{PDOC00041}
{PS00042; HTH_CRP_1}
{PS51063; HTH_CRP_2}
{BEGIN}
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* Crp-type HTH domain signature and profile *
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The  crp-type  HTH  domain  is  a  DNA-binding, winged helix-turn-helix (wHTH)
domain  of  about 70-75 amino acids present in transcription regulators of the
crp-fnr  family,  involved  in  the  control  of virulence factors, enzymes of
aromatic  ring  degradation,  nitrogen  fixation,  photosynthesis, and various
types  of  respiration.  The  crp-fnr  family is named after the first members
identified  in  E.coli: the well characterized cyclic AMP receptor protein CRP
or  CAP  (catabolite activator protein) and the fumarate and nitrate reductase
regulator  Fnr.  crp-type  HTH  domain  proteins occur in most bacteria and in
chloroplasts  of  red  algae.  The  DNA-binding  HTH  domain is located in the
C-terminal  part;  the  N-terminal  part of the proteins of the crp-fnr family
contains    a    nucleotide-binding    domain    (see   <PDOC00691>)   and   a
dimerization/linker   helix   occurs   in   between.  The  crp-fnr  regulators
predominantly  act  as  transcription  activators,  but  can also be important
repressors,  and  respond to diverse intracellular and exogenous signals, such
as  cAMP,  anoxia,  redox  state,  oxidative  and  nitrosative  stress, carbon
monoxide, nitric oxide or temperature [1,2].

The  structure  of the crp-type DNA-binding domain (see <PDB:1LB2>) shows that
the  helices (H) forming the helix-turn-helix motif (H2-H3) are flanked by two
beta-hairpin  (B)  wings,  in  the  topology  H1-B1-B2-H2-H3-B3-B4. Helix 3 is
termed  the  recognition helix, as in most wHTHs it binds the DNA major groove
[3,4,5].

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

 - Escherichia  coli  crp  (also  known  as  cAMP  receptor),  a  protein that
   complexes   with   cAMP   and   regulates   the  transcription  of  several
   catabolite-sensitive operons.
 - Escherichia  coli fnr, a protein that activates genes for proteins involved
   in a variety of anaerobic electron transport systems.
 - Rhizobium   leguminosarum  fnrN,  a  transcription  regulator  of  nitrogen
   fixation.
 - Rhodobacter  sphaeroides  fnrL, a transcription activator of genes for heme
   biosynthesis,   bacteriochlorophyll   synthesis  and  the  light-harvesting
   complex LHII.
 - Rhizobiacae  fixK,  a  protein that regulates nitrogen fixation genes, both
   positively and negatively.
 - Lactobacillus  casei  fnr-like  protein  flp, a putative regulatory protein
   linked to the trpDCFBA operon.
 - Cyanobacteria  ntcA,  a  regulator  of  the  expression of genes subject to
   nitrogen control.
 - Xanthomonas  campestris  clp,  a  protein  involved  in  the  regulation of
   phytopathogenicity.  Clp  controls the production of extracellular enzymes,
   xanthan gum and pigment, either positively or negatively.

The  'helix-turn-helix'  DNA-binding motif of these proteins is located in the
C-terminal  part  of the sequence. The pattern we use to detect these proteins
starts  two residues before the HTH motif and ends two residues before the end
of helix 3. We also developed a profile that covers the entire wHTH, including
helix 1 and strand 4, and which allows a more sensitive detection.

-Consensus pattern: [LIVM]-[STAG]-[RHNWM]-x(2)-[LIM]-[GA]-x-[LIVMFYAS]-
                    [LIVSC]-[GA]-x-[STACN]-x(2)-[MST]-x(1,2)-[GSTN]-R-x-
                    [LIVMF]-x(2)-[LIVMF]
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in Swiss-Prot: 1.

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

-Last update: April 2006 / Pattern revised.

[ 1] Irvine A.S., Guest J.R.
     "Lactobacillus casei contains a member of the CRP-FNR family."
     Nucleic Acids Res. 21:753-753(1993).
     PubMed=8441692
[ 2] Koerner H., Sofia H.J., Zumft W.G.
     FEMS Microbiol. Rev. 27:559-592(2003).
[ 3] Busby S., Ebright R.H.
     "Transcription activation by catabolite activator protein (CAP)."
     J. Mol. Biol. 293:199-213(1999).
     PubMed=10550204; DOI=10.1006/jmbi.1999.3161
[ 4] Lanzilotta W.N., Schuller D.J., Thorsteinsson M.V., Kerby R.L.,
     Roberts G.P., Poulos T.L.
     "Structure of the CO sensing transcription activator CooA."
     Nat. Struct. Biol. 7:876-880(2000).
     PubMed=11017196; DOI=10.1038/82820
[ 5] Huffman J.L., Brennan R.G.
     "Prokaryotic transcription regulators: more than just the
     helix-turn-helix motif."
     Curr. Opin. Struct. Biol. 12:98-106(2002).
     PubMed=11839496

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