APP iso8 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:  apical part of cell; astrocyte projection; axon; cell surface; cell-cell junction; ciliary rootlet; clathrin-coated pit; COPII-coated ER to Golgi transport vesicle; cytoplasm; cytosol; dendritic shaft; dendritic spine; early endosome; endoplasmic reticulum lumen; endosome; endosome lumen; extracellular region; extracellular space; Golgi apparatus; Golgi lumen; Golgi-associated vesicle; growth cone filopodium; growth cone lamellipodium; integral component of membrane; integral component of plasma membrane; main axon; membrane raft; neuromuscular junction; nuclear envelope lumen; perikaryon; perinuclear region of cytoplasm; plasma membrane; platelet alpha granule lumen; presynaptic active zone; receptor complex; recycling endosome; rough endoplasmic reticulum; smooth endoplasmic reticulum; spindle midzone; synapse; synaptic vesicle; trans-Golgi network membrane
Molecular Function:  DNA binding; enzyme binding; growth factor receptor binding; heparin binding; identical protein binding; peptidase activator activity; protein binding; PTB domain binding; receptor activator activity; serine-type endopeptidase inhibitor activity; signaling receptor binding; transition metal ion binding
Biological Process:  adult locomotory behavior; amyloid fibril formation; astrocyte activation; astrocyte activation involved in immune response; axo-dendritic transport; axon midline choice point recognition; axonogenesis; cell adhesion; cellular copper ion homeostasis; cellular process; cellular protein metabolic process; cellular response to amyloid-beta; cellular response to cAMP; cellular response to copper ion; cellular response to manganese ion; cellular response to nerve growth factor stimulus; cellular response to norepinephrine stimulus; cholesterol metabolic process; cognition; collateral sprouting in absence of injury; dendrite development; endocytosis; extracellular matrix organization; forebrain development; G protein-coupled receptor signaling pathway; innate immune response; ionotropic glutamate receptor signaling pathway; learning; learning or memory; locomotory behavior; mating behavior; microglia development; modulation of age-related behavioral decline; modulation of excitatory postsynaptic potential; mRNA polyadenylation; negative regulation of cell proliferation; negative regulation of endopeptidase activity; negative regulation of gene expression; negative regulation of long-term synaptic potentiation; negative regulation of neuron differentiation; neuromuscular process controlling balance; neuron apoptotic process; neuron projection development; neuron projection maintenance; neuron remodeling; Notch signaling pathway; platelet degranulation; positive regulation of amyloid fibril formation; positive regulation of amyloid-beta formation; positive regulation of astrocyte activation; positive regulation of chemokine biosynthetic process; positive regulation of DNA-binding transcription factor activity; positive regulation of ERK1 and ERK2 cascade; positive regulation of G2/M transition of mitotic cell cycle; positive regulation of gene expression; positive regulation of interleukin-1 beta biosynthetic process; positive regulation of interleukin-6 biosynthetic process; positive regulation of JNK cascade; positive regulation of long-term synaptic potentiation; positive regulation of microglial cell activation; positive regulation of mitotic cell cycle; positive regulation of NF-kappaB transcription factor activity; positive regulation of NIK/NF-kappaB signaling; positive regulation of peptidase activity; positive regulation of peptidyl-serine phosphorylation; positive regulation of peptidyl-threonine phosphorylation; positive regulation of phosphorylation; positive regulation of protein binding; positive regulation of protein metabolic process; positive regulation of protein phosphorylation; positive regulation of signaling receptor activity; positive regulation of T cell migration; positive regulation of transcription by RNA polymerase II; positive regulation of tumor necrosis factor biosynthetic process; post-translational protein modification; protein phosphorylation; regulation of epidermal growth factor-activated receptor activity; regulation of gene expression; regulation of long-term neuronal synaptic plasticity; regulation of multicellular organism growth; regulation of NMDA receptor activity; regulation of peptidyl-tyrosine phosphorylation; regulation of presynapse assembly; regulation of spontaneous synaptic transmission; regulation of synapse structure or activity; regulation of translation; regulation of Wnt signaling pathway; response to interleukin-1; response to lead ion; response to oxidative stress; smooth endoplasmic reticulum calcium ion homeostasis; suckling behavior; synapse organization; synaptic growth at neuromuscular junction; tumor necrosis factor production; visual learning
Disease: Alzheimer Disease; Cerebral Amyloid Angiopathy, App-related
Reference #:  P05067-8 (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; Amyloid-beta A4 protein; 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: 84,819 Da
Basal Isoelectric point: 4.71  Predict pI for various phosphorylation states
CST Pathways:  Alzheimer's Disease  |  Apoptosis Regulation
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
Select Structure to View Below

APP iso8

Protein Structure Not Found.

Cross-references to other databases:  cBioPortal  |  Wikipedia  |  Pfam  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene  |  Ensembl Protein