Human Anti-APP Recombinant Antibody (BA0277) (CBMAB-0081CQ)

Amyloid Beta Precursor Protein

This gene encodes a cell surface receptor and transmembrane precursor protein that is cleaved by secretases to form a number of peptides. Some of these peptides are secreted and can bind to the acetyltransferase complex APBB1/TIP60 to promote transcriptional activation, while others form the protein basis of the amyloid plaques found in the brains of patients with Alzheimer disease. APP gene contains 19 exons and spans more than 170 kb. APP has several isoforms generated by alternative splicing of exons 1-13, 13a, and 14-18. The predominant transcripts are APP695 (exons 1-6, 9-18, not 13a), APP751 (exons 1-7, 9-18, not 13a), and APP770 (exons 1-18, not 13a). Mutations in this gene have been implicated in autosomal dominant Alzheimer disease and cerebroarterial amyloidosis (cerebral amyloid angiopathy). Multiple transcript variants encoding several different isoforms have been found for this gene.

Amyloid Beta (A4) Precursor Protein; Alzheimer Disease Amyloid Protein; Cerebral Vascular Amyloid Peptide; Peptidase Nexin-II; Protease Nexin-II; PN-II; PreA4; ABPP; APPI; CVAP; AD1; Beta-Amyloid Peptide(1-40); Beta-Amyloid Peptide(1-42); Beta-Amyloid Peptide; Alzheimer Disease; CTFgamma; ABETA; AAA; PN2; A4

Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on neighboring cells promotes synaptogenesis (PubMed:25122912). Involved in cell mobility and transcription regulation through protein-protein interactions. Can promote transcription activation through binding to APBB1-KAT5 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 (By similarity). Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1 (By similarity). By acting as a kinesin I membrane receptor, plays a role in axonal anterograde transport of cargo towards synapes in axons (PubMed:17062754, PubMed:23011729). Involved in copper homeostasis/oxidative stress through copper ion reduction. In vitro, copper-metallated APP induces neuronal death directly or is potentiated through Cu2+-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. The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons. Provides Cu2+ ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1.
Amyloid-beta peptides are lipophilic metal chelators with metal-reducing activity. Bind transient metals such as copper, zinc and iron. In vitro, can reduce Cu2+ and Fe3+ to Cu+ and Fe2+, respectively. Amyloid-beta protein 42 is a more effective reductant than amyloid-beta protein 40. Amyloid-beta peptides bind to lipoproteins and apolipoproteins E and J in the CSF and to HDL particles in plasma, inhibiting metal-catalyzed oxidation of lipoproteins. APP42-beta may activate mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Interaction with overexpressed HADH2 leads to oxidative stress and neurotoxicity. Also binds GPC1 in lipid rafts.
Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain.
The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.
N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6).

Activation of MAPK activity Source: ARUK-UCL
Activation of MAPKKK activity Source: ARUK-UCL
Adenylate cyclase-activating G protein-coupled receptor signaling pathway Source: ARUK-UCL
Adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway Source: ARUK-UCL
Adult locomotory behavior Source: UniProtKB
Amyloid fibril formation Source: ParkinsonsUK-UCL
Antibacterial humoral response Source: UniProtKB
Antifungal humoral response Source: UniProtKB
Antimicrobial humoral immune response mediated by antimicrobial peptide Source: UniProtKB
Associative learning Source: ARUK-UCL
Astrocyte activation Source: ARUK-UCL
Astrocyte activation involved in immune response Source: ARUK-UCL
Axo-dendritic transport Source: UniProtKB
Axon midline choice point recognition Source: UniProtKB
Axonogenesis Source: UniProtKB
Calcium-mediated signaling Source: ARUK-UCL
Cell adhesion Source: UniProtKB-KW
Cellular copper ion homeostasis Source: UniProtKB
Cellular process Source: ParkinsonsUK-UCL
Cellular protein metabolic process Source: Reactome
Cellular response to amyloid-beta Source: ARUK-UCL
Cellular response to cAMP Source: Ensembl
Cellular response to copper ion Source: Ensembl
Cellular response to manganese ion Source: Ensembl
Cellular response to nerve growth factor stimulus Source: Ensembl
Cellular response to norepinephrine stimulus Source: Ensembl
Cholesterol metabolic process Source: Ensembl
Cognition Source: UniProtKB
Collateral sprouting in absence of injury Source: UniProtKB
Defense response to Gram-negative bacterium Source: UniProtKB
Defense response to Gram-positive bacterium Source: UniProtKB
Dendrite development Source: UniProtKB
Endocytosis Source: UniProtKB
Extracellular matrix organization Source: UniProtKB
Forebrain development Source: Ensembl
G protein-coupled receptor signaling pathway Source: ARUK-UCL
Innate immune response Source: UniProtKB
Ionotropic glutamate receptor signaling pathway Source: UniProtKB
Learning Source: ARUK-UCL
Learning or memory Source: ARUK-UCL
Lipoprotein metabolic process Source: ARUK-UCL
Locomotory behavior Source: UniProtKB
Mating behavior Source: UniProtKB
Memory Source: ARUK-UCL
Microglia development Source: ARUK-UCL
Microglial cell activation Source: ARUK-UCL
Modulation of age-related behavioral decline Source: ARUK-UCL
Modulation of excitatory postsynaptic potential Source: ARUK-UCL
mRNA polyadenylation Source: UniProtKB
Negative regulation of blood circulation Source: ARUK-UCL
Negative regulation of canonical Wnt signaling pathway Source: ARUK-UCL
Negative regulation of cell population proliferation Source: UniProtKB
Negative regulation of gene expression Source: ARUK-UCL
Negative regulation of long-term synaptic potentiation Source: ARUK-UCL
Negative regulation of mitochondrion organization Source: ARUK-UCL
Negative regulation of neuron death Source: ARUK-UCL
Negative regulation of neuron differentiation Source: Ensembl
Negative regulation of pri-miRNA transcription by RNA polymerase II Source: ARUK-UCL
Negative regulation of protein localization to nucleus Source: ARUK-UCL
Negative regulation of transcription by RNA polymerase II Source: ARUK-UCL
Neuromuscular process controlling balance Source: Ensembl
Neuron apoptotic process Source: UniProtKB
Neuron projection development Source: UniProtKB
Neuron projection maintenance Source: ARUK-UCL
Neuron remodeling Source: UniProtKB
Notch signaling pathway Source: UniProtKB-KW
Platelet degranulation Source: Reactome
Positive regulation of 1-phosphatidylinositol-3-kinase activity Source: ARUK-UCL
Positive regulation of amyloid fibril formation Source: ARUK-UCL
Positive regulation of apoptotic process Source: ARUK-UCL
Positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process Source: ARUK-UCL
Positive regulation of cell activation Source: ARUK-UCL
Positive regulation of cellular response to thapsigargin Source: ARUK-UCL
Positive regulation of cellular response to tunicamycin Source: ARUK-UCL
Positive regulation of chemokine production Source: ARUK-UCL
Positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: ARUK-UCL
Positive regulation of cytosolic calcium ion concentration Source: ARUK-UCL
Positive regulation of DNA-binding transcription factor activity Source: ARUK-UCL
Positive regulation of endothelin production Source: ARUK-UCL
Positive regulation of ERK1 and ERK2 cascade Source: ARUK-UCL
Positive regulation of excitatory postsynaptic potential Source: ARUK-UCL
Positive regulation of G2/M transition of mitotic cell cycle Source: Ensembl
Positive regulation of gene expression Source: ARUK-UCL
Positive regulation of glycolytic process Source: ARUK-UCL
Positive regulation of G protein-coupled receptor internalization Source: ARUK-UCL
Positive regulation of G protein-coupled receptor signaling pathway Source: ARUK-UCL
Positive regulation of histone acetylation Source: ARUK-UCL
Positive regulation of inflammatory response Source: ARUK-UCL
Positive regulation of interferon-gamma production Source: ARUK-UCL
Positive regulation of interleukin-1 beta production Source: ARUK-UCL
Positive regulation of interleukin-6 production Source: ARUK-UCL
Positive regulation of JNK cascade Source: ARUK-UCL
Positive regulation of long-term synaptic potentiation Source: ARUK-UCL
Positive regulation of MAPK cascade Source: ARUK-UCL
Positive regulation of membrane protein ectodomain proteolysis Source: ARUK-UCL
Positive regulation of mitotic cell cycle Source: UniProtKB
Positive regulation of monocyte chemotaxis Source: ARUK-UCL
Positive regulation of neuron apoptotic process Source: ARUK-UCL
Positive regulation of neuron death Source: ARUK-UCL
Positive regulation of neuron differentiation Source: ARUK-UCL
Positive regulation of NF-kappaB transcription factor activity Source: ARUK-UCL
Positive regulation of NIK/NF-kappaB signaling Source: ARUK-UCL
Positive regulation of nitric oxide biosynthetic process Source: ARUK-UCL
Positive regulation of oxidative stress-induced neuron death Source: ARUK-UCL
Positive regulation of peptidyl-serine phosphorylation Source: ARUK-UCL
Positive regulation of peptidyl-threonine phosphorylation Source: ARUK-UCL
Positive regulation of phosphorylation Source: ARUK-UCL
Positive regulation of protein binding Source: ARUK-UCL
Positive regulation of protein import Source: ARUK-UCL
Positive regulation of protein kinase A signaling Source: ARUK-UCL
Positive regulation of protein kinase B signaling Source: ARUK-UCL
Positive regulation of protein metabolic process Source: ARUK-UCL
Positive regulation of protein phosphorylation Source: ARUK-UCL
Positive regulation of protein tyrosine kinase activity Source: ARUK-UCL
Positive regulation of receptor binding Source: ARUK-UCL
Positive regulation of response to endoplasmic reticulum stress Source: ARUK-UCL
Positive regulation of superoxide anion generation Source: ARUK-UCL
Positive regulation of tau-protein kinase activity Source: ARUK-UCL
Positive regulation of T cell migration Source: ARUK-UCL
Positive regulation of transcription by RNA polymerase II Source: ARUK-UCL
Positive regulation of tumor necrosis factor production Source: ARUK-UCL
Post-Golgi vesicle-mediated transport Source: Reactome
Post-translational protein modification Source: Reactome
Protein homooligomerization Source: ARUK-UCL
Protein insertion into ER membrane Source: Reactome
Protein phosphorylation Source: UniProtKB
Protein tetramerization Source: ARUK-UCL
Protein trimerization Source: ARUK-UCL
Purinergic nucleotide receptor signaling pathway Source: Reactome
Regulation of acetylcholine-gated cation channel activity Source: ARUK-UCL
Regulation of amyloid-beta clearance Source: ARUK-UCL
Regulation of amyloid fibril formation Source: ARUK-UCL
Regulation of dendritic spine maintenance Source: ARUK-UCL
Regulation of epidermal growth factor-activated receptor activity Source: UniProtKB
Regulation of gene expression Source: ARUK-UCL
Regulation of long-term neuronal synaptic plasticity Source: ARUK-UCL
Regulation of multicellular organism growth Source: UniProtKB
Regulation of NMDA receptor activity Source: ARUK-UCL
Regulation of peptidyl-tyrosine phosphorylation Source: ARUK-UCL
Regulation of presynapse assembly Source: SynGO
Regulation of response to calcium ion Source: ARUK-UCL
Regulation of spontaneous synaptic transmission Source: ARUK-UCL
Regulation of synapse structure or activity Source: UniProtKB
Regulation of toll-like receptor signaling pathway Source: ARUK-UCL
Regulation of transcription by RNA polymerase II Source: ARUK-UCL
Regulation of translation Source: UniProtKB
Regulation of Wnt signaling pathway Source: ARUK-UCL
Response to interleukin-1 Source: ARUK-UCL
Response to lead ion Source: Ensembl
Response to oxidative stress Source: Ensembl
Response to yeast Source: UniProtKB
Smooth endoplasmic reticulum calcium ion homeostasis Source: Ensembl
Suckling behavior Source: Ensembl
Synapse organization Source: ARUK-UCL
Synaptic growth at neuromuscular junction Source: Ensembl
Visual learning Source: UniProtKB

Early endosome; Cell membrane; Membrane; Perikaryon; Growth cone; Clathrin-coated pit; Cytoplasmic vesicle. Cell surface protein that rapidly becomes internalized via clathrin-coated pits. Only a minor proportion is present at the cell membrane; most of the protein is present in intracellular vesicles (PubMed:20580937). During maturation, the immature APP (N-glycosylated in the endoplasmic reticulum) moves to the Golgi complex where complete maturation occurs (O-glycosylated and sulfated). After alpha-secretase cleavage, soluble APP is released into the extracellular space and the C-terminal is internalized to endosomes and lysosomes. Some APP accumulates in secretory transport vesicles leaving the late Golgi compartment and returns to the cell surface. APP sorts to the basolateral surface in epithelial cells. During neuronal differentiation, the Thr-743 phosphorylated form is located mainly in growth cones, moderately in neurites and sparingly in the cell body (PubMed:10341243). Casein kinase phosphorylation can occur either at the cell surface or within a post-Golgi compartment. Associates with GPC1 in perinuclear compartments. Colocalizes with SORL1 in a vesicular pattern in cytoplasm and perinuclear regions.
Soluble APP-beta: Secreted
Amyloid-beta protein 42: Cell surface. Associates with FPR2 at the cell surface and the complex is then rapidly internalized.
Gamma-secretase C-terminal fragment 59: Cytoplasm; Nucleus. Located to both the cytoplasm and nuclei of neurons. It can be translocated to the nucleus through association with APBB1 (Fe65) (PubMed:11544248). In dopaminergic neurons, the phosphorylated Thr-743 form is localized to the nucleus (By similarity).

Alzheimer disease 1 (AD1): A familial early-onset form of Alzheimer disease. It can be associated with cerebral amyloid angiopathy. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituents of these plaques are neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42, that are produced by the proteolysis of the transmembrane APP protein. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products, such as C31, are also implicated in neuronal death.
Cerebral amyloid angiopathy, APP-related (CAA-APP): A hereditary localized amyloidosis due to amyloid-beta A4 peptide(s) deposition in the cerebral vessels. The principal clinical characteristics are recurrent cerebral and cerebellar hemorrhages, recurrent strokes, cerebral ischemia, cerebral infarction, and progressive mental deterioration. Patients develop cerebral hemorrhage because of the severe cerebral amyloid angiopathy. Parenchymal amyloid deposits are rare and largely in the form of pre-amyloid lesions or diffuse plaque-like structures. They are Congo red negative and lack the dense amyloid cores commonly present in Alzheimer disease. Some affected individuals manifest progressive aphasic dementia, leukoencephalopathy, and occipital calcifications.

Extracellular: 18-701 aa
Helical: 702-722 aa
Cytoplasmic: 723-770 aa

Proteolytically processed under normal cellular conditions. Cleavage either by alpha-secretase, beta-secretase or theta-secretase leads to generation and extracellular release of soluble APP peptides, S-APP-alpha and S-APP-beta, and the retention of corresponding membrane-anchored C-terminal fragments, C80, C83 and C99. Subsequent processing of C80 and C83 by gamma-secretase yields P3 peptides. This is the major secretory pathway and is non-amyloidogenic. Alternatively, presenilin/nicastrin-mediated gamma-secretase processing of C99 releases the amyloid-beta proteins, amyloid-beta protein 40 and amyloid-beta protein 42, major components of amyloid plaques, and the cytotoxic C-terminal fragments, gamma-CTF(50), gamma-CTF(57) and gamma-CTF(59). PSEN1 cleavage is more efficient with C83 than with C99 as substrate (in vitro) (PubMed:30630874). Many other minor amyloid-beta peptides, amyloid-beta 1-X peptides, are found in cerebral spinal fluid (CSF) including the amyloid-beta X-15 peptides, produced from the cleavage by alpha-secretase and all terminating at Gln-686.
Proteolytically cleaved by caspases during neuronal apoptosis. Cleavage at Asp-739 by either CASP6, CASP8 or CASP9 results in the production of the neurotoxic C31 peptide and the increased production of amyloid-beta peptides.
N-glycosylated (PubMed:2900137). N- and O-glycosylated (PubMed:2649245). O-glycosylation on Ser and Thr residues with core 1 or possibly core 8 glycans. Partial tyrosine glycosylation (Tyr-681) is found on some minor, short amyloid-beta peptides (amyloid-beta 1-15, 1-16, 1-17, 1-18, 1-19 and 1-20) but not found on amyloid-beta protein 38, amyloid-beta protein 40 nor on amyloid-beta protein 42. Modification on a tyrosine is unusual and is more prevelant in AD patients. Glycans had Neu5AcHex(Neu5Ac)HexNAc-O-Tyr, Neu5AcNeu5AcHex(Neu5Ac)HexNAc-O-Tyr and O-AcNeu5AcNeu5AcHex(Neu5Ac)HexNAc-O-Tyr structures, where O-Ac is O-acetylation of Neu5Ac. Neu5AcNeu5Ac is most likely Neu5Ac 2,8Neu5Ac linked. O-glycosylations in the vicinity of the cleavage sites may influence the proteolytic processing. Appicans are L-APP isoforms with O-linked chondroitin sulfate.
Phosphorylation in the C-terminal on tyrosine, threonine and serine residues is neuron-specific (PubMed:10341243). Phosphorylation can affect APP processing, neuronal differentiation and interaction with other proteins (PubMed:10341243). Phosphorylated on Thr-743 in neuronal cells by Cdc5 kinase and Mapk10, in dividing cells by Cdc2 kinase in a cell-cycle dependent manner with maximal levels at the G2/M phase and, in vitro, by GSK-3-beta (PubMed:8131745, PubMed:11146006). The Thr-743 phosphorylated form causes a conformational change which reduces binding of Fe65 family members (PubMed:11517218). In dopaminergic (DA) neurons, phosphorylation on Thr-743 by LRKK2 promotes the production and the nuclear translocation of the APP intracellular domain (AICD) which induces DA neuron apoptosis (PubMed:28720718). Phosphorylation on Tyr-757 is required for SHC binding (PubMed:11877420). Phosphorylated in the extracellular domain by casein kinases on both soluble and membrane-bound APP. This phosphorylation is inhibited by heparin (PubMed:8999878).
Extracellular binding and reduction of copper, results in a corresponding oxidation of Cys-144 and Cys-158, and the formation of a disulfide bond. In vitro, the APP-Cu+ complex in the presence of hydrogen peroxide results in an increased production of amyloid-beta-containing peptides.
Trophic-factor deprivation triggers the cleavage of surface APP by beta-secretase to release sAPP-beta which is further cleaved to release an N-terminal fragment of APP (N-APP).
Amyloid-beta peptides are degraded by IDE.
Sulfated on tyrosine residues.