mscR Resolved · high auto-curated
H37Rv Rv2259 · MTBC0 mtbc0_002402 ·
361 aa · 2558352–2559437 (+) ·
RefSeq NP_216775.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | S-nitrosomycothiol reductase MscR |
|---|---|
| MTBC0 PGAP re-annotation | S-(hydroxymethyl)mycothiol dehydrogenase |
| Revised (this work) | S-(hydroxymethyl)mycothiol dehydrogenase. Pfam: ADH_N (PF08240.18), ADH_zinc_N (PF00107.33), ADH_zinc_N_2 (PF13602.13). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53533
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | S-nitrosomycothiol reductase MscR |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| Preferred name | adhE2 |
| eggNOG description | alcohol dehydrogenase |
| Orthologous group | COG1062 |
| EC number |
EC 1.1.1.306
|
| KEGG orthology |
K00153
|
| Gene Ontology (6) |
GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0044424, GO:0044464
|
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 | 0.809 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 7 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
ADH_N | PF08240.18 | 1.5e-26 | 28–148 | Alcohol dehydrogenase GroES-like domain |
ADH_zinc_N | PF00107.33 | 2.6e-29 | 190–322 | Zinc-binding dehydrogenase |
ADH_zinc_N_2 | PF13602.13 | 1.2e-08 | 223–354 | Zinc-binding dehydrogenase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv2258c (transcriptional regulator), high confidence from genomic context alone (score 706 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2260 hyp |
hypothetical protein | 959 | 958 ctx | neighborhood:882 cooccurence:633 |
Rv2258c |
transcriptional regulator | 706 | 706 ctx | neighborhood:692 |
Rv2257c hyp |
hypothetical protein | 702 | 703 ctx | neighborhood:689 |
Rv0774c hyp |
hypothetical protein | 548 | 528 | coexpression:445 |
Rv1639c hyp |
hypothetical protein | 547 | 527 | coexpression:444 |
Rv1288 hyp |
hypothetical protein | 547 | 527 | coexpression:442 |
Rv1886c fbpB |
diacylglycerol acyltransferase/mycolyltransferase Ag85B | 547 | 527 | coexpression:444 |
Rv3803c fbpD |
MPT51/MPB51 antigen | 546 | 526 | coexpression:443 |
Rv3804c fbpA |
diacylglycerol acyltransferase/mycolyltransferase Ag85A | 546 | 525 | coexpression:442 |
Rv0129c fbpC |
diacylglycerol acyltransferase/mycolyltransferase Ag85C | 544 | 524 | coexpression:440 |
Rv3045 adhC |
NADP-dependent alcohol dehydrogenase | 543 | 516 | |
Rv1862 adhA |
alcohol dehydrogenase A | 522 | 493 | |
Rv0190 ricR hyp |
hypothetical protein | 484 | 464 | coexpression:433 |
Rv0967 csoR |
copper-sensing transcriptional repressor CsoR | 469 | 448 | coexpression:429 |
Rv0412c glnX |
membrane protein | 468 | 447 | coexpression:429 |
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: S-nitrosomycothiol reductase MscR
- MTBC0 PGAP product: S-(hydroxymethyl)mycothiol dehydrogenase
- Pfam (hmmscan --cut_ga): ADH_N PF08240.18 (E=2e-26), ADH_zinc_N PF00107.33 (E=3e-29), ADH_zinc_N_2 PF13602.13 (E=1e-08)
- (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_216775.1)
- Domains: Pfam-A via hmmscan --cut_ga — ADH_N (PF08240.18), ADH_zinc_N (PF00107.33), ADH_zinc_N_2 (PF13602.13)
- 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 O53533 (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 —
27 functional partner(s); context anchor
Rv2258c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002402|Rv2259|mscR MSQTVRGVIARQKGEPVELVNIVVPDPGPGEAVVDVTACGVCHTDLTYREGGINDEYPFLLGHEAAGIIEAVGPGVTAVEPGDFVILNWRAVCGQCRACKRGRPRYCFDTFNAEQKMTLTDGTELTAALGIGAFADKTLVHSGQCTKVDPAADPAVAGLLGCGVMAGLGAAINTGGVTRDDTVAVIGCGGVGDAAIAGAALVGAKRIIAVDTDDTKLDWARTFGATHTVNAREVDVVQAIGGLTDGFGADVVIDAVGRPETYQQAFYARDLAGTVVLVGVPTPDMRLDMPLVDFFSHGGALKSSWYGDCLPESDFPTLIDLYLQGRLPLQRFVSERIGLEDVEEAFHKMHGGKVLRSVVML