{PDOC00477}
{PS00552; HTH_MERR_1}
{PS50937; HTH_MERR_2}
{BEGIN}
**********************************************
* MerR-type HTH domain signature and profile *
**********************************************

The  merR-type  HTH  domain  is  a DNA-binding, winged helix-turn-helix (wHTH)
domain  of  about  70  residues  present in the merR family of transcriptional
regulators. The family is named after the merR regulator of mercury resistance
operons  of  Gram-negative  bacteria  found on transposons Tn21 and Tn501 [1].
MerR-type   regulators  are  present  in  diverse  bacterial  genera,  in  the
cytoplasm. The helix-turn-helix DNA-binding motif is located in the N-terminal
part  of  these  transcriptional  regulators  and is followed by a coiled-coil
region.  The C-terminal part of merR-type regulators contains effector binding
regions   that  are  specific  to  the  effector  recognized.  Most  merR-type
transcriptional  regulators  respond  to  environmental  stimuli,  like  heavy
metals,  oxidative  stress  or antibiotics and a subgroup of metalloregulators
are bacterial transcription activators that respond to metal ions [2].

Several  structures of merR-type transcriptional regulators have been resolved
and  their  N-terminal  DNA-binding domains are ascribed to the superfamily of
winged-helix proteins, containing a four-helix (H) bundle and a three-stranded
antiparallel   beta-sheet  (B)  in  the  topology:  B1-H1-H2-B2-B3-H3-H4  (see
<PDB:1JBG>)  [3].  The  helix-turn-helix  motif comprises the first and second
helices, the second being called the recognition helix. The HTH is involved in
DNA-binding  into  the  major  groove,  where the recognition helix makes most
DNA-contacts.  The  second  DNA-binding  element  is  wing W1, composed of the
second and third beta-strands and their connecting loop. The third DNA-binding
element,  wing  W2,  is  not a loop like in typical winged-helix proteins, but
another  H-T-H  motif  formed  by  helices  three  and four. In a typical merR
regulator,  the  HTH  and  two wings bind the promoter of the regulated operon
between the -35 and -10 regions in a spacer of 19/20 bp and longer than usual,
distorting   the   operator   DNA  and  causing  RNA  polymerase  to  initiate
transcription [2]. Most merR-like transcriptional regulators are dimers.

Some proteins known to contain a merR-type HTH domain:

 - Tn501  merR,  mercuric resistance operon regulatory protein. In the absence
   of  mercury merR represses transcription by binding tightly, as a dimer, to
   the  'mer'  operator  region;  when  mercury is present the dimeric complex
   binds  a  single  ion and becomes a potent transcriptional activator, while
   remaining bound to the mer site.
 - Bacillus subtilis bltR, bmrR and mtaN (ywnD), transcriptional activators of
   the blr and bmr transporters involved in multidrug resistance.
 - Escherichia  coli  soxR,  responds  to  oxidative stress and autoregulatory
   controls a superoxide response regulon.
 - Bradyrhizobium  japonicum nolA, a transcriptional regulator involved in the
   genotype-specific nodulation of soybeans.
 - Streptomyces  lividans tipA, a transcriptional activator which binds to and
   is activated by the antibiotic thiostrepton.
 - Escherichia coli zntR, a zinc-responsive regulator of zntA ATPase.
 - Escherichia coli cueR, a regulator of the copper efflux regulon.

The  pattern  we  developed starts at position 2 of the helix-turn-helix motif
and  extends  three  residues  upstream  of  its C-terminal extremity. We also
developed  a  profile that covers the entire wHTH, including the first strand,
H-T-H motif, wings W1 and W2 and which allows a more sensitive detection.

-Consensus pattern: [GSA]-x-[LIVMFA]-[ASM]-x(2)-[STACLIV]-[GSDENQR]-[LIVC]-
                    [STANHK]-x(3)-[LIVM]-[RHF]-x-[YW]-[DEQ]-x(2,3)-[GHDNQ]-
                    [LIVMF](2)
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Last update: October 2003 / Text revised; profile added.

[ 1] Helmann J.D., Wang Y., Mahler I., Walsh C.T.
     "Homologous metalloregulatory proteins from both gram-positive and
     gram-negative bacteria control transcription of mercury resistance
     operons."
     J. Bacteriol. 171:222-229(1989).
     PubMed=2492496
[ 2] Brown N.L., Stoyanov J.V., Kidd S.P., Hobman J.L.
     "The MerR family of transcriptional regulators."
     FEMS Microbiol. Rev. 27:145-163(2003).
     PubMed=12829265
[ 3] Zheleznova-Heldwein E.E., Brennan R.G.
     Nature 409:378-382(2001).

--------------------------------------------------------------------------------
PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and
distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives
(CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html
--------------------------------------------------------------------------------

{END}