HIPA_ECOLI
ID HIPA_ECOLI Reviewed; 440 AA.
AC P23874; P76139; P76880; P77507;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2003, sequence version 2.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Serine/threonine-protein kinase toxin HipA;
DE Short=Ser/Thr-protein kinase HipA;
DE EC=2.7.11.1 {ECO:0000269|PubMed:19150849};
DE AltName: Full=Toxin HipA;
GN Name=hipA; OrderedLocusNames=b1507, JW1500;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12;
RX PubMed=1715862; DOI=10.1128/jb.173.18.5732-5739.1991;
RA Black D.S., Kelly A.J., Mardis M.J., Moyed H.S.;
RT "Structure and organization of hip, an operon that affects lethality due to
RT inhibition of peptidoglycan or DNA synthesis.";
RL J. Bacteriol. 173:5732-5739(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [4]
RP PROTEIN SEQUENCE OF 134-157, FUNCTION AS A KINASE, ACTIVE SITE,
RP PHOSPHORYLATION AT SER-150, ANTIBIOTIC TOLERANCE, AND MUTAGENESIS OF
RP SER-150; ASP-309 AND ASP-332.
RC STRAIN=K12;
RX PubMed=17041039; DOI=10.1128/jb.01237-06;
RA Correia F.F., D'Onofrio A., Rejtar T., Li L., Karger B.L., Makarova K.,
RA Koonin E.V., Lewis K.;
RT "Kinase activity of overexpressed HipA is required for growth arrest and
RT multidrug tolerance in Escherichia coli.";
RL J. Bacteriol. 188:8360-8367(2006).
RN [5]
RP MUTANT HIPA7 ISOLATION, FUNCTION IN ANTIBIOTIC TOLERANCE, AND ROLE IN
RP PERSISTENCE.
RC STRAIN=K12;
RX PubMed=6348026; DOI=10.1128/jb.155.2.768-775.1983;
RA Moyed H.S., Bertrand K.P.;
RT "hipA, a newly recognized gene of Escherichia coli K-12 that affects
RT frequency of persistence after inhibition of murein synthesis.";
RL J. Bacteriol. 155:768-775(1983).
RN [6]
RP CLONING.
RC STRAIN=K12;
RX PubMed=3516974; DOI=10.1128/jb.166.2.399-403.1986;
RA Moyed H.S., Broderick S.H.;
RT "Molecular cloning and expression of hipA, a gene of Escherichia coli K-12
RT that affects frequency of persistence after inhibition of murein
RT synthesis.";
RL J. Bacteriol. 166:399-403(1986).
RN [7]
RP FUNCTION AS A TOXIN, FUNCTION AS A TRANSCRIPTIONAL REPRESSOR, AND
RP DISRUPTION PHENOTYPE.
RC STRAIN=K12;
RX PubMed=8021189; DOI=10.1128/jb.176.13.4081-4091.1994;
RA Black D.S., Irwin B., Moyed H.S.;
RT "Autoregulation of hip, an operon that affects lethality due to inhibition
RT of peptidoglycan or DNA synthesis.";
RL J. Bacteriol. 176:4081-4091(1994).
RN [8]
RP FUNCTION AS A TOXIN, FUNCTION IN PERSISTENCE, REQUIREMENT FOR (P)PPGPP, AND
RP MUTAGENESIS OF GLY-22; ASP-88 AND ASP-291.
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=14622409; DOI=10.1046/j.1365-2958.2003.03779.x;
RA Korch S.B., Henderson T.A., Hill T.M.;
RT "Characterization of the hipA7 allele of Escherichia coli and evidence that
RT high persistence is governed by (p)ppGpp synthesis.";
RL Mol. Microbiol. 50:1199-1213(2003).
RN [9]
RP FUNCTION AS A TOXIN.
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=16707675; DOI=10.1128/jb.01740-05;
RA Korch S.B., Hill T.M.;
RT "Ectopic overexpression of wild-type and mutant hipA genes in Escherichia
RT coli: effects on macromolecular synthesis and persister formation.";
RL J. Bacteriol. 188:3826-3836(2006).
RN [10]
RP FUNCTION, SUBUNIT, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF GLY-22 AND
RP ASP-291.
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=20616060; DOI=10.1073/pnas.1004333107;
RA Rotem E., Loinger A., Ronin I., Levin-Reisman I., Gabay C., Shoresh N.,
RA Biham O., Balaban N.Q.;
RT "Regulation of phenotypic variability by a threshold-based mechanism
RT underlies bacterial persistence.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:12541-12546(2010).
RN [11]
RP FUNCTION, AND ROLE IN PPGPP RESPONSE.
RX PubMed=23667235; DOI=10.1128/jb.02210-12;
RA Bokinsky G., Baidoo E.E., Akella S., Burd H., Weaver D.,
RA Alonso-Gutierrez J., Garcia-Martin H., Lee T.S., Keasling J.D.;
RT "HipA-triggered growth arrest and beta-lactam tolerance in Escherichia coli
RT are mediated by RelA-dependent ppGpp synthesis.";
RL J. Bacteriol. 195:3173-3182(2013).
RN [12]
RP SUBUNIT, AND MODELING OF INTERACTION.
RX PubMed=24089363; DOI=10.1002/jmr.2300;
RA Li C., Wang Y., Wang Y., Chen G.;
RT "Interaction investigations of HipA binding to HipB dimer and HipB dimer +
RT DNA complex: a molecular dynamics simulation study.";
RL J. Mol. Recognit. 26:556-567(2013).
RN [13]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=K12 / BW25113;
RX PubMed=23329678; DOI=10.1099/mic.0.063784-0;
RA Zhao J., Wang Q., Li M., Heijstra B.D., Wang S., Liang Q., Qi Q.;
RT "Escherichia coli toxin gene hipA affects biofilm formation and DNA
RT release.";
RL Microbiology 159:633-640(2013).
RN [14]
RP FUNCTION, INTERACTION WITH HIPB, SUBUNIT, AND MASS SPECTROMETRY.
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=24095282; DOI=10.1016/j.molcel.2013.08.045;
RA Germain E., Castro-Roa D., Zenkin N., Gerdes K.;
RT "Molecular mechanism of bacterial persistence by HipA.";
RL Mol. Cell 52:248-254(2013).
RN [15]
RP FUNCTION.
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=24343429; DOI=10.1038/ncomms4001;
RA Kaspy I., Rotem E., Weiss N., Ronin I., Balaban N.Q., Glaser G.;
RT "HipA-mediated antibiotic persistence via phosphorylation of the glutamyl-
RT tRNA-synthetase.";
RL Nat. Commun. 4:3001-3001(2013).
RN [16]
RP RETRACTED PAPER.
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=25848049; DOI=10.1073/pnas.1423536112;
RA Germain E., Roghanian M., Gerdes K., Maisonneuve E.;
RT "Stochastic induction of persister cells by HipA through (p)ppGpp-mediated
RT activation of mRNA endonucleases.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:5171-5176(2015).
RN [17]
RP RETRACTION NOTICE OF PUBMED:25848049.
RX PubMed=31110010; DOI=10.1073/pnas.1906160116;
RA Germain E., Roghanian M., Gerdes K., Maisonneuve E.;
RL Proc. Natl. Acad. Sci. U.S.A. 116:11077-11077(2019).
RN [18]
RP FUNCTION, AND MUTAGENESIS OF GLY-22 AND ASP-291.
RX PubMed=25425348; DOI=10.1111/mmi.12884;
RA Cho J., Rogers J., Kearns M., Leslie M., Hartson S.D., Wilson K.S.;
RT "Escherichia coli persister cells suppress translation by selectively
RT disassembling and degrading their ribosomes.";
RL Mol. Microbiol. 95:352-364(2015).
RN [19]
RP FUNCTION AS A TOXIN.
RC STRAIN=B / BL21-DE3;
RX PubMed=28430938; DOI=10.1093/femsle/fnx086;
RA Maeda Y., Lin C.Y., Ishida Y., Inouye M., Yamaguchi Y., Phadtare S.;
RT "Characterization of YjjJ toxin of Escherichia coli.";
RL FEMS Microbiol. Lett. 0:0-0(2017).
RN [20] {ECO:0007744|PDB:2WIU}
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) IN COMPLEX WITH HIPB, AND SUBUNIT.
RC STRAIN=K12 / DH5-alpha;
RX PubMed=19622872; DOI=10.1107/s0907444909018800;
RA Evdokimov A., Voznesensky I., Fennell K., Anderson M., Smith J.F.,
RA Fisher D.A.;
RT "New kinase regulation mechanism found in HipBA: a bacterial persistence
RT switch.";
RL Acta Crystallogr. D 65:875-879(2009).
RN [21] {ECO:0007744|PDB:3DNT, ECO:0007744|PDB:3DNU, ECO:0007744|PDB:3DNV, ECO:0007744|PDB:3FBR, ECO:0007744|PDB:3HZI}
RP X-RAY CRYSTALLOGRAPHY (1.54 ANGSTROMS) ALONE AND IN COMPLEX WITH MG-ATP,
RP HIPB AND DNA, FUNCTION AS A KINASE, CATALYTIC ACTIVITY, ATP-BINDING,
RP DNA-BINDING, SUBSTRATE, AND SUBUNIT.
RX PubMed=19150849; DOI=10.1126/science.1163806;
RA Schumacher M.A., Piro K.M., Xu W., Hansen S., Lewis K., Brennan R.G.;
RT "Molecular mechanisms of HipA-mediated multidrug tolerance and its
RT neutralization by HipB.";
RL Science 323:396-401(2009).
RN [22] {ECO:0007744|PDB:3TPB, ECO:0007744|PDB:3TPD, ECO:0007744|PDB:3TPE, ECO:0007744|PDB:3TPT, ECO:0007744|PDB:3TPV}
RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) PHOSPHORYLATED AND
RP NON-PHOSPHORYLATED AND IN COMPLEX WITH ATP, ATP-BINDING, ACTIVITY
RP REGULATION, AND PHOSPHORYLATION AT SER-150.
RX PubMed=22999936; DOI=10.1016/j.celrep.2012.08.013;
RA Schumacher M.A., Min J., Link T.M., Guan Z., Xu W., Ahn Y.H.,
RA Soderblom E.J., Kurie J.M., Evdokimov A., Moseley M.A., Lewis K.,
RA Brennan R.G.;
RT "Role of unusual P loop ejection and autophosphorylation in HipA-mediated
RT persistence and multidrug tolerance.";
RL Cell Rep. 2:518-525(2012).
RN [23] {ECO:0007744|PDB:4YG7, ECO:0007744|PDB:5K98}
RP X-RAY CRYSTALLOGRAPHY (3.77 ANGSTROMS) OF 2-437 IN COMPLEX WITH HIPB AND
RP DNA, FUNCTION, SUBUNIT, AND MUTAGENESIS OF GLY-22; PRO-86 AND ASP-88.
RX PubMed=26222023; DOI=10.1038/nature14662;
RA Schumacher M.A., Balani P., Min J., Chinnam N.B., Hansen S., Vulic M.,
RA Lewis K., Brennan R.G.;
RT "HipBA-promoter structures reveal the basis of heritable multidrug
RT tolerance.";
RL Nature 524:59-64(2015).
CC -!- FUNCTION: Toxic component of a type II toxin-antitoxin (TA) system,
CC first identified by mutations that increase production of persister
CC cells, a fraction of cells that are phenotypic variants not killed by
CC antibiotics, which lead to multidrug tolerance (PubMed:6348026,
CC PubMed:8021189, PubMed:16707675, PubMed:26222023). Persistence may be
CC ultimately due to global remodeling of the persister cell's ribosomes
CC (PubMed:25425348). Phosphorylates Glu-tRNA-ligase (AC P04805, gltX, on
CC 'Ser-239') in vivo (PubMed:24095282, PubMed:24343429). Phosphorylation
CC of GltX prevents it from being charged, leading to an increase in
CC uncharged tRNA(Glu). This induces amino acid starvation and the
CC stringent response via RelA/SpoT and increased (p)ppGpp levels, which
CC inhibits replication, transcription, translation and cell wall
CC synthesis, reducing growth and leading to persistence and multidrug
CC resistance (PubMed:24095282, PubMed:24343429). Once the level of HipA
CC exceeds a threshold cells become dormant, and the length of dormancy is
CC determined by how much HipA levels exceed the threshold
CC (PubMed:20616060). The hipA7 mutation (a double G22S D291A mutation)
CC leads to increased generation of persister cells (cells that survive
CC antibiotic treatment) probably by entering into a dormant state, as
CC well as cold-sensitivity (PubMed:14622409, PubMed:16707675). Wild-type
CC cells produce persisters at a frequency of 10(-6) to 10(-5) whereas
CC hipA7 cells produce about 100-fold more persisters (PubMed:14622409,
CC PubMed:16707675, PubMed:25425348). hipA7 decreases the affinity for
CC antitoxin HipB, leading to increased HipA levels and persistence
CC (PubMed:20616060); depending on the protein level, can be toxic enough
CC to reduce cell growth or even kill cells. Generation of persister cells
CC requires (p)ppGpp as cells lacking relA or relA/spoT generate fewer or
CC no persister cells respectively compared to hipA7 (PubMed:14622409).
CC The toxic effect of HipA is neutralized by its cognate antitoxin HipB
CC (PubMed:20616060). Also neutralized by overexpression of gltX
CC (PubMed:24343429, PubMed:28430938). With HipB acts as a corepressor for
CC transcription of the hipBA promoter (PubMed:8021189); binding of HipA-
CC HipB to DNA induces a 70 degree bend (PubMed:19150849,
CC PubMed:26222023). This brings together and dimerizes 2 HipA molecules,
CC which distorts the promoter region, preventing sigma-factor binding;
CC additionally HipA and HipB would physically prevent RNA core polymerase
CC from contacting the -35 promoter box (PubMed:26222023). May play a role
CC in biofilm formation (PubMed:23329678). {ECO:0000269|PubMed:14622409,
CC ECO:0000269|PubMed:16707675, ECO:0000269|PubMed:17041039,
CC ECO:0000269|PubMed:19150849, ECO:0000269|PubMed:20616060,
CC ECO:0000269|PubMed:23329678, ECO:0000269|PubMed:23667235,
CC ECO:0000269|PubMed:24095282, ECO:0000269|PubMed:24343429,
CC ECO:0000269|PubMed:25425348, ECO:0000269|PubMed:26222023,
CC ECO:0000269|PubMed:28430938, ECO:0000269|PubMed:6348026,
CC ECO:0000269|PubMed:8021189}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:19150849};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000269|PubMed:19150849};
CC -!- ACTIVITY REGULATION: Once phosphorylated no longer has kinase activity.
CC {ECO:0000269|PubMed:22999936}.
CC -!- SUBUNIT: Forms a HipA(2)HipB(2) heterotetramer which can interact with
CC a single operator on DNA (PubMed:19150849). When 2 operators are
CC present each HipB dimer contacts 1 HipA molecule, which are brought
CC together by the DNA bend and dimerize, blocking the HipA active site
CC and inactivating its toxic activity (PubMed:26222023). Mutations
CC present in allele hipA7 (G22S and D291A) decrease the affinity of HipA
CC for HipB (PubMed:20616060). {ECO:0000269|PubMed:19150849,
CC ECO:0000269|PubMed:19622872, ECO:0000269|PubMed:20616060,
CC ECO:0000269|PubMed:22999936, ECO:0000269|PubMed:24089363,
CC ECO:0000269|PubMed:24095282, ECO:0000269|PubMed:26222023}.
CC -!- INTERACTION:
CC P23874; P75989: bluR; NbExp=2; IntAct=EBI-560590, EBI-560582;
CC P23874; P23873: hipB; NbExp=2; IntAct=EBI-560590, EBI-1129654;
CC -!- PTM: Autophosphorylates intermolecularly on Ser-150; phosphorylated
CC form not seen to bind ATP and no longer has kinase activity.
CC {ECO:0000269|PubMed:17041039, ECO:0000269|PubMed:22999936}.
CC -!- MASS SPECTROMETRY: Mass=49143.80; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:24095282};
CC -!- MASS SPECTROMETRY: Mass=49223.80; Method=MALDI; Note=Phosphorylated
CC form.; Evidence={ECO:0000269|PubMed:24095282};
CC -!- DISRUPTION PHENOTYPE: A hipA or a hipB-hipA operon deletion have no
CC visible phenotype (PubMed:20616060). Initially cells lacking hipA or
CC the hipBA operon were thought not to produce persister cells at a high
CC frequency; this was later shown to be a strain-specific phenotype
CC (PubMed:8021189). A hipA or a hipB-hipA operon deletion show decreased
CC biofilm production in the absence of antibiotics (PubMed:23329678).
CC {ECO:0000269|PubMed:20616060, ECO:0000269|PubMed:23329678,
CC ECO:0000269|PubMed:8021189}.
CC -!- MISCELLANEOUS: The hipA7 allele (G22S and D291A) as well as a P86L
CC mutation have been identified in E.coli isolates from human patients
CC with urinary tract infections, showing the mutations may be clinically
CC relevant (PubMed:26222023). {ECO:0000269|PubMed:26222023}.
CC -!- SIMILARITY: Belongs to the HipA Ser/Thr kinase family. {ECO:0000305}.
CC -!- CAUTION: Has been reported to phosphorylate EF-Tu in vitro (on 'Thr-
CC 383') (PubMed:19150849). According to another report, does not
CC phosphorylate EF-Tu (PubMed:19622872). {ECO:0000305|PubMed:19150849,
CC ECO:0000305|PubMed:19622872}.
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DR EMBL; M61242; AAA56878.1; -; Genomic_DNA.
DR EMBL; U00096; AAC74580.1; -; Genomic_DNA.
DR EMBL; AP009048; BAA15179.2; -; Genomic_DNA.
DR PIR; F64904; F64904.
DR RefSeq; NP_416024.1; NC_000913.3.
DR RefSeq; WP_001125439.1; NZ_SSZK01000001.1.
DR PDB; 2WIU; X-ray; 2.35 A; A/C=1-440.
DR PDB; 3DNT; X-ray; 1.66 A; A/B=1-440.
DR PDB; 3DNU; X-ray; 1.54 A; A=1-440.
DR PDB; 3DNV; X-ray; 2.68 A; A=1-440.
DR PDB; 3FBR; X-ray; 3.50 A; A=1-437.
DR PDB; 3HZI; X-ray; 2.98 A; A=1-440.
DR PDB; 3TPB; X-ray; 1.88 A; A=1-440.
DR PDB; 3TPD; X-ray; 1.50 A; A=1-440.
DR PDB; 3TPE; X-ray; 1.90 A; A=1-440.
DR PDB; 3TPT; X-ray; 2.25 A; A/B=1-440.
DR PDB; 3TPV; X-ray; 2.30 A; B=1-440.
DR PDB; 4YG7; X-ray; 3.77 A; D/K=2-437.
DR PDB; 5K98; X-ray; 3.99 A; A/D=2-440.
DR PDBsum; 2WIU; -.
DR PDBsum; 3DNT; -.
DR PDBsum; 3DNU; -.
DR PDBsum; 3DNV; -.
DR PDBsum; 3FBR; -.
DR PDBsum; 3HZI; -.
DR PDBsum; 3TPB; -.
DR PDBsum; 3TPD; -.
DR PDBsum; 3TPE; -.
DR PDBsum; 3TPT; -.
DR PDBsum; 3TPV; -.
DR PDBsum; 4YG7; -.
DR PDBsum; 5K98; -.
DR AlphaFoldDB; P23874; -.
DR SMR; P23874; -.
DR BioGRID; 4260220; 11.
DR ComplexPortal; CPX-180; HipBA toxin-antitoxin complex.
DR DIP; DIP-9898N; -.
DR IntAct; P23874; 4.
DR STRING; 511145.b1507; -.
DR ChEMBL; CHEMBL4524022; -.
DR iPTMnet; P23874; -.
DR jPOST; P23874; -.
DR PaxDb; P23874; -.
DR PRIDE; P23874; -.
DR EnsemblBacteria; AAC74580; AAC74580; b1507.
DR EnsemblBacteria; BAA15179; BAA15179; BAA15179.
DR GeneID; 946064; -.
DR KEGG; ecj:JW1500; -.
DR KEGG; eco:b1507; -.
DR PATRIC; fig|1411691.4.peg.760; -.
DR EchoBASE; EB0438; -.
DR eggNOG; COG3550; Bacteria.
DR HOGENOM; CLU_030167_2_1_6; -.
DR InParanoid; P23874; -.
DR OMA; SDIPLGM; -.
DR PhylomeDB; P23874; -.
DR BioCyc; EcoCyc:EG10443-MON; -.
DR BioCyc; MetaCyc:EG10443-MON; -.
DR EvolutionaryTrace; P23874; -.
DR PRO; PR:P23874; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR CollecTF; EXPREG_00000970; -.
DR GO; GO:0005829; C:cytosol; IDA:EcoCyc.
DR GO; GO:0032993; C:protein-DNA complex; IPI:CollecTF.
DR GO; GO:0110001; C:toxin-antitoxin complex; IPI:ComplexPortal.
DR GO; GO:0005524; F:ATP binding; IDA:EcoCyc.
DR GO; GO:0001217; F:DNA-binding transcription repressor activity; IPI:CollecTF.
DR GO; GO:0000287; F:magnesium ion binding; IDA:EcoCyc.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:EcoCyc.
DR GO; GO:0043565; F:sequence-specific DNA binding; EXP:CollecTF.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IPI:CollecTF.
DR GO; GO:0022611; P:dormancy process; IDA:EcoCyc.
DR GO; GO:0043086; P:negative regulation of catalytic activity; IDA:EcoCyc.
DR GO; GO:0036289; P:peptidyl-serine autophosphorylation; IDA:EcoCyc.
DR GO; GO:0040008; P:regulation of growth; IDA:ComplexPortal.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:ComplexPortal.
DR GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR GO; GO:0044010; P:single-species biofilm formation; IMP:EcoCyc.
DR InterPro; IPR012893; HipA-like_C.
DR InterPro; IPR017508; HipA_N1.
DR Pfam; PF13657; Couple_hipA; 1.
DR Pfam; PF07804; HipA_C; 1.
DR TIGRFAMs; TIGR03071; couple_hipA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic resistance; ATP-binding;
KW Direct protein sequencing; DNA-binding; Kinase; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Repressor;
KW Serine/threonine-protein kinase; Toxin-antitoxin system; Transferase.
FT CHAIN 1..440
FT /note="Serine/threonine-protein kinase toxin HipA"
FT /id="PRO_0000083988"
FT DNA_BIND 379..382
FT /evidence="ECO:0000269|PubMed:19150849"
FT ACT_SITE 309
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:17041039"
FT BINDING 152..157
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:22999936,
FT ECO:0007744|PDB:3DNT, ECO:0007744|PDB:3FBR,
FT ECO:0007744|PDB:3HZI, ECO:0007744|PDB:3TPT"
FT BINDING 181
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:22999936,
FT ECO:0007744|PDB:3DNT, ECO:0007744|PDB:3HZI,
FT ECO:0007744|PDB:3TPT"
FT BINDING 234..236
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:22999936,
FT ECO:0007744|PDB:3DNT, ECO:0007744|PDB:3FBR,
FT ECO:0007744|PDB:3HZI, ECO:0007744|PDB:3TPT"
FT BINDING 311..314
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:22999936,
FT ECO:0007744|PDB:3DNT, ECO:0007744|PDB:3FBR,
FT ECO:0007744|PDB:3HZI, ECO:0007744|PDB:3TPT"
FT BINDING 331..332
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:22999936,
FT ECO:0007744|PDB:3DNT, ECO:0007744|PDB:3FBR,
FT ECO:0007744|PDB:3HZI, ECO:0007744|PDB:3TPT"
FT MOD_RES 150
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:17041039,
FT ECO:0000269|PubMed:22999936"
FT MUTAGEN 22
FT /note="G->S: Loss of toxicity, does not confer high
FT persistence. Single mutation has decreased affinity for
FT HipB-operator. Loss of toxicity, high levels of persister
FT cells and cold sensitivity, decreased affinity for HipB; in
FT hipA7; when associated with A-291."
FT /evidence="ECO:0000269|PubMed:14622409,
FT ECO:0000269|PubMed:20616060, ECO:0000269|PubMed:26222023"
FT MUTAGEN 86
FT /note="P->L: High levels of persister cells formed which
FT survive better than wild-type in ampicillin or
FT ciprofloxacin, decreased affinity for HipB-operator."
FT /evidence="ECO:0000269|PubMed:26222023"
FT MUTAGEN 88
FT /note="D->N: Loss of toxicity, still confers high levels of
FT persister cells. Decreased affinity for HipB-operator."
FT /evidence="ECO:0000269|PubMed:14622409,
FT ECO:0000269|PubMed:26222023"
FT MUTAGEN 150
FT /note="S->A: No phosphorylation; cells grow normally."
FT /evidence="ECO:0000269|PubMed:17041039"
FT MUTAGEN 291
FT /note="D->A: Retains toxicity and high persistence but not
FT cold-sensitive. Loss of toxicity, high levels of persister
FT cells and cold sensitivity, decreased affinity for HipB; in
FT hipA7; when associated with S-22."
FT /evidence="ECO:0000269|PubMed:14622409,
FT ECO:0000269|PubMed:20616060"
FT MUTAGEN 309
FT /note="D->Q: Loss of autophosphorylation; cells grow
FT normally; protein can accumulate to high levels in E.coli."
FT /evidence="ECO:0000269|PubMed:17041039"
FT MUTAGEN 332
FT /note="D->Q: Loss of autophosphorylation; cells grow
FT normally."
FT /evidence="ECO:0000269|PubMed:17041039"
FT CONFLICT 40
FT /note="P -> Q (in Ref. 1; AAA56878)"
FT /evidence="ECO:0000305"
FT CONFLICT 214..215
FT /note="GL -> WV (in Ref. 1; AAA56878)"
FT /evidence="ECO:0000305"
FT CONFLICT 274
FT /note="G -> R (in Ref. 1; AAA56878)"
FT /evidence="ECO:0000305"
FT STRAND 3..8
FT /evidence="ECO:0007829|PDB:3TPD"
FT STRAND 11..18
FT /evidence="ECO:0007829|PDB:3TPD"
FT STRAND 24..28
FT /evidence="ECO:0007829|PDB:3TPD"
FT HELIX 30..34
FT /evidence="ECO:0007829|PDB:3TPD"
FT STRAND 35..37
FT /evidence="ECO:0007829|PDB:3DNV"
FT STRAND 49..52
FT /evidence="ECO:0007829|PDB:3DNT"
FT HELIX 55..62
FT /evidence="ECO:0007829|PDB:3TPD"
FT STRAND 65..67
FT /evidence="ECO:0007829|PDB:2WIU"
FT HELIX 69..79
FT /evidence="ECO:0007829|PDB:3TPD"
FT STRAND 82..85
FT /evidence="ECO:0007829|PDB:3TPV"
FT HELIX 86..93
FT /evidence="ECO:0007829|PDB:3TPD"
FT STRAND 98..100
FT /evidence="ECO:0007829|PDB:3DNT"
FT STRAND 101..104
FT /evidence="ECO:0007829|PDB:3TPD"
FT STRAND 114..116
FT /evidence="ECO:0007829|PDB:3FBR"
FT STRAND 117..119
FT /evidence="ECO:0007829|PDB:3TPD"
FT HELIX 122..130
FT /evidence="ECO:0007829|PDB:3TPD"
FT TURN 131..133
FT /evidence="ECO:0007829|PDB:3DNU"
FT HELIX 137..139
FT /evidence="ECO:0007829|PDB:3DNT"
FT STRAND 149..152
FT /evidence="ECO:0007829|PDB:3TPE"
FT STRAND 153..155
FT /evidence="ECO:0007829|PDB:3DNU"
FT STRAND 158..163
FT /evidence="ECO:0007829|PDB:3TPD"
FT STRAND 166..170
FT /evidence="ECO:0007829|PDB:3TPD"
FT STRAND 178..181
FT /evidence="ECO:0007829|PDB:3TPD"
FT STRAND 185..188
FT /evidence="ECO:0007829|PDB:3TPE"
FT STRAND 189..191
FT /evidence="ECO:0007829|PDB:3FBR"
FT STRAND 193..196
FT /evidence="ECO:0007829|PDB:3TPE"
FT HELIX 199..212
FT /evidence="ECO:0007829|PDB:3TPD"
FT STRAND 220..225
FT /evidence="ECO:0007829|PDB:3TPD"
FT STRAND 228..234
FT /evidence="ECO:0007829|PDB:3TPD"
FT STRAND 236..240
FT /evidence="ECO:0007829|PDB:3TPD"
FT STRAND 247..249
FT /evidence="ECO:0007829|PDB:3TPD"
FT STRAND 252..254
FT /evidence="ECO:0007829|PDB:3TPD"
FT HELIX 255..258
FT /evidence="ECO:0007829|PDB:3TPD"
FT HELIX 263..265
FT /evidence="ECO:0007829|PDB:3TPD"
FT HELIX 268..270
FT /evidence="ECO:0007829|PDB:3TPD"
FT HELIX 275..282
FT /evidence="ECO:0007829|PDB:3TPD"
FT HELIX 288..304
FT /evidence="ECO:0007829|PDB:3TPD"
FT HELIX 312..314
FT /evidence="ECO:0007829|PDB:3TPD"
FT STRAND 316..319
FT /evidence="ECO:0007829|PDB:3TPD"
FT HELIX 321..323
FT /evidence="ECO:0007829|PDB:3TPD"
FT STRAND 325..327
FT /evidence="ECO:0007829|PDB:3TPD"
FT HELIX 337..339
FT /evidence="ECO:0007829|PDB:3TPD"
FT STRAND 342..344
FT /evidence="ECO:0007829|PDB:3TPD"
FT HELIX 347..349
FT /evidence="ECO:0007829|PDB:3TPD"
FT STRAND 351..358
FT /evidence="ECO:0007829|PDB:3TPD"
FT STRAND 361..365
FT /evidence="ECO:0007829|PDB:3TPD"
FT HELIX 366..368
FT /evidence="ECO:0007829|PDB:3TPD"
FT HELIX 371..381
FT /evidence="ECO:0007829|PDB:3TPD"
FT HELIX 385..407
FT /evidence="ECO:0007829|PDB:3TPD"
FT STRAND 412..414
FT /evidence="ECO:0007829|PDB:3FBR"
FT HELIX 416..434
FT /evidence="ECO:0007829|PDB:3TPD"
SQ SEQUENCE 440 AA; 49276 MW; 378771C4CAB55319 CRC64;
MPKLVTWMNN QRVGELTKLA NGAHTFKYAP EWLASRYARP LSLSLPLQRG NITSDAVFNF
FDNLLPDSPI VRDRIVKRYH AKSRQPFDLL SEIGRDSVGA VTLIPEDETV THPIMAWEKL
TEARLEEVLT AYKADIPLGM IREENDFRIS VAGAQEKTAL LRIGNDWCIP KGITPTTHII
KLPIGEIRQP NATLDLSQSV DNEYYCLLLA KELGLNVPDA EIIKAGNVRA LAVERFDRRW
NAERTVLLRL PQEDMCQTFG LPSSVKYESD GGPGIARIMA FLMGSSEALK DRYDFMKFQV
FQWLIGATDG HAKNFSVFIQ AGGSYRLTPF YDIISAFPVL GGTGIHISDL KLAMGLNASK
GKKTAIDKIY PRHFLATAKV LRFPEVQMHE ILSDFARMIP AALDNVKTSL PTDFPENVVT
AVESNVLRLH GRLSREYGSK
