topA Resolved · high auto-curated
H37Rv Rv3646c · MTBC0 mtbc0_003863 ·
934 aa · 4108158–4110962 (-) ·
RefSeq NP_218163.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | DNA topoisomerase I |
|---|---|
| MTBC0 PGAP re-annotation | type I DNA topoisomerase |
| Revised (this work) | Type I DNA topoisomerase. Pfam: Toprim (PF01751.29), Topoisom_bac (PF01131.26), Toprim_C_rpt (PF13368.12). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WG49
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | DNA topoisomerase 1 |
| EC (curated) |
EC 5.6.2.1
|
| Curated function | Releases the supercoiling and torsional tension of DNA, which is introduced during the DNA replication and transcription, by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(5'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 3'-OH DNA strand. The free DNA strand then undergoes passage around the unbroken strand, thus removing DNA supercoils. Finally, in the religa. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
L Replication, recombination and repair
|
|---|---|
| Preferred name | topA |
| eggNOG description | Releases the supercoiling and torsional tension of DNA, which is introduced during the DNA replication and transcription, by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(5'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 3'-OH DNA strand. The free DNA strand then undergoes passage around the unbroken strand, thus removing DNA supercoils. Finally, in the religation step, the DNA 3'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone |
| Orthologous group | COG0550 |
| EC number |
EC 5.99.1.2
|
| KEGG orthology |
K03168
|
| Gene Ontology (54) |
GO:0000287, GO:0003674, GO:0003824, GO:0003916, GO:0003917, GO:0005488, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829 +42 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 | 0.286 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 11 synonymous, 9 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 |
|---|---|---|---|---|
Toprim | PF01751.29 | 1.6e-20 | 20–141 | Toprim domain |
Topoisom_bac | PF01131.26 | 3.5e-112 | 156–603 | DNA topoisomerase |
Toprim_C_rpt | PF13368.12 | 3.7e-23 | 860–914 | Topoisomerase C-terminal repeat |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: cspA (cold shock protein A), high confidence from genomic context alone (score 709 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2529 hyp |
hypothetical protein | 964 | 953 | experimental:883 database:615 |
Rv1278 hyp |
hypothetical protein | 895 | 879 | database:654 |
Rv2737c recA |
recombinase A | 954 | 844 | experimental:446 database:635 textmining:720 |
Rv1629 polA |
DNA polymerase I | 962 | 809 | database:605 textmining:811 |
Rv1277 hyp |
hypothetical protein | 846 | 784 | database:654 |
Rv2090 |
5'-3' exonuclease | 821 | 749 | database:605 |
Rv1329c dinG |
ATP-dependent helicase DinG | 835 | 723 | database:639 textmining:429 |
Rv3647c hyp |
hypothetical protein | 715 | 715 ctx | neighborhood:711 |
Rv3648c cspA |
cold shock protein A | 719 | 709 ctx | neighborhood:656 |
Rv0002 dnaN |
DNA polymerase III subunit beta | 834 | 694 | database:588 textmining:481 |
Rv3859c gltB |
glutamate synthase large subunit | 780 | 690 | coexpression:649 |
Rv2478c hyp |
hypothetical protein | 738 | 657 | coexpression:515 |
Rv2116 lppK |
lipoprotein LppK | 787 | 652 | database:588 textmining:415 |
Rv2380c mbtE |
peptide synthetase | 626 | 612 | database:511 |
Rv1407 fmu |
16S rRNA m5C967 methyltransferase | 723 | 611 ctx | neighborhood:544 |
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 topoisomerase I
- MTBC0 PGAP product: type I DNA topoisomerase
- Pfam (hmmscan --cut_ga): Toprim PF01751.29 (E=2e-20), Topoisom_bac PF01131.26 (E=3e-112), Toprim_C_rpt PF13368.12 (E=4e-23)
- (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_218163.1)
- Domains: Pfam-A via hmmscan --cut_ga — Toprim (PF01751.29), Topoisom_bac (PF01131.26), Toprim_C_rpt (PF13368.12)
- 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
COG0550 - Curated reference: UniProt P9WG49 (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 —
205 functional partner(s); context anchor
cspA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003863|Rv3646c|topA MADPKTKGRGSGGNGSGRRLVIVESPTKARKLASYLGSGYIVESSRGHIRDLPRAASDVPAKYKSQPWARLGVNVDADFEPLYIISPEKRSTVSELRGLLKDVDELYLATDGDREGEAIAWHLLETLKPRIPVKRMVFHEITEPAIRAAAEHPRDLDIDLVDAQETRRILDRLYGYEVSPVLWKKVAPKLSAGRVQSVATRIIVARERDRMAFRSAAYWDILAKLDASVSDPDAAPPTFSARLTAVAGRRVATGRDFDSLGTLRKGDEVIVLDEGSATALAAGLDGTQLTVASAEEKPYARRPYPPFMTSTLQQEASRKLRFSAERTMSIAQRLYENGYITYMRTDSTTLSESAINAARTQARQLYGDEYVAPAPRQYTRKVKNAQEAHEAIRPAGETFATPDAVRRELDGPNIDDFRLYELIWQRTVASQMADARGMTLSLRITGMSGHQEVVFSATGRTLTFPGFLKAYVETVDELVGGEADDAERRLPHLTPGQRLDIVELTPDGHATNPPARYTEASLVKALEELGIGRPSTYSSIIKTIQDRGYVHKKGSALVPSWVAFAVTGLLEQHFGRLVDYDFTAAMEDELDEIAAGNERRTNWLNNFYFGGDHGVPDSVARSGGLKKLVGINLEGIDAREVNSIKLFDDTHGRPIYVRVGKNGPYLERLVAGDTGEPTPQRANLSDSITPDELTLQVAEELFATPQQGRTLGLDPETGHEIVAREGRFGPYVTEILPEPAADAAAAAQGVKKRQKAAGPKPRTGSLLRSMDLQTVTLEDALRLLSLPRVVGVDPASGEEITAQNGRYGPYLKRGNDSRSLVTEDQIFTITLDEALKIYAEPKRRGRQSASAPPLRELGTDPASGKPMVIKDGRFGPYVTDGETNASLRKGDDVASITDERAAELLADRRARGPAKRPARKAARKVPAKKAAKRD