PICK1
Domain
The AH domain mediates binding to F-actin.
The unoccupied PDZ domain is probably involved in allosteric modulation by forming an intramolecular bridge with the AH domain leading to a 'closed' formation. Binding of a PDZ ligand, such as GRIA2, allows enhanced interactions with F-actin and the Arp2/3 complex thus enhanced inhibition of actin polymerization (By similarity).
Function
Probable adapter protein that bind to and organize the subcellular localization of a variety of membrane proteins containing some PDZ recognition sequence. Involved in the clustering of various receptors, possibly by acting at the receptor internalization level. Plays a role in synaptic plasticity by regulating the trafficking and internalization of AMPA receptors. May be regulated upon PRKCA activation. May regulate ASIC1/ASIC3 channel. Regulates actin polymerization by inhibiting the actin-nucleating activity of the Arp2/3 complex; the function is competitive with nucleation promoting factors and is linked to neuronal morphology regulation and AMPA receptor (AMPAR) endocytosis. Via interaction with the Arp2/3 complex involved in regulation of synaptic plasicity of excitatory synapses and required for spine shrinkage during long-term depression (LTD). Involved in regulation of astrocyte morphology, antagonistic to Arp2/3 complex activator WASL/N-WASP function.
Post-translational modifications
Phosphorylation at Thr-82 appears to inhibit the interaction with AMPA receptors.
Palmitoylation on Cys-413 is essential for long-term synaptic depression (LTD).
Tissue Specificity
Ubiquitous.
Cellular localization
- Cytoplasm
- Perinuclear region
- Membrane
- Peripheral membrane protein
- Membrane
- Lipid-anchor
- Postsynaptic density
- Synapse
- Synaptosome
- Cytoplasm
- Cytoskeleton
- Also membrane-associated, present at excitatory synapses.
Alternative names
PRKCABP, PICK1, PRKCA-binding protein, Protein interacting with C kinase 1, Protein kinase C-alpha-binding protein