Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | dehydrogenase/reductase |
|---|
| MTBC0 PGAP re-annotation | FAD/NAD(P)-binding oxidoreductase |
|---|
| Revised (this work) | FAD/NAD(P)-binding oxidoreductase. Pfam: Pyr_redox_2 (PF07992.21). |
|---|
Auto-curated: this verdict and function were generated by rules from
PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O07255
TrEMBL · unreviewed
· Evidence at protein level
|
|---|
| UniProt name | Possible dehydrogenase/reductase |
|---|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|
| eggNOG description | Pyridine nucleotide-disulphide oxidoreductase |
|---|
| Orthologous group | COG0446 |
|---|
| EC number |
EC 1.8.5.4
|
|---|
| KEGG orthology |
K17218
|
|---|
| KEGG pathways |
map00920
|
|---|
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 |
0.896 · relaxed/neutral
|
|---|
| Polymorphic sites (≥ 0.1% of strains) |
4 synonymous, 10 missense, 0 nonsense, 1 frameshift
|
|---|
| Disruption |
1 distinct premature-stop/frameshift site(s); most common in
0.93% of strains
(1351) · 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 |
|---|
Pyr_redox_2 | PF07992.21 |
3.2e-20 | 4–312 |
Pyridine nucleotide-disulphide oxidoreductase |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|
Rv2391 sirA |
sulfite reductase |
923 |
916 |
database:900 |
Rv0391 metZ |
O-succinylhomoserine sulfhydrylase |
912 |
904 |
database:900 |
Rv1079 metB |
cystathionine gamma-synthase |
912 |
904 |
database:900 |
Rv3684 |
lyase |
908 |
903 |
database:900 |
Rv2334 cysK1 |
O-acetylserine sulfhydrylase |
907 |
901 |
database:900 |
Rv1905c aao |
D-amino acid oxidase |
853 |
834 |
experimental:821 |
Rv0415 thiO |
thiamine biosynthesis oxidoreductase ThiO |
853 |
834 |
experimental:821 |
Rv1298 rpmE |
50S ribosomal protein L31 |
684 |
684 |
coexpression:684 |
Rv1412 ribC |
riboflavin synthase |
684 |
684 |
coexpression:684 |
Rv0939 |
bifunctional 2-hydroxyhepta-2,4-diene-1,7-dioate isomerase/cyclase/dehydrase |
702 |
668 |
database:583 |
Rv3461c rpmJ |
50S ribosomal protein L36 |
660 |
660 |
coexpression:412 experimental:446 |
Rv3040c hyp |
hypothetical protein |
651 |
636 |
database:583 |
Rv1637c hyp |
hypothetical protein |
651 |
636 |
database:583 |
Rv2300c |
metallo-hydrolase |
651 |
636 |
database:583 |
Rv2260 hyp |
hypothetical protein |
651 |
636 |
database:583 |
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/reductase
- MTBC0 PGAP product: FAD/NAD(P)-binding oxidoreductase
- Pfam (hmmscan --cut_ga): Pyr_redox_2 PF07992.21 (E=3e-20)
- (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_214845.1)
- Domains: Pfam-A via hmmscan --cut_ga — Pyr_redox_2 (PF07992.21)
- 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
COG0446
- Curated reference: UniProt
O07255
(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 —
119 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000351|Rv0331|
MSKTVLILGAGVGGLTTADTLRQLLPPEDRIILVDRSFDGTLGLSLLWVLRGWRRPDDVRVRPTAASLPGVEMVTATVAHIDIAAQVVHTDNSVIGYDALVIALGAALNTDAVPGLSDALDADVAGQFYTLDGAAELRAKVEALEHGRIAVAIAGVPFKCPAAPFEAAFLIAAQLGDRYATGTVQIDTFTPDPLPMPVAGPEVGEALVSMLKDHGVGFHPRKALARVDEAARTMHFGDGTSEPFDLLAVVPPHVPSAAARSAGLSESGWIPVDPRTLSTSADNVWAIGDATVLTLPNGKPLPKAAVFAEAQAAVVAHGVARHLGYDVAERHFTGTGACYVETGDHQAAKGDGDFFAPSAPSVTLYPPSREFHEEKVAQELAWLTRWKT
Spot an error? Suggest an improvement