adh Resolved · high auto-curated

H37Rv Rv1530 · MTBC0 mtbc0_001637 · 367 aa · 1741182–1742285 (+) · RefSeq NP_216046.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)alcohol dehydrogenase
MTBC0 PGAP re-annotationzinc-binding dehydrogenase
Revised (this work)Zinc-binding dehydrogenase. Pfam: ADH_N (PF08240.18), ADH_zinc_N (PF00107.33).

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

Curated reference (UniProt)

UniProt P9WQC3 SwissProt · reviewed · Evidence at protein level
UniProt nameProbable alcohol dehydrogenase adh
EC (curated) EC 1.1.1.1

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
Preferred nameadh
eggNOG descriptionalcohol dehydrogenase
Orthologous groupCOG1063
EC number EC 1.1.1.1, EC 1.1.1.14
KEGG orthology K00001, K00008
KEGG pathways map00010, map00040, map00051, map00071, map00350, map00625, map00626, map00830, map00980, map00982, map01100, map01110, map01120, map01130, map01220
KEGG modules M00014

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 0.668 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 7 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.12% of strains (171) · 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
ADH_NPF08240.18 1.1e-2229–147 Alcohol dehydrogenase GroES-like domain
ADH_zinc_NPF00107.33 1.7e-20193–325 Zinc-binding dehydrogenase

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

Closest characterised functional partner: Rv3726 (dehydrogenase), high confidence from genomic context alone (score 739 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0223c aldehyde dehydrogenase 924 920 database:900
Rv3293 pcd piperideine-6-carboxylic acid dehydrogenase 924 920 database:900
Rv0768 aldA aldehyde dehydrogenase AldA 924 920 database:900
Rv0458 aldehyde dehydrogenase 924 920 database:900
Rv0147 aldehyde dehydrogenase 923 920 database:900
Rv3170 aofH flavin-containing monoamine oxidase 913 908 database:900
Rv1703c methyltransferase 904 905 database:900
Rv1833c dhmA2 haloalkane dehalogenase 906 903 database:900
Rv2579 dhaA haloalkane dehalogenase 906 902 database:900
Rv2296 dhmA1 haloalkane dehalogenase 906 902 database:900
Rv3252c alkB transmembrane alkane 1-monooxygenase AlkB 904 901 database:900
Rv1531 hyp hypothetical protein 833 833 ctx neighborhood:801
Rv3726 dehydrogenase 738 739 ctx cooccurence:738
Rv1529 fadD24 fatty-acid--CoA ligase FadD24 527 528 ctx neighborhood:517
Rv1862 adhA alcohol dehydrogenase A 482 457

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: alcohol dehydrogenase
  • MTBC0 PGAP product: zinc-binding dehydrogenase
  • Pfam (hmmscan --cut_ga): ADH_N PF08240.18 (E=1e-22), ADH_zinc_N PF00107.33 (E=2e-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_216046.1)
  • Domains: Pfam-A via hmmscan --cut_ga — ADH_N (PF08240.18), ADH_zinc_N (PF00107.33)
  • 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 COG1063
  • Curated reference: UniProt P9WQC3 (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 — 40 functional partner(s); context anchor Rv3726
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001637|Rv1530|adh
MSDGAVVRALVLEAPRRLVVRQYRLPRIGDDDALVRVEACGLCGTDHEQYTGELAGGFAFVPGHETVGTIAAIGPRAEQRWGVSAGDRVAVEVFQSCRQCANCRGGEYRRCVRHGLADMYGFIPVDREPGLWGGYAEYQYLAPDSMVLRVAGDLSPEVATLFNPLGAGIRWGVTIPETKPGDVVAVLGPGIRGLCAAAAAKGAGAGFVMVTGLGPRDADRLALAAQFGADLAVDVAIDDPVAALTEQTGGLADVVVDVTAKAPAAFAQAIALARPAGTVVVAGTRGVGSGAPGFSPDVVVFKELRVLGALGVDATAYRAALDLLVSGRYPFASLPRRCVRLEGAEDLLATMAGERDGVPPIHGVLTP