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PROSITE documentation PDOC50805 [for PROSITE entry PS50805]

Krueppel-associated box (KRAB) profile





Description

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.

Technical section

PROSITE method (with tools and information) covered by this documentation:

KRAB, PS50805; Krueppel-associated box (KRAB) profile  (MATRIX)


References

1AuthorsBellefroid E.J., Poncelet D.A., Lecocq P.J., Revelant O., Martial J.A.
TitleThe evolutionarily conserved Kruppel-associated box domain defines a subfamily of eukaryotic multifingered proteins.
SourceProc. Natl. Acad. Sci. U.S.A. 88:3608-3612(1991).
PubMed ID2023909

2AuthorsMargolin J.F., Friedman J.R., Meyer W.K.-H., Vissing H., Thiesen H.-J., Rauscher F.J. III
TitleKruppel-associated boxes are potent transcriptional repression domains.
SourceProc. Natl. Acad. Sci. U.S.A. 91:4509-4513(1994).
PubMed ID8183939

3AuthorsWitzgall R., O'Leary E., Leaf A., Oenaldi D., Bonventre J.V.
TitleThe Kruppel-associated box-A (KRAB-A) domain of zinc finger proteins mediates transcriptional repression.
SourceProc. Natl. Acad. Sci. U.S.A. 91:4514-4518(1994).
PubMed ID8183940

4AuthorsPeng H., Begg G.E., Schultz D.C., Friedman J.R., Jensen D.E., Speicher D.W., Rauscher F.J. III
TitleReconstitution 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.
SourceJ. Mol. Biol. 295:1139-1162(2000).
PubMed ID10653693
DOI10.1006/jmbi.1999.3402

5AuthorsPeng H., Begg G.E., Harper S.L., Friedman J.R., Speicher D.W., Rauscher F.J. III
TitleBiochemical analysis of the Kruppel-associated box (KRAB) transcriptional repression domain.
SourceJ. Biol. Chem. 275:18000-18010(2000).
PubMed ID10748030
DOI10.1074/jbc.M001499200

6AuthorsMark C., Abrink M., Hellman L.
TitleComparative analysis of KRAB zinc finger proteins in rodents and man: evidence for several evolutionarily distinct subfamilies of KRAB zinc finger genes.
SourceDNA Cell Biol. 18:381-396(1999).
PubMed ID10360839



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