Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | alkyldihydroxyacetonephosphate synthase |
| MTBC0 PGAP re-annotation | FAD-binding oxidoreductase |
| Revised (this work) | FAD-binding oxidoreductase. Pfam: FAD_binding_4 (PF01565.29), FAD-oxidase_C (PF02913.25). |
Auto-curated: this verdict and function were generated by rules from
PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O05784
TrEMBL · unreviewed
· Evidence at protein level
|
| UniProt name | Possible alkyldihydroxyacetonephosphate synthase AgpS |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
| Preferred name | agpS |
| eggNOG description | FAD linked oxidases, C-terminal domain |
| Orthologous group | COG0277 |
| EC number |
EC 2.5.1.26
|
| KEGG orthology |
K00803
|
| KEGG pathways |
map00565, map01100, map04146
|
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 |
0.423 · purifying
|
| Polymorphic sites (≥ 0.1% of strains) |
5 synonymous, 6 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 |
FAD_binding_4 | PF01565.29 |
3.3e-30 | 94–229 |
FAD binding domain |
FAD-oxidase_C | PF02913.25 |
1.2e-47 | 269–522 |
FAD linked oxidases, C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
Rv2251 |
flavoprotein |
915 |
915 |
database:900 |
Rv1551 plsB1 |
acyltransferase PlsB |
622 |
606 |
database:549 |
Rv2482c plsB2 |
glycerol-3-phosphate acyltransferase |
621 |
605 |
database:549 |
Rv3806c ubiA |
decaprenyl-phosphate phosphoribosyltransferase |
589 |
569 |
database:552 |
Rv1310 atpD |
ATP synthase subunit beta |
573 |
557 |
database:538 |
Rv3108 hyp |
hypothetical protein |
547 |
547 ctx |
neighborhood:545 |
Rv1305 atpE |
ATP synthase subunit C |
536 |
537 |
database:526 |
Rv3633 hyp |
hypothetical protein |
547 |
531 |
database:463 |
Rv1501 hyp |
hypothetical protein |
543 |
526 |
database:463 |
Rv0694 mftD |
mycofactocin system heme/flavin oxidoreductase MftD |
537 |
517 |
|
Rv1872c lldD2 |
L-lactate dehydrogenase |
583 |
514 |
|
Rv3029c fixA |
electron transfer flavoprotein subunit beta |
523 |
500 |
|
Rv3028c fixB |
electron transfer flavoprotein subunit alpha |
521 |
497 |
|
Rv1213 glgC |
glucose-1-phosphate adenylyltransferase |
450 |
451 |
database:434 |
Rv3417c groEL1 |
chaperonin GroEL |
468 |
449 |
|
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: alkyldihydroxyacetonephosphate synthase
- MTBC0 PGAP product: FAD-binding oxidoreductase
- Pfam (hmmscan --cut_ga): FAD_binding_4 PF01565.29 (E=3e-30), FAD-oxidase_C PF02913.25 (E=1e-47)
- (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_217623.1)
- Domains: Pfam-A via hmmscan --cut_ga — FAD_binding_4 (PF01565.29), FAD-oxidase_C (PF02913.25)
- 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
O05784
(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 —
31 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003303|Rv3107c|agpS
MRSWWGWGTVEDALSDQETQALQSRVAALVSGHDLSDHPPPDLTALGLAAPRVSPPASLAALCSSDLVDRAGHARGKAYRDIARNLQGQLDHLPDLIARPRSEQDVIDVLDWCAREGIAVIPYGGGSSVVGGVEPRFDEPVVTVDVTAMSAVLEIDRVSRAARIQAGAFGPSIEHQLRPHDLTLRHFPQSFGFSTLGGWLATRSGGHFATLYTHIDDLTESLRIVTPVGISESRRLPGSGAGPSPDRLFLGSEGTLGIITEAWMRLQHRPRWQVTVSVVFDDWAAAVAATRTIAQAGLYPANCRLLDPAEALLNAGTSVGGGLLVLAFESADHPIDPWLHRAVAITAEHGGTVTAQRSRGTTSDATEHNAAANWRSAFLRMPYQRDALVRRGVIAETFETACTWDGFDTLHAAVTDAARTAIWKVCGTGVVTCRFTHVYPDGPAPYYGIYAGGRWGSLDAQWDEIKAAVSEAISASGGTITHHHAVGRDHRAWYDRQRPDPFAAALRAAKSALDPAGILNPGVLLGR
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