pdc Resolved · high auto-curated

H37Rv Rv0853c · MTBC0 mtbc0_000908 · 560 aa · 952587–954269 (-) · RefSeq NP_215368.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)alpha-keto-acid decarboxylase
MTBC0 PGAP re-annotationalpha-keto-acid decarboxylase
Revised (this work)Alpha-keto-acid decarboxylase. Pfam: TPP_enzyme_N (PF02776.24), TPP_enzyme_M (PF00205.29), TPP_enzyme_C (PF02775.27).

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

Curated reference (UniProt)

UniProt P9WG37 SwissProt · reviewed · Evidence at protein level
UniProt nameAlpha-keto-acid decarboxylase
EC (curated) EC 4.1.1.-
Curated functionDecarboxylates branched-chain and aromatic alpha-keto acids to aldehydes.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category G Carbohydrate transport and metabolism
H Coenzyme transport and metabolism
Preferred namepdc
eggNOG descriptionBelongs to the TPP enzyme family
Orthologous groupCOG3961
EC number EC 4.1.1.74
KEGG orthology K04103, K21431
KEGG pathways map00380, map01100
Gene Ontology (12) GO:0003674, GO:0003824, GO:0005575, GO:0005622, GO:0005623, GO:0005886, GO:0016020, GO:0016829, GO:0016830, GO:0016831, 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 0.697 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 10 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.11% of strains (160) · clonal

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
TPP_enzyme_NPF02776.24 1.3e-2815–124 Thiamine pyrophosphate enzyme, N-terminal TPP binding domain
TPP_enzyme_MPF00205.29 1.3e-08210–326 Thiamine pyrophosphate enzyme, central domain
TPP_enzyme_CPF02775.27 1.4e-20403–539 Thiamine pyrophosphate enzyme, C-terminal TPP binding domain

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: far (fatty-acid-CoA racemase), medium confidence from genomic context alone (score 576 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0856 hyp hypothetical protein 707 707 ctx neighborhood:706
Rv0854 hyp hypothetical protein 624 624 ctx neighborhood:618
Rv1862 adhA alcohol dehydrogenase A 635 586 database:500
Rv0855 far fatty-acid-CoA racemase 576 576 ctx neighborhood:571
Rv0363c fba fructose-bisphosphate aldolase 591 529 coexpression:420
Rv2683 hyp hypothetical protein 512 512 coexpression:453
Rv3086 adhD alcohol dehydrogenase D 547 510 database:500
Rv0857 hyp hypothetical protein 429 429 ctx neighborhood:427
Rv1437 pgk phosphoglycerate kinase 514 406 coexpression:406
Rv1023 eno enolase 472 381
Rv0946c pgi glucose-6-phosphate isomerase 467 337
Rv2332 mez malate oxidoreductase 418 332
Rv1438 tpi triosephosphate isomerase 418 320
Rv3002c ilvN acetolactate synthase small subunit 745 317 textmining:643
Rv0189c ilvD dihydroxy-acid dehydratase 687 252 textmining:599

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: alpha-keto-acid decarboxylase
  • MTBC0 PGAP product: alpha-keto-acid decarboxylase
  • Pfam (hmmscan --cut_ga): TPP_enzyme_N PF02776.24 (E=1e-28), TPP_enzyme_M PF00205.29 (E=1e-08), TPP_enzyme_C PF02775.27 (E=1e-20)
  • (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_215368.1)
  • Domains: Pfam-A via hmmscan --cut_ga — TPP_enzyme_N (PF02776.24), TPP_enzyme_M (PF00205.29), TPP_enzyme_C (PF02775.27)
  • 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 COG3961
  • Curated reference: UniProt P9WG37 (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 — 30 functional partner(s); context anchor far
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000908|Rv0853c|pdc
MTPQKSDACSDPVYTVGDYLLDRLAELGVSEIFGVPGDYNLQFLDHIVAHPTIRWVGSANELNAGYAADGYGRLRGMSAVVTTFGVGELSVTNAIAGSYAEHVPVVHIVGGPTKDAQGTRRALHHSLGDGDFEHFLRISREITCAQANLMPATAGREIDRVLSEVREQKRPGYILLSSDVARFPTEPPAAPLPRYPGGTSPRALSLFTKAAIELIADHQLTVLADLLVHRLQAVKELEALLAADVVPHATLMWGKSLLDESSPNFLGIYAGAASAERVRAAIEGAPVLVTAGVVFTDMVSGFFSQRIDPARTIDIGQYQSSVADQVFAPLEMSAALQALATILTGRGISSPPVVPPPAEPPPAMPARDEPLTQQMVWDRVCSALTPGNVVLADQGTSFYGMADHRLPQGVTFIGQPLWGSIGYTLPAAVGAAVAHPDRRTVLLIGDGAAQLTVQELGTFSREGLSPVIVVVNNDGYTVERAIHGETAPYNDIVSWNWTELPSALGVTNHLAFRAQTYGQLDDALTVAAARRDRMVLVEVVLPRLEIPRLLGQLVGSMAPQ