bkdA Family assigned · medium auto-curated
H37Rv Rv2497c · MTBC0 mtbc0_002659 ·
367 aa · 2833883–2834986 (-) ·
RefSeq NP_217013.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | 3-methyl-2-oxobutanoate dehydrogenase subunit alpha |
|---|---|
| MTBC0 PGAP re-annotation | pyruvate dehydrogenase (acetyl-transferring) E1 component subunit alpha |
| Revised (this work) | Pyruvate dehydrogenase (acetyl-transferring) E1 component subunit alpha. Pfam: E1_dh (PF00676.26), DXP_synthase_N (PF13292.12). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WIS3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | 3-methyl-2-oxobutanoate dehydrogenase subunit alpha |
| EC (curated) |
EC 1.2.4.4
|
| Curated function | Component of the branched-chain alpha-keto dehydrogenase complex, which catalyzes the overall conversion of alpha-keto acids derived from the branched-chain amino-acids valine, leucine and isoleucine to acyl-CoA and CO(2). The complex contains multiple copies of three enzymatic components: branched-chain alpha-keto acid decarboxylase (E1), lipoamide acyltransferase (E2) and lipoamide dehydrogenase (E3) (By similarity). The E1 subunit catalyzes the first step with the decarboxylation of the alpha-ketoacid forming an enzyme-product intermediate (By similarity). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| Preferred name | pdhA |
| eggNOG description | Dehydrogenase E1 component |
| Orthologous group | COG1071 |
| EC number |
EC 1.2.4.1, EC 1.2.4.4
|
| KEGG orthology |
K00161, K00166
|
| KEGG pathways |
map00010, map00020, map00280, map00620, map00640, map01100, map01110, map01120, map01130, map01200, map04066, map04922, map05230
|
| KEGG modules |
M00036, M00307
|
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 | 0.332 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 1 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 |
|---|---|---|---|---|
E1_dh | PF00676.26 | 6.9e-86 | 48–332 | Dehydrogenase E1 component |
DXP_synthase_N | PF13292.12 | 6.1e-06 | 148–208 | 1-deoxy-D-xylulose-5-phosphate synthase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: bkdC (branched-chain keto acid dehydrogenase E2 component), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2495c bkdC |
branched-chain keto acid dehydrogenase E2 component | 999 | 1000 ctx | neighborhood:879 cooccurence:773 coexpression:925 experimental:415 database:957 textmining:720 |
Rv2496c bkdB |
3-methyl-2-oxobutanoate dehydrogenase subunit beta | 999 | 1000 ctx | neighborhood:879 fusion:900 cooccurence:774 coexpression:942 experimental:829 database:965 textmining:682 |
Rv0462 lpdC |
dihydrolipoamide dehydrogenase | 989 | 985 | coexpression:500 database:956 |
Rv2215 dlaT |
pyruvate dehydrogenase E2 component dihydrolipoamide acyltransferase | 981 | 974 ctx | cooccurence:746 coexpression:603 experimental:415 database:591 |
Rv1248c kgd |
multifunctional 2-oxoglutarate dehydrogenase E1 component /2-oxoglutarate dehydrogenase dihydrolipoyllysine-residue succinyltransferase | 975 | 962 | coexpression:600 experimental:415 database:844 |
Rv2332 mez |
malate oxidoreductase | 932 | 907 | database:900 |
Rv1734c hyp |
hypothetical protein | 930 | 907 | coexpression:598 experimental:415 database:591 |
Rv1617 pykA |
pyruvate kinase | 923 | 907 | database:900 |
Rv2967c pca |
pyruvate carboxylase | 910 | 906 | database:900 |
Rv2455c korA |
2-oxoglutarate oxidoreductase subunit KorA | 949 | 905 | database:900 textmining:497 |
Rv2241 aceE |
pyruvate dehydrogenase E1 component | 970 | 904 | database:900 textmining:703 |
Rv1127c ppdK |
pyruvate, phosphate dikinase PpdK | 911 | 904 | database:900 |
Rv0694 mftD |
mycofactocin system heme/flavin oxidoreductase MftD | 906 | 903 | database:900 |
Rv1872c lldD2 |
L-lactate dehydrogenase | 906 | 903 | database:900 |
Rv2454c korB |
2-oxoglutarate oxidoreductase subunit KorB | 926 | 902 | database:900 |
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: 3-methyl-2-oxobutanoate dehydrogenase subunit alpha
- MTBC0 PGAP product: pyruvate dehydrogenase (acetyl-transferring) E1 component subunit alpha
- Pfam (hmmscan --cut_ga): E1_dh PF00676.26 (E=7e-86), DXP_synthase_N PF13292.12 (E=6e-06)
- (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_217013.1)
- Domains: Pfam-A via hmmscan --cut_ga — E1_dh (PF00676.26), DXP_synthase_N (PF13292.12)
- 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
COG1071 - Curated reference: UniProt P9WIS3 (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 —
69 functional partner(s); context anchor
bkdC - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002659|Rv2497c|bkdA MGEGSRRPSGMLMSVDLEPVQLVGPDGTPTAERRYHRDLPEETLRWLYEMMVVTRELDTEFVNLQRQGELALYTPCRGQEAAQVGAAACLRKTDWLFPQYRELGVYLVRGIPPGHVGVAWRGTWHGGLQFTTKCCAPMSVPIGTQTLHAVGAAMAAQRLDEDSVTVAFLGDGATSEGDVHEALNFAAVFTTPCVFYVQNNQWAISMPVSRQTAAPSIAHKAIGYGMPGIRVDGNDVLACYAVMAEAAARARAGDGPTLIEAVTYRLGPHTTADDPTRYRSQEEVDRWATLDPIPRYRTYLQDQGLWSQRLEEQVTARAKHVRSELRDAVFDAPDFDVDEVFTTVYAEITPGLQAQREQLRAELARTD