dnaA Resolved · high auto-curated

H37Rv Rv0001 · MTBC0 mtbc0_000001 · 507 aa · 1–1524 (+) · RefSeq NP_214515.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)chromosomal replication initiator protein DnaA
MTBC0 PGAP re-annotationchromosomal replication initiator protein DnaA
Revised (this work)Chromosomal replication initiator protein DnaA. Pfam: Bac_DnaA (PF00308.25), IstB_IS21 (PF01695.24), AAA (PF00004.36), Bac_DnaA_C (PF08299.18).

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

Curated reference (UniProt)

UniProt P9WNW3 SwissProt · reviewed · Evidence at protein level
UniProt nameChromosomal replication initiator protein DnaA
EC (curated) EC 3.6.4.-
Curated functionPlays an essential role in the initiation and regulation of chromosomal replication. ATP-DnaA binds to the origin of replication (oriC) to initiate formation of the DNA replication initiation complex once per cell cycle. Binds the DnaA box (a 9 base pair repeat at the origin) and separates the double-stranded (ds)DNA. Forms a right-handed helical filament on oriC DNA; dsDNA binds to the exterior of the filament while single-stranded (ss)DNA is stabiized in the filament's interior. The ATP-DnaA-oriC complex binds and stabilizes one strand of the AT-rich DNA unwinding element (DUE), permitting l.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category L Replication, recombination and repair
Preferred namednaA
eggNOG descriptionit binds specifically double-stranded DNA at a 9 bp consensus (dnaA box) 5'-TTATC CA A CA A-3'. DnaA binds to ATP and to acidic phospholipids
Orthologous groupCOG0593
KEGG orthology K02313
KEGG pathways map02020, map04112
Gene Ontology (114) GO:0000166, GO:0003674, GO:0003676, GO:0003677, GO:0003688, GO:0003690, GO:0003824, GO:0005488, GO:0005524, GO:0005575, GO:0005618, GO:0005622 +102 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 0.634 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 7 synonymous, 14 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
Bac_DnaAPF00308.25 9.8e-78168–329 Bacterial DnaA ATPAse domain
IstB_IS21PF01695.24 6.2e-07204–307 IstB-like ATP binding protein
AAAPF00004.36 1.1e-04205–323 ATPase family associated with various cellular activities (AAA)
Bac_DnaA_CPF08299.18 4.6e-27415–480 Bacterial dnaA protein helix-turn-helix

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

Closest characterised functional partner: dnaN (DNA polymerase III subunit beta), high confidence from genomic context alone (score 966 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0002 dnaN DNA polymerase III subunit beta 998 966 ctx cooccurence:520 coexpression:711 experimental:737 textmining:965
Rv2116 lppK lipoprotein LppK 932 924 coexpression:707 experimental:737
Rv0058 dnaB replicative DNA helicase 959 796 experimental:785 textmining:812
Rv0003 recF DNA replication/repair protein RecF 958 712 coexpression:520 textmining:862
Rv3918c parA chromosome partitioning protein ParA 725 606
Rv3213c SOJ/ParA-like protein 693 571
Rv1708 initiation inhibitor protein 774 555 textmining:515
Rv3923c rnpA ribonuclease P protein component 834 552 coexpression:477 textmining:645
Rv3921c yidC membrane protein insertase YidC 770 539 textmining:522
Rv0113 gmhA phosphoheptose isomerase 554 495 experimental:469
Rv3116 moeB2 molybdenum cofactor biosynthesis protein MoeB 479 480 coexpression:415
Rv3206c moeB1 adenylyltransferase/sulfurtransferase MoeZ 475 476 coexpression:410
Rv1298 rpmE 50S ribosomal protein L31 446 447 coexpression:428
Rv2986c hupB DNA-binding protein HU 636 429 experimental:417
Rv1674c transcriptional regulator 460 429 coexpression:410

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: chromosomal replication initiator protein DnaA
  • MTBC0 PGAP product: chromosomal replication initiator protein DnaA
  • Pfam (hmmscan --cut_ga): Bac_DnaA PF00308.25 (E=1e-77), IstB_IS21 PF01695.24 (E=6e-07), AAA PF00004.36 (E=1e-04), Bac_DnaA_C PF08299.18 (E=5e-27)
  • (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_214515.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Bac_DnaA (PF00308.25), IstB_IS21 (PF01695.24), AAA (PF00004.36), Bac_DnaA_C (PF08299.18)
  • 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 COG0593
  • Curated reference: UniProt P9WNW3 (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 — 97 functional partner(s); context anchor dnaN
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000001|Rv0001|dnaA
MTDDPGSGFTTVWNAVVSELNGDPKVDDGPSSDANLSAPLTPQQRAWLNLVQPLTIVEGFALLSVPSSFVQNEIERHLRAPITDALSRRLGHQIQLGVRIAPPATDEADDTTVPPSENPATTSPDTTTDNDEIDDSAAARGDNQHSWPSYFTERPHNTDSATAGVTSLNRRYTFDTFVIGASNRFAHAAALAIAEAPARAYNPLFIWGESGLGKTHLLHAAGNYAQRLFPGMRVKYVSTEEFTNDFINSLRDDRKVAFKRSYRDVDVLLVDDIQFIEGKEGIQEEFFHTFNTLHNANKQIVISSDRPPKQLATLEDRLRTRFEWGLITDVQPPELETRIAILRKKAQMERLAVPDDVLELIASSIERNIRELEGALIRVTAFASLNKTPIDKALAEIVLRDLIADANTMQISAATIMAATAEYFDTTVEELRGPGKTRALAQSRQIAMYLCRELTDLSLPKIGQAFGRDHTTVMYAQRKILSEMAERREVFDHVKELTTRIRQRSKR