lpdC Resolved · high auto-curated
H37Rv Rv0462 · MTBC0 mtbc0_000486 ·
464 aa · 555979–557373 (+) ·
RefSeq NP_214976.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | dihydrolipoamide dehydrogenase |
|---|---|
| MTBC0 PGAP re-annotation | dihydrolipoyl dehydrogenase |
| Revised (this work) | Dihydrolipoyl dehydrogenase. Pfam: Pyr_redox_2 (PF07992.21), FAD_oxidored (PF12831.14), GIDA (PF01134.29), FAD_binding_2 (PF00890.31), 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 |
P9WHH9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Dihydrolipoyl dehydrogenase |
| EC (curated) |
EC 1.8.1.4
|
| Curated function | Lipoamide dehydrogenase is an essential component of the alpha-ketoacid dehydrogenase complexes, namely the pyruvate dehydrogenase (PDH) complex, the branched-chain alpha-ketoacid dehydrogenase (BCKADH) complex, and likely also the 2-oxoglutarate dehydrogenase (ODH) complex. Catalyzes the reoxidation of dihydrolipoyl groups which are covalently attached to the lipoate acyltransferase components (E2) of the complexes. Is also able to catalyze the transhydrogenation of NADH and thio-NAD(+) in the absence of D,L-lipoamide, and the NADH-dependent reduction of quinones in vitro.; FUNCTION: Together. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| Preferred name | lpd |
| eggNOG description | 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 (53) |
GO:0000166, GO:0003674, GO:0003824, GO:0004148, GO:0005488, GO:0005515, GO:0005575, GO:0005576, GO:0005622, GO:0005623, GO:0005737, GO:0005829 +41 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 | 0.551 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 5 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 |
|---|---|---|---|---|
Pyr_redox_2 | PF07992.21 | 2.3e-67 | 4–324 | Pyridine nucleotide-disulphide oxidoreductase |
FAD_oxidored | PF12831.14 | 1.7e-07 | 5–39 | FAD dependent oxidoreductase |
GIDA | PF01134.29 | 7.0e-06 | 5–60 | Glucose inhibited division protein A |
FAD_binding_2 | PF00890.31 | 4.2e-05 | 5–34 | FAD binding domain |
Pyr_redox | PF00070.34 | 2.9e-20 | 174–250 | Pyridine nucleotide-disulphide oxidoreductase |
Pyr_redox_dim | PF02852.29 | 5.0e-35 | 346–452 | Pyridine nucleotide-disulphide oxidoreductase, dimerisation domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: dlaT (pyruvate dehydrogenase E2 component dihydrolipoamide acyltransferase), high confidence from genomic context alone (score 995 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 | 1000 | coexpression:756 experimental:970 database:954 textmining:776 |
Rv2215 dlaT |
pyruvate dehydrogenase E2 component dihydrolipoamide acyltransferase | 999 | 995 ctx | cooccurence:546 coexpression:476 experimental:443 database:955 textmining:827 |
Rv2496c bkdB |
3-methyl-2-oxobutanoate dehydrogenase subunit beta | 996 | 995 | coexpression:647 experimental:465 database:960 |
Rv2495c bkdC |
branched-chain keto acid dehydrogenase E2 component | 995 | 995 ctx | cooccurence:617 coexpression:454 experimental:443 database:955 |
Rv2497c bkdA |
3-methyl-2-oxobutanoate dehydrogenase subunit alpha | 989 | 985 | coexpression:500 database:956 |
Rv1826 gcvH |
glycine cleavage system protein H | 983 | 976 | database:961 |
Rv2211c gcvT |
aminomethyltransferase | 976 | 974 | database:955 |
Rv2241 aceE |
pyruvate dehydrogenase E1 component | 986 | 945 | coexpression:436 database:900 textmining:764 |
Rv1832 gcvB |
glycine dehydrogenase | 942 | 920 | database:900 |
Rv1093 glyA1 |
serine hydroxymethyltransferase | 921 | 917 | database:900 |
Rv0070c glyA2 |
serine hydroxymethyltransferase | 919 | 915 | database:900 |
Rv2455c korA |
2-oxoglutarate oxidoreductase subunit KorA | 929 | 905 | database:900 |
Rv0400c fadE7 |
acyl-CoA dehydrogenase FadE7 | 906 | 905 | database:900 |
Rv2454c korB |
2-oxoglutarate oxidoreductase subunit KorB | 917 | 901 | database:900 |
Rv0463 |
membrane protein | 889 | 889 ctx | neighborhood:882 |
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: dihydrolipoamide dehydrogenase
- MTBC0 PGAP product: dihydrolipoyl dehydrogenase
- Pfam (hmmscan --cut_ga): Pyr_redox_2 PF07992.21 (E=2e-67), FAD_oxidored PF12831.14 (E=2e-07), GIDA PF01134.29 (E=7e-06), FAD_binding_2 PF00890.31 (E=4e-05), Pyr_redox PF00070.34 (E=3e-20), Pyr_redox_dim PF02852.29 (E=5e-35)
- (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_214976.1)
- 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 (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 P9WHH9 (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 —
123 functional partner(s); context anchor
dlaT - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000486|Rv0462|lpdC MTHYDVVVLGAGPGGYVAAIRAAQLGLSTAIVEPKYWGGVCLNVGCIPSKALLRNAELVHIFTKDAKAFGISGEVTFDYGIAYDRSRKVAEGRVAGVHFLMKKNKITEIHGYGTFADANTLLVDLNDGGTESVTFDNAIIATGSSTRLVPGTSLSANVVTYEEQILSRELPKSIIIAGAGAIGMEFGYVLKNYGVDVTIVEFLPRALPNEDADVSKEIEKQFKKLGVTILTATKVESIADGGSQVTVTVTKDGVAQELKAEKVLQAIGFAPNVEGYGLDKAGVALTDRKAIGVDDYMRTNVGHIYAIGDVNGLLQLAHVAEAQGVVAAETIAGAETLTLGDHRMLPRATFCQPNVASFGLTEQQARNEGYDVVVAKFPFTANAKAHGVGDPSGFVKLVADAKHGELLGGHLVGHDVAELLPELTLAQRWDLTASELARNVHTHPTMSEALQECFHGLVGHMINF