HIPA_ECOL6
ID HIPA_ECOL6 Reviewed; 440 AA.
AC Q8FHF4;
DT 09-JAN-2013, integrated into UniProtKB/Swiss-Prot.
DT 22-JAN-2014, sequence version 2.
DT 03-AUG-2022, entry version 95.
DE RecName: Full=Serine/threonine-protein kinase toxin HipA;
DE Short=Ser/Thr-protein kinase HipA;
DE EC=2.7.11.1;
DE AltName: Full=Toxin HipA;
GN Name=hipA; OrderedLocusNames=c1940;
OS Escherichia coli O6:H1 (strain CFT073 / ATCC 700928 / UPEC).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=199310;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CFT073 / ATCC 700928 / UPEC;
RX PubMed=12471157; DOI=10.1073/pnas.252529799;
RA Welch R.A., Burland V., Plunkett G. III, Redford P., Roesch P., Rasko D.,
RA Buckles E.L., Liou S.-R., Boutin A., Hackett J., Stroud D., Mayhew G.F.,
RA Rose D.J., Zhou S., Schwartz D.C., Perna N.T., Mobley H.L.T.,
RA Donnenberg M.S., Blattner F.R.;
RT "Extensive mosaic structure revealed by the complete genome sequence of
RT uropathogenic Escherichia coli.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:17020-17024(2002).
RN [2]
RP DISRUPTION PHENOTYPE.
RC STRAIN=CFT073 / ATCC 700928 / UPEC;
RX PubMed=23055930; DOI=10.1371/journal.ppat.1002954;
RA Norton J.P., Mulvey M.A.;
RT "Toxin-antitoxin systems are important for niche-specific colonization and
RT stress resistance of uropathogenic Escherichia coli.";
RL PLoS Pathog. 8:E1002954-E1002954(2012).
CC -!- FUNCTION: Toxic component of a type II toxin-antitoxin (TA) system.
CC Phosphorylates Glu-tRNA-ligase (GltX, on 'Ser-239') in vivo.
CC Phosphorylation of GltX prevents it from being charged, leading to an
CC increase in uncharged tRNA(Glu). This induces amino acid starvation and
CC the stringent response via RelA/SpoT and increased ppGpp levels, which
CC inhibits replication, transcription, translation and cell wall
CC synthesis, reducing growth and leading to multidrug resistance and
CC persistence. Low level expression of HipA induces dormancy and
CC depending on the protein level, can be toxic enough to reduce cell
CC growth or even kill cells. Low levels of wild-type HipA lead to high
CC beta-lactam antibiotic tolerance of the survivor cells, also dependent
CC on relA and relA/spoT. The toxic effect of HipA is neutralized by its
CC cognate antitoxin HipB. With HipB acts as a corepressor for
CC transcription of the hipBA promoter; binding to DNA induces a 70 degree
CC bend (By similarity). {ECO:0000250|UniProtKB:P23874}.
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 -!- 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;
CC -!- SUBUNIT: Forms a HipA(2)HipB(2) heterotetramer which can interact with
CC DNA. {ECO:0000250|UniProtKB:P23874}.
CC -!- PTM: Autophosphorylates intermolecularly on Ser-150; phosphorylated
CC form not seen to bind ATP and no longer has kinase activity.
CC {ECO:0000250|UniProtKB:P23874}.
CC -!- DISRUPTION PHENOTYPE: Deletion of the hipB-hipA operon has no effect on
CC virulence in mouse infection; the disrupted strain is as virulent as
CC wild-type. {ECO:0000269|PubMed:23055930}.
CC -!- SIMILARITY: Belongs to the HipA Ser/Thr kinase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAN80398.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAN80398.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AE014075; AAN80398.1; ALT_SEQ; Genomic_DNA.
DR STRING; 199310.c1940; -.
DR EnsemblBacteria; AAN80398; AAN80398; c1940.
DR KEGG; ecc:c1940; -.
DR eggNOG; COG3550; Bacteria.
DR HOGENOM; CLU_030167_2_1_6; -.
DR BioCyc; ECOL199310:C1940-MON; -.
DR Proteomes; UP000001410; Chromosome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
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 3: Inferred from homology;
KW ATP-binding; Kinase; Nucleotide-binding; Phosphoprotein; 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_0000420796"
FT ACT_SITE 309
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P23874"
FT BINDING 152..157
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P23874"
FT BINDING 181
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P23874"
FT BINDING 234..236
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P23874"
FT BINDING 311..314
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P23874"
FT BINDING 331..332
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P23874"
FT MOD_RES 150
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P23874"
SQ SEQUENCE 440 AA; 49315 MW; 96D947E7D1953CCB CRC64;
MPKLVTWMNN QRVGELTKLA NGAHTFKYAP EWLASRYARP LSLSLPLQRG NITSDAVFNF
FDNLLPDSPI VRDRIVKRYH AKSRQPFDLL SEIGRDSVGA VTLIPEDETV TCPIMAWEKL
TEARLEEVLT AYKADIPLGM IREENDFRIS VAGAQEKTAL LRIGNDWCIP KGITPTTHII
KLPIGEIRQP NATLDLSQSV DNEYYCLLLA KELGLNVPDA EIIKAGRVRA LAVKRFDRRW
NTERTVLLRL PQEDMCQTFG LPSSVKYESD GGPGIAQIMA FLMGSSEALK DRYDFMKFQV
FQWLIGATDG HAKNFSVFIQ AGGSYRLTPF YDIISAFPVL GGTGIHISDL KLAMGLNASK
GKKTAIDKXY PRHFXATAKV LKFPEVXMHE ILXDFARMIP AALDNVKNSL PXDFPEXVVT
AVETNVLRLH GRLSPEYXXK
