lpdA Resolved · high auto-curated
H37Rv Rv3303c · MTBC0 mtbc0_003511 ·
471 aa · 3711537–3713018 (-) ·
RefSeq NP_217820.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | NAD(P)H quinone reductase LpdA |
|---|---|
| MTBC0 PGAP re-annotation | NAD(P)H-quinone dehydrogenase |
| Revised (this work) | NAD(P)H-quinone dehydrogenase. Pfam: Pyr_redox_2 (PF07992.21), 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 |
P9WHH7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | NAD(P)H dehydrogenase |
| EC (curated) |
EC 1.6.5.2
|
| Curated function | May contribute to virulence by increasing resistance to reactive oxygen intermediates. It can reduce 2,6-dimethyl-1,4-benzoquinone (DMBQ), 5-hydroxy-1,4-naphthaquinone (5-HNQ) and menadione. NADPH is the physiological reductant rather than NADH. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| Preferred name | lpdA |
| eggNOG description | Pyruvate 2-oxoglutarate dehydrogenase complex, dihydrolipoamide dehydrogenase |
| Orthologous group | COG1249 |
| EC number |
EC 1.8.1.4
|
| KEGG orthology |
K00382
|
| KEGG pathways |
map00010, map00020, map00260, map00280, map00620, map00630, map00640, map01100, map01110, map01120, map01130, map01200
|
| KEGG modules |
M00009, M00011, M00036, M00307, M00532
|
| Gene Ontology (25) |
GO:0000166, GO:0003674, GO:0003824, GO:0003955, GO:0005488, GO:0008150, GO:0008152, GO:0009405, GO:0016491, GO:0016651, GO:0016655, GO:0036094 +13 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 | 0.657 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 6 missense, 1 nonsense, 0 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 98.67% of strains (143282) · reference-fixed |
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 | 1.4e-50 | 4–332 | Pyridine nucleotide-disulphide oxidoreductase |
Pyr_redox | PF00070.34 | 1.2e-16 | 184–262 | Pyridine nucleotide-disulphide oxidoreductase |
Pyr_redox_dim | PF02852.29 | 3.0e-25 | 352–461 | Pyridine nucleotide-disulphide oxidoreductase, dimerisation domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: glpD2 (glycerol-3-phosphate dehydrogenase), high confidence from genomic context alone (score 971 excluding text-mining).
| 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:755 experimental:970 database:844 textmining:553 |
Rv3302c glpD2 |
glycerol-3-phosphate dehydrogenase | 983 | 971 ctx | neighborhood:869 coexpression:791 textmining:447 |
Rv2496c bkdB |
3-methyl-2-oxobutanoate dehydrogenase subunit beta | 968 | 958 ctx | cooccurence:472 coexpression:645 experimental:465 database:617 |
Rv2495c bkdC |
branched-chain keto acid dehydrogenase E2 component | 953 | 951 ctx | cooccurence:663 coexpression:453 experimental:443 database:565 |
Rv2215 dlaT |
pyruvate dehydrogenase E2 component dihydrolipoamide acyltransferase | 965 | 924 ctx | cooccurence:468 coexpression:464 experimental:443 database:565 textmining:570 |
Rv2497c bkdA |
3-methyl-2-oxobutanoate dehydrogenase subunit alpha | 899 | 880 ctx | cooccurence:462 coexpression:497 database:580 |
Rv0843 |
dehydrogenase | 877 | 870 ctx | cooccurence:414 coexpression:497 database:580 |
Rv1734c hyp |
hypothetical protein | 866 | 860 | coexpression:451 experimental:443 database:565 |
Rv1826 gcvH |
glycine cleavage system protein H | 857 | 805 ctx | cooccurence:485 database:622 |
Rv0526 |
thioredoxin | 809 | 801 | experimental:410 database:550 |
Rv3300c hyp |
hypothetical protein | 870 | 779 ctx | neighborhood:759 textmining:437 |
Rv1017c prsA |
ribose-phosphate pyrophosphokinase | 793 | 777 | database:615 |
Rv3304 hyp |
hypothetical protein | 951 | 762 ctx | neighborhood:757 textmining:805 |
Rv2211c gcvT |
aminomethyltransferase | 778 | 760 | database:569 |
Rv2874 dipZ |
integral membrane C-type cytochrome biogenesis protein DipZ | 765 | 753 | experimental:410 database:550 |
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: NAD(P)H quinone reductase LpdA
- MTBC0 PGAP product: NAD(P)H-quinone dehydrogenase
- Pfam (hmmscan --cut_ga): Pyr_redox_2 PF07992.21 (E=1e-50), Pyr_redox PF00070.34 (E=1e-16), Pyr_redox_dim PF02852.29 (E=3e-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_217820.1)
- Domains: Pfam-A via hmmscan --cut_ga — Pyr_redox_2 (PF07992.21), 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 P9WHH7 (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 —
109 functional partner(s); context anchor
glpD2 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003511|Rv3303c|lpdA MVTRIVILGGGPAGYEAALVAATSHPETTQVTVIDCDGIGGAAVLDDCVPSKTFIASTGLRTELRRAPHLGFHIDFDDAKISLPQIHARVKTLAAAQSADITAQLLSMGVQVIAGRGELIDSTPGLARHRIKATAADGSTSEHEADVVLVATGASPRILPSAQPDGERILTWRQLYDLDALPDHLIVVGSGVTGAEFVDAYTELGVPVTVVASQDHVLPYEDADAALVLEESFAERGVRLFKNARAASVTRTGAGVLVTMTDGRTVEGSHALMTIGSVPNTSGLGLERVGIQLGRGNYLTVDRVSRTSATGIYAAGDCTGLLPLASVAAMQGRIAMYHALGEGVSPIRLRTVAATVFTRPEIAAVGVPQSVIDAGSVAARTIMLPLRTNARAKMSEMRHGFVKIFCRRSTGVVIGGVVVAPIASELILPIAVAVQNRITVNELAQTLAVYPSLSGSITEAARRLMAHDDLD