gyrA Family assigned · medium auto-curated

H37Rv Rv0006 · MTBC0 mtbc0_000006 · 838 aa · 7302–9818 (+) · RefSeq NP_214520.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)DNA gyrase subunit A
MTBC0 PGAP re-annotationDNA topoisomerase (ATP-hydrolyzing) subunit A
Revised (this work)DNA topoisomerase (ATP-hydrolyzing) subunit A. Pfam: DNA_topoisoIV (PF00521.27), DNA_gyraseA_C (PF03989.19).

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

Curated reference (UniProt)

UniProt P9WG47 SwissProt · reviewed · Evidence at protein level
UniProt nameDNA gyrase subunit A
EC (curated) EC 5.6.2.2
Curated functionA type II topoisomerase that negatively supercoils closed circular double-stranded (ds) DNA in an ATP-dependent manner to maintain chromosomes in an underwound state, while in the absence of ATP it relaxes supercoiled dsDNA. Also catalyzes the interconversion of other topological isomers of dsDNA rings, including catenanes. Gyrase from M.tuberculosis has higher decatenation than supercoiling activity compared to E.coli; as M.tuberculosis only has 1 type II topoisomerase, gyrase has to fulfill the decatenation function of topoisomerase IV as well. At comparable concentrations M.tuberculosis gyr.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category L Replication, recombination and repair
Preferred namegyrA
eggNOG descriptionA type II topoisomerase that negatively supercoils closed circular double-stranded (ds) DNA in an ATP-dependent manner to modulate DNA topology and maintain chromosomes in an underwound state. Negative supercoiling favors strand separation, and DNA replication, transcription, recombination and repair, all of which involve strand separation. Also able to catalyze the interconversion of other topological isomers of dsDNA rings, including catenanes and knotted rings. Type II topoisomerases break and join 2 DNA strands simultaneously in an ATP-dependent manner
Orthologous groupCOG0188
EC number EC 5.99.1.3
KEGG orthology K02469
Gene Ontology (66) GO:0000166, GO:0000287, GO:0003674, GO:0003824, GO:0003916, GO:0003918, GO:0005488, GO:0005524, GO:0005575, GO:0005618, GO:0005623, GO:0005886 +54 more

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 0.438 · purifying
Polymorphic sites (≥ 0.1% of strains) 17 synonymous, 22 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
DNA_topoisoIVPF00521.27 3.6e-15239–483 DNA gyrase/topoisomerase IV, subunit A
DNA_gyraseA_CPF03989.19 1.3e-12515–562 DNA gyrase C-terminal domain, beta-propeller

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

Closest characterised functional partner: gyrB (DNA gyrase subunit B), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0005 gyrB DNA gyrase subunit B 999 1000 ctx neighborhood:830 cooccurence:773 coexpression:942 experimental:981 textmining:989
Rv0007 membrane protein 946 943 ctx neighborhood:775 coexpression:757
Rv1797 eccE5 ESX-5 type VII secretion system protein EccE 746 746 coexpression:746
Rv3806c ubiA decaprenyl-phosphate phosphoribosyltransferase 784 738 coexpression:730
Rv1307 atpH ATP synthase subunit b/delta 682 682 coexpression:658
Rv0640 rplK 50S ribosomal protein L11 713 676 coexpression:589
Rv0641 rplA 50S ribosomal protein L1 655 617 coexpression:538
Rv0002 dnaN DNA polymerase III subunit beta 887 615 ctx neighborhood:604 textmining:719
Rv2373c dnaJ2 chaperone protein DnaJ 720 614 ctx cooccurence:599
Rv0350 dnaK chaperone protein DnaK 747 609 ctx cooccurence:513
Rv2150c ftsZ cell division protein FtsZ 870 597 textmining:692
Rv1650 pheT phenylalanine--tRNA ligase subunit beta 675 575 coexpression:430
Rv0705 rpsS 30S ribosomal protein S19 595 575 coexpression:415
Rv0667 rpoB DNA-directed RNA polymerase subunit beta 980 549 coexpression:455 textmining:959
Rv0003 recF DNA replication/repair protein RecF 861 548 ctx neighborhood:525 textmining:707

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: DNA gyrase subunit A
  • MTBC0 PGAP product: DNA topoisomerase (ATP-hydrolyzing) subunit A
  • Pfam (hmmscan --cut_ga): DNA_topoisoIV PF00521.27 (E=4e-152), DNA_gyraseA_C PF03989.19 (E=1e-12)
  • (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_214520.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DNA_topoisoIV (PF00521.27), DNA_gyraseA_C (PF03989.19)
  • 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 COG0188
  • Curated reference: UniProt P9WG47 (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 — 157 functional partner(s); context anchor gyrB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000006|Rv0006|gyrA
MTDTTLPPDDSLDRIEPVDIQQEMQRSYIDYAMSVIVGRALPEVRDGLKPVHRRVLYAMFDSGFRPDRSHAKSARSVAETMGNYHPHGDASIYDTLVRMAQPWSLRYPLVDGQGNFGSPGNDPPAAMRYTEARLTPLAMEMLREIDEETVDFIPNYDGRVQEPTVLPSRFPNLLANGSGGIAVGMATNIPPHNLRELADAVFWALENHDADEEETLAAVMGRVKGPDFPTAGLIVGSQGTADAYKTGRGSIRMRGVVEVEEDSRGRTSLVITELPYQVNHDNFITSIAEQVRDGKLAGISNIEDQSSDRVGLRIVIEIKRDAVAKVVINNLYKHTQLQTSFGANMLAIVDGVPRTLRLDQLIRYYVDHQLDVIVRRTTYRLRKANERAHILRGLVKALDALDEVIALIRASETVDIARAGLIELLDIDEIQAQAILDMQLRRLAALERQRIIDDLAKIEAEIADLEDILAKPERQRGIVRDELAEIVDRHGDDRRTRIIAADGDVSDEDLIAREDVVVTITETGYAKRTKTDLYRSQKRGGKGVQGAGLKQDDIVAHFFVCSTHDLILFFTTQGRVYRAKAYDLPEASRTARGQHVANLLAFQPEERIAQVIQIRGYTDAPYLVLATRNGLVKKSKLTDFDSNRSGGIVAVNLRDNDELVGAVLCSADDDLLLVSANGQSIRFSATDEALRPMGRATSGVQGMRFNIDDRLLSLNVVREGTYLLVATSGGYAKRTAIEEYPVQGRGGKGVLTVMYDRRRGRLVGALIVDDDSELYAVTSGGGVIRTAARQVRKAGRQTKGVRLMNLGEGDTLLAIARNAEESGDDNAVDANGADQTGN