{PDOC50805}
{PS50805; KRAB}
{BEGIN}
******************************************
* Krueppel-associated box (KRAB) profile *
******************************************

The Krueppel-associated  box  (KRAB) is a domain of around 75 amino acids that
is found in the N-terminal part of about one third of eukaryotic Krueppel-type
C2H2 zinc  finger proteins (ZFPs) (see <PDOC00028>). It is enriched in charged
amino acids and can be divided into subregions A and B, which are predicted to
fold into  two  amphipathic  alpha-helices.  The  KRAB  A  and  B boxes can be
separated by  variable spacer segments and many KRAB proteins contain only the
A box [1].

The KRAB  domain functions as a transcriptional repressor when tethered to the
template DNA by a DNA-binding domain. A sequence of 45 amino acids in the KRAB
A subdomain  has been shown to be necessary and sufficient for transcriptional
repression. The  B  box  does  not  repress  by itself but does potentiate the
repression exerted  by the KRAB A subdomain [2,3]. Gene silencing requires the
binding of  the KRAB domain to the RING-B box-coiled coil (RBCC) domain of the
KAP-1/TIF1-beta corepressor.  As  KAP-1  binds to the heterochromatin proteins
HP1, it  has  been  proposed  that  the  KRAB-ZFP-bound  target  gene could be
silenced following recruitment to heterochromatin [4,5].

KRAB-ZFPs probably  constitute  the  single  largest  class  of  transcription
factors within  the  human  genome  [6]. Although the function of KRAB-ZFPs is
largely unknown,   they   appear   to   play   important   roles  during  cell
differentiation and development.

The profile we developed spans the complete KRAB domain.

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

-Last update: December 2001 / First entry.

[ 1] Bellefroid E.J., Poncelet D.A., Lecocq P.J., Revelant O.,
     Martial J.A.
     "The evolutionarily conserved Kruppel-associated box domain defines a
     subfamily of eukaryotic multifingered proteins."
     Proc. Natl. Acad. Sci. U.S.A. 88:3608-3612(1991).
     PubMed=2023909
[ 2] Margolin J.F., Friedman J.R., Meyer W.K.-H., Vissing H., Thiesen H.-J.,
     Rauscher F.J. III
     "Kruppel-associated boxes are potent transcriptional repression
     domains."
     Proc. Natl. Acad. Sci. U.S.A. 91:4509-4513(1994).
     PubMed=8183939
[ 3] Witzgall R., O'Leary E., Leaf A., Oenaldi D., Bonventre J.V.
     "The Kruppel-associated box-A (KRAB-A) domain of zinc finger proteins
     mediates transcriptional repression."
     Proc. Natl. Acad. Sci. U.S.A. 91:4514-4518(1994).
     PubMed=8183940
[ 4] Peng H., Begg G.E., Schultz D.C., Friedman J.R., Jensen D.E.,
     Speicher D.W., Rauscher F.J. III
     "Reconstitution of the KRAB-KAP-1 repressor complex: a model system
     for defining the molecular anatomy of RING-B box-coiled-coil
     domain-mediated protein-protein interactions."
     J. Mol. Biol. 295:1139-1162(2000).
     PubMed=10653693; DOI=10.1006/jmbi.1999.3402
[ 5] Peng H., Begg G.E., Harper S.L., Friedman J.R., Speicher D.W.,
     Rauscher F.J. III
     "Biochemical analysis of the Kruppel-associated box (KRAB)
     transcriptional repression domain."
     J. Biol. Chem. 275:18000-18010(2000).
     PubMed=10748030; DOI=10.1074/jbc.M001499200
[ 6] Mark C., Abrink M., Hellman L.
     "Comparative analysis of KRAB zinc finger proteins in rodents and man:
     evidence for several evolutionarily distinct subfamilies of KRAB zinc
     finger genes."
     DNA Cell Biol. 18:381-396(1999).
     PubMed=10360839

--------------------------------------------------------------------------------
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}