adhD Resolved · high auto-curated
H37Rv Rv3086 · MTBC0 mtbc0_003280 ·
368 aa · 3473145–3474251 (+) ·
RefSeq NP_217602.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | alcohol dehydrogenase D |
|---|---|
| MTBC0 PGAP re-annotation | NDMA-dependent alcohol dehydrogenase |
| Revised (this work) | NDMA-dependent alcohol 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 |
P9WQB9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Putative alcohol dehydrogenase D |
| EC (curated) |
EC 1.1.1.1
|
| Curated function | Required for maintaining the appropriate mycolic acid composition and permeability of the envelope on its exposure to acidic pH. |
UniProt still lists this protein as Putative alcohol dehydrogenase D; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| Preferred name | adhD_1 |
| eggNOG description | alcohol dehydrogenase |
| Orthologous group | COG1062 |
| EC number |
EC 1.1.1.1, EC 1.1.1.284
|
| KEGG orthology |
K00121
|
| KEGG pathways |
map00010, map00071, map00350, map00625, map00626, map00680, map00830, map00980, map00982, map01100, map01110, map01120, map01130, map01200, map01220, map05204
|
| Gene Ontology (19) |
GO:0005575, GO:0005618, GO:0005623, GO:0008150, GO:0009268, GO:0009628, GO:0010447, GO:0030312, GO:0040007, GO:0044110, GO:0044116, GO:0044117 +7 more
|
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 | 0.688 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 2 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.10% of strains (146) · 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
ADH_N | PF08240.18 | 8.7e-28 | 26–155 | Alcohol dehydrogenase GroES-like domain |
ADH_zinc_N | PF00107.33 | 6.1e-24 | 195–327 | Zinc-binding dehydrogenase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mymA (FAD-containing monooxygenase MymA), high confidence from genomic context alone (score 962 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3083 mymA |
FAD-containing monooxygenase MymA | 982 | 962 ctx | neighborhood:721 coexpression:869 textmining:561 |
Rv3084 lipR |
acetyl-hydrolase LipR | 991 | 960 ctx | neighborhood:721 coexpression:862 textmining:803 |
Rv3085 sadH |
oxidoreductase SadH | 991 | 959 ctx | neighborhood:721 coexpression:860 textmining:810 |
Rv3089 fadD13 |
long chain-fatty-acid--CoA ligase FadD13 | 983 | 955 ctx | neighborhood:693 coexpression:860 textmining:650 |
Rv3088 tgs4 |
diacyglycerol O-acyltransferase | 978 | 955 ctx | neighborhood:693 coexpression:860 textmining:546 |
Rv3087 |
diacyglycerol O-acyltransferase | 977 | 953 ctx | neighborhood:675 coexpression:860 textmining:548 |
Rv0233 nrdB |
ribonucleoside-diphosphate reductase subunit beta NrdB | 730 | 730 | coexpression:730 |
Rv0458 |
aldehyde dehydrogenase | 630 | 612 | database:500 |
Rv1639c hyp |
hypothetical protein | 551 | 531 | coexpression:448 |
Rv1886c fbpB |
diacylglycerol acyltransferase/mycolyltransferase Ag85B | 548 | 528 | coexpression:445 |
Rv1288 hyp |
hypothetical protein | 548 | 528 | coexpression:443 |
Rv3045 adhC |
NADP-dependent alcohol dehydrogenase | 553 | 526 | |
Rv3803c fbpD |
MPT51/MPB51 antigen | 546 | 526 | coexpression:443 |
Rv0129c fbpC |
diacylglycerol acyltransferase/mycolyltransferase Ag85C | 546 | 525 | coexpression:442 |
Rv0774c hyp |
hypothetical protein | 545 | 525 | coexpression:441 |
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 D
- MTBC0 PGAP product: NDMA-dependent alcohol dehydrogenase
- Pfam (hmmscan --cut_ga): ADH_N PF08240.18 (E=9e-28), ADH_zinc_N PF00107.33 (E=6e-24)
- (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_217602.1)
- 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
COG1062 - Curated reference: UniProt P9WQB9 (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 —
38 functional partner(s); context anchor
mymA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003280|Rv3086|adhD MKTTAAVLFEAGKPFELMELDLDGPGPGEVLVKYTAAGLCHSDLHLTDGDLPPRFPIVGGHEGSGVIEEVGAGVTRVKPGDHVVCSFIPNCGTCRYCCTGRQNLCDMGATILEGCMPDGSFRFHSQGTDFGAMCMLGTFAERATVSQHSVVKVDDWLPLETAVLVGCGVPSGWGTAVNAGNLRAGDTAVIYGVGGLGINAVQGATAAGCKYVVVVDPVAFKRETALKFGATHAFADAASAAAKVDELTWGQGADAALILVGTVDDEVVSAATAVIGKGGTVVITGLADPAKLTVHVSGTDLTLHEKTIKGSLFGSCNPQYDIVRLLRLYDAGQLMLDELVTTTYNLEQVNQGYQDLRDGKNIRGVIVH