adhA Family assigned · medium auto-curated

H37Rv Rv1862 · MTBC0 mtbc0_001975 · 346 aa · 2127583–2128623 (+) · RefSeq NP_216378.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)alcohol dehydrogenase A
MTBC0 PGAP re-annotationzinc-binding alcohol dehydrogenase family protein
Revised (this work)Zinc-binding alcohol dehydrogenase family protein. Pfam: ADH_N (PF08240.18).

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

Curated reference (UniProt)

UniProt P9WQC1 SwissProt · reviewed · Evidence at protein level
UniProt nameProbable alcohol dehydrogenase AdhA
EC (curated) EC 1.1.1.1

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred nameadhA
eggNOG descriptionalcohol dehydrogenase
Orthologous groupCOG1064
EC number EC 1.1.1.1
KEGG orthology K13953
KEGG pathways map00010, map00071, map00350, map00625, map00626, map00830, map00980, map00982, map01100, map01110, map01120, map01130, map01220

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 0.291 · purifying
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 4 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
ADH_NPF08240.18 1.0e-2638–152 Alcohol dehydrogenase GroES-like domain

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

Closest characterised functional partner: Rv1861 (transmembrane protein), high confidence from genomic context alone (score 797 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3293 pcd piperideine-6-carboxylic acid dehydrogenase 920 915 database:900
Rv0458 aldehyde dehydrogenase 919 914 database:900
Rv0223c aldehyde dehydrogenase 919 914 database:900
Rv0147 aldehyde dehydrogenase 919 914 database:900
Rv0768 aldA aldehyde dehydrogenase AldA 918 914 database:900
Rv3170 aofH flavin-containing monoamine oxidase 904 905 database:900
Rv1703c methyltransferase 907 904 database:900
Rv1833c dhmA2 haloalkane dehalogenase 904 904 database:900
Rv2296 dhmA1 haloalkane dehalogenase 903 904 database:900
Rv2579 dhaA haloalkane dehalogenase 903 904 database:900
Rv3252c alkB transmembrane alkane 1-monooxygenase AlkB 924 900 database:900
Rv1861 transmembrane protein 796 797 ctx neighborhood:790
Rv0162c adhE1 zinc-type alcohol dehydrogenase subunit E 760 746 ctx cooccurence:594
Rv0853c pdc alpha-keto-acid decarboxylase 635 586 database:500
Rv1859 modC molybdenum ABC transporter ATP-binding protein ModC 550 551 ctx neighborhood:544

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 A
  • MTBC0 PGAP product: zinc-binding alcohol dehydrogenase family protein
  • Pfam (hmmscan --cut_ga): ADH_N PF08240.18 (E=1e-26)
  • (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_216378.1)
  • Domains: Pfam-A via hmmscan --cut_ga — ADH_N (PF08240.18)
  • 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 COG1064
  • Curated reference: UniProt P9WQC1 (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 — 58 functional partner(s); context anchor Rv1861
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001975|Rv1862|adhA
MVSPATTATMSAWQVRRPGPMDTGPLERVTTRVPRPAPSELLVAVHACGVCRTDLHVTEGDLPVHRERVIPGHEVVGEVIEVGSAVGAAAGGEFDRGDRVGIAWLRHTCGVCKYCRRGSENLCPQSRYTGWDADGGYAEFTTVPAAFAHHLPSGYSDSELAPLLCAGIIGYRSLLRTELPPGGRLGLYGFGGSAHITAQVALAQGAEIHVMTRGARARKLALQLGAASAQDAADRPPVPLDAAILFAPVGDLVLPALEALDRGGILAIAGIHLTDIPDLNYQQHLFQERQIRSVTSNTRADARAFFDFAAQHHIEVTTPEYPLGQADRALGDLSAGRIAGAAVLLI