Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | pyridine nucleotide transhydrogenase |
|---|
| MTBC0 PGAP re-annotation | Si-specific NAD(P)(+) transhydrogenase |
|---|
| Revised (this work) | Si-specific NAD(P)(+) transhydrogenase. Pfam: Pyr_redox_2 (PF07992.21), FAD_oxidored (PF12831.14), GIDA (PF01134.29), FAD_binding_2 (PF00890.31), Pyr_redox_3 (PF13738.13), Pyr_redox (PF00070.34), Pyr_redox_dim (PF02852.29). |
|---|
Auto-curated: this verdict and function were generated by rules from
PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WHH5
SwissProt · reviewed
· Evidence at protein level
|
|---|
| UniProt name | Probable soluble pyridine nucleotide transhydrogenase |
|---|
| EC (curated) |
EC 1.6.1.1
|
|---|
| Curated function | Conversion of NADPH, generated by peripheral catabolic pathways, to NADH, which can enter the respiratory chain for energy generation. |
|---|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|
| Preferred name | sthA |
|---|
| eggNOG description | pyridine |
|---|
| Orthologous group | COG1249 |
|---|
| EC number |
EC 1.6.1.1
|
|---|
| KEGG orthology |
K00322
|
|---|
| KEGG pathways |
map00760, map01100
|
|---|
| Gene Ontology (13) |
GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0016020, GO:0030312, GO:0044424, GO:0044444, GO:0044464 +1 more
|
|---|
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 |
0.468 · purifying
|
|---|
| Polymorphic sites (≥ 0.1% of strains) |
5 synonymous, 6 missense, 1 nonsense, 1 frameshift
|
|---|
| Disruption |
2 distinct premature-stop/frameshift site(s); most common in
0.61% of strains
(891) · 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 |
|---|
Pyr_redox_2 | PF07992.21 |
1.6e-60 | 4–325 |
Pyridine nucleotide-disulphide oxidoreductase |
FAD_oxidored | PF12831.14 |
8.4e-11 | 5–74 |
FAD dependent oxidoreductase |
GIDA | PF01134.29 |
1.9e-04 | 5–147 |
Glucose inhibited division protein A |
FAD_binding_2 | PF00890.31 |
1.6e-04 | 5–40 |
FAD binding domain |
Pyr_redox_3 | PF13738.13 |
1.0e-07 | 132–309 |
Pyridine nucleotide-disulphide oxidoreductase |
Pyr_redox | PF00070.34 |
7.7e-20 | 178–252 |
Pyridine nucleotide-disulphide oxidoreductase |
Pyr_redox_dim | PF02852.29 |
4.6e-25 | 345–453 |
Pyridine nucleotide-disulphide oxidoreductase, dimerisation domain |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|
Rv1248c kgd |
multifunctional 2-oxoglutarate dehydrogenase E1 component /2-oxoglutarate dehydrogenase dihydrolipoyllysine-residue succinyltransferase |
999 |
999 |
coexpression:754 experimental:970 database:844 |
Rv2496c bkdB |
3-methyl-2-oxobutanoate dehydrogenase subunit beta |
955 |
937 |
coexpression:645 experimental:465 database:617 |
Rv2438c nadE |
glutamine-dependent NAD(+) synthetase |
932 |
924 |
database:919 |
Rv1151c cobB |
NAD-dependent protein deacylase |
919 |
914 |
database:900 |
Rv2215 dlaT |
pyruvate dehydrogenase E2 component dihydrolipoamide acyltransferase |
943 |
907 |
coexpression:454 experimental:443 database:565 textmining:416 |
Rv0157 pntB |
NAD(P) transhydrogenase subunit beta PntB |
963 |
901 |
database:900 textmining:642 |
Rv1695 ppnK |
inorganic polyphosphate/ATP-NAD kinase |
907 |
901 |
database:900 |
Rv2421c nadD |
nicotinate-nucleotide adenylyltransferase |
904 |
901 |
database:900 |
Rv0156 pntAb |
NAD(P) transhydrogenase subunit alpha PntAb |
980 |
900 |
database:900 textmining:813 |
Rv0155 pntAa |
NAD(P) transhydrogenase subunit alpha PntAa |
965 |
900 |
database:900 textmining:670 |
Rv3199c nudC |
NADH pyrophosphatase |
910 |
900 |
database:900 |
Rv0212c nadR |
transcriptional regulator NadR |
900 |
900 |
database:900 |
Rv2495c bkdC |
branched-chain keto acid dehydrogenase E2 component |
905 |
898 |
coexpression:451 experimental:443 database:565 |
Rv1734c hyp |
hypothetical protein |
874 |
864 |
coexpression:454 experimental:443 database:565 |
Rv0843 |
dehydrogenase |
851 |
818 |
coexpression:500 database:580 |
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: pyridine nucleotide transhydrogenase
- MTBC0 PGAP product: Si-specific NAD(P)(+) transhydrogenase
- Pfam (hmmscan --cut_ga): Pyr_redox_2 PF07992.21 (E=2e-60), FAD_oxidored PF12831.14 (E=8e-11), GIDA PF01134.29 (E=2e-04), FAD_binding_2 PF00890.31 (E=2e-04), Pyr_redox_3 PF13738.13 (E=1e-07), Pyr_redox PF00070.34 (E=8e-20), Pyr_redox_dim PF02852.29 (E=5e-25)
- (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_217229.1)
- Domains: Pfam-A via hmmscan --cut_ga — Pyr_redox_2 (PF07992.21), FAD_oxidored (PF12831.14), GIDA (PF01134.29), FAD_binding_2 (PF00890.31), Pyr_redox_3 (PF13738.13), Pyr_redox (PF00070.34), Pyr_redox_dim (PF02852.29)
- 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
COG1249
- Curated reference: UniProt
P9WHH5
(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 —
90 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002887|Rv2713|sthA
MREYDIVVIGSGPGGQKAAIASAKLGKSVAIVERGRMLGGVCVNTGTIPSKTLREAVLYLTGMNQRELYGASYRVKDRITPADLLARTQHVIGKEVDVVRNQLMRNRVDLIVGHGRFIDPHTILVEDQARREKTTVTGDYIIIATGTRPARPSGVEFDEERVLDSDGILDLKSLPSSMVVVGAGVIGIEYASMFAALGTKVTVVEKRDNMLDFCDPEVVEALKFHLRDLAVTFRFGEEVTAVDVGSAGTVTTLASGKQIPAETVMYSAGRQGQTDHLDLHNAGLEVQGRGRIFVDDRFQTKVDHIYAVGDVIGFPALAATSMEQGRLAAYHAFGEPTDGITELQPIGIYSIPEVSYVGATEVELTKSSIPYEVGVARYRELARGQIAGDSYGMLKLLVSTEDLKLLGVHIFGTSATEMVHIGQAVMGCGGSVEYLVDAVFNYPTFSEAYKNAALDVMNKMRALNQFRR
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