DLG1

Disks large homolog 1 (DLG1), also known as synapse-associated protein 97 or SAP97, is a is_associated_with::protein that in humans is encoded by the SAP97 is_associated_with::gene.

SAP97 is a mammalian MAGUK-family member protein that is similar to the Drosophila protein is_associated_with::Dlg1 (the protein is alternatively referred to as hDlg1, and the human gene is DLG1). SAP97 is expressed throughout the body in is_associated_with::epithelial cells. In the brain it is involved in the trafficking of is_associated_with::ionotropic receptors from the is_associated_with::endoplasmic Reticulum to the is_associated_with::plasma membrane, and may be involved in the trafficking is_associated_with::AMPAR during synaptic plasticity.

Function
SAP97 is expressed throughout the body in epithelial cells, including the kidney and brain. There is some evidence that SAP97 regulates cell-to-cell adhesion during cell death, and may interact with is_associated_with::HPV. In the brain, SAP97's function is involved in the trafficking of transmembrane receptors from the ER to the plasma membrane.

SAP97's function has been investigated by reducing its expression by knockout or increasing its expression is_associated_with::heterologously. Mice in which the SAP97 gene has been knocked out die perinatally, have a is_associated_with::cleft palate, and deficiencies in renal function. is_associated_with::Overexpression of SAP97 in mammalian neurons leads to increased synaptic strength.

Clinical significance
Mutations in DLG1 are associated to Crohn's Disease.

Structure
SAP97's protein structure consists of an alternatively-spliced n-terminal domain, three is_associated_with::PDZ domains, an is_associated_with::SH3 domain, hook domain, I3 domain, and finally an inactive is_associated_with::guanylate kinase (GK) domain. Each of these domains has specific interacting partners that help define SAP97's unique function.

The n-terminal of SAP97 can be alternatively spliced to contain a double-cysteine/palmitoylation site (α-isoform), or an L27 domain (β-isoform. The L27 domain is involved in SAP97 is_associated_with::oligomerization with other SAP97 molecules, CASK, and other L27-domain-containing proteins.  There is also a is_associated_with::myosin VI binding site near n-terminal which may be involved in the internalization of AMPAR.

Each of SAP97's PDZ domains have different binding partners, including the AMPAR subunit GluR1 for the first PDZ domain, and is_associated_with::neuroligin for the last. SAP97's I3 domain is unique to SAP97 among the MAGUK family, and is known to regulate the post-synaptic localization of SAP97 and to bind the protein 4.1N. The GK domain allows SAP97 to bind to is_associated_with::GKAP/SAPAP-family proteins.