Seems to be an adapter protein in the postsynaptic density (PSD) of excitatory synapses that interconnects receptors of the postsynaptic membrane including NMDA-type and metabotropic glutamate receptors, and the actin-based cytoskeleton. May play a role in the structural and functional organization of the dendritic spine and synaptic junction.
Expressed in epithelial cells (at protein level). All isoforms except isoform 7 are expressed predominantly in brain, with highest levels in olfactory bulb, cerebral cortex, cerebellum, central gray matter and hippocampus. Moderate levels of expression are seen in the caudate putamen, thalamic nuclei and brain stem. In cerebellum primarily expressed in Purkinje cells. Isoform 7 is not expressed in brain but expressed in liver, cholangiocytes and thymus. Isoform 7 is present in pancreas, colonic mucosa and thymocytes (at protein level).
Belongs to the SHANK family. Contains 1 PDZ (DHR) domain. Contains 1 SAM (sterile alpha motif) domain. Contains 1 SH3 domain.
Expressed during early postnatal brain development, especially in the caudate putamen and thalamic nuclei. Expression in the cerebral cortex, the hippocampus and the cerebellum is moderate to high at P5 and shows a stable expression throughout development. Isoforms 1, 2, 4 and 6 are predominantly expressed in cerebellum up to the age of approximately 3 weeks. Isoform 1 expression decreases during development of cortex but slightly increases in cerebellum.
The PDZ domain is required for interaction with GRID2, PLCB3, SLC9A3 and CFTR.
Apical cell membrane. Cytoplasm. Cell junction, synapse. Cell junction, synapse, postsynaptic cell membrane, postsynaptic density. Cell projection, growth cone. Cell projection, dendritic spine. Colocalizes with cortactin in growth cones in differentiating hippocampal neurons. Present in the dendritic spines of cerebellar Purkinje cells (By similarity). Colocalizes with cortactin in growth cones in differentiating hippocampal neurons. Colocalized with PDE4D to the apical membrane of colonic crypt cells.