bkdB Family assigned · medium auto-curated

H37Rv Rv2496c · MTBC0 mtbc0_002658 · 348 aa · 2832826–2833872 (-) · RefSeq NP_217012.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)3-methyl-2-oxobutanoate dehydrogenase subunit beta
MTBC0 PGAP re-annotation3-methyl-2-oxobutanoate dehydrogenase subunit beta
Revised (this work)3-methyl-2-oxobutanoate dehydrogenase subunit beta. Pfam: Transket_pyr (PF02779.30), Transketolase_C (PF02780.26).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt P9WIS1 SwissProt · reviewed · Evidence at protein level
UniProt name3-methyl-2-oxobutanoate dehydrogenase subunit beta
EC (curated) EC 1.2.4.4
Curated functionComponent 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 namepdhB
eggNOG descriptionPyruvate 2-oxoglutarate dehydrogenase complex, dehydrogenase
Orthologous groupCOG0022
EC number EC 1.2.4.1
KEGG orthology K00162
KEGG pathways map00010, map00020, map00620, map01100, map01110, map01120, map01130, map01200, map04066, map04922, map05230
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 1.017 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 3 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)

PfamAccessioni-EvalueResiduesDescription
Transket_pyrPF02779.30 1.5e-3525–199 Transketolase, pyrimidine binding domain
Transketolase_CPF02780.26 1.3e-35215–336 Transketolase, C-terminal domain

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).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2495c bkdC branched-chain keto acid dehydrogenase E2 component 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 fusion:900 cooccurence:774 coexpression:942 experimental:829 database:965 textmining:682
Rv0843 dehydrogenase 999 1000 ctx fusion:899 cooccurence:774 coexpression:728 experimental:829 database:662 textmining:415
Rv1248c kgd multifunctional 2-oxoglutarate dehydrogenase E1 component /2-oxoglutarate dehydrogenase dihydrolipoyllysine-residue succinyltransferase 999 998 coexpression:752 experimental:955 database:844 textmining:430
Rv0462 lpdC dihydrolipoamide dehydrogenase 996 995 coexpression:647 experimental:465 database:960
Rv2215 dlaT pyruvate dehydrogenase E2 component dihydrolipoamide acyltransferase 993 993 ctx cooccurence:753 coexpression:671 experimental:773 database:627
Rv1017c prsA ribose-phosphate pyrophosphokinase 989 987 coexpression:407 experimental:869 database:844
Rv1734c hyp hypothetical protein 984 976 coexpression:670 experimental:773 database:627 textmining:407
Rv3303c lpdA NAD(P)H quinone reductase LpdA 968 958 ctx cooccurence:472 coexpression:645 experimental:465 database:617
Rv2855 mtr mycothione reductase 950 946 coexpression:645 experimental:465 database:617
Rv0794c oxidoreductase 943 939 coexpression:648 experimental:465 database:617
Rv2713 sthA pyridine nucleotide transhydrogenase 955 937 coexpression:645 experimental:465 database:617
Rv2332 mez malate oxidoreductase 947 925 database:900
Rv2967c pca pyruvate carboxylase 926 917 database:900
Rv1617 pykA pyruvate kinase 937 909 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 beta
  • MTBC0 PGAP product: 3-methyl-2-oxobutanoate dehydrogenase subunit beta
  • Pfam (hmmscan --cut_ga): Transket_pyr PF02779.30 (E=1e-35), Transketolase_C PF02780.26 (E=1e-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_217012.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Transket_pyr (PF02779.30), Transketolase_C (PF02780.26)
  • 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 COG0022
  • Curated reference: UniProt P9WIS1 (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 — 114 functional partner(s); context anchor bkdC
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002658|Rv2496c|bkdB
MTQIADRPARPDETLAVAVSDITQSLTMVQAINRALYDAMAADERVLVFGEDVAVEGGVFRVTEGLADTFGADRCFDTPLAESAIIGIAVGLALRGFVPVPEIQFDGFSYPAFDQVVSHLAKYRTRTRGEVDMPVTVRIPSFGGIGAAEHHSDSTESYWVHTAGLKVVVPSTPGDAYWLLRHAIACPDPVMYLEPKRRYHGRGMVDTSRPEPPIGHAMVRRSGTDVTVVTYGNLVSTALSSADTAEQQHDWSLEVIDLRSLAPLDFDTIAASIQRTGRCVVMHEGPRSLGYGAGLAARIQEEMFYQLEAPVLRACGFDTPYPPARLEKLWLPGPDRLLDCVERVLRQP