ID   HIPB_ECOLI              Reviewed;          88 AA.
AC   P23873;
DT   01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1991, sequence version 1.
DT   24-JAN-2024, entry version 162.
DE   RecName: Full=Antitoxin HipB;
GN   Name=hipB; OrderedLocusNames=b1508, JW1501;
OS   Escherichia coli (strain K12).
OC   Bacteria; Pseudomonadota; 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 / W3110 / ATCC 27325 / DSM 5911;
RX   PubMed=9097039; DOI=10.1093/dnares/3.6.363;
RA   Aiba H., Baba T., Fujita K., Hayashi K., Inada T., Isono K., Itoh T.,
RA   Kasai H., Kashimoto K., Kimura S., Kitakawa M., Kitagawa M., Makino K.,
RA   Miki T., Mizobuchi K., Mori H., Mori T., Motomura K., Nakade S.,
RA   Nakamura Y., Nashimoto H., Nishio Y., Oshima T., Saito N., Sampei G.,
RA   Seki Y., Sivasundaram S., Tagami H., Takeda J., Takemoto K., Takeuchi Y.,
RA   Wada C., Yamamoto Y., Horiuchi T.;
RT   "A 570-kb DNA sequence of the Escherichia coli K-12 genome corresponding to
RT   the 28.0-40.1 min region on the linkage map.";
RL   DNA Res. 3:363-377(1996).
RN   [3]
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   [4]
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   [5]
RP   PROTEIN SEQUENCE OF 1-6, CHARACTERIZATION, DNA-BINDING, FUNCTION AS A
RP   TRANSCRIPTIONAL REPRESSOR, SUBUNIT, AND 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   [6]
RP   FUNCTION, SUBUNIT, AND DISRUPTION PHENOTYPE.
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   [7]
RP   ACTIVITY REGULATION, CLEAVAGE BY LON, AND MUTAGENESIS OF 73-ALA--TRP-88 AND
RP   TRP-88.
RX   PubMed=22720069; DOI=10.1371/journal.pone.0039185;
RA   Hansen S., Vulic M., Min J., Yen T.J., Schumacher M.A., Brennan R.G.,
RA   Lewis K.;
RT   "Regulation of the Escherichia coli HipBA toxin-antitoxin system by
RT   proteolysis.";
RL   PLoS ONE 7:E39185-E39185(2012).
RN   [8]
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   [9]
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   [10]
RP   FUNCTION AS AN ANTITOXIN FOR YJJJ.
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   [11] {ECO:0007744|PDB:2WIU}
RP   X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) IN COMPLEX WITH HIPA, 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   [12] {ECO:0007744|PDB:3DNV, ECO:0007744|PDB:3HZI}
RP   X-RAY CRYSTALLOGRAPHY (2.68 ANGSTROMS) IN COMPLEX WITH HIPA AND DNA,
RP   FUNCTION, 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   [13] {ECO:0007744|PDB:4YG1, ECO:0007744|PDB:4YG4, ECO:0007744|PDB:4YG7, ECO:0007744|PDB:5K98}
RP   X-RAY CRYSTALLOGRAPHY (3.25 ANGSTROMS) OF 1-72 IN COMPLEX WITH DNA AND IN
RP   COMPLEX WITH HIPA AND DNA, FUNCTION, AND SUBUNIT.
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).
RN   [14] {ECO:0007744|PDB:4Z58, ECO:0007744|PDB:4Z59, ECO:0007744|PDB:4Z5C, ECO:0007744|PDB:4Z5D, ECO:0007744|PDB:4Z5H}
RP   X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 3-74.
RA   Min J., Wang A., Brennan R.G., Schumacher M.A.;
RT   "Molecular mechanism on hipBA gene regulation.";
RL   Submitted (APR-2015) to the PDB data bank.
CC   -!- FUNCTION: Antitoxin component of a type II toxin-antitoxin (TA) system.
CC       Neutralizes the toxic effect of cognate toxin HipA (PubMed:20616060).
CC       Also neutralizes the toxic effect of non-cognate toxin YjjJ
CC       (PubMed:28430938). Binds to operator sites with the consensus sequence
CC       5-'TATCCN(8)GGATA-3' to repress the hipBA operon promoter
CC       (PubMed:8021189, PubMed:19150849); binding of HipB(2) to DNA induces a
CC       70 degree bend (PubMed:19150849). This forces HipA dimerization, which
CC       blocks HipA's active site and thus its toxic action (PubMed:26222023).
CC       May play a role in biofilm formation (PubMed:23329678).
CC       {ECO:0000269|PubMed:19150849, ECO:0000269|PubMed:20616060,
CC       ECO:0000269|PubMed:23329678, ECO:0000269|PubMed:26222023,
CC       ECO:0000269|PubMed:28430938, ECO:0000269|PubMed:8021189}.
CC   -!- ACTIVITY REGULATION: Degraded by Lon protease; degradation is inhibited
CC       in a HipA-HipB complex and when bound to the operator consensus
CC       sequence dsDNA. {ECO:0000269|PubMed:22720069}.
CC   -!- SUBUNIT: Homodimer (PubMed:8021189). Binds operator DNA sites in the
CC       absence of HipA, inducing a 70 degree bend in consecutive operators and
CC       deforming DNA between the operators so that HipB dimers bind on
CC       opposite faces of the DNA (PubMed:26222023). Forms a HipA(2)HipB(2)
CC       heterotetramer which can interact with a single operator site on DNA,
CC       inducing a 70 degree bend (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). HipA-HipB-
CC       induced bending also distorts the -35 and -10 boxes of the promoter and
CC       probably prevents sigma-factor binding, and additionally bound HipB and
CC       HipA block RNA polymerase access to the -35 box, thus repressing the
CC       operon (PubMed:26222023). This complex also blocks the toxic activity
CC       of HipA (PubMed:19150849). Mutations present in allele hipA7 (G22S and
CC       D291A) decrease the affinity of HipA for HipB (PubMed:20616060).
CC       {ECO:0000269|PubMed:19150849, ECO:0000269|PubMed:19622872,
CC       ECO:0000269|PubMed:20616060, ECO:0000269|PubMed:24089363,
CC       ECO:0000269|PubMed:26222023, ECO:0000269|PubMed:8021189}.
CC   -!- INTERACTION:
CC       P23873; P23874: hipA; NbExp=2; IntAct=EBI-1129654, EBI-560590;
CC   -!- PTM: Degraded by Lon protease in vivo; half-life is 17 minutes in wild-
CC       type cells and over 200 minutes in a lon deletion strain. In vitro
CC       degradation by Lon is Mg(2+)-ATP-dependent (PubMed:22720069).
CC       {ECO:0000269|PubMed:22720069}.
CC   -!- DISRUPTION PHENOTYPE: Cannot be disrupted, suggesting it is a
CC       functional antitoxin; no visible phenotype when the hipBA operon is
CC       deleted (PubMed:8021189, PubMed:20616060). A hipA or a hipB-hipA operon
CC       deletion show decreased biofilm production in the absence of
CC       antibiotics (PubMed:23329678). {ECO:0000269|PubMed:20616060,
CC       ECO:0000269|PubMed:23329678, ECO:0000269|PubMed:8021189}.
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DR   EMBL; M61242; AAA56877.1; -; Genomic_DNA.
DR   EMBL; U00096; AAC74581.1; -; Genomic_DNA.
DR   EMBL; AP009048; BAA15180.1; -; Genomic_DNA.
DR   PIR; A38112; A38112.
DR   RefSeq; NP_416025.1; NC_000913.3.
DR   RefSeq; WP_001301023.1; NZ_SSZK01000001.1.
DR   PDB; 2WIU; X-ray; 2.35 A; B/D=1-88.
DR   PDB; 3DNV; X-ray; 2.68 A; B=1-88.
DR   PDB; 3HZI; X-ray; 2.98 A; B=1-88.
DR   PDB; 4YG1; X-ray; 3.25 A; A/B/C/D=1-72.
DR   PDB; 4YG4; X-ray; 3.50 A; A/B/C/D=4-74.
DR   PDB; 4YG7; X-ray; 3.77 A; B/C/E/G=4-74.
DR   PDB; 4Z58; X-ray; 2.50 A; A=4-74.
DR   PDB; 4Z59; X-ray; 2.30 A; A=4-74.
DR   PDB; 4Z5C; X-ray; 2.50 A; A/B=4-74.
DR   PDB; 4Z5D; X-ray; 2.15 A; A/B=4-74.
DR   PDB; 4Z5H; X-ray; 2.10 A; A=3-74.
DR   PDB; 5K98; X-ray; 3.99 A; B/P=1-88.
DR   PDBsum; 2WIU; -.
DR   PDBsum; 3DNV; -.
DR   PDBsum; 3HZI; -.
DR   PDBsum; 4YG1; -.
DR   PDBsum; 4YG4; -.
DR   PDBsum; 4YG7; -.
DR   PDBsum; 4Z58; -.
DR   PDBsum; 4Z59; -.
DR   PDBsum; 4Z5C; -.
DR   PDBsum; 4Z5D; -.
DR   PDBsum; 4Z5H; -.
DR   PDBsum; 5K98; -.
DR   AlphaFoldDB; P23873; -.
DR   SMR; P23873; -.
DR   BioGRID; 4260221; 72.
DR   ComplexPortal; CPX-180; HipBA toxin-antitoxin complex.
DR   DIP; DIP-9899N; -.
DR   IntAct; P23873; 2.
DR   STRING; 511145.b1508; -.
DR   jPOST; P23873; -.
DR   PaxDb; 511145-b1508; -.
DR   EnsemblBacteria; AAC74581; AAC74581; b1508.
DR   GeneID; 946065; -.
DR   KEGG; ecj:JW1501; -.
DR   KEGG; eco:b1508; -.
DR   PATRIC; fig|1411691.4.peg.759; -.
DR   EchoBASE; EB0437; -.
DR   eggNOG; COG1396; Bacteria.
DR   HOGENOM; CLU_066192_47_2_6; -.
DR   InParanoid; P23873; -.
DR   OMA; HALEVHC; -.
DR   OrthoDB; 5891007at2; -.
DR   PhylomeDB; P23873; -.
DR   BioCyc; EcoCyc:EG10442-MONOMER; -.
DR   BioCyc; MetaCyc:EG10442-MONOMER; -.
DR   EvolutionaryTrace; P23873; -.
DR   PRO; PR:P23873; -.
DR   Proteomes; UP000000318; Chromosome.
DR   Proteomes; UP000000625; Chromosome.
DR   CollecTF; EXPREG_00000960; -.
DR   GO; GO:0032993; C:protein-DNA complex; IPI:CollecTF.
DR   GO; GO:0110001; C:toxin-antitoxin complex; IPI:ComplexPortal.
DR   GO; GO:0001046; F:core promoter sequence-specific DNA binding; IDA:EcoCyc.
DR   GO; GO:0001217; F:DNA-binding transcription repressor activity; IPI:CollecTF.
DR   GO; GO:0042803; F:protein homodimerization activity; IDA:EcoCyc.
DR   GO; GO:0043565; F:sequence-specific DNA binding; IDA:EcoCyc.
DR   GO; GO:0000976; F:transcription cis-regulatory region binding; IPI:CollecTF.
DR   GO; GO:0006351; P:DNA-templated transcription; IDA:EcoCyc.
DR   GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:EcoCyc.
DR   GO; GO:0006355; P:regulation of DNA-templated transcription; IDA:ComplexPortal.
DR   GO; GO:0040008; P:regulation of growth; IDA:ComplexPortal.
DR   CDD; cd00093; HTH_XRE; 1.
DR   DisProt; DP02899; -.
DR   Gene3D; 1.10.260.40; lambda repressor-like DNA-binding domains; 1.
DR   InterPro; IPR001387; Cro/C1-type_HTH.
DR   InterPro; IPR010982; Lambda_DNA-bd_dom_sf.
DR   Pfam; PF01381; HTH_3; 1.
DR   SMART; SM00530; HTH_XRE; 1.
DR   SUPFAM; SSF47413; lambda repressor-like DNA-binding domains; 1.
DR   PROSITE; PS50943; HTH_CROC1; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Direct protein sequencing; DNA-binding; Reference proteome;
KW   Repressor; Toxin-antitoxin system; Transcription; Transcription regulation.
FT   CHAIN           1..88
FT                   /note="Antitoxin HipB"
FT                   /id="PRO_0000149726"
FT   DOMAIN          17..71
FT                   /note="HTH cro/C1-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00257,
FT                   ECO:0000269|PubMed:19150849"
FT   DNA_BIND        21..47
FT                   /note="H-T-H motif"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00257,
FT                   ECO:0000269|PubMed:19150849"
FT   MUTAGEN         73..88
FT                   /note="Missing: Increased half-life in vivo and in vitro,
FT                   no change in DNA or HipA-binding."
FT                   /evidence="ECO:0000269|PubMed:22720069"
FT   MUTAGEN         88
FT                   /note="W->A: No change in DNA or HipA-binding."
FT                   /evidence="ECO:0000269|PubMed:22720069"
FT   HELIX           10..23
FT                   /evidence="ECO:0007829|PDB:4Z5H"
FT   HELIX           28..35
FT                   /evidence="ECO:0007829|PDB:4Z5H"
FT   HELIX           39..47
FT                   /evidence="ECO:0007829|PDB:4Z5H"
FT   HELIX           49..51
FT                   /evidence="ECO:0007829|PDB:4Z5H"
FT   HELIX           54..63
FT                   /evidence="ECO:0007829|PDB:4Z5H"
FT   STRAND          66..72
FT                   /evidence="ECO:0007829|PDB:4Z5D"
SQ   SEQUENCE   88 AA;  10016 MW;  63C0E13C1C06CBDA CRC64;
     MMSFQKIYSP TQLANAMKLV RQQNGWTQSE LAKKIGIKQA TISNFENNPD NTTLTTFFKI
     LQSLELSMTL CDAKNASPES TEQQNLEW
//