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: 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 |
P9WJJ1
SwissProt · reviewed
· Evidence at protein level
|
|---|
| UniProt name | NADH dehydrogenase-like protein Rv1812c |
|---|
| EC (curated) |
EC 1.6.-.-
|
|---|
Functional vocabulary (eggNOG-mapper, orthology transfer)
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 |
0.754 · relaxed/neutral
|
|---|
| Polymorphic sites (≥ 0.1% of strains) |
2 synonymous, 4 missense, 0 nonsense, 1 frameshift
|
|---|
| Disruption |
1 distinct premature-stop/frameshift site(s); most common in
0.14% of strains
(209) · 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 |
3.4e-49 | 3–307 |
Pyridine nucleotide-disulphide oxidoreductase |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|
Rv3628 ppa |
inorganic pyrophosphatase |
496 |
472 |
coexpression:411 |
Rv0489 gpm1 |
2,3-bisphosphoglycerate-dependent phosphoglycerate mutase |
458 |
459 |
experimental:454 |
Rv3156 nuoL |
NADH-quinone oxidoreductase subunit L |
478 |
433 |
coexpression:418 |
Rv1813c hyp |
hypothetical protein |
666 |
426 ctx |
neighborhood:418 textmining:441 |
Rv1248c kgd |
multifunctional 2-oxoglutarate dehydrogenase E1 component /2-oxoglutarate dehydrogenase dihydrolipoyllysine-residue succinyltransferase |
484 |
424 |
coexpression:417 |
Rv1240 mdh |
malate dehydrogenase |
468 |
414 |
|
Rv3339c icd1 |
isocitrate dehydrogenase |
443 |
409 |
coexpression:407 |
Rv0572c hyp |
hypothetical protein |
853 |
288 |
textmining:803 |
Rv1937 |
oxygenase |
415 |
235 |
|
Rv1734c hyp |
hypothetical protein |
634 |
232 |
textmining:544 |
Rv2390c hyp |
hypothetical protein |
496 |
167 |
textmining:421 |
Rv1735c |
membrane protein |
546 |
112 |
textmining:510 |
Rv0571c hyp |
hypothetical protein |
653 |
100 |
textmining:630 |
Rv2631 rtcB |
RNA-splicing ligase RtcB |
446 |
98 |
textmining:411 |
Rv2003c hyp |
hypothetical protein |
688 |
96 |
textmining:670 |
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): Pyr_redox_2 PF07992.21 (E=3e-49)
- (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_216328.1)
- 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
COG1252
- Curated reference: UniProt
P9WJJ1
(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 —
25 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001924|Rv1812c|
MTRVVVIGSGFAGLWAALGAARRLDELAVPAGTVDVMVVSNKPFHDIRVRNYEADLSACRIPLGDVLGPAGVAHVTAEVTAIDADGRRVTTSTGASYSYDRLVLASGSHVVKPALPGLAEFGFDVDTYDGAVRLQQHLQGLAGGPLTSAAATVVVVGAGLTGIETACELPGRLHALFARGDGVTPRVVLIDHNPFVGSDMGLSARPVIEQALLDNGVETRTGVSVAAVSPGGVTLSSGERLAAATVVWCAGMRASRLTEQLPVARDRLGRLQVDDYLRVIGVPAMFAAGDVAAARMDDEHLSVMSCQHGRPMGRYAGCNVINDLFDQPLLALRIPWYVTVLDLGSAGAVYTEGWERKVVSQGAPAKTTKQSINTRRIYPPLNGSRADLLAAAAPRVQPRP
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