SCY1-like protein 2 (SCYL2)

SCY1-like protein 2 (SCYL2) is a pseudokinase that participates in the regulation of clathrin-mediated vesicle trafficking at the plasma membrane, trans-Golgi network, and endosomal system[3][4][6]. Its protein structure includes an N-terminal pseudokinase domain (lacking key catalytic residues), a central HEAT repeat domain for protein-protein interactions, and a coiled-coil domain at the C-terminus[2][3]. It binds both clathrin and adaptor protein complexes and modulates membrane trafficking, including receptor turnover through lysosomal degradation (notably impacting Wnt signaling via Frizzled 5)[3][4]. SCYL2 is essential for proper cell development, neuronal signaling, and organogenesis, with mutations linked to multisystem neurodevelopmental disorders and syndromes such as arthrogryposis multiplex congenita and acute liver failure[1][4]. In cancer, SCYL2 is overexpressed in several tumor types and correlates with poor prognosis, suggesting a role in cell proliferation and migration[2][8]. There are currently no drugs that directly target SCYL2, but reduction of its expression by RNAi techniques impairs proliferation of cancer cells, highlighting its functional importance in cell growth regulation[2][4].

Other names

CVAK104KIAA1360AMC4AMCNACCCoated vesicle-associated kinase of 104 kDaSCY1-like pseudokinase 2SCY1-like 2SCY1-like, kinase-like 2

Null for direct targeted drugs. For experimental manipulation, RNA interference (shRNA, siRNA) has been used for downregulation in cancer cell models.