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 α-helices. The KRAB A and B boxes can be
separated by variable spacer segments and many KRAB proteins contain only the
A box .
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-β 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 . 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.
December 2001 / First entry.
PROSITE method (with tools and information) covered by this documentation:
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.
PROSITE is copyright. It is produced by the SIB Swiss Institute
Bioinformatics. There are no restrictions on its use by non-profit
institutions as long as its content is in no way modified. Usage by and
for commercial entities requires a license agreement. For information
about the licensing scheme send an email to
or see: prosite_license.html.