Krüppel associated box

The Krüppel associated box (KRAB) domain is a category of transcriptional repression domains present in approximately 200 human zinc finger protein-based transcription factors. The KRAB domain typically consists of about 75 amino acid residues whilst the minimal repression module is approximately 45 amino acid residues. It is predicted to function through protein-protein interactions via two amphipathic helices. Substitutions for the conserved residues abolish repression.

Over 10 independently encoded KRAB domains have been shown to be effective repressors of transcription, suggesting this activity to be a common property of the domain.

Evolution of the KRAB domain
The KRAB domain has been found in association with the C2H2-Zinc finger proteins and is confined to mammalian genomes. The KRAB containing C2H2-ZNF genes constitute the largest sub-family of zinc finger genes. More than half of the C2H2-ZNF genes are associated with a KRAB domain in the human genome. They are more prone to clustering and are found in large clusters on the human genome.

Examples of KRAB-ZFPs include ZNF43, ZNF184, ZNF91, HPF4, HTF10 and HTF34.