Species Reactivity
Bovine, Human, Monkey, Mouse
Specificity
Recognizes human Amyloid Precursor Protein (APP), KPI Domain. Species crossreactivity: mouse, monkey and bovine.
Preparation and Storage
May be stored at 4 degree C for short-term only. Aliquot to avoid repeated freezing and thawing. Store at -20 degree C. Aliquots are stable for at least 12 months. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap.
Other Notes
Small volumes of anti-Amyloid Precursor Protein, Kpi Domain antibody vial(s) may occasionally become entrapped in the seal of the product vial during shipment and storage. If necessary, briefly centrifuge the vial on a tabletop centrifuge to dislodge any liquid in the container`s cap. Certain products may require to ship with dry ice and additional dry ice fee may apply.
Amyloid Precursor Protein (APP) is an integral membrane protein with a large ectodomain, a transmembrane domain, and a short cytoplasmic tail. APP is proteolytically cleaved by b-secretase (BACE) to generate the APP N-terminal fragment (sbAPP) with Mr100kD and a C-terminal fragment (C99) with Mr12kD. The smaller 12kD fragment can be further cleaved by g-secretase, an enzyme activity recently attributed to presenilin-2. This second cleavage produces the insoluble b-amyloid (Ab), a peptide of ~4kD. The accumulation of b-amyloid in intracellular neurofibrillary tangles and extracellular plaques is observed in the brains of Alzheimer's disease patients and Downs's Syndrome patients.
Suitable for use in Western Blot, Immunoprecipitation, Immunocytochemistry and Immunohistochemistry.
Dilution: Western blot: 1:250-1:1000
Immunoprecipitation: Requires reduction and alkylation of disulfide bonds. Immunocytochemistry: On Cos7 and NteraZ cell lines, requires reduction and alkylation of disulfide bonds.
Immunohistochemistry: Works on formaldehyde fixed, paraffin embedded tissue, requires reduction and alkylation of disulfide bonds or microwaving.
To reduce: Incubate the slide or Blot in TBS (PBS) + 50mM 2-mercaptoethanol at 37 degree C for 3 h in the dark. Wash twice with TBS, then incubate in TBS (PBS) + 20 mg/ ml of Iodoacetic acid for 30 min at RT. Wash twice with TBS (PBS), block and process as usual.
Optimal dilutions to be determined by researcher.
NCBI Summary for Amyloid Precursor Protein, Kpi Domain
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. In addition, two of the peptides are antimicrobial peptides, having been shown to have bacteriocidal and antifungal activities. 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. [provided by RefSeq, Aug 2014]
UniProt Comments for Amyloid Precursor Protein, Kpi Domain
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: Apoptosis; Receptor, misc.; Membrane protein, integral; Transcription factor; Cell surface
Chromosomal Location of Human Ortholog: 21q21.3
Cellular Component: Golgi apparatus; extracellular space; cell surface; integral to plasma membrane; integral to membrane; coated pit; intercellular junction; cytosol; ER to Golgi transport vesicle; lipid raft; ciliary rootlet; perinuclear region of cytoplasm; nuclear envelope lumen; cytoplasm; synapse; dendritic shaft; neuromuscular junction; endosome; receptor complex; intracellular membrane-bound organelle; extracellular region; dendritic spine; axon; apical part of cell; plasma membrane; spindle midzone
Molecular Function: serine-type endopeptidase inhibitor activity; heparin binding; identical protein binding; protein binding; enzyme binding; protease activator activity; DNA binding; transition metal ion binding; PTB domain binding; acetylcholine receptor binding; receptor binding
Biological Process: extracellular matrix organization and biogenesis; adult locomotory behavior; locomotory behavior; mRNA polyadenylation; positive regulation of mitotic cell cycle; protein amino acid phosphorylation; regulation of translation; platelet degranulation; synaptic growth at neuromuscular junction; forebrain development; dendrite development; collateral sprouting in the absence of injury; visual learning; cell adhesion; neuromuscular process controlling balance; neurite development; platelet activation; cholesterol metabolic process; Notch signaling pathway; cellular copper ion homeostasis; regulation of epidermal growth factor receptor activity; axon cargo transport; mating behavior; regulation of multicellular organism growth; endocytosis; axon midline choice point recognition; smooth endoplasmic reticulum calcium ion homeostasis; neuron apoptosis; negative regulation of neuron differentiation; axonogenesis; suckling behavior; ionotropic glutamate receptor signaling pathway; regulation of synapse structure and activity; regulation of protein binding; innate immune response; positive regulation of transcription from RNA polymerase II promoter; response to oxidative stress; blood coagulation; neuron remodeling
Disease: Alzheimer Disease
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