ruvA Resolved · high auto-curated

H37Rv Rv2593c · MTBC0 mtbc0_002760 · 196 aa · 2947783–2948373 (-) · RefSeq NP_217109.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)Holliday junction ATP-dependent DNA helicase RuvA
MTBC0 PGAP re-annotationHolliday junction branch migration protein RuvA
Revised (this work)Holliday junction branch migration protein RuvA. Pfam: RuvA_N (PF01330.28), HHH_5 (PF14520.13), RuvA_C (PF07499.20).

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

Curated reference (UniProt)

UniProt P9WGW3 SwissProt · reviewed · Evidence at protein level
UniProt nameHolliday junction branch migration complex subunit RuvA
Curated functionThe RuvA-RuvB-RuvC complex processes Holliday junction (HJ) DNA during genetic recombination and DNA repair, while the RuvA-RuvB complex plays an important role in the rescue of blocked DNA replication forks via replication fork reversal (RFR). Binds HJ DNA. RuvA specifically binds to HJ cruciform DNA, conferring on it an open structure. The RuvB hexamer acts as an ATP-dependent pump, pulling dsDNA into and through the RuvAB complex. HJ branch migration allows RuvC to scan DNA until it finds its consensus sequence, where it cleaves and resolves the cruciform DNA.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category L Replication, recombination and repair
Preferred nameruvA
eggNOG descriptionThe RuvA-RuvB complex in the presence of ATP renatures cruciform structure in supercoiled DNA with palindromic sequence, indicating that it may promote strand exchange reactions in homologous recombination. RuvAB is a helicase that mediates the Holliday junction migration by localized denaturation and reannealing. RuvA stimulates, in the presence of DNA, the weak ATPase activity of RuvB
Orthologous groupCOG0632
EC number EC 3.6.4.12
KEGG orthology K03550
KEGG pathways map03440
Gene Ontology (56) GO:0000724, GO:0000725, GO:0003674, GO:0003678, GO:0003824, GO:0004386, GO:0005575, GO:0005623, GO:0005886, GO:0006139, GO:0006259, GO:0006281 +44 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 0.201 · 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
RuvA_NPF01330.28 6.6e-221–61 RuvA N terminal domain
HHH_5PF14520.13 4.1e-1471–129 Helix-hairpin-helix domain
RuvA_CPF07499.20 7.0e-10151–192 RuvA, C-terminal domain

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

Closest characterised functional partner: ruvB (Holliday junction ATP-dependent DNA helicase RuvB), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2592c ruvB Holliday junction ATP-dependent DNA helicase RuvB 999 1000 ctx neighborhood:882 cooccurence:765 coexpression:976 experimental:928 textmining:934
Rv2594c ruvC crossover junction endodeoxyribonuclease RuvC 999 998 ctx neighborhood:882 coexpression:910 experimental:699 textmining:933
Rv2600 integral membrane protein 604 603 ctx neighborhood:601
Rv2596 vapC40 ribonuclease VapC40 572 572 ctx neighborhood:567
Rv2595 vapB40 antitoxin VapB40 554 555 ctx neighborhood:552
Rv3433c nnr bifunctional ADP-dependent (S)-NAD(P)H-hydrate dehydratase/NAD(P)H-hydrate epimerase 546 546
Rv1901 cinA competence damage-inducible protein CinA 552 535
Rv2737c recA recombinase A 925 510 coexpression:471 textmining:854
Rv3198c uvrD2 ATP-dependent DNA helicase UvrD 615 492
Rv1696 recN DNA repair protein RecN 815 486 textmining:656
Rv3202c adnA ATP-dependent DNA helicase 513 467
Rv1014c pth peptidyl-tRNA hydrolase 460 460 coexpression:425
Rv2152c murC UDP-N-acetylmuramate--alanine ligase 451 452 ctx cooccurence:407
Rv1629 polA DNA polymerase I 706 440 textmining:498
Rv0949 uvrD1 ATP-dependent DNA helicase UvrD 751 429 textmining:583

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: Holliday junction ATP-dependent DNA helicase RuvA
  • MTBC0 PGAP product: Holliday junction branch migration protein RuvA
  • Pfam (hmmscan --cut_ga): RuvA_N PF01330.28 (E=7e-22), HHH_5 PF14520.13 (E=4e-14), RuvA_C PF07499.20 (E=7e-10)
  • (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_217109.1)
  • Domains: Pfam-A via hmmscan --cut_ga — RuvA_N (PF01330.28), HHH_5 (PF14520.13), RuvA_C (PF07499.20)
  • 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 COG0632
  • Curated reference: UniProt P9WGW3 (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 — 74 functional partner(s); context anchor ruvB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002760|Rv2593c|ruvA
MIASVRGEVLEVALDHVVIEAAGVGYRVNATPATLATLRQGTEARLITAMIVREDSMTLYGFPDGETRDLFLTLLSVSGVGPRLAMAALAVHDAPALRQVLADGNVAALTRVPGIGKRGAERMVLELRDKVGVAATGGALSTNGHAVRSPVVEALVGLGFAAKQAEEATDTVLAANHDATTSSALRSALSLLGKAR