:526 |
Rv3633 hyp |
hypothetical protein |
545 |
529 |
database:463 |
Rv1501 hyp |
hypothetical protein |
543 |
527 |
database:463 |
Rv0694 mftD |
mycofactocin system heme/flavin oxidoreductase MftD |
536 |
516 |
|
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: oxidoreductase
- MTBC0 PGAP product: FAD-binding oxidoreductase
- Pfam (hmmscan --cut_ga): FAD_binding_4 PF01565.29 (E=1e-28), BBE PF08031.18 (E=9e-14)
- (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_216242.1)
- Domains: Pfam-A via hmmscan --cut_ga — FAD_binding_4 (PF01565.29), BBE (PF08031.18)
- 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
COG0277
- Curated reference: UniProt
P71984
(TrEMBL, unreviewed; Inferred from homology)
- 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 —
50 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001838|Rv1726|
MTATLTKTLGSLDDFRGTLCVPGDPDYPRVRAIWNGQVAREPALIATCHDACDVRTVLRRAVDAGMVTAVRGGGHNVAGTALCDGGVVIDLSAMRAVSLDPATGRVRVQGGATLADLDHATVPFARVAPAGIVTTTGVGGLTLGGGVGWTTRRFGLSCDNLVAVRLVTAAGDYLSVDDERDPELMWGLRGGGGNFGIVTEFEFATHPFGPVAVAGFVVYRLDDGPAVLRGYRQFAAAAPEEVTTIVVLRHAPPAPWIPVDQRGKPVVMIGAVHTGSIQTGIEALRPVKSLARPVADTVWPTPFLAHQAVLDASNPAGHRYYWKSDHLAELNDEAIDLLVEQTAQLSSPDSLIGIFQLGGAAARGGERSCFPSRHARFMVNYATHWTEAREDDLHRQWTRDAIEALAPYGLGTAYVNFTADDAPMHVETLYSTTEFSRLVTLKNRLDPDNVFRNNHNIRPSA
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