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Protein Page:
APP (human)

Overview
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. Note: This description may include information from UniProtKB.
Protein type: Apoptosis; Cell surface; Membrane protein, integral; Receptor, misc.; Transcription factor
Chromosomal Location of Human Ortholog: 21q21.3
Cellular Component: axon; cell surface; cytoplasm; cytosol; dendritic shaft; dendritic spine; endosome; extracellular region; extracellular space; Golgi apparatus; integral to membrane; integral to plasma membrane; intracellular membrane-bound organelle; lipid raft; nuclear envelope lumen; perinuclear region of cytoplasm; plasma membrane; receptor complex; synapse; trans-Golgi network membrane
Molecular Function: DNA binding; enzyme binding; identical protein binding; protein binding; PTB domain binding; receptor binding; serine-type endopeptidase inhibitor activity
Biological Process: adult locomotory behavior; axon cargo transport; axon midline choice point recognition; axonogenesis; cellular copper ion homeostasis; cellular process; cellular protein metabolic process; collateral sprouting in the absence of injury; dendrite development; endocytosis; extracellular matrix organization and biogenesis; innate immune response; ionotropic glutamate receptor signaling pathway; locomotory behavior; mating behavior; mRNA polyadenylation; neurite development; neuron apoptosis; neuron remodeling; platelet degranulation; positive regulation of mitotic cell cycle; protein amino acid phosphorylation; regulation of epidermal growth factor receptor activity; regulation of multicellular organism growth; regulation of synapse structure and activity; regulation of translation; visual learning
Disease: Alzheimer Disease
Reference #:  P05067 (UniProtKB)
Alt. Names/Synonyms: A4; AAA; ABETA; ABPP; AD1; AICD-50; AICD-57; AICD-59; AID(50); AID(57); AID(59); Alzheimer disease amyloid protein; amyloid beta (A4) precursor protein; Amyloid beta A4 protein; Amyloid intracellular domain 50; Amyloid intracellular domain 57; Amyloid intracellular domain 59; APP; APPI; beta-amyloid peptide; Beta-amyloid protein 40; Beta-amyloid protein 42; Beta-APP40; Beta-APP42; C31; C80; C83; C99; Cerebral vascular amyloid peptide; CTFgamma; CVAP; Gamma-CTF(50); Gamma-CTF(57); Gamma-CTF(59); Gamma-secretase C-terminal fragment 50; Gamma-secretase C-terminal fragment 57; Gamma-secretase C-terminal fragment 59; N-APP; P3(40); P3(42); peptidase nexin-II; PN-II; PN2; PreA4; Protease nexin-II; S-APP-alpha; S-APP-beta; Soluble APP-alpha; Soluble APP-beta
Gene Symbols: APP
Molecular weight: 86,943 Da
Basal Isoelectric point: 4.73  Predict pI for various phosphorylation states
CST Pathways:  Alzheimer's Disease  |  Apoptosis Regulation
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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APP

Protein Structure Not Found.
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