pntAa Family assigned · medium auto-curated
H37Rv Rv0155 · MTBC0 mtbc0_000167 ·
366 aa · 183968–185068 (+) ·
RefSeq NP_214669.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | NAD(P) transhydrogenase subunit alpha PntAa |
|---|---|
| MTBC0 PGAP re-annotation | Re/Si-specific NAD(P)(+) transhydrogenase subunit alpha |
| Revised (this work) | Re/Si-specific NAD(P)(+) transhydrogenase subunit alpha. Pfam: AlaDh_PNT_N (PF05222.22), AlaDh_PNT_C (PF01262.28). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P96832
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | NAD(P) transhydrogenase subunit alpha part 1 |
| EC (curated) |
EC 7.1.1.1
|
| Curated function | The transhydrogenation between NADH and NADP is coupled to respiration and ATP hydrolysis and functions as a proton pump across the membrane. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| Preferred name | pntAA |
| eggNOG description | NAD(P) transhydrogenase, alpha subunit |
| Orthologous group | COG3288 |
| EC number |
EC 1.6.1.2
|
| KEGG orthology |
K00324
|
| KEGG pathways |
map00760, map01100
|
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 | 0.082 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 9 synonymous, 2 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 |
|---|---|---|---|---|
AlaDh_PNT_N | PF05222.22 | 1.4e-38 | 12–141 | Alanine dehydrogenase/PNT, N-terminal domain |
AlaDh_PNT_C | PF01262.28 | 1.9e-61 | 146–362 | Alanine dehydrogenase/PNT, C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: pntB (NAD(P) transhydrogenase subunit beta PntB), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0157 pntB |
NAD(P) transhydrogenase subunit beta PntB | 999 | 1000 ctx | neighborhood:882 fusion:900 cooccurence:774 coexpression:936 experimental:829 database:900 textmining:905 |
Rv0156 pntAb |
NAD(P) transhydrogenase subunit alpha PntAb | 999 | 999 ctx | neighborhood:882 cooccurence:774 coexpression:799 database:900 textmining:833 |
Rv1151c cobB |
NAD-dependent protein deacylase | 909 | 904 | database:900 |
Rv2421c nadD |
nicotinate-nucleotide adenylyltransferase | 908 | 903 | database:900 |
Rv1695 ppnK |
inorganic polyphosphate/ATP-NAD kinase | 913 | 901 | database:900 |
Rv3199c nudC |
NADH pyrophosphatase | 900 | 901 | database:900 |
Rv2713 sthA |
pyridine nucleotide transhydrogenase | 965 | 900 | database:900 textmining:670 |
Rv2438c nadE |
glutamine-dependent NAD(+) synthetase | 909 | 900 | database:900 |
Rv0212c nadR |
transcriptional regulator NadR | 900 | 900 | database:900 |
Rv0154c fadE2 |
acyl-CoA dehydrogenase FadE2 | 508 | 508 ctx | neighborhood:505 |
Rv0668 rpoC |
DNA-directed RNA polymerase subunit beta' | 487 | 487 | coexpression:487 |
Rv3001c ilvC |
ketol-acid reductoisomerase | 457 | 437 | coexpression:437 |
Rv1650 pheT |
phenylalanine--tRNA ligase subunit beta | 540 | 254 | textmining:409 |
Rv1133c metE |
5-methyltetrahydropteroyltriglutamate--homocysteine methyltransferase | 448 | 51 | textmining:443 |
Rv3399 |
S-adenosylmethionine-dependent methyltransferase | 415 | 49 | textmining:411 |
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: NAD(P) transhydrogenase subunit alpha PntAa
- MTBC0 PGAP product: Re/Si-specific NAD(P)(+) transhydrogenase subunit alpha
- Pfam (hmmscan --cut_ga): AlaDh_PNT_N PF05222.22 (E=1e-38), AlaDh_PNT_C PF01262.28 (E=2e-61)
- (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_214669.1)
- Domains: Pfam-A via hmmscan --cut_ga — AlaDh_PNT_N (PF05222.22), AlaDh_PNT_C (PF01262.28)
- 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
COG3288 - Curated reference: UniProt P96832 (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 —
18 functional partner(s); context anchor
pntB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000167|Rv0155|pntAa MTDPQTQSTRVGVVAESGPDERRVALVPKAVASLVNRGVAVVVEAGAGERALLPDELYTAVGASIGDAWAADVVVKVAPPTAAEVGRLRGGQTLIGFLAPRNADNSIGALTQAGVQAFALEAIPRISRAQVMDALSSQANVSGYKAVLLAASESTRFFPMLTTAAGTVKPATVLVLGVGVAGLQALATAKRLGARTTGYDVRPEVADQVRSVGAQWLDLGISASGEGGYARELTDDERAQQQKALEEAISGFDVVITTALVPGRPAPTLVTAAAVEAMKPGSVVVDLAGETGGNCELTEPGRTVVKHDVTIAAPLNLPATMPEHASELYSKNITALLDLLIKDGRLAPDFDDEVIAQSCVTRGKDS