Rv3726 Resolved · high auto-curated
H37Rv Rv3726 · MTBC0 mtbc0_003951 ·
397 aa · 4195542–4196735 (+) ·
RefSeq NP_218243.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | dehydrogenase |
|---|---|
| MTBC0 PGAP re-annotation | zinc-binding dehydrogenase |
| Revised (this work) | Zinc-binding dehydrogenase. 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 |
O69693
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Possible dehydrogenase |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| Preferred name | adhE2_1 |
| eggNOG description | Dehydrogenase |
| Orthologous group | COG1063 |
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 | 2.437 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 7 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.18% of strains (256) · 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 | 6.0e-11 | 23–136 | Alcohol dehydrogenase GroES-like domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: adh (alcohol dehydrogenase), high confidence from genomic context alone (score 739 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1530 adh |
alcohol dehydrogenase | 738 | 739 ctx | cooccurence:738 |
Rv3086 adhD |
alcohol dehydrogenase D | 513 | 493 ctx | cooccurence:425 |
Rv0162c adhE1 |
zinc-type alcohol dehydrogenase subunit E | 511 | 491 ctx | cooccurence:426 |
Rv3725 |
oxidoreductase | 476 | 454 ctx | neighborhood:427 |
Rv1569 bioF1 |
8-amino-7-oxononanoate synthase | 486 | 453 | coexpression:422 |
Rv0032 bioF2 |
8-amino-7-oxononanoate synthase | 486 | 453 | coexpression:422 |
Rv1862 adhA |
alcohol dehydrogenase A | 475 | 450 | |
Rv1194c hyp |
hypothetical protein | 438 | 439 ctx | cooccurence:436 |
Rv2370c hyp |
hypothetical protein | 438 | 438 ctx | cooccurence:433 |
Rv1453 |
transcriptional activator protein | 436 | 437 ctx | cooccurence:431 |
Rv0761c adhB |
alcohol dehydrogenase B | 453 | 430 | |
Rv3846 sodA |
superoxide dismutase | 455 | 429 | coexpression:428 |
Rv3727 |
oxidoreductase | 417 | 417 ctx | neighborhood:415 |
Rv1326c glgB |
1,4-alpha-glucan branching protein | 444 | 412 | coexpression:405 |
Rv1562c treZ |
malto-oligosyltrehalose trehalohydrolase | 443 | 411 | coexpression:404 |
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: dehydrogenase
- MTBC0 PGAP product: zinc-binding dehydrogenase
- Pfam (hmmscan --cut_ga): ADH_N PF08240.18 (E=6e-11)
- (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_218243.1)
- 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
COG1063 - Curated reference: UniProt O69693 (TrEMBL, unreviewed; 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 —
19 functional partner(s); context anchor
adh - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003951|Rv3726| MKAVTCTNAKLEVVDRPSPAPAKGQLLLDVLRCGICGSDLHARLHCDELADVMAESGYHAFMRSNQQVVFGHEFCGEVVDYGPGTRRTPRRGTPVVAMPLLRRGNKEVHGIGLSTMAPGAYAERLVVEQSLTFPVPNGLAPEIAALTEPMAVGWHAVRRGEVGKGDVAIVIGCGPIGLAVICMLKSRGVHTVIASDFSPGRRALATACGADSVVDPVQDSPYAVAAGLGQGNRHLQSILDAFDLAVGTVERLQRLRLPWWHLWRAAEAAGAATPKRPVIFECVGVPGIIDGIIASAPLFSRVVVVGVCMGSDHIRPAMAINKEINLRFVLGYTPLEFRDTLHMLADGKVNAAPLITGTVGLPGVAAAFDALGDPEAHAKIMIDPKSNAASPQPFRVE