Summary: Nuclear envelope localisation domain
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KASH domains Edit Wikipedia article
|Nuclear envelope localisation domain|
KASH domains are conserved C-terminal protein regions less than ~30 amino acids. KASH is an acronym for Klarsicht, ANC-1, Syne Homology. KASH domains always follow a transmembrane domain. Most proteins containing KASH domains are thought to be involved in the positioning of the nucleus in the cell. It is thought that KASH domains interact with proteins containing SUN domains in the space between the outer and inner nuclear membranes to bridge the nuclear envelope and transfer force from the nucleoskeleton to the cytoplasmic cytoskeleton. KASH proteins are thought to largely localize to the outer nuclear membrane, although there are reports of inner nuclear membrane localization of some KASH protein isoforms.
 Examples of KASH proteins
- Nesprins-1, 2, and 3 (also called Synes, Mynes, Nuance, Enaptin)
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.
Nuclear envelope localisation domain Provide feedback
The KASH (for Klarsicht/ANC-1/Syne-1 homology) or KLS domain is a highly hydrophobic nuclear envelope localisation domain of approximately 60 amino acids comprising a 20-amino-acid transmembrane region and a 30-35-residue C-terminal region that lies between the inner and the outer nuclear membranes . During meiotic prophase, telomeres cluster to form a bouquet arrangement of chromosomes. SUN and KASH domain proteins form complexes that span both membranes of the nuclear envelope. The KASH domain links the dynein motor complex of the microtubules, through the outer nuclear membrane to the Sad1 domain in the inner nuclear membrane which then interacts with the bouquet proteins Bqt1 and Bqt2 that are complexed with Bqt4, Rap1 and Taz1 and attached to the telomere . SUN domain-containing proteins are essential for recruiting KASH domain proteins at the outer nuclear membrane, and KASH domains provide a generic NE tethering device for functionally distinct proteins whose cytoplasmic domains mediate nuclear positioning, maintain physical connections with other cellular organelles, and possibly even influence chromosome dynamics .
Chikashige Y, Yamane M, Okamasa K, Tsutsumi C, Kojidani T, Sato M, Haraguchi T, Hiraoka Y;, J Cell Biol. 2009;187:413-427.: Membrane proteins Bqt3 and -4 anchor telomeres to the nuclear envelope to ensure chromosomal bouquet formation. PUBMED:19948484 EPMC:19948484
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR012315
The KASH (Klarsicht/ANC-1/Syne-1 homology), or KLS domain is a highly hydrophobic nuclear envelope localization domain of approximately 60 amino acids comprising a 20-amino-acid transmembrane region and a 30-35-residue C-terminal region that lies between the inner and the outer nuclear membranes. The KASH domain is found in association with other domains, such as spectrin repeats and CH, at the C terminus of proteins tethered to the nuclear membrane in diverse cell types [PUBMED:10556085, PUBMED:10878022, PUBMED:12169658, PUBMED:12408964, PUBMED:15579692].
Some proteins known to contain a KASH domain are listed below:
- Caenorhabditis elegans nuclear anchorage protein 1 (ANC-1).
- Drosophila Klarsicht (Klar), a protein associated with nuclei and required for a subset of nuclear migrations.
- Drosophila MSP-300.
- Vetebrate nesprin-1 and -2 (also known as Syne-1 and -2). They are associated with emerin and lamin A at the nuclear envelope of muscle cells and other cell types.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Cellular component||integral to membrane (GO:0016021)|
|Molecular function||actin binding (GO:0003779)|
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Curation and family details
|Author:||Finn R, Coggill P|
|Number in seed:||20|
|Number in full:||319|
|Average length of the domain:||56.40 aa|
|Average identity of full alignment:||58 %|
|Average coverage of the sequence by the domain:||1.68 %|
|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:||4|
|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 KASH domain has been found. There are 2 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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