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Escherichia coli K-12 substr. MG1655 Protein: HipB antitoxin and DNA-binding transcriptional repressor



Gene: hipB Accession Numbers: EG10442 (EcoCyc), b1508, ECK1501

Regulation Summary Diagram: ?

Component of: HipAB toxin/antitoxin complex and DNA-binding transcriptional repressor (extended summary available)

Subunit composition of HipB antitoxin and DNA-binding transcriptional repressor = [HipB]2

Summary:
HipB is the antitoxin of the HipAB toxin-antitoxin system.

The HipAB toxin-antitoxin system appears to be regulated at the level of HipB stability. Degradation of HipB is mainly dependent on the Lon protease, and is dependent on an unstructured 16 amino acid domain at the C terminus of the protein [Hansen12].

A bioinformatic analysis revealed that there are a total of 39 HipB-binding palindromic sequences, TATCCN(x)GGATA, in the promoter regions of 33 genes in the Escherichia coli genome, where N represents any nucleotide and x is the number of nucleotides, from 1 to 30. The functions of these 33 genes are involved in different processes, such as persistence, metabolism, transcriptional regulation, mismatch repair, membrane proteins, transporter proteins, and inner membrane proteins [Lin13].

HipB: "high persistence" [Moyed83]

Locations: cytosol

Map Position: [1,590,200 <- 1,590,466] (34.27 centisomes)
Length: 267 bp / 88 aa

Molecular Weight of Polypeptide: 10.016 kD (from nucleotide sequence), 10.0 kD (experimental) [Black91 ]

Molecular Weight of Multimer: 26.0 kD (experimental) [Black94]

Unification Links: ASAP:ABE-0005024 , EchoBASE:EB0437 , EcoGene:EG10442 , EcoliWiki:b1508 , ModBase:P23873 , OU-Microarray:b1508 , PortEco:hipB , PR:PRO_000022890 , Protein Model Portal:P23873 , RefSeq:NP_416025 , RegulonDB:EG10442 , SMR:P23873 , String:511145.b1508 , UniProt:P23873

Relationship Links: InterPro:IN-FAMILY:IPR001387 , InterPro:IN-FAMILY:IPR010982 , PDB:RELATED-TO:3DNV , PDB:Structure:2WIU , PDB:Structure:3HZI , Pfam:IN-FAMILY:PF01381 , Prosite:IN-FAMILY:PS50943 , Smart:IN-FAMILY:SM00530

Gene-Reaction Schematic: ?

Genetic Regulation Schematic: ?

GO Terms:

Biological Process: GO:0006351 - transcription, DNA-templated Inferred from experiment Inferred by computational analysis [UniProtGOA11a, Black94]
GO:0006355 - regulation of transcription, DNA-templated Inferred by computational analysis [UniProtGOA11a]
Molecular Function: GO:0043565 - sequence-specific DNA binding Inferred from experiment Inferred by computational analysis [GOA01a, Black94]
GO:0003677 - DNA binding Inferred by computational analysis [UniProtGOA11a, GOA01a]
Cellular Component: GO:0005829 - cytosol

MultiFun Terms: information transfer RNA related Transcription related
regulation type of regulation transcriptional level repressor

DNA binding site length: 20 base-pairs

Symmetry: Inverted Repeat

Consensus DNA Binding Sequence: tTATCCgctatagcGGATAa

Regulated Transcription Units (4 total): ?

Notes:

Essentiality data for hipB knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 1]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 2]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 1]

Credits:
Created 05-Feb-2009 by Keseler I , SRI International


Subunit of: HipAB toxin/antitoxin complex and DNA-binding transcriptional repressor

Synonyms: HipBA

Subunit composition of HipAB toxin/antitoxin complex and DNA-binding transcriptional repressor = [(HipB)2][HipA]2
         HipB antitoxin and DNA-binding transcriptional repressor = (HipB)2
         serine/threonine kinase HipA = HipA (extended summary available)

Summary:
The transcriptional repressor HipB, for "High persistence," is negatively autoregulated and controls the transcription of a critical persistence factor [Kawano09, Lewis05a, Keren04, Black91, Korch03, Balaban04]. hipB foms an operon with hipA, and the products of this operon are classified as a toxin (HipA)-antitoxin (HipB) system. This HipAB system is involved in the high persistence, which is the capacity of the bacteria to survive prolonged exposure to antibiotics [Balaban04, Inouye06], and Kawano et al. also showed that this system is important for survival during the long-term stationary phase [Kawano09, Lewis05a, Keren04].

The crystal structure of the HipB-HipA-DNA complex has been solved at 2.68 Å resolution [Schumacher09]. The complex is tetrameric and is comprised of a HipB homodimer that interacts with DNA, sandwiched by a monomer of HipA on each side [Schumacher09]. In the HipB-HipA complex, each monomer of HipA interacts with two monomers of HipB [Schumacher09, Evdokimov09]. HipB is an antitoxin that counteracts and neutralizes the HipA toxin, and HipA is toxic in the absence of its binding partner HipB [Schumacher09, Black94, Black91]. Although HipA does not bind the Hip regulatory region, it plays an indirect role via its binding to HipB.

HipB contains a helix-turn-helix motif near the N terminus and is a Cro-like DNA-binding protein. It binds to four operator sites with the conserved inverted repeat sequence motif TATCCN8GGATA, and its binding occurs cooperatively and almost simultaneously on the same face of the DNA helix. HipB forms dimers in solution [Black94, Schumacher09].

Reviews: [Yamaguchi11, Jayaraman08]

Relationship Links: PDB:Structure:3DNV , PDB:Structure:3DNW

GO Terms:

Biological Process: GO:0045892 - negative regulation of transcription, DNA-templated Inferred from experiment [Black94]
Molecular Function: GO:0043565 - sequence-specific DNA binding Inferred from experiment [Black94]

DNA binding site length: 20 base-pairs

Symmetry: Inverted Repeat

Consensus DNA Binding Sequence: tTATCCgctatAGCGGATAa

Regulated Transcription Units (2 total): ?

Notes:


Sequence Features

Feature Class Location Citations Comment
Conserved-Region 17 -> 71
[UniProt09]
UniProt: HTH cro/C1-type;
DNA-Binding-Region 28 -> 47
[UniProt10a]
UniProt: H-T-H motif; Non-Experimental Qualifier: potential;


Gene Local Context (not to scale): ?

Transcription Unit:

Notes:

History:
1/26/1998 (pkarp) Merged genes G7994/hipB and EG10442/hipB


References

Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

Balaban04: Balaban NQ, Merrin J, Chait R, Kowalik L, Leibler S (2004). "Bacterial persistence as a phenotypic switch." Science 305(5690);1622-5. PMID: 15308767

Black91: Black DS, Kelly AJ, Mardis MJ, Moyed HS (1991). "Structure and organization of hip, an operon that affects lethality due to inhibition of peptidoglycan or DNA synthesis." J Bacteriol 173(18);5732-9. PMID: 1715862

Black94: Black DS, Irwin B, Moyed HS (1994). "Autoregulation of hip, an operon that affects lethality due to inhibition of peptidoglycan or DNA synthesis." J Bacteriol 1994;176(13);4081-91. PMID: 8021189

Evdokimov09: Evdokimov A, Voznesensky I, Fennell K, Anderson M, Smith JF, Fisher DA (2009). "New kinase regulation mechanism found in HipBA: a bacterial persistence switch." Acta Crystallogr D Biol Crystallogr 65(Pt 8);875-9. PMID: 19622872

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

Hansen12: Hansen S, Vulic M, Min J, Yen TJ, Schumacher MA, Brennan RG, Lewis K (2012). "Regulation of the Escherichia coli HipBA Toxin-Antitoxin System by Proteolysis." PLoS One 7(6);e39185. PMID: 22720069

Inouye06: Inouye M (2006). "The discovery of mRNA interferases: implication in bacterial physiology and application to biotechnology." J Cell Physiol 209(3);670-6. PMID: 17001682

Jayaraman08: Jayaraman R (2008). "Bacterial persistence: some new insights into an old phenomenon." J Biosci 33(5);795-805. PMID: 19179767

Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394

Kawano09: Kawano H, Hirokawa Y, Mori H (2009). "Long-term survival of Escherichia coli lacking the HipBA toxin-antitoxin system during prolonged cultivation." Biosci Biotechnol Biochem 73(1);117-23. PMID: 19129642

Keren04: Keren I, Shah D, Spoering A, Kaldalu N, Lewis K (2004). "Specialized persister cells and the mechanism of multidrug tolerance in Escherichia coli." J Bacteriol 186(24);8172-80. PMID: 15576765

Korch03: Korch SB, Henderson TA, Hill TM (2003). "Characterization of the hipA7 allele of Escherichia coli and evidence that high persistence is governed by (p)ppGpp synthesis." Mol Microbiol 50(4);1199-213. PMID: 14622409

Lewis05a: Lewis K (2005). "Persister cells and the riddle of biofilm survival." Biochemistry (Mosc) 70(2);267-74. PMID: 15807669

Lin13: Lin CY, Awano N, Masuda H, Park JH, Inouye M (2013). "Transcriptional Repressor HipB Regulates the Multiple Promoters in Escherichia coli." J Mol Microbiol Biotechnol 23(6);440-447. PMID: 24089053

Moyed83: Moyed HS, Bertrand KP (1983). "hipA, a newly recognized gene of Escherichia coli K-12 that affects frequency of persistence after inhibition of murein synthesis." J Bacteriol 155(2);768-75. PMID: 6348026

Schumacher09: Schumacher MA, Piro KM, Xu W, Hansen S, Lewis K, Brennan RG (2009). "Molecular mechanisms of HipA-mediated multidrug tolerance and its neutralization by HipB." Science 323(5912);396-401. PMID: 19150849

UniProt09: UniProt Consortium (2009). "UniProt version 15.8 released on 2009-10-01 00:00:00." Database.

UniProt10a: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." Database.

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

Yamaguchi11: Yamaguchi Y, Park JH, Inouye M (2011). "Toxin-antitoxin systems in bacteria and archaea." Annu Rev Genet 45;61-79. PMID: 22060041


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
Page generated by SRI International Pathway Tools version 18.5 on Tue Nov 25, 2014, biocyc13.