DLG1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1PDR, 2M3M, 2OQS, 2X7Z, 3RL7, 3RL8, 3W9Y, 4AMH, 4G69
Identifiers
Aliases	DLG1, DLGH1, SAP-97, SAP97, dJ1061C18.1.1, hdlg, B130052P05Rik, E-dlg/SAP97, mKIAA4187, discs large homolog 1, scribble cell polarity complex component, discs large MAGUK scaffold protein 1
External IDs	OMIM: 601014 MGI: 107231 HomoloGene: 20869 GeneCards: DLG1
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3q29 Start 197,042,560 bp[1] End 197,299,330 bp[1]
Gene location (Mouse) Chr. Chromosome 16 (mouse)[2] Band 16 B2|16 22.4 cM Start 31,482,261 bp[2] End 31,693,947 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in endothelial cell corpus callosum inferior olivary nucleus inferior ganglion of vagus nerve subthalamic nucleus hair follicle external globus pallidus Brodmann area 23 retinal pigment epithelium postcentral gyrus Top expressed in globus pallidus medullary collecting duct primary motor cortex conjunctival fornix olfactory tubercle Paneth cell utricle condyle substantia nigra cerebellar vermis More reference expression data BioGPS More reference expression data
Gene ontology Molecular function phosphatase binding phosphoprotein phosphatase activity transmembrane transporter binding cytoskeletal protein binding protein C-terminus binding ionotropic glutamate receptor binding kinase binding mitogen-activated protein kinase kinase binding guanylate kinase activity protein binding molecular adaptor activity protein kinase binding L27 domain binding ligand-gated ion channel activity potassium channel regulator activity cadherin binding structural constituent of postsynaptic density Cellular component cytoplasm cytosol postsynaptic membrane membrane cell-cell junction bicellular tight junction node of Ranvier synapse perinuclear region of cytoplasm cytoplasmic side of plasma membrane microtubule nucleus cell projection membrane membrane raft ionotropic glutamate receptor complex extracellular exosome Golgi apparatus lateral plasma membrane intercalated disc neuromuscular junction myelin sheath abaxonal region lateral loop endoplasmic reticulum membrane MPP7-DLG1-LIN7 complex sarcolemma postsynaptic density cell junction basolateral plasma membrane plasma membrane endoplasmic reticulum immunological synapse basement membrane apical plasma membrane neuron projection postsynaptic density membrane glutamatergic synapse Biological process embryonic skeletal system morphogenesis ureteric bud development positive regulation of actin filament polymerization positive regulation of potassium ion transport negative regulation of p38MAPK cascade amyloid precursor protein metabolic process tissue morphogenesis reproductive structure development membrane raft organization hard palate development endothelial cell proliferation smooth muscle tissue development negative regulation of epithelial cell proliferation regulation of sodium ion transmembrane transport astral microtubule organization actin filament organization mitotic cell cycle checkpoint signaling receptor clustering establishment or maintenance of cell polarity negative regulation of T cell proliferation branching involved in ureteric bud morphogenesis regulation of myelination cortical microtubule organization establishment or maintenance of epithelial cell apical/basal polarity viral process T cell cytokine production T cell activation peristalsis receptor localization to synapse negative regulation of protein kinase B signaling regulation of NIK/NF-kappaB signaling negative regulation of transcription by RNA polymerase II nervous system development regulation of cell shape establishment of centrosome localization immunological synapse formation cortical actin cytoskeleton organization protein localization lens development in camera-type eye bicellular tight junction assembly positive regulation of cell population proliferation negative regulation of ERK1 and ERK2 cascade activation of protein kinase activity negative regulation of mitotic cell cycle regulation of membrane potential protein localization to plasma membrane GDP metabolic process ion transmembrane transport protein dephosphorylation GMP metabolic process chemical synaptic transmission regulation of ventricular cardiac muscle cell action potential regulation of potassium ion import regulation of voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization regulation of potassium ion export across plasma membrane MAPK cascade cell-cell adhesion maintenance of postsynaptic density structure neurotransmitter receptor localization to postsynaptic specialization membrane positive regulation of protein localization to plasma membrane regulation of NMDA receptor activity Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1739 13383 Ensembl ENSG00000075711 ENSMUSG00000022770 UniProt Q12959 Q811D0 RefSeq (mRNA) NM_001098424 NM_001204386 NM_001204387 NM_001204388 NM_001290983 NM_004087 NM_001363865 NM_001366203 NM_001366204 NM_001366205 NM_001366206 NM_001366207 NM_001366208 NM_001366209 NM_001366210 NM_001366211 NM_001366212 NM_001366213 NM_001366214 NM_001366215 NM_001366216 NM_001366217 NM_001366218 NM_001366219 NM_001366220 NM_001366221 NM_001366222 NM_001252433 NM_001252434 NM_001252435 NM_001252436 NM_007862 NM_001357281 NM_001357282 RefSeq (protein) NP_001091894 NP_001191315 NP_001191316 NP_001191317 NP_001277912 NP_004078 NP_001350794 NP_001353132 NP_001353133 NP_001353134 NP_001353135 NP_001353136 NP_001353137 NP_001353138 NP_001353139 NP_001353140 NP_001353141 NP_001353142 NP_001353143 NP_001353144 NP_001353145 NP_001353146 NP_001353147 NP_001353148 NP_001353149 NP_001353150 NP_001353151 NP_001239362 NP_001239363 NP_001239364 NP_001239365 NP_031888 NP_001344210 NP_001344211 Location (UCSC) Chr 3: 197.04 – 197.3 Mb Chr 16: 31.48 – 31.69 Mb PubMed search [3] [4]
Wikidata
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Discs large homolog 1 (DLG1), also known as synapse-associated protein 97 or SAP97, is a scaffold protein that in humans is encoded by the SAP97 gene.

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

Function

SAP97 is expressed throughout the body in epithelial cells, including the kidney and brain.^[5] There is some evidence that SAP97 regulates cell-to-cell adhesion during cell death, and may interact with HPV. In the brain, SAP97's function is involved in the trafficking of transmembrane receptors from the ER to the plasma membrane.^[6]

SAP97's function has been investigated by reducing its expression by knockout or increasing its expression heterologously. Mice in which the SAP97 gene has been knocked out die perinatally, have a cleft palate, and deficiencies in renal function.^[7][8] Overexpression of SAP97 in mammalian neurons leads to increased synaptic strength.^[9]

Clinical significance

Mutations in DLG1 are associated to Crohn's Disease.^[10]

Structure

SAP97's protein structure consists of an alternatively-spliced n-terminal domain, three PDZ domains, an SH3 domain, hook domain, I3 domain, and finally an inactive 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 oligomerization with other SAP97 molecules, CASK, and other L27-domain-containing proteins.^[11] There is also a myosin VI binding site near n-terminal which may be involved in the internalization of AMPAR.^[12][13]

Each of SAP97's PDZ domains have different binding partners, including the AMPAR subunit GluR1^[14][15] for the first PDZ domain, and 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^[9] and to bind the protein 4.1N. The GK domain allows SAP97 to bind to GKAP/SAPAP-family proteins.

References

Further reading

External links

• Drosophila discs large 1 - The Interactive Fly