pntAb Family assigned · medium auto-curated

H37Rv Rv0156 · MTBC0 mtbc0_000168 · 110 aa · 185069–185401 (+) · RefSeq NP_214670.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)NAD(P) transhydrogenase subunit alpha PntAb
MTBC0 PGAP re-annotationNAD(P) transhydrogenase subunit alpha
Revised (this work)NAD(P) transhydrogenase subunit alpha. Pfam: PNTB_4TM (PF12769.13).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt P96833 TrEMBL · unreviewed · Evidence at protein level
UniProt nameproton-translocating NAD(P)(+) transhydrogenase
EC (curated) EC 7.1.1.1
Curated functionThe 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 namepntAB
eggNOG descriptionNADP transhydrogenase
Orthologous groupCOG3288
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 0.172 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 4 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)

PfamAccessioni-EvalueResiduesDescription
PNTB_4TMPF12769.13 4.4e-319–93 4TM region of pyridine nucleotide transhydrogenase, mitoch

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).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0157 pntB NAD(P) transhydrogenase subunit beta PntB 999 1000 ctx neighborhood:882 cooccurence:774 coexpression:939 experimental:829 database:900 textmining:786
Rv0155 pntAa NAD(P) transhydrogenase subunit alpha PntAa 999 999 ctx neighborhood:882 cooccurence:774 coexpression:799 database:900 textmining:833
Rv1151c cobB NAD-dependent protein deacylase 909 904 database:900
Rv1695 ppnK inorganic polyphosphate/ATP-NAD kinase 916 901 database:900
Rv2438c nadE glutamine-dependent NAD(+) synthetase 909 901 database:900
Rv2421c nadD nicotinate-nucleotide adenylyltransferase 907 901 database:900
Rv3199c nudC NADH pyrophosphatase 903 901 database:900
Rv0212c nadR transcriptional regulator NadR 900 901 database:900
Rv2713 sthA pyridine nucleotide transhydrogenase 980 900 database:900 textmining:813
Rv0668 rpoC DNA-directed RNA polymerase subunit beta' 485 485 coexpression:485
Rv0154c fadE2 acyl-CoA dehydrogenase FadE2 441 442 ctx neighborhood:437
Rv3001c ilvC ketol-acid reductoisomerase 459 439 coexpression:439
Rv1650 pheT phenylalanine--tRNA ligase subunit beta 540 254 textmining:409

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 PntAb
  • MTBC0 PGAP product: NAD(P) transhydrogenase subunit alpha
  • Pfam (hmmscan --cut_ga): PNTB_4TM PF12769.13 (E=4e-31)
  • (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_214670.1)
  • Domains: Pfam-A via hmmscan --cut_ga — PNTB_4TM (PF12769.13)
  • 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 COG3288
  • Curated reference: UniProt P96833 (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 — 13 functional partner(s); context anchor pntB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000168|Rv0156|pntAb
MYNELLENLAILVLSGFVGFAVISKVPNTLHTPLMSGTNAIHGIVVLGALVVFGEIEHPSLVLQVILFVAVVFGTLNVIGGFIVTDRMLGMFKAKKPAVPAKPDRDEALR