HypT belongs to the LysR-type transcriptional regulator family, which protects cells from HOCl damage |CITS: |. It regulates several genes upon hypochlorite stress, which increases cellular viability by reducing the intracellular iron levels |CITS: |. This assumes a primary role for HypT in downregulating iron acquisition genes in order to prevent further synthesis of iron uptake proteins |CITS: |.
HypT is specifically activated by HOCl by methionine oxidation, protecting the cells from the detrimental effects of HOCl) |CITS: |. HypT belongs to the large family of LTTRs and is conserved in α-, β-, and γ-proteobacteria and eukaryotes (Xenopus tropicalis), which suggests conservation of the HOCl response in evolution and its maintenance throughout the kingdoms |CITS: |.
Based on microarray analysis, HypT upregulates genes involved in cysteine and methionine biosynthesis and sulfur metabolism upon hypochlorite stress. On the other hand, genes involved in iron acquisition and homeostasis upon hypochlorite stress are downregulated by YjiE |CITS: |.
HypT has five cysteine residues which contribute to control the DNA-binding activity of HypT in vitro |CITS: |. Cys150 is required for stability, Cys4 is important for oligomerization of HypT to dodecamers, and Cys4 oxidation may be a checkpoint in the activation process of HypT |CITS: |.
The building block of HypT is likely a dimer; similar to other LTTRs, it forms unusually large oligomers, as dodecameric ring-like structures, in vitro that undergo large DNA-induced conformational changes to form dimers and tetramers |CITS: |.
Studies based on the dynamic oligomers showed that oxidized small HypT oligomers (tetramers) are the activation-competent species, whereas the docameric ring-like structures are the storage form |CITS: |.Read more >
In the presence of hypochlorite, HypT becomes active due to oxidation of three methionines (Met123, Met206, and Met230). A probable conformational change upon oxidation allows the protein to bind DNA to regulate transcription. Oxidation of HypT is reversed by the presence of the methionine sulfoxide reductases MsrA and MsrB, resulting in an inactive protein |CITS:[ 23690622]|.
|Connectivity class:||Local Regulator|
|Length:||912 bp / 303 aa|
|TU(s) encoding the TF:||
|Regulated gene(s)||cydA, cydB, cysH, fecA, fecB, fecC, fecD, fecE, metB, metI, metL, metN, metQ|
|Multifun term(s) of regulated gene(s)||
MultiFun Term (List of genes associated to the multifun term)
cydA, cydB, fecC, fecD, metI
Fe aquisition (4)
fecA, fecB, fecC, fecE
ABC superfamily, membrane component (3)
fecC, fecD, metI
electron acceptors (2)
ABC superfamily, periplasmic binding component (2)
ABC superfamily ATP binding cytoplasmic component (2)
sulfur metabolism (1)
Beta barrel porins (The Outer Membrane Porin (OMP) Functional Superfamily) (1)
amino acids (1)
threonine catabolism (1)
|Regulated operon(s)||cydAB, cysJIH, fecABCDE, metBL, metNIQ|
|First gene in the operon(s)||cydA, cysH, fecA, metB, metN|
|Simple and complex regulons|
|Simple and complex regulatory phrases||Regulatory phrase (List of promoters regulated by the phrase)|
|Functional conformation||Function||Promoter||Sigma factor||Central Rel-Pos||Distance to first Gene||Genes||Sequence||LeftPos||RightPos||Evidence (Confirmed, Strong, Weak)||References|
|HypT-Met-oxidized||activator||cydAp1||Sigma70||nd||nd||cydA, cydB||nd||nd||[BPP], [GEA]|||
|HypT-Met-oxidized||repressor||fecAp||Sigma19||nd||nd||fecA, fecB, fecC, fecD, fecE||nd||nd||[GEA]||, |
|HypT-Met-oxidized||activator||metBp||Sigma70||nd||nd||metB, metL||nd||nd||[GEA]||, |
|HypT-Met-oxidized||activator||metNp||Sigma70||nd||nd||metN, metI, metQ||nd||nd||[BPP], [GEA]||, |
|Evolutionary conservation of regulatory elements|
 Gebendorfer KM., Drazic A., Le Y., Gundlach J., Bepperling A., Kastenmuller A., Ganzinger KA., Braun N., Franzmann TM., Winter J., 2012, Identification of a Hypochlorite-specific Transcription Factor from Escherichia coli., J Biol Chem. 287(9):6892-903
 Drazic A., Miura H., Peschek J., Le Y., Bach NC., Kriehuber T., Winter J., 2013, Methionine oxidation activates a transcription factor in response to oxidative stress., Proc Natl Acad Sci U S A. 110(23):9493-8