DLG1

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	MGI: 107231 HomoloGene: 20869 GeneCards: DLG1
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3q29 Start 197,042,560 bp[1] End 197,299,300 bp[1]
Gene location (Mouse) Chr. Chromosome 16 (mouse)[2] Band 16 B2|16 22.4 cM Start 31,663,443 bp[2] End 31,875,129 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • phosphatase binding • phosphoprotein phosphatase activity • ion channel 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 • protein complex scaffold activity • protein kinase binding • L27 domain binding • ligand-gated ion channel activity • potassium channel regulator activity • cadherin binding 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 • cell 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 • basal lamina • MPP7-DLG1-LIN7 complex • sarcolemma • postsynaptic density • cell junction • basolateral plasma membrane • plasma membrane • endoplasmic reticulum • immunological 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 • receptor clustering • positive regulation of establishment of protein localization to plasma membrane • 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 • single organismal cell-cell adhesion • negative regulation of protein kinase B signaling • regulation of NIK/NF-kappaB signaling • negative regulation of transcription from RNA polymerase II promoter • 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 • cellular protein complex localization • bicellular tight junction assembly • positive regulation of cell 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 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_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_001239362 NP_001239363 NP_001239364 NP_001239365 NP_031888 NP_001344210 NP_001344211
Location (UCSC)	Chr 3: 197.04 – 197.3 Mb	Chr 16: 31.66 – 31.88 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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