UniProt Accession

 HIPA_ECOLI;  P23874;  P76139;  P76880;  P77507

Genbank Protein ID

 M61242;  U00096;  AP009048

Genbank Nucleotide ID

 AAA56878.1;  AAC74580.1;  BAA15179.2

Protein Name

 Serine/threonine-protein kinase HipA

Protein Synonyms/Alias

 Ser/Thr-protein kinase HipA

Gene Name

 hipA

Gene Synonyms/Alias

 b1507, JW1500

Created Date

 3-June-2014

Organism

 Escherichia coli (strain K12)

NCBI Taxa ID

 83333

Phosphorylation

Reference

 [1]Phosphoproteome analysis of E. coli reveals evolutionary conservation of bacterial Ser/Thr/Tyr phosphorylation.
 Macek B,Gnad F,Soufi B,Kumar C,Olsen JV,Mijakovic I,Mann M
 Mol. Cell Proteomics 2008, Feb;7(2):299-307. [PMID:17938405]

Functional Description From UniProt

 FUNCTION: Toxic component of a toxin-antitoxin (TA) module Phosphorylates Glu-tRNA-ligase (GltX, on 'Ser-239') in vivo 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 ppGpp levels, which inhibits replication, transcription, translation and cell wall synthesis, reducing growth and leading to multidrug resistance and persistence. 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. Wild-type cells produce persisters at a frequency of 10(-6) to 10(-5) whereas mutant hipA7 cells produce persisters at a frequency of 10(-2). Generation of persister cells requires ppGpp as cells lacking relA or relA/spoT generate fewer or no persister cells respectively compared to hipA7. Low level expression of HipA induces dormancy and depending on the protein level, can be toxic enough to reduce cell growth or even kill cells. Low levels of wild-type HipA lead to high beta- lactam antibiotic tolerance of the survivor cells, also dependent on relA and relA/spoT. The toxic effect of HipA is neutralized by its cognate antitoxin HipB. With HipB acts as a corepressor for transcription of the hipBA promoter; binding to DNA induces a 70 degree bend

Sequence Annotation From UniProt

 MOD_RES 150 150 Phosphoserine; by autocatalysis

Key Word From UniProt

 3D-structure; Antibioticresistance; ATP-binding; Completeproteome; Directproteinsequencing; DNA-binding; Kinase; Nucleotide-binding; Phosphoprotein; Referenceproteome; Repressor; Serine/threonine-proteinkinase; Toxin; Transferase

Protein Sequence

  GO:0005524   F:ATP binding IDA:EcoCyc
  GO:0003677   F:DNA binding IEA:UniProtKB-KW
  GO:0000287   F:magnesium ion binding IDA:EcoCyc
  GO:0004674   F:protein serine/threonine kinase activity IDA:EcoCyc
  GO:0022611   P:dormancy process IDA:EcoCyc
  GO:0043086   P:negative regulation of catalytic activity IDA:EcoCyc
  GO:0036289   P:peptidyl-serine autophosphorylation IDA:EcoCyc
  GO:0046677   P:response to antibiotic IEA:UniProtKB-KW
  GO:0044010   P:single-species biofilm formation IMP:EcoCyc

  IPR012893   HipA-like_C.
  IPR017508   HipA_N1.
  IPR012894   HipA_N2.

  PF13657   Couple_hipA.
  PF07804   HipA_C.
  PF07805   HipA_N.