{PDOC51062}
{PS51062; RUNT}
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* Runt domain profile *
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The Runt domain is a ~128 amino acid region that is characteristic of the RUNX
family of  heterodimeric eukaryotic transcription factors. The family includes
genes from  drosophila,  chicken and mammals that are involved in a wide range
of developmental   processes,  from  sex  determination  and  neurogenesis  in
drosophila to hematopoiesis and osteoblast differentiation in mouse and human.
The Runt domain confers DNA binding ability to the consensus core PyGPyGGT and
mediates the  interaction  of  mammalian  RUNX proteins with the beta-subunit,
designated core-binding factor beta (CBFbeta), which increases the DNA binding
affinity of the heterodimer [1,2].

The Runt  domain  adopts the fold of an immunoglobulin (Ig)-like beta sandwich
(see <PDB:1EAQ; B>). However, an N-terminal alpha helix, which precedes the Ig
domain is also part of the evolutionary conserved Runt domain. The helix packs
through hydrophobic interactions against the bulk of the domain that is formed
by 12  beta  strands  (10 antiparallel and two parallel strands). Two chloride
ions bind  to  the  native  Runt  domain  of which one is situated at the DNA-
binding surface.  The  transition  from  the  uncomplexed  Runt  domain to the
CBFbeta and/or  DNA-bound  form  is  accompanied  by  considerable  structural
rearrangements. Once  a  Runt-CBFbeta or a Runt-DNA complex has formed, almost
identical changes  accompany  the  transition  from  the  binary  Runt-CBFbeta
complex to  the  ternary  complex  including  DNA  and the transition from the
binary Runt-DNA  complex  to  the  ternary  complex  with CBFbeta, even though
CBFbeta and  DNA  bind  to  different surfaces on Runt. This suggests that the
function of CBFbeta is to convert the Runt domain into a DNA-binding competent
conformation before   actually   binding   to   DNA   and  to  stabilize  this
conformation [2].

Some proteins known to contain a Runt domain are listed below:

 - Mammalian  RUNX1 or acute myeloid leukemia protein 1 (AML1). It is together
   with CBFbeta essential for hematopoiesis.
 - Mammalian   RUNX2   (AML3/PEBP2alphaA/CBFalpha1).   It   is  essential  for
   osteoblast differentiation and bone formation.
 - Mammalian RUNX3. It is essential for antiproliferation and apoptosis of the
   gastric epithelium.
 - Chicken runt B protein.
 - Drosophila segmentation protein Runt. It plays a pivotal role in regulating
   the expression of other pair-rule genes such as eve, ftz, and h.
 - Drosophila lozenge protein.

The profile we developed covers the entire Runt domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: January 2005 / First entry.

[ 1] Levanon D., Eisenstein M., Groner Y.
     "Site-directed mutagenesis supports a three-dimensional model of the
     runt domain."
     J. Mol. Biol. 277:509-512(1998).
     PubMed=9533875
[ 2] Baeckstroem S., Wolf-Watz M., Grundstroem C., Haerd T., Grundstroem T.,
     Sauer U.H.
     J. Mol. Biol. 322:259-272(2002).

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