PROSITE documentation PDOC50805Krueppel-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 α-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-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 [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.
Last update:December 2001 / First entry.
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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). | |
| PubMed ID | 2023909 |
| 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). | |
| PubMed ID | 8183939 |
| 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). | |
| PubMed ID | 8183940 |
| 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). | |
| PubMed ID | 10653693 | |
| DOI | 10.1006/jmbi.1999.3402 |
| 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). | |
| PubMed ID | 10748030 | |
| DOI | 10.1074/jbc.M001499200 |
| 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). | |
| PubMed ID | 10360839 |
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