Toxic component of a type II toxin-antitoxin (TA) system, first identified by mutations that increase production of persister cells, a fraction of cells that are phenotypic variants not killed by antibiotics, which lead to multidrug tolerance (PubMed:6348026, PubMed:8021189, PubMed:16707675, PubMed:26222023). Persistence may be ultimately due to global remodeling of the persister cell's ribosomes (PubMed:25425348). Phosphorylates Glu-tRNA-ligase (AC P04805, gltX, on 'Ser-239') in vivo (PubMed:24095282, PubMed:24343429). Phosphorylation of GltX prevents it from being charged, leading to an increase in uncharged tRNA(Glu). This induces amino acid starvation and the stringent response via RelA/SpoT and increased (p)ppGpp levels, which inhibits replication, transcription, translation and cell wall synthesis, reducing growth and leading to persistence and multidrug resistance (PubMed:24095282, PubMed:24343429). Once the level of HipA exceeds a threshold cells become dormant, and the length of dormancy is determined by how much HipA levels exceed the threshold (PubMed:20616060). The hipA7 mutation (a double G22S D291A mutation) leads to increased generation of persister cells (cells that survive antibiotic treatment) probably by entering into a dormant state, as well as cold-sensitivity (PubMed:14622409, PubMed:16707675). Wild-type cells produce persisters at a frequency of 10(-6) to 10(-5) whereas hipA7 cells produce about 100-fold more persisters (PubMed:14622409, PubMed:16707675, PubMed:25425348). hipA7 decreases the affinity for antitoxin HipB, leading to increased HipA levels and persistence (PubMed:20616060); depending on the protein level, can be toxic enough to reduce cell growth or even kill cells. Generation of persister cells requires (p)ppGpp as cells lacking relA or relA/spoT generate fewer or no persister cells respectively compared to hipA7 (PubMed:14622409). The toxic effect of HipA is neutralized by its cognate antitoxin HipB (PubMed:20616060). Also neutralized by overexpression of gltX (PubMed:24343429, PubMed:28430938). With HipB acts as a corepressor for transcription of the hipBA promoter (PubMed:8021189); binding of HipA-HipB to DNA induces a 70 degree bend (PubMed:19150849, PubMed:26222023). This brings together and dimerizes 2 HipA molecules, which distorts the promoter region, preventing sigma-factor binding; additionally HipA and HipB would physically prevent RNA core polymerase from contacting the -35 promoter box (PubMed:26222023). May play a role in biofilm formation (PubMed:23329678). ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein] ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein] Once phosphorylated no longer has kinase activity. Forms a HipA(2)HipB(2) heterotetramer which can interact with a single operator on DNA (PubMed:19150849). When 2 operators are present each HipB dimer contacts 1 HipA molecule, which are brought together by the DNA bend and dimerize, blocking the HipA active site and inactivating its toxic activity (PubMed:26222023). Mutations present in allele hipA7 (G22S and D291A) decrease the affinity of HipA for HipB (PubMed:20616060). Autophosphorylates intermolecularly on Ser-150; phosphorylated form not seen to bind ATP and no longer has kinase activity. Phosphorylated form. A hipA or a hipB-hipA operon deletion have no visible phenotype (PubMed:20616060). Initially cells lacking hipA or the hipBA operon were thought not to produce persister cells at a high frequency; this was later shown to be a strain-specific phenotype (PubMed:8021189). A hipA or a hipB-hipA operon deletion show decreased biofilm production in the absence of antibiotics (PubMed:23329678). The hipA7 allele (G22S and D291A) as well as a P86L mutation have been identified in E.coli isolates from human patients with urinary tract infections, showing the mutations may be clinically relevant (PubMed:26222023). Belongs to the HipA Ser/Thr kinase family. Has been reported to phosphorylate EF-Tu in vitro (on 'Thr-383') (PubMed:19150849). According to another report, does not phosphorylate EF-Tu (PubMed:19622872).