App Peptide - C-Terminal Region Blocking Peptide

APP: a cell surface receptor that influences neurite growth, neuronal adhesion and axonogenesis. Cleaved by secretases to form a number of peptides, some of which bind to the acetyltransferase complex Fe65/TIP60 to promote transcriptional activation. The Abeta peptide is released from the cell, its extracellular deposition and accumulation form the main components of amyloid plaques in Alzheimer's disease. Mutations in this gene have been implicated in autosomal dominant Alzheimer disease and cerebroarterial amyloidosis. Can promote transcription activation through binding to Fe65-Tip60 and inhibits Notch signaling through interaction with Numb. Couples to apoptosis-inducing pathways such as those mediated by G(O) and JIP. Inhibits G(O) alpha ATPase activity. Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1. Involved in copper homeostasis/oxidative stress through copper ion reduction. In vitro, copper-metallated APP induces neuronal death directly or is potentiated through Cu(2+)-mediated low-density lipoprotein oxidation. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV. Induces a RAGE-dependent pathway that activates p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons. Provides Cu(2+) ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1. Binds, via its C-terminus, to the PID domain of several cytoplasmic proteins, including APBB family members, the APBA family, JIP1, SHC1 and, NUMB and DAB1. Binding to DAB1 inhibits its serine phosphorylation. Associates with microtubules in the presence of ATP and in a kinesin-dependent manner. Amyloid beta-42 binds nAChRA7 in hippocampal neurons. Beta-amyloid associates with HADH2. Soluble APP binds, via its N-terminal head, to FBLN1. Expressed in all fetal tissues examined with highest levels in brain, kidney, heart and spleen. Weak expression in liver. In adult brain, highest expression found in the frontal lobe of the cortex and in the anterior perisylvian cortex- opercular gyri. Moderate expression in the cerebellar cortex, the posterior perisylvian cortex-opercular gyri and the temporal associated cortex. Weak expression found in the striate, extra- striate and motor cortices. Expressed in cerebrospinal fluid, and plasma. 10 isoforms of the human protein are produced by alternative splicing. Isoform APP695 is the predominant form in neuronal tissue, isoform APP751 and isoform APP770 are widely expressed in non- neuronal cells. Isoform APP751 is the most abundant form in T-lymphocytes. Appican is expressed in astrocytes. The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Belongs to the APP family.

Protein type: Membrane protein, integral; Transcription factor; Cell surface; Receptor, misc.; Apoptosis

Cellular Component: apical part of cell; axon; cell surface; ciliary rootlet; coated pit; cytoplasm; cytoplasmic vesicle; endosome; ER to Golgi transport vesicle; extracellular space; Golgi apparatus; growth cone; integral to membrane; intercellular junction; intracellular membrane-bound organelle; lipid raft; membrane; neuromuscular junction; neuron projection; nuclear envelope lumen; perinuclear region of cytoplasm; plasma membrane; receptor complex; rough endoplasmic reticulum; spindle midzone; terminal button

Molecular Function: acetylcholine receptor binding; DNA binding; enzyme binding; heparin binding; identical protein binding; metal ion binding; protease activator activity; protease inhibitor activity; protein binding; PTB domain binding; receptor binding; serine-type endopeptidase inhibitor activity; transition metal ion binding

Biological Process: adult locomotory behavior; antibacterial humoral response; antifungal humoral response; apoptosis; axon cargo transport; axon midline choice point recognition; axonogenesis; cell adhesion; cellular copper ion homeostasis; cholesterol metabolic process; collateral sprouting in the absence of injury; defense response to Gram-negative bacterium; defense response to Gram-positive bacterium; dendrite development; endocytosis; extracellular matrix organization and biogenesis; forebrain development; innate immune response; ionotropic glutamate receptor signaling pathway; locomotory behavior; mating behavior; mRNA polyadenylation; negative regulation of neuron differentiation; negative regulation of peptidase activity; nervous system development; neurite development; neuromuscular process controlling balance; neuron apoptosis; neuron remodeling; Notch signaling pathway; positive regulation of mitotic cell cycle; positive regulation of transcription from RNA polymerase II promoter; protein amino acid phosphorylation; protein homooligomerization; regulation of epidermal growth factor receptor activity; regulation of gene expression; regulation of multicellular organism growth; regulation of protein binding; regulation of synapse structure and activity; regulation of translation; response to oxidative stress; response to yeast; smooth endoplasmic reticulum calcium ion homeostasis; suckling behavior; synaptic growth at neuromuscular junction; visual learning