ndhA Resolved · high auto-curated
H37Rv Rv0392c · MTBC0 mtbc0_000411 ·
470 aa · 474591–476003 (-) ·
RefSeq NP_214906.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | NADH dehydrogenase NdhA |
|---|---|
| MTBC0 PGAP re-annotation | NAD(P)/FAD-dependent oxidoreductase |
| Revised (this work) | NAD(P)/FAD-dependent oxidoreductase. Pfam: Pyr_redox_2 (PF07992.21), Pyr_redox (PF00070.34). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P95200
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Type II NADH:quinone oxidoreductase NdhA |
| EC (curated) |
EC 1.6.5.9
|
| Curated function | Alternative, nonproton pumping NADH:quinone oxidoreductase that delivers electrons to the respiratory chain by oxidation of NADH and reduction of quinones. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| Preferred name | ndh |
| eggNOG description | Pyridine nucleotide-disulphide oxidoreductase |
| Orthologous group | COG1252 |
| EC number |
EC 1.6.99.3
|
| KEGG orthology |
K03885
|
| KEGG pathways |
map00190
|
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 | 0.943 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 12 missense, 2 nonsense, 7 frameshift |
| Disruption | 9 distinct premature-stop/frameshift site(s); most common in 2.59% of strains (3754) · convergent |
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 | 1.6e-48 | 16–340 | Pyridine nucleotide-disulphide oxidoreductase |
Pyr_redox | PF00070.34 | 2.3e-06 | 173–256 | Pyridine nucleotide-disulphide oxidoreductase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv2531c (amino acid decarboxylase), medium confidence from genomic context alone (score 548 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2531c |
amino acid decarboxylase | 548 | 548 ctx | neighborhood:544 |
Rv0393 hyp |
hypothetical protein | 536 | 535 ctx | neighborhood:535 |
Rv3628 ppa |
inorganic pyrophosphatase | 493 | 469 | coexpression:407 |
Rv0489 gpm1 |
2,3-bisphosphoglycerate-dependent phosphoglycerate mutase | 459 | 460 | experimental:454 |
Rv3156 nuoL |
NADH-quinone oxidoreductase subunit L | 566 | 427 | coexpression:412 |
Rv1248c kgd |
multifunctional 2-oxoglutarate dehydrogenase E1 component /2-oxoglutarate dehydrogenase dihydrolipoyllysine-residue succinyltransferase | 480 | 420 | coexpression:413 |
Rv3339c icd1 |
isocitrate dehydrogenase | 446 | 412 | coexpression:410 |
Rv1240 mdh |
malate dehydrogenase | 457 | 402 | |
Rv2195 qcrA |
ubiquinol-cytochrome C reductase rieske iron-sulfur subunit | 622 | 317 | textmining:470 |
Rv1622c cydB |
cytochrome D ubiquinol oxidase subunit II CydB | 441 | 269 | |
Rv3457c rpoA |
DNA-directed RNA polymerase subunit alpha | 433 | 245 | |
Rv2785c rpsO |
30S ribosomal protein S15 | 450 | 226 | |
Rv0247c |
succinate dehydrogenase iron-sulfur subunit | 547 | 171 | textmining:476 |
Rv1310 atpD |
ATP synthase subunit beta | 441 | 171 | |
Rv2890c rpsB |
30S ribosomal protein S2 | 405 | 161 |
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: NADH dehydrogenase NdhA
- MTBC0 PGAP product: NAD(P)/FAD-dependent oxidoreductase
- Pfam (hmmscan --cut_ga): Pyr_redox_2 PF07992.21 (E=2e-48), Pyr_redox PF00070.34 (E=2e-06)
- (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_214906.1)
- Domains: Pfam-A via hmmscan --cut_ga — Pyr_redox_2 (PF07992.21), Pyr_redox (PF00070.34)
- 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 P95200 (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 —
24 functional partner(s); context anchor
Rv2531c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000411|Rv0392c|ndhA MTLSSGEPSAVGGRHRVVIIGSGFGGLNAAKALKRADVDITLISKTTTHLFQPLLYQVATGILSEGDIAPTTRLILRRQKNVRVLLGEVNAIDLKAQTVTSKLMDMTTVTPYDSLIVAAGAQQSYFGNDEFATFAPGMKTIDDALELRGRILGAFEAAEVSTDHAERERRLTFVVVGAGPTGVEVAGQIVELAERTLAGAFRTITPSECRVILLDAAPAVLPPMGPKLGLKAQRRLEKMDVEVQLNAMVTAVDYKGITIKEKDGGERRIECACKVWAAGVAASPLGKMIAEGSDGTEIDRAGRVIVEPDLTVKGHPNVFVVGDLMFVPGVPGVAQGAIQGARYATTVIKHMVKGNDDPANRKPFHYFNKGSMATISRHSAVAQVGKLEFAGYFAWLAWLVLHLVYLVGYRNRIAALFAWGISFMGRARGQMAITSQMIYARLVMTLMEQQAQGALAAAEQAEHAEQEAAG