Klarsicht/ANC-1/Syne Homology (KASH) Domain
The KASH domain is the conserved C-terminal transmembrane domain from nesprin/SYNE family proteins that anchors to the outer nuclear membrane (ONM). Defined by Starr & Han (2002). Used to tether proteins to the outer nuclear membrane in engineered constructs.
Origin: C. elegans ANC-1 / human SYNE1/SYNE2 (nesprin) family
Characteristics
~20 aa transmembrane domain + short luminal C-terminal tail that binds SUN domain proteins in the perinuclear space. Part of the LINC complex (Linker of Nucleoskeleton and Cytoskeleton). Requires the perinuclear space SUN-domain interaction for stable ONM retention.
Applications: Anchoring proteins, nanobodies, or actuators to the outer nuclear membrane. Engineering nuclear positioning. Tethering cytoskeletal elements or signaling molecules to the nuclear envelope. Used in LINC complex disruption studies.
Limitations: Requires SUN domain partners for stable retention—expression in cells lacking SUN1/SUN2 may reduce efficiency. C-terminal placement required (domain is at the natural C-terminus of nesprin proteins). Large cargo may affect nuclear positioning.
Sequence
References
- Starr et al. (2002). Role of ANC-1 in tethering nuclei to the actin cytoskeleton. Science - Starr 2002 KASH