Recombinant Human DAG1 protein

일반 정보

기능

The dystroglycan complex is involved in a number of signaling events and processes including laminin deposition and extracellular matrix assembly, acetylcholine receptor clustering, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cell migration, epithelial polarization, and epithelium branching morphogenesis (By similarity). Required for the formation of photoreceptor ribbon synapses, and long-term maintenance of inhibitory synapses in cerebellar Purkinje cells (By similarity). Also involved in the positive regulation of cartilage formation through agrin (AGRN) binding and up-regulation of SOX9, a transcription factor that plays a key role in chondrocytes differentiation (PubMed : 26290588).. Alpha-dystroglycan. Extracellular peripheral glycoprotein that acts as a receptor for extracellular matrix proteins containing laminin-G domains. As a receptor for laminin is involved in extracellular matrix assembly, and activation of the PI3K/AKT pathway regulating cell apoptotic signals in muscle (By similarity). Binding of laminin LAMA1 to alpha-dystroglycan also initiates a signaling cascade in which Src kinases, c-Src or c-Fyn, phosphorylate syntrophin modifying its interaction with the adapter protein GRB2; this triggers recruitment of guanyl-nucleotide exchange factor SOS1 and activation of RAC1, finally resulting in c-Jun phosphorylation by MAPK8/JNK1 (By similarity). As a receptor for laminin LAMA1 is also involved in epithelium branching morphogenesis in salivary glang and lung (By similarity). Receptor for laminin-2 (LAMA2) and agrin in peripheral nerve Schwann cells (By similarity). Also acts as a receptor for laminin LAMA5 (By similarity). In muscle cells, it is a receptor for laminin-1 (also known as laminin-111 or EHS laminin) and is involved in the stimulation of agrin-induced acetylcholine receptor (AChR) clustering, and formation of the synaptic basement membrane. It is required for acetylcholinesterase (AChE) localization at the neuromuscular junctions (NMJ) through its binding with perlecan (HSPG2) and is, therefore, involved in the down-regulation of colinergic synaptic transmission (By similarity). In the retina, it is required for the formation of photoreceptor ribbon synapses through its interaction with pikachurin (EGFLAM) (By similarity). Involved in the positive regulation of cartilage formation through agrin (AGRN) binding and up-regulation of SOX9, a transcription factor that plays a key role in chondrocytes differentiation (PubMed : 26290588).. Beta-dystroglycan. Transmembrane protein that plays important roles in connecting the extracellular matrix to the cytoskeleton. Acts as a cell adhesion receptor in both muscle and non-muscle tissues. Receptor for both DMD and UTRN and, through these interactions, scaffolds axin to the cytoskeleton. Also functions in cell adhesion-mediated signaling and implicated in cell polarity.. Alpha-dystroglycan. (Microbial infection) Acts as a receptor for lassa virus and lymphocytic choriomeningitis virus glycoprotein and class C new-world arenaviruses (PubMed : 16254364, PubMed : 17360738, PubMed : 19324387). Acts as a Schwann cell receptor for Mycobacterium leprae, the causative organism of leprosy, but only in the presence of the G-domain of LAMA2 (PubMed : 9851927).

Post-translational modifications

Alpha-dystroglycan. O-glycosylated. POMGNT1 catalyzes the initial addition of N-acetylglucosamine, giving rise to the GlcNAc(beta1-2)Man(alpha1-)O-Ser/Thr moiety and thus providing the necessary basis for the addition of further carbohydrate moieties (PubMed:27493216). Heavily O-glycosylated comprising of up to two thirds of its mass and the carbohydrate composition differs depending on tissue type. Mucin-type O-glycosylation is important for ligand binding activity. O-mannosylation is found in high abundance in both brain and muscle where the most abundant glycan is Sia-alpha-2-3-Gal-beta-1-4-Glc-NAc-beta-1-2-Man. In muscle, glycosylation on Thr-317, Thr-319 and Thr-379 by a phosphorylated O-mannosyl glycan with the structure 2-(N-acetylamido)-2-deoxygalactosyl-beta-1,3-2-(N-acetylamido)-2-deoxyglucosyl-beta-1,4-6-phosphomannose is mediated by like-acetylglucosaminyltransferase (LARGE1) protein and is required for laminin binding (PubMed:20044576, PubMed:21987822, PubMed:23723439, PubMed:24256719). Glycosylation by LARGE1 is also required for perlecan binding (By similarity). The O-glycosyl hexose on Thr-367, Thr-369, Thr-372, Thr-381 and Thr-388 is probably mannose. O-glycosylated in the N-terminal region with a core 1 or possibly core 8 glycan. The brain form displays a unique glycosylation pattern which is absent in other tissues; this form shows enhanced binding to laminin LAMA5 compared to the skeletal muscle form (By similarity).. Alpha-dystroglycan. (Microbial infection) O-mannosylation is required for binding lymphocytic choriomeningitis virus, Old World Lassa fever virus, and clade C New World arenaviruses.. Beta-dystroglycan. N-glycosylated.. Autolytic cleavage produces the alpha and beta subunits. In cutaneous cells, as well as in certain pathological conditions, shedding of beta-dystroglycan can occur releasing a peptide of about 30 kDa.. SRC-mediated phosphorylation of the PPXY motif of the beta subunit recruits SH2 domain-containing proteins, but inhibits binding to WWW domain-containing proteins, DMD and UTRN. This phosphorylation also inhibits nuclear entry.

Subcellular localisation

Cytoskeleton