atpA Family assigned · medium auto-curated

H37Rv Rv1308 · MTBC0 mtbc0_001400 · 549 aa · 1472267–1473916 (+) · RefSeq NP_215824.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ATP synthase subunit alpha
MTBC0 PGAP re-annotationF0F1 ATP synthase subunit alpha
Revised (this work)F0F1 ATP synthase subunit alpha. Pfam: ATP-synt_ab_N (PF02874.30), ATP-synt_ab (PF00006.32), ATP-synt_ab_C (PF00306.33).

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

Curated reference (UniProt)

UniProt P9WPU7 SwissProt · reviewed · Evidence at protein level
UniProt nameATP synthase subunit alpha
EC (curated) EC 7.1.2.2
Curated functionProduces ATP from ADP in the presence of a proton gradient across the membrane. The alpha chain is a regulatory subunit.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category F Nucleotide transport and metabolism
Preferred nameatpA
eggNOG descriptionProduces ATP from ADP in the presence of a proton gradient across the membrane. The alpha chain is a regulatory subunit
Orthologous groupCOG0056
EC number EC 3.6.3.14
KEGG orthology K02111
KEGG pathways map00190, map00195, map01100
KEGG modules M00157
Gene Ontology (10) GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0008150, GO:0016020, GO:0030312, GO:0040007, GO:0044464, GO:0071944

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 0.245 · purifying
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 3 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
ATP-synt_ab_NPF02874.30 5.9e-1729–95 ATP synthase alpha/beta family, beta-barrel domain
ATP-synt_abPF00006.32 1.5e-77152–375 ATP synthase alpha/beta family, nucleotide-binding domain
ATP-synt_ab_CPF00306.33 1.0e-49382–507 ATP synthase alpha/beta chain, C terminal domain

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: atpH (ATP synthase subunit b/delta), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1307 atpH ATP synthase subunit b/delta 999 1000 ctx neighborhood:817 coexpression:999 experimental:999 database:983 textmining:897
Rv1304 atpB ATP synthase subunit A 999 1000 ctx neighborhood:738 cooccurence:735 coexpression:958 experimental:928 database:972 textmining:824
Rv1305 atpE ATP synthase subunit C 999 1000 ctx neighborhood:783 coexpression:923 experimental:928 database:982 textmining:870
Rv1311 atpC ATP synthase subunit epsilon 999 1000 ctx neighborhood:812 coexpression:967 experimental:928 database:984 textmining:804
Rv1306 atpF ATP synthase subunit B 999 1000 ctx neighborhood:817 coexpression:925 experimental:997 database:900 textmining:854
Rv1310 atpD ATP synthase subunit beta 999 1000 ctx neighborhood:823 coexpression:968 experimental:997 database:984 textmining:518
Rv1309 atpG ATP synthase subunit gamma 999 1000 ctx neighborhood:882 fusion:697 cooccurence:774 coexpression:973 experimental:997 database:965 textmining:916
Rv1507c hyp hypothetical protein 985 984 coexpression:730 experimental:829 database:662
Rv1248c kgd multifunctional 2-oxoglutarate dehydrogenase E1 component /2-oxoglutarate dehydrogenase dihydrolipoyllysine-residue succinyltransferase 970 950 coexpression:920 textmining:428
Rv3628 ppa inorganic pyrophosphatase 950 935 database:900
Rv3148 nuoD NADH-quinone oxidoreductase subunit D 936 917 ctx fusion:483 coexpression:812
Rv0641 rplA 50S ribosomal protein L1 899 888 coexpression:817 experimental:413
Rv0703 rplW 50S ribosomal protein L23 907 873 coexpression:849
Rv0707 rpsC 30S ribosomal protein S3 902 872 coexpression:848
Rv0721 rpsE 30S ribosomal protein S5 892 870 coexpression:846

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: ATP synthase subunit alpha
  • MTBC0 PGAP product: F0F1 ATP synthase subunit alpha
  • Pfam (hmmscan --cut_ga): ATP-synt_ab_N PF02874.30 (E=6e-17), ATP-synt_ab PF00006.32 (E=2e-77), ATP-synt_ab_C PF00306.33 (E=1e-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_215824.1)
  • Domains: Pfam-A via hmmscan --cut_ga — ATP-synt_ab_N (PF02874.30), ATP-synt_ab (PF00006.32), ATP-synt_ab_C (PF00306.33)
  • 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 COG0056
  • Curated reference: UniProt P9WPU7 (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 — 228 functional partner(s); context anchor atpH
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001400|Rv1308|atpA
MAELTIPADDIQSAIEEYVSSFTADTSREEVGTVVDAGDGIAHVEGLPSVMTQELLEFPGGILGVALNLDEHSVGAVILGDFENIEEGQQVKRTGEVLSVPVGDGFLGRVVNPLGQPIDGRGDVDSDTRRALELQAPSVVHRQGVKEPLQTGIKAIDAMTPIGRGQRQLIIGDRKTGKTAVCVDTILNQRQNWESGDPKKQVRCVYVAIGQKGTTIAAVRRTLEEGGAMDYTTIVAAAASESAGFKWLAPYTGSAIAQHWMYEGKHVLIIFDDLTKQAEAYRAISLLLRRPPGREAYPGDVFYLHSRLLERCAKLSDDLGGGSLTGLPIIETKANDISAYIPTNVISITDGQCFLETDLFNQGVRPAINVGVSVSRVGGAAQIKAMKEVAGSLRLDLSQYRELEAFAAFASDLDAASKAQLERGARLVELLKQPQSQPMPVEEQVVSIFLGTGGHLDSVPVEDVRRFETELLDHMRASEEEILTEIRDSQKLTEEAADKLTEVIKNFKKGFAATGGGSVVPDEHVEALDEDKLAKEAVKVKKPAPKKKK