Summary: KRAB box
This is the Wikipedia entry entitled "Kruppel associated box". More...
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KRAB box Provide feedback
The KRAB domain (or Kruppel-associated box) is present in about a third of zinc finger proteins containing C2H2 fingers. The KRAB domain is found to be involved in protein-protein interactions [2,3]. The KRAB domain is generally encoded by two exons. The regions coded by the two exons are known as KRAB-A and KRAB-B. The A box plays an important role in repression by binding to corepressors, while the B box is thought to enhance this repression brought about by the A box. KRAB-containing proteins are thought to have critical functions in cell proliferation and differentiation, apoptosis and neoplastic transformation .
Thiesen HJ, Bellefroid E, Revelant O, Martial JA; , Nucleic Acids Res 1991;19:3996-3996.: Conserved KRAB protein domain identified upstream from the zinc finger region of Kox 8. PUBMED:1861988 EPMC:1861988
Kim SS, Chen YM, O'Leary E, Witzgall R, Vidal M, Bonventre JV; , Proc Natl Acad Sci U S A 1996;93:15299-15304.: A novel member of the RING finger family, KRIP-1, associates with the KRAB-A transcriptional repressor domain of zinc finger proteins. PUBMED:8986806 EPMC:8986806
Friedman JR, Fredericks WJ, Jensen DE, Speicher DW, Huang XP, Neilson EG, Rauscher FJ; , Genes Dev 1996;10:2067-2078.: KAP-1, a novel corepressor for the highly conserved KRAB repression domain. PUBMED:8769649 EPMC:8769649
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR001909
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) [PUBMED:14519192]. It is enriched in charged amino acids and can be divided into subregions A and B, which are predicted to fold into two amphipathic alpha-helices. The KRAB A and B boxes can be separated by variable spacer segments and many KRAB proteins contain only the A box [PUBMED:2023909].
The functions currently known for members of the KRAB-containing protein family include transcriptional repression of RNA polymerase I, II, and III promoters, binding and splicing of RNA, and control of nucleolus function. 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 [PUBMED:8183939, PUBMED:8183940]. Gene silencing requires the binding of the KRAB domain to the RING-B box-coiled coil (RBCC) domain of the KAP-1/TIF1-beta 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 [PUBMED:10653693, PUBMED:10748030].
KRAB-ZFPs probably constitute the single largest class of transcription factors within the human genome [PUBMED:10360839]. Although the function of KRAB-ZFPs is largely unknown, they appear to play important roles during cell differentiation and development. The KRAB domain is generally encoded by two exons. The regions coded by the two exons are known as KRAB-A and KRAB-B.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Cellular component||intracellular (GO:0005622)|
|Molecular function||nucleic acid binding (GO:0003676)|
|Biological process||regulation of transcription, DNA-dependent (GO:0006355)|
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We make a range of alignments for each Pfam-A family:
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Curation and family details
|Seed source:||Bateman A|
|Number in seed:||69|
|Number in full:||10165|
|Average length of the domain:||40.40 aa|
|Average identity of full alignment:||54 %|
|Average coverage of the sequence by the domain:||7.64 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||22|
|Download:||download the raw HMM for this family|
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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the KRAB domain has been found. There are 1 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
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