Calsyntenin-1 (CST-1; also Alcadein-alpha) is a 140 - 150 kDa member of the Alcadein family of molecules. It is expressed in the ER/Golgi and on the plasma membranes of almost all neurons. Calsyntenin-1 is a calcium-binding protein that may regulate post-synaptic signaling and Amyloid Precursor Protein (APP) cleavage and gene activation. Notably, when cleaved in a manner similar to APP, its intracellular fragment antagonizes APP AICD gene activation.
Mature human CST-1 is a 953 amino acid (aa) type I transmembrane protein. It contains two cadherin domains (aa 38 - 265) in its extracellular region (aa 29 - 859) and a 101 aa cytoplasmic tail. Extracellular cleavage occurs at Met825 Ala826, generating a soluble 115 kDa ECD. Isoforms involve a 78 aa substitution for aa 917 - 981, plus deletions of aa 72 - 81 and 507 - 525. Over aa 30 - 851, human CST-1 shares 92% aa identity with mouse CST-1.