Species predicted to react based on 100% sequence homology:Human
Specificity / Sensitivity
Phospho-GKAP (Ser346) Antibody recognizes endogenous levels of GKAP protein only when phosphorylated at Ser346.
Source / Purification
Polyclonal antibodies are produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Ser346 of human GKAP protein. Antibodies are purified by protein A and peptide affinity chromatography.
Background
Guanylate kinase-associated protein (GKAP, DLGAP1 or SAPAP1) is part of the postsynaptic scaffolding complex that includes the PSD-95, SAP90, and SHANK proteins (1-3). GKAP links the synaptic protein SHANK to a PSD-95 complex that includes NMDA glutamate receptors (3,4). Synaptic activity induces ubiquitination of GKAP protein by the E3 ubiquitin ligase TRIM3, which results in decreased GKAP protein levels through degradation (5,6). GKAP protein turnover is regulated by a CaMKII-dependent, bidirectional mechanism. Synaptic over-excitation leads to CaMKIIα-mediated GKAP phosphorylation at Ser346, which induces polyubiquitination of GKAP and removal of the scaffold protein from synapses. In contrast, during low-level synaptic activity CaMKIIβ phosphorylates GKAP, which triggers dissociation of GKAP from the motor protein complex responsible for GKAP transport to the base of the synapse and its subsequent incorporation into the postsynaptic density (7).