UniProt functional annotation for P03004

UniProt code: P03004.

Organism: Escherichia coli (strain K12).
Taxonomy: Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales; Enterobacteriaceae; Escherichia.
 
Function: Plays a key role in the initiation and regulation of chromosomal replication. Binds in an ATP-dependent fashion to the origin of replication (oriC) to initiate formation of the DNA replication initiation complex exactly once per cell cycle. Binds the DnaA box (consensus sequence 5'-TTATC[CA]A[CA]A-3'); subsequent binding of DNA polymerase III subunits leads to replisome formation. The DnaA- ATP form converts to DnaA-ADP; once converted to ADP the protein cannot initiate replication, ensuring only 1 round of replication per cell cycle. DnaA can inhibit its own gene expression as well as that of other genes such as dam, rpoH, ftsA and mioC.
 
Function: Also required for replication of plasmid DNA; binds 4 dnaA boxes in the minimal plasmid RK2 replication origin (oriV).
 
Activity regulation: Acetylation decreases the binding abilities to ATP and ADP and leads to inhibition of DNA replication initiation. {ECO:0000269|PubMed:27484197}.
Subunit: Some 20 DnaA protein molecules bind their sites in oriC. Forms the RIDA (regulatory inactivation of DnaA) complex with ATP-DnaA, ADP- Hda and the DNA-loaded sliding beta clamp (dnaN). Interacts with DiaA; this stimulates the association of DnaA with the origin of replication. {ECO:0000269|PubMed:17699754, ECO:0000269|PubMed:18977760}.
Subcellular location: Cytoplasm.
Ptm: Acetylated at Lys-178 by PatZ. Deacetylated by CobB. Is also acetylated nonenzymatically by acetyl-phosphate. Acetylation level increases in a growth phase-dependent manner and peaks at the stationnary phase. {ECO:0000269|PubMed:27484197}.
Miscellaneous: At least 4 systems specifically target DnaA to prevent more than 1 round of replication initiation per cell cycle. 1: SeqA binds to and sequesters hemimethylated oriC, preventing DnaA binding. 2: ATP-DnaA binds to the chromosomal datA locus, sequestering ATP-DnaA. 3: ATP-DnaA binds to its own promoter, repressing transcription. 4: RIDA (regulatory inactivation of DnaA) via Hda and the DNA-loaded beta clamp hydrolyzes ATP-DnaA to ADP-DnaA.
Similarity: Belongs to the DnaA family. {ECO:0000305}.
Sequence caution: Sequence=AAA62053.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.