Rv2559c Resolved · high auto-curated

H37Rv Rv2559c · MTBC0 mtbc0_002727 · 452 aa · 2902116–2903474 (-) · RefSeq NP_217075.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationreplication-associated recombination protein A
Revised (this work)Replication-associated recombination protein A. Pfam: RuvB_N (PF05496.19), Sigma54_activ_2 (PF14532.13), AAA (PF00004.36), AAA_5 (PF07728.21), AAA_assoc_2 (PF16193.12), MgsA_C (PF12002.14).

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

Curated reference (UniProt)

UniProt P9WQN1 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized AAA domain-containing protein Rv2559c

UniProt still lists this protein as Uncharacterized AAA domain-containing protein Rv2559c; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category L Replication, recombination and repair
Preferred namerarA
eggNOG descriptionaaa ATPase
Orthologous groupCOG2256
KEGG orthology K07478

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 0.253 · purifying
Polymorphic sites (≥ 0.1% of strains) 3 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
RuvB_NPF05496.19 1.6e-1235–153 Holliday junction DNA helicase RuvB P-loop domain
Sigma54_activ_2PF14532.13 3.6e-0666–177 Sigma-54 interaction domain
AAAPF00004.36 1.8e-1468–171 ATPase family associated with various cellular activities (AAA)
AAA_5PF07728.21 5.3e-0868–159 AAA domain (dynein-related subfamily)
AAA_assoc_2PF16193.12 5.7e-25202–277 AAA C-terminal domain
MgsA_CPF12002.14 1.8e-67278–443 MgsA AAA+ ATPase C terminal

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

PartnerProductScoreNo text-miningChannels (≥400)
Rv2560 hyp hypothetical protein 773 774 ctx neighborhood:773
Rv2566 hyp hypothetical protein 600 600 ctx neighborhood:599
Rv2438c nadE glutamine-dependent NAD(+) synthetase 579 576 coexpression:489
Rv2847c cysG multifunctional uroporphyrin-III C-methyltransferase/precorrin-2 oxidase/ferrochelatase 411 412
Rv1650 pheT phenylalanine--tRNA ligase subunit beta 408 409
Rv2116 lppK lipoprotein LppK 439 406 experimental:404
Rv2603c transcriptional regulator 405 406
Rv0002 dnaN DNA polymerase III subunit beta 438 405 experimental:404
Rv2592c ruvB Holliday junction ATP-dependent DNA helicase RuvB 461 404
Rv1537 dinX DNA polymerase IV 428 391
Rv3056 dinP DNA polymerase IV 2 405 366
Rv2101 helZ helicase HelZ 425 341
Rv2593c ruvA Holliday junction ATP-dependent DNA helicase RuvA 415 326
Rv1901 cinA competence damage-inducible protein CinA 471 306
Rv1629 polA DNA polymerase I 574 287 textmining:428

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: hypothetical protein
  • MTBC0 PGAP product: replication-associated recombination protein A
  • Pfam (hmmscan --cut_ga): RuvB_N PF05496.19 (E=2e-12), Sigma54_activ_2 PF14532.13 (E=4e-06), AAA PF00004.36 (E=2e-14), AAA_5 PF07728.21 (E=5e-08), AAA_assoc_2 PF16193.12 (E=6e-25), MgsA_C PF12002.14 (E=2e-67)
  • (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_217075.1)
  • Domains: Pfam-A via hmmscan --cut_ga — RuvB_N (PF05496.19), Sigma54_activ_2 (PF14532.13), AAA (PF00004.36), AAA_5 (PF07728.21), AAA_assoc_2 (PF16193.12), MgsA_C (PF12002.14)
  • 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 COG2256
  • Curated reference: UniProt P9WQN1 (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 — 15 functional partner(s)
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002727|Rv2559c|
MPEAVSDGLFDVPGVPMTSGHDLGASAGAPLAVRMRPASLDEVVGQDHLLAPGSPLRRLVEGSGVASVILYGPPGSGKTTLAALISQATGRRFEALSALSAGVKEVRAVIENSRKALLHGEQTVLFIDEVHRFSKTQQDALLSAVEHRVVLLVAATTENPSFSVVAPLLSRSLILQLRPLTAEDTRAVVQRAIDDPRGLGRAVAVAPEAVDLLVQLAAGDARRALTALEVAAEAAQAAGELVSVQTIERSVDKAAVRYDRDGDQHYDVVSAFIKSVRGSDVDAALHYLARMLVAGEDPRFIARRLMILASEDIGMADPSALQVAVAAAQTVALIGMPEAQLTLAHATIHLATAPKSNAVTTALAAAMNDIKAGKAGLVPAHLRDGHYSGAAALGNAQGYKYSHDDPDGVVAQQYPPDELVDVDYYRPTGRGGEREIAGRLDRLRAIIRKKRG