Sad1 and UNC84 domain containing protein 2 (SUN2)

Sad1 and UNC84 domain containing protein 2 (SUN2) is an inner nuclear membrane (INM) protein and a component of the LINC (Linker of Nucleoskeleton and Cytoskeleton) complex[2][3][5]. SUN2 spans the inner nuclear membrane and interacts in the perinuclear space with KASH-domain proteins (such as Nesprins) to physically connect the nucleoskeleton to the cytoskeleton[3][5]. SUN2 forms trimers via its coiled-coil domains to bind KASH proteins and is involved in mechanotransduction, positioning of the nucleus, and maintenance of nuclear shape[3]. Its regulated degradation involves ubiquitination by the SCF^βTrCP^ ubiquitin ligase, extraction from the membrane by the p97 ATPase, and proteasomal degradation, which is tightly controlled by Casein Kinase 2 (CK2) and the phosphatase CTDNEP1[1][2]. Disruption or accumulation of non-degradable SUN2 causes severe nuclear architecture defects, impairs DNA damage repair, and can result in chromosomal instability during mitosis[1][2]. Mutations in SUN2 have been linked to muscular dystrophy and other nuclear envelope disorders[3][5]. To date, SUN2 is not recognized as a direct therapeutic drug target or receptor, and there are no known drugs specifically targeting SUN2.

Other names

SUN domain-containing protein 2SUN2FRIGGKIAA0668RAB5IPUNC84BRab5IPProtein unc-84 homolog BRab5-interacting proteinSad1/unc-84 protein-like 2rab5IPSad1 unc-84 domain protein 2nuclear envelope protein