Induces KLC1 association with vesicles and functions as a cargo in axonal anterograde transport. Complex formation with APBA2 and APP, stabilizes APP metabolism and enhances APBA2-mediated suppression of beta-APP40 secretion, due to the retardation of intracellular APP maturation. In complex with APBA2 and C99, a C-terminal APP fragment, abolishes C99 interaction with PSEN1 and thus APP C99 cleavage by gamma-secretase, most probably through stabilization of the direct interaction between APBA2 and APP. The intracellular fragment AlcICD suppresses APBB1-dependent transactivation stimulated by APP C-terminal intracellular fragment (AICD), most probably by competing with AICD for APBB1-binding. May modulate calcium-mediated postsynaptic signals.
Expressed in the brain and, a lower level, in the heart, skeletal muscle, kidney and placenta. Accumulates in dystrophic neurites around the amyloid core of Alzheimer disease senile plaques (at protein level).
Contains 2 cadherin domains.
The cytoplasmic domain is involved in interaction with APBA2, as well as the binding of synaptic Ca(2+).
Proteolytically processed under normal cellular conditions. A primary zeta-cleavage generates a large extracellular (soluble) N-terminal domain (sAlc) and a short C-terminal transmembrane fragment (CTF1). A secondary cleavage catalyzed by presenilin gamma-secretase within the transmembrane domain releases the beta-Alc-alpha chain in the extracellular milieu and produces an intracellular fragment (AlcICD). This processing is strongly suppressed in the tripartite complex formed with APBA2 and APP, which seems to prevent the association with PSEN1.
Endoplasmic reticulum membrane. Golgi apparatus membrane. Cell projection. Cell junction > synapse > postsynaptic cell membrane. Nucleus. Neurite tips. Localized in the postsynaptic membrane of both excitatory and inhibitory synapses (By similarity). The AlcICD fragment is translocated to the nucleus upon interaction with APBB1.