CLSTN1
Domain
The cytoplasmic domain binds synaptic Ca(2+).
Function
Postsynaptic adhesion molecule that binds to presynaptic neurexins to mediate both excitatory and inhibitory synapse formation (By similarity). Promotes synapse development by acting as a cell adhesion molecule at the postsynaptic membrane, which associates with neurexin-alpha at the presynaptic membrane (By similarity). Also functions as a cargo in axonal anterograde transport by acting as a molecular adapter that promotes KLC1 association with vesicles (PubMed:21385839). 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 (PubMed:12972431).
Soluble Alc-alpha
As intracellular fragment AlcICD, suppresses APBB1-dependent transactivation stimulated by APP C-terminal intracellular fragment (AICD), most probably by competing with AICD for APBB1-binding (PubMed:15037614).
CTF1-alpha
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 (PubMed:15037614).
Post-translational modifications
Proteolytically processed under normal cellular conditions (PubMed:15037614). A primary zeta-cleavage generates a large extracellular (soluble) N-terminal domain (sAlc) and a short C-terminal transmembrane fragment (CTF1) (PubMed:15037614). 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) (PubMed:15037614). This processing is strongly suppressed in the tripartite complex formed with APBA2 and APP, which seems to prevent the association with PSEN1 (PubMed:15037614).
Sequence Similarities
Belongs to the calsyntenin family.
Tissue Specificity
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).
Cellular localization
- Postsynaptic cell membrane
- Single-pass type I membrane protein
- Endoplasmic reticulum membrane
- Single-pass type I membrane protein
- Golgi apparatus membrane
- Single-pass type I membrane protein
- Cell projection
- Neuron projection
- Localized in the postsynaptic membrane of both excitatory and inhibitory synapses.
- Soluble Alc-alpha
- Nucleus
- The AlcICD fragment is translocated to the nucleus upon interaction with APBB1.
Alternative names
CS1, KIAA0911, CLSTN1, Calsyntenin-1, Alcadein-alpha, Alzheimer-related cadherin-like protein, Non-classical cadherin XB31alpha, Alc-alpha