Recombinant Human Calsyntenin-2 Protein, CF

Calsyntenin-2, also called Alc-gamma (Alcadein-gamma; gene name CLSTN2) is a 120-135 kDa glycoprotein that is a member of the Alcadein family of cadherin domain‑containing type I transmembrane molecules (1, 2). Mature human Calsyntenin-2 is a 935 amino acid (aa) protein with two extracellular cadherin domains. Proteolytic cleavage by ADAM10 and gamma -secretase generates a 105-110 kDa extracellular domain termed soluble alc-gamma, and a 25 kDa, highly acidic, calcium-binding intracellular domain termed Alc gamma ICD (1-3). The soluble alc-gamma portion of human Calsyntenin-2 (aa 21-831) shares 95%, 94%, 96%, 95% and 94% aa identity with mouse, rat, canine, bovine and equine Calsyntenin-2, respectively. A potential isoform variant shows a premature truncation after Gln608. Calsyntenins are predominantly expressed in the ER/Golgi and post-synaptic plasma membranes of neurons (1). While nearly all neurons express Calsyntenin 1, Calsyntenin-2 is mainly found in subpopulations GABAergic  neurons of cortical layers 5 and 6, cerebellum (in Purkinje cells), amygdale (basolateral cells), hippocampus (pyramidal cells and hilus interneurons) and some brain stem neurons (1). Calsyntenin-2 interacts with amyloid precursor protein (APP) through its binding protein, APBA2/X11L, where it is thought to regulate APP cleavage, and likely impacts post-synaptic signaling and gene activation (2, 3). Notably, Alc gamma ICD binds APBA1/FE65 and antagonizes amyloid intracellular domain (AICD) gene activation (3). Polymorphisms of the Calsyntenin-2 gene, in combination with polymorphisms of the brain signaling regulator KIBRA, are thought to modulate episodic memory performance (4, 5).