uvrD2 Resolved · high auto-curated

H37Rv Rv3198c · MTBC0 mtbc0_003401 · 700 aa · 3591251–3593353 (-) · RefSeq NP_217714.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ATP-dependent DNA helicase UvrD
MTBC0 PGAP re-annotationATP-dependent DNA helicase UvrD2
Revised (this work)ATP-dependent DNA helicase UvrD2. Pfam: UvrD-helicase (PF00580.28), AAA_19 (PF13245.13), UvrD_C (PF13361.13), HRDC (PF00570.29).

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

Curated reference (UniProt)

UniProt P9WMP9 SwissProt · reviewed · Evidence at protein level
UniProt nameATP-dependent DNA helicase UvrD2
EC (curated) EC 5.6.2.4
Curated functionDNA-dependent ATPase, stimulated equally by ss- and dsDNA. Has both ATPase and helicase activities, and translocates along ssDNA displacing bound streptavidin. Its essentiality for growth does not depend on its helicase activity.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category L Replication, recombination and repair
Preferred nameuvrD2
eggNOG descriptionDNA helicase
Orthologous groupCOG0210
EC number EC 3.6.4.12
KEGG orthology K03657
KEGG pathways map03420, map03430
Gene Ontology (28) GO:0000287, GO:0003674, GO:0003678, GO:0003824, GO:0004386, GO:0005488, GO:0006996, GO:0008094, GO:0008150, GO:0009987, GO:0016043, GO:0016462 +16 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 0.296 · purifying
Polymorphic sites (≥ 0.1% of strains) 10 synonymous, 8 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
UvrD-helicasePF00580.28 9.2e-5612–287 UvrD/REP helicase N-terminal domain
AAA_19PF13245.13 6.1e-2616–271 AAA domain
UvrD_CPF13361.13 1.0e-19453–560 UvrD-like helicase C-terminal domain
HRDCPF00570.29 1.3e-21630–696 HRDC domain

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

Closest characterised functional partner: adnA (ATP-dependent DNA helicase), high confidence from genomic context alone (score 891 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3201c adnB ATP-dependent DNA helicase 959 959 database:900
Rv0949 uvrD1 ATP-dependent DNA helicase UvrD 950 926 database:900
Rv3202c adnA ATP-dependent DNA helicase 890 891 ctx cooccurence:563 database:540
Rv2737c recA recombinase A 814 744 experimental:632
Rv1633 uvrB excinuclease ABC subunit UvrB 931 690 experimental:564 textmining:788
Rv0002 dnaN DNA polymerase III subunit beta 699 658 experimental:456
Rv3198A glutaredoxin protein 603 589 ctx neighborhood:587
Rv1638 uvrA excinuclease ABC subunit UvrA 876 580 textmining:717
Rv0937c mku non-homologous end joining protein Ku 669 543 database:540
Rv2343c dnaG DNA primase 579 541 ctx cooccurence:467
Rv1650 pheT phenylalanine--tRNA ligase subunit beta 538 537
Rv0667 rpoB DNA-directed RNA polymerase subunit beta 550 508 experimental:431
Rv3014c ligA DNA ligase A 545 503 coexpression:486
Rv0058 dnaB replicative DNA helicase 566 501
Rv2593c ruvA Holliday junction ATP-dependent DNA helicase RuvA 615 492

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-dependent DNA helicase UvrD
  • MTBC0 PGAP product: ATP-dependent DNA helicase UvrD2
  • Pfam (hmmscan --cut_ga): UvrD-helicase PF00580.28 (E=9e-56), AAA_19 PF13245.13 (E=6e-26), UvrD_C PF13361.13 (E=1e-19), HRDC PF00570.29 (E=1e-21)
  • (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_217714.1)
  • Domains: Pfam-A via hmmscan --cut_ga — UvrD-helicase (PF00580.28), AAA_19 (PF13245.13), UvrD_C (PF13361.13), HRDC (PF00570.29)
  • 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 COG0210
  • Curated reference: UniProt P9WMP9 (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 — 50 functional partner(s); context anchor adnA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003401|Rv3198c|uvrD2
MSIASDPLIAGLDDQQREAVLAPRGPVCVLAGAGTGKTRTITHRIASLVASGHVAAGQVLAVTFTQRAAGEMRSRLRALDAAARTGSGVGAVQALTFHAAAYRQLRYFWSRVIADTGWQLLDSKFAVVARAASRTRLHASTDDVRDLAGEIEWAKASLIGPEEYVTAVAAARRDPPLDAAQIAAVYSEYEALKARGDGVTLLDFDDLLLHTAAAIENDAAVAEEFQDRYRCFVVDEYQDVTPLQQRVLSAWLGDRDDLTVVGDANQTIYSFTGASPRFLLDFSRRFPDAAVVRLERDYRSTPQVVSLANRVIAAARGRVAGSKLRLSGQREPGPVPSFHEHSDEPAEAATVAASIARLIASGTPPSEVAILYRVNAQSEVYEEALTQAGIAYQVRGGEGFFNRQEIKQALLALQRVSERDTDAALSDVVRAVLAPLGLTAQPPVGTRARERWEALTALAELVDDELAQRPALQLPGLLAELRRRAEARHPPVVQGVTLASLHAAKGLEWDAVFLVGLADGTLPISHALAHGPNSEPVEEERRLLYVGITRARVHLALSWALSRSPGGRQSRKPSRFLNGIAPQTRADPVPGTSRRNRGAAARCRICNNELNTSAAVMLRRCETCAADVDEELLLQLKSWRLSTAKEQNVPAYVVFTDNTLIAIAELLPTDDAALIAIPGIGARKLEQYGSDVLQLVRGRT