KRAB krueppel associated box
SMART ACC:	SM000349
Description:	-
InterPro ACC:	IPR001909
InterPro abstract:	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 … expand 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 α-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 ]. The KRAB domain is generally encoded by two exons. The regions coded by the two exons are known as KRAB-A and KRAB-B. Although the function of KRAB-ZFPs is largely unknown, they appear to play important roles during cell differentiation and development. These proteins have been shown to play important roles in cell differentiation and organ development, and in regulating viral replication and transcription. A KRAB domain may consist of an A-box, or of an A-box plus either a B-box, a divergent B-box (b), or a C-box. Only the A-box is included in this model. The A-box is needed for repression, the B- and C- boxes are not. KRAB-ZFPs have one or two KRAB domains at their amino-terminal end, and multiple C2H2 zinc finger motifs at their C-termini. Some KRAB-ZFPs also contain a SCAN domain which mediates homo- and hetero-oligomerization. The KRAB domain is a protein-protein interaction module which represses transcription through recruiting corepressors. A key mechanism appears to be the following: KRAB-AFPs tethered to DNA recruit, via their KRAB domain, the repressor KAP1 (KRAB-associated protein-1, also known as transcription intermediary factor 1 beta, KRAB-A interacting protein and tripartite motif protein 28). The KAP1/ KRAB-AFP complex in turn recruits the heterochromatin protein 1 (HP1) family, and other chromatin modulating proteins, leading to transcriptional repression through heterochromatin formation [ PUBMED:25609696 ]. collapse
GO process:	regulation of DNA-templated transcription (GO:0006355)
Family alignment:	View the Family alignment or the Alignment consensus sequence
There are 50 777 KRAB domains in 49 028 proteins in SMART's NRDB database.

Taxonomic distribution of proteins containing KRAB domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing KRAB domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

Relevant references for this domain

Primary literature for the KRAB domain is listed below. Automatically-derived, secondary literature is also available.

KEGG pathways involving proteins which contain this domain

This information is based on the mapping of SMART genomic protein database to KEGG orthologous groups. Percentages are related to the number of proteins containing a KRAB domain which could be assigned to a KEGG orthologous group, and not all proteins containing KRAB domains. Please note that proteins can be included in multiple pathways, ie. the numbers below will not add to 100%.

KEGG pathways

Some of these pathways are included in the interactive Pathways Explorer overview maps. Select an overview map and click the button below to highlight them in iPath.

KEGG orthologous groups

Some of these KOs are included in the interactive Pathways Explorer overview maps. Select an overview map and click the button below to highlight them in iPath.

3D structures in PDB containing this domain

Links to other resources describing this domain

InterPro	IPR001909