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1  structure 46  species 0  interactions 10165  sequences 1426  architectures

Family: KRAB (PF01352)

Summary: KRAB box

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This is the Wikipedia entry entitled "Kruppel associated box". More...

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

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 [4].

Literature references

  1. 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

  2. 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

  3. 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

  4. Urrutia R; , Genome Biol 2003;4:231.: KRAB-containing zinc-finger repressor proteins. PUBMED:14519192 EPMC:14519192


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.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(69)
Full
(10165)
Representative proteomes NCBI
(8709)
Meta
(1)
RP15
(382)
RP35
(388)
RP55
(643)
RP75
(4775)
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Format an alignment

  Seed
(69)
Full
(10165)
Representative proteomes NCBI
(8709)
Meta
(1)
RP15
(382)
RP35
(388)
RP55
(643)
RP75
(4775)
Alignment:
Format:
Order:
Sequence:
Gaps:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(69)
Full
(10165)
Representative proteomes NCBI
(8709)
Meta
(1)
RP15
(382)
RP35
(388)
RP55
(643)
RP75
(4775)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

Pfam alignments:

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Bateman A
Previous IDs: none
Type: Family
Author: 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 information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.4 20.4
Trusted cut-off 20.4 20.4
Noise cut-off 20.3 20.3
Model length: 41
Family (HMM) version: 22
Download: download the raw HMM for this family

Species distribution

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Structures

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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