DLG1: the human homologue of the Drosophila discs large tumor suppressor is an essential multidomain scaffolding protein required for normal development. Recruits channels, receptors and signaling molecules to discrete plasma membrane domains in polarized cells. May play a role in adherens junction assembly, signal transduction, cell proliferation, synaptogenesis and lymphocyte activation. Interacts through its guanylate kinase-like domain with DLGAP1/2/3/4, and MAP1A. May interact with PTEN, HTR2A and LRFN1. Interacts through its PDZ domains with NMDAR2A, KV1.1, KV1.2, KV1.3, KV1.4, KV1.5, GLUR1, GPR124 and GPR125. Interacts with cytoskeleton-associated proteins EPB41 and EZR. Found in a complex with KV1.5 and CAV3. Found in a complex with APC and CTNNB1. Interacts with CDH1 through binding to PIK3R1. Forms multiprotein complexes with CASK, LIN7A, LIN7B, LIN7C, APBA1, and KCNJ12. Interacts through its guanylate kinase-like domain with KIF13B. Forms a tripartite complex composed of DLG1, MPP7 and LIN7A/C. May interact with TJAP1. Interacts with TOPK and the HTLV-1 viral Tax and HPV-18 E6 papillomavirus (HPV) oncoproteins. The alternatively spliced domain I3 corresponding to amino acids (636-669) of isoform 4 is an EPB41 binding site mediating association to membranes in polarized and non-polarized cells. The PDZ domains may also mediate association to membranes by binding to EPB41 and GPR124 together with the L27 domain that binds CASK and DLG2. The L27 domain may regulate DLG1 self-association. The N-terminal alternatively spliced region is capable of binding several SH3 domains and also moderates the level of protein oligomerization. Processes such as wound healing and tissue maintenance dictate that cells maintain dynamic control of junction assembly and disassembly. Many pathologic processes such as cancer and invasion of host cells by microbes affect these pathways. The HPV-18 E6 oncogene sequesters INADL and its paralog MPDZ as well as DLG1 and targets them for degradation, contributing to loss of polarity. Seven human isoforms produced by alternative splicing have been described.
Protein type: Motility/polarity/chemotaxis; Adaptor/scaffold
Cellular Component: basal lamina; basal plasma membrane; basolateral plasma membrane; cell junction; cell projection membrane; cytoplasm; cytosol; endoplasmic reticulum; endoplasmic reticulum membrane; Golgi apparatus; immunological synapse; intercellular junction; internal side of plasma membrane; ionotropic glutamate receptor complex; lateral loop; lateral plasma membrane; lipid raft; microtubule; microvillus; neuromuscular junction; neuron projection; nucleus; paranode region of axon; perinuclear region of cytoplasm; plasma membrane; postsynaptic density; postsynaptic membrane; presynaptic membrane; synapse; T-tubule; tight junction
Molecular Function: guanylate kinase activity; ionotropic glutamate receptor binding; mitogen-activated protein kinase kinase binding; PDZ domain binding; phosphatase binding; potassium channel regulator activity; protein binding; protein C-terminus binding; protein complex scaffold; protein kinase binding
Biological Process: actin filament organization; activation of protein kinase activity; amyloid precursor protein metabolic process; astral microtubule organization and biogenesis; cell adhesion; cell-cell adhesion; cortical actin cytoskeleton organization and biogenesis; cortical microtubule organization and biogenesis; embryonic skeletal morphogenesis; endothelial cell proliferation; establishment and/or maintenance of epithelial cell polarity; establishment of centrosome localization; formation of immunological synapse; GDP metabolic process; GMP metabolic process; hard palate development; lens development in camera-type eye; lipid raft organization and biogenesis; negative regulation of epithelial cell proliferation; negative regulation of mitotic cell cycle; negative regulation of protein kinase B signaling cascade; negative regulation of T cell proliferation; negative regulation of transcription from RNA polymerase II promoter; nervous system development; peristalsis; positive regulation of actin filament polymerization; positive regulation of cell proliferation; positive regulation of potassium ion transport; protein localization; receptor clustering; regulation of cell shape; regulation of membrane potential; regulation of myelination; regulation of protein localization; reproductive structure development; smooth muscle development; synaptic transmission; T cell activation; T cell cytokine production; tissue morphogenesis; ureteric bud branching; ureteric bud development
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