{PDOC00924}
{PS01204; REL_1}
{PS50254; REL_2}
{BEGIN}
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* NF-kappa-B/Rel/dorsal domain signature and profile *
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Various studies  (reviewed  in  [1-5])  have allowed the characterization of a
family of  eukaryotic  transcription factors with basic impact on oncogenesis,
embryonic development and  differentiation including immune response and acute
phase reaction.  Most  of  these  transcription  factors bind as dimers to the
consensus DNA  sequence  motif  5'-GGGRNNYYCC-3'  termed kappa-B according the
first  described factor-binding  sequence  motif located in the immunoglobulin
kappa light chain enhancer region.

Proteins of  this  family  appear  to  be  regulated,  at  least  in  part, by
subcellular localization  whereby the inactive cytoplasmic forms become active
transcriptional  control  proteins by translocation to the nucleus. Members of
the  Rel  family  share  a highly  conserved 300 amino acids domain termed Rel
homology domain (RHD) which is located towards  the amino terminus. The unique
C-terminal is  thought  to  be  involved  in  gene  activation and cytoplasmic
anchoring functions.

Proteins known to contain a RHD domain are listed below:

 - Both subunits of vertebrate nuclear factor NF-kappa-B. The active NF-kappa-
   B is  a heterodimer of an about 50 Kd DNA-binding subunit (p50 or p49, p52)
   and the transcription factor p65.
 - Mammalian  transcription factor RelB, which stimulates promoter activity in
   the presence of the 50 Kd subunit of NF-kappa-B.
 - Vertebrate  proto-oncogene  c-rel,  a  protein  that  may  play  a  role in
   differentiation and lymphopoiesis.
 - Avian  reticuloendotheliosis  virus p58 v-rel, a transforming protein which
   induces acute leucemia in juvenile birds.
 - Drosophila    embryonic    polarity   dorsal protein.  The concentration of
   this morphogenetic  protein in the  nucleus  during  the  blastoderm  stage
   determines the lateral or ventral identity of a cell. It directly  controls
   the  expression of zygotically  active  genes crucial for development along
   this axis.
 - Drosophila  dorsal-related  immunity  factor  (gene  Dif) which mediates an
   immune response in the larvae.
 - Mammalian  nuclear  factor  of  activated  T  cells  (NFAT);  a  family  of
   transcription factors  that    play   a role in the inducible expression of
   cytokine genes in T cells.

For several  proteins  it  has  been demonstrated ([1] and references therein)
that the Rel homology domain includes:

 (1) a  DNA-binding domain, which binds to the consensus  DNA  sequence  motif
     5'-GGGRNNYYCC-3' (except  for  dorsal, which recognizes the related motif
     5'-GRGAAAANCC-3');
 (2) a  dimerization  domain,  which  is located in the C-terminal part of the
     RHD;
 (3) a PKA phosphorylation site (see <PDOC00004>) (except in RelB);
 (4) a nuclear localization signal (NLS),  which consists of a stretch of four
     or five basic residues.

As a  signature  for  this  family we selected a region that is located at the
N-terminal of the RHD. This region includes a conserved cysteine that seems to
be essential  for  DNA-binding  in  p50  [6]. We also developed a profile that
spans completly the RHD.

-Consensus pattern: F-R-Y-x-C-E-G
-Sequences known to belong to this class detected by the pattern: ALL,  except
 members of the NFAT family.
-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: December 2001 / Text revised; profile added.

[ 1] Kabrun N., Enrietto P.J.
     "The Rel family of proteins in oncogenesis and differentiation."
     Semin. Cancer Biol. 5:103-112(1994).
     PubMed=8061327
[ 2] Blank V., Kourilsky P., Israel A.
     "NF-kappa B and related proteins: Rel/dorsal homologies meet
     ankyrin-like repeats."
     Trends Biochem. Sci. 17:135-140(1992).
     PubMed=1533967
[ 3] Gerondakis S.
     Current Biol. 1:103-105(1991).
[ 4] Gilmore T.D.
     "Malignant transformation by mutant Rel proteins."
     Trends Genet. 7:318-322(1991).
     PubMed=1781029
[ 5] Gilmore T.D.
     "NF-kappa B, KBF1, dorsal, and related matters."
     Cell 62:841-843(1990).
     PubMed=2203533
[ 6] Mitomo K., Nakayama K., Fujimoto K., Sun X., Seki S., Yamamoto K.-I.
     "Two different cellular redox systems regulate the DNA-binding
     activity of the p50 subunit of NF-kappa B in vitro."
     Gene 145:197-203(1994).
     PubMed=8056331

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