hsaG Resolved · high auto-curated

H37Rv Rv3535c · MTBC0 mtbc0_003752 · 303 aa · 3997266–3998177 (-) · RefSeq NP_218052.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)acetaldehyde dehydrogenase
MTBC0 PGAP re-annotationacetaldehyde dehydrogenase (acetylating)
Revised (this work)Acetaldehyde dehydrogenase (acetylating). Pfam: AcetDehyd-dimer (PF09290.17).

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

Curated reference (UniProt)

UniProt P9WQH3 SwissProt · reviewed · Evidence at protein level
UniProt namePropanal dehydrogenase
EC (curated) EC 1.2.1.10, EC 1.2.1.87
Curated functionInvolved in cholesterol degradation. Catalyzes the conversion of propanal to propanoyl-CoA, using NAD(+) and coenzyme A. Has a broad substrate specificity, and can also use acetaldehyde, butyrlaldehyde, isobutyrlaldehyde and pentaldehyde as substrates.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category Q Secondary metabolites biosynthesis, transport and catabolism
Preferred namehsaG
eggNOG descriptionCatalyzes the conversion of acetaldehyde to acetyl-CoA, using NAD( ) and coenzyme A. Is the final enzyme in the meta- cleavage pathway for the degradation of aromatic compounds
Orthologous groupCOG4569
EC number EC 1.2.1.10
KEGG orthology K04073
KEGG pathways map00360, map00362, map00620, map00621, map00622, map00650, map01100, map01120, map01220
KEGG modules M00545, M00569
Gene Ontology (9) GO:0003674, GO:0003824, GO:0008150, GO:0008152, GO:0008774, GO:0016491, GO:0016620, GO:0016903, GO:0055114

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 0.348 · purifying
Polymorphic sites (≥ 0.1% of strains) 3 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
AcetDehyd-dimerPF09290.17 1.2e-60127–272 Prokaryotic acetaldehyde dehydrogenase, dimerisation

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

Closest characterised functional partner: hsaF (4-hydroxy-2-oxovalerate aldolase), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3534c hsaF 4-hydroxy-2-oxovalerate aldolase 999 1000 ctx neighborhood:881 cooccurence:774 coexpression:802 experimental:999 database:900 textmining:932
Rv3469c mhpE 4-hydroxy-2-oxovalerate aldolase MhpE 999 1000 ctx cooccurence:774 experimental:987 database:900
Rv3536c hsaE hydratase 999 996 ctx neighborhood:879 cooccurence:772 coexpression:852 textmining:828
Rv3710 leuA 2-isopropylmalate synthase 985 984 experimental:788 database:900
Rv3546 fadA5 acetyl-CoA acetyltransferase FadA 936 906 database:900
Rv0768 aldA aldehyde dehydrogenase AldA 911 906 database:900
Rv0223c aldehyde dehydrogenase 909 905 database:900
Rv0147 aldehyde dehydrogenase 915 904 database:900
Rv0458 aldehyde dehydrogenase 913 904 database:900
Rv3293 pcd piperideine-6-carboxylic acid dehydrogenase 908 904 database:900
Rv3523 ltp3 lipid carrier protein 954 901 database:900 textmining:563
Rv0859 fadA acyltransferase 914 901 database:900
Rv2501c accA1 acetyl/propionyl-CoA carboxylase subuit alpha 905 901 database:900
Rv2455c korA 2-oxoglutarate oxidoreductase subunit KorA 905 901 database:900
Rv1867 hyp hypothetical protein 905 901 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: acetaldehyde dehydrogenase
  • MTBC0 PGAP product: acetaldehyde dehydrogenase (acetylating)
  • Pfam (hmmscan --cut_ga): AcetDehyd-dimer PF09290.17 (E=1e-60)
  • (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_218052.1)
  • Domains: Pfam-A via hmmscan --cut_ga — AcetDehyd-dimer (PF09290.17)
  • 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 COG4569
  • Curated reference: UniProt P9WQH3 (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 — 48 functional partner(s); context anchor hsaF
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003752|Rv3535c|hsaG
MPSKAKVAIVGSGNISTDLLYKLLRSEWLEPRWMVGIDPESDGLARAAKLGLETTHEGVDWLLAQPDKPDLVFEATSAYVHRDAAPKYAEAGIRAIDLTPAAVGPAVIPPANLREHLDAPNVNMITCGGQATIPIVYAVSRIVEVPYAEIVASVASVSAGPGTRANIDEFTKTTARGVQTIGGAARGKAIIILNPADPPMIMRDTIFCAIPTDADREAIAASIHDVVKEVQTYVPGYRLLNEPQFDEPSINSGGQALVTTFVEVEGAGDYLPPYAGNLDIMTAAATKVGEEIAKETLVVGGAR