|PROSITE documentation PDOC50805|
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.Last update:
December 2001 / First entry.
PROSITE method (with tools and information) covered by this documentation:
|1||Authors||Bellefroid E.J. Poncelet D.A. Lecocq P.J. Revelant O. Martial J.A.|
|Title||The evolutionarily conserved Kruppel-associated box domain defines a subfamily of eukaryotic multifingered proteins.|
|Source||Proc. Natl. Acad. Sci. U.S.A. 88:3608-3612(1991).|
|2||Authors||Margolin J.F. Friedman J.R. Meyer W.K.-H. Vissing H. Thiesen H.-J. Rauscher F.J. III|
|Title||Kruppel-associated boxes are potent transcriptional repression domains.|
|Source||Proc. Natl. Acad. Sci. U.S.A. 91:4509-4513(1994).|
|3||Authors||Witzgall R. O'Leary E. Leaf A. Oenaldi D. Bonventre J.V.|
|Title||The Kruppel-associated box-A (KRAB-A) domain of zinc finger proteins mediates transcriptional repression.|
|Source||Proc. Natl. Acad. Sci. U.S.A. 91:4514-4518(1994).|
|4||Authors||Peng H. Begg G.E. Schultz D.C. Friedman J.R. Jensen D.E. Speicher D.W. Rauscher F.J. III|
|Title||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.|
|Source||J. Mol. Biol. 295:1139-1162(2000).|
|5||Authors||Peng H. Begg G.E. Harper S.L. Friedman J.R. Speicher D.W. Rauscher F.J. III|
|Title||Biochemical analysis of the Kruppel-associated box (KRAB) transcriptional repression domain.|
|Source||J. Biol. Chem. 275:18000-18010(2000).|
|6||Authors||Mark C. Abrink M. Hellman L.|
|Title||Comparative analysis of KRAB zinc finger proteins in rodents and man: evidence for several evolutionarily distinct subfamilies of KRAB zinc finger genes.|
|Source||DNA Cell Biol. 18:381-396(1999).|