bkdC Family assigned · medium auto-curated
H37Rv Rv2495c · MTBC0 mtbc0_002657 ·
393 aa · 2831648–2832829 (-) ·
RefSeq NP_217011.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | branched-chain keto acid dehydrogenase E2 component |
|---|---|
| MTBC0 PGAP re-annotation | dihydrolipoamide acetyltransferase family protein |
| Revised (this work) | Dihydrolipoamide acetyltransferase family protein. Pfam: Biotin_lipoyl (PF00364.29), E3_binding (PF02817.23), 2-oxoacid_dh (PF00198.29). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O06159
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Dihydrolipoyllysine-residue acyltransferase component of branched-chain alpha-ketoacid dehydrogenase complex |
| EC (curated) |
EC 2.3.1.168
|
| 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). The E2 subunit accepts, and transfers to coenzyme A, acyl groups that are generated by the branched-chain alpha-keto acid decarboxylase component (By similarity). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| Preferred name | pdhC |
| eggNOG description | Dihydrolipoamide acetyltransferase component of pyruvate dehydrogenase complex |
| Orthologous group | COG0508 |
| EC number |
EC 2.3.1.12
|
| KEGG orthology |
K00627
|
| KEGG pathways |
map00010, map00020, map00620, map01100, map01110, map01120, map01130, map01200
|
| KEGG modules |
M00307
|
| Gene Ontology (8) |
GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0016020, GO:0030312, GO:0044464, GO:0071944
|
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 | 0.37 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 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 |
|---|---|---|---|---|
Biotin_lipoyl | PF00364.29 | 3.9e-17 | 10–81 | Biotin-requiring enzyme |
E3_binding | PF02817.23 | 6.8e-12 | 118–154 | e3 binding domain |
2-oxoacid_dh | PF00198.29 | 2.0e-69 | 167–391 | 2-oxoacid dehydrogenases acyltransferase (catalytic domain) |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: bkdB (3-methyl-2-oxobutanoate dehydrogenase subunit beta), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2496c bkdB |
3-methyl-2-oxobutanoate dehydrogenase subunit beta | 999 | 1000 ctx | neighborhood:882 cooccurence:773 coexpression:940 experimental:773 database:961 textmining:697 |
Rv2497c bkdA |
3-methyl-2-oxobutanoate dehydrogenase subunit alpha | 999 | 1000 ctx | neighborhood:879 cooccurence:773 coexpression:925 experimental:415 database:957 textmining:720 |
Rv0462 lpdC |
dihydrolipoamide dehydrogenase | 995 | 995 ctx | cooccurence:617 coexpression:454 experimental:443 database:955 |
Rv2241 aceE |
pyruvate dehydrogenase E1 component | 984 | 978 | coexpression:629 experimental:439 database:900 |
Rv0843 |
dehydrogenase | 983 | 978 ctx | cooccurence:772 coexpression:599 experimental:415 database:591 |
Rv2501c accA1 |
acetyl/propionyl-CoA carboxylase subuit alpha | 983 | 977 ctx | neighborhood:723 database:900 |
Rv1248c kgd |
multifunctional 2-oxoglutarate dehydrogenase E1 component /2-oxoglutarate dehydrogenase dihydrolipoyllysine-residue succinyltransferase | 977 | 976 | coexpression:673 experimental:770 database:625 |
Rv0896 gltA2 |
citrate synthase 1 | 961 | 955 | coexpression:424 database:900 |
Rv0889c citA |
citrate synthase 2 | 961 | 955 | coexpression:424 database:900 |
Rv1131 prpC |
methylcitrate synthase PrpC | 958 | 955 | coexpression:424 database:900 |
Rv3303c lpdA |
NAD(P)H quinone reductase LpdA | 953 | 951 ctx | cooccurence:663 coexpression:453 experimental:443 database:565 |
Rv0951 sucC |
succinyl-CoA ligase subunit beta | 955 | 941 | coexpression:662 database:800 |
Rv0408 pta |
phosphate acetyltransferase | 955 | 939 | database:900 |
Rv0952 sucD |
succinyl-CoA ligase subunit alpha | 950 | 937 | coexpression:648 database:800 |
Rv3285 accA3 |
bifunctional protein acetyl-/propionyl-CoA carboxylase subunit alpha AccA | 923 | 920 | 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: branched-chain keto acid dehydrogenase E2 component
- MTBC0 PGAP product: dihydrolipoamide acetyltransferase family protein
- Pfam (hmmscan --cut_ga): Biotin_lipoyl PF00364.29 (E=4e-17), E3_binding PF02817.23 (E=7e-12), 2-oxoacid_dh PF00198.29 (E=2e-69)
- (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_217011.1)
- Domains: Pfam-A via hmmscan --cut_ga — Biotin_lipoyl (PF00364.29), E3_binding (PF02817.23), 2-oxoacid_dh (PF00198.29)
- 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
COG0508 - Curated reference: UniProt O06159 (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 —
142 functional partner(s); context anchor
bkdB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002657|Rv2495c|bkdC MSGEDSIRSFPVPDLGEGLQEVTVTCWSVAVGDDVEINQTLCSVETAKAEVEIPSPYAGRIVELGGAEGDVLKVGAELVRIDTGPTAVAQPNGEGAVPTLVGYGADAAIETSRRTSRPLAAPVVRKLAKELAVDLAALQRGSGAGGVITRADVLAAARGGVGAGPDVRPVHGVHARMAEKMTLSHKEIPTAKASVEVICAELLRLRDRFVSAAPEITPFALTLRLLVIALKHNVILNSTWVDSGEGPQVHVHRGVHLGFGAATERGLLVPVVTDAQDKNTRELASRVAELITGAREGTLTPAELRGSTFTVSNFGALGVDDGVPVINHPEAAILGLGAIKPRPVVVGGEVVARPTMTLTCVFDHRVVDGAQVAQFMCELRDLIESPETALLDL