Rv2997 Resolved · high auto-curated
H37Rv Rv2997 · MTBC0 mtbc0_003184 ·
480 aa · 3376408–3377850 (+) ·
RefSeq NP_217513.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | dehydrogenase |
|---|---|
| MTBC0 PGAP re-annotation | NAD(P)/FAD-dependent oxidoreductase |
| Revised (this work) | NAD(P)/FAD-dependent oxidoreductase. Pfam: Thi4 (PF01946.24), FAD_oxidored (PF12831.14), NAD_binding_8 (PF13450.13). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6YAU3
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | Possible alanine rich dehydrogenase |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| eggNOG description | Dehydrogenase |
| Orthologous group | COG1233 |
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 | 0.657 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 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 |
|---|---|---|---|---|
Thi4 | PF01946.24 | 4.1e-06 | 1–40 | Thi4 family |
FAD_oxidored | PF12831.14 | 1.6e-06 | 2–41 | FAD dependent oxidoreductase |
NAD_binding_8 | PF13450.13 | 2.0e-08 | 5–58 | NAD(P)-binding Rossmann-like domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: serA1 (D-3-phosphoglycerate dehydrogenase), medium confidence from genomic context alone (score 593 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3397c phyA |
phytoene synthase | 694 | 666 | coexpression:654 |
Rv2996c serA1 |
D-3-phosphoglycerate dehydrogenase | 595 | 593 ctx | neighborhood:586 |
Rv2995c leuB |
3-isopropylmalate dehydrogenase | 588 | 573 ctx | neighborhood:568 |
Rv2850c |
magnesium chelatase | 544 | 478 | coexpression:412 |
Rv2998 hyp |
hypothetical protein | 416 | 416 ctx | neighborhood:416 |
Rv2096c pafB |
proteasome accessory factor B | 401 | 401 | |
Rv2062c cobN |
cobalamin biosynthesis protein CobN | 412 | 357 |
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: NAD(P)/FAD-dependent oxidoreductase
- Pfam (hmmscan --cut_ga): Thi4 PF01946.24 (E=4e-06), FAD_oxidored PF12831.14 (E=2e-06), NAD_binding_8 PF13450.13 (E=2e-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_217513.1)
- Domains: Pfam-A via hmmscan --cut_ga — Thi4 (PF01946.24), FAD_oxidored (PF12831.14), NAD_binding_8 (PF13450.13)
- 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
COG1233 - Curated reference: UniProt I6YAU3 (TrEMBL, unreviewed; Predicted)
- 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 —
7 functional partner(s); context anchor
serA1 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003184|Rv2997| MDVTVVGSGPNGLATAVICARAGLNVQVVEAQATFGGGARSAADFEFPEVLHDVCSAVHPLALASPFFAEFDLPARGVTLTVPDIAYANPLPGRPAAIAYHDLAHTCAKLDDGASWRRLLGPLVAHSETVVEFMLSDKRSLPTALGSVLRLGLRMLAQGTPAWRSLAGEDARALFTGVAAHAISPLPSLVSAGAGLMLATLAHSVGWPIPVGGTQAIADALIADLRAHGGRLAAGVEITEPQRSVVVFDTAPTALLRVYRDKLPHRYAKALRRYRFRAGIAKVDFVLSDEIPWSDPRLRRAATLHLGGTRDQMARAEADVAAGRHADWPMVLAACPHVADPGRIDETGRRPFWTYAHVPSGSTLDATETVTSVLERFAPGFRDIVVAARAVPAARMADHNANYVGGDITVGANSTWRAIAGPTPRLNPWRTPIPKVYLCSAATPPGAGVHGMCGWYAARTLLRTEFGITRMPPLGHELRP