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p(HGNC:APP)

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Entity

Name
APP
Namespace
hgnc
Namespace Version
20180828
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/1b20f0637c395f8aa89c2e2e342d7b704062c242/external/hgnc-symbols.belns

Appears in Networks 32

A role for APP in Wnt signalling links synapse loss with β-amyloid production. v1.0.0

Identification of a novel aspartic protease (Asp 2) as beta-secretase v1.0.0

Amyloid β oligomers (AβOs) in Alzheimer’s disease v1.0.0

Amyloid Precursor Protein Trafficking, Processing, and Function v1.0.0

Amyloid Precursor Protein Trafficking, Processing, and Function by Thinakaran, et al., 2008

APP processing in Alzheimer's disease v1.0.1

APP processing in Alzheimer's disease

Proteolytic processing of Alzeimer's beta-amyloid precursor protein v1.0.1

Nicotinic acetylcholine receptor signalling: roles in Alzheimer's disease and amyloid neuroprotection. v1.0.0

Alzheimer's Disease: Targeting the Cholinergic System v1.0.0

M1 muscarinic acetylcholine receptor in Alzheimer’s disease v1.0.0

This file encodes the article M1 muscarinic acetylcholine receptor in Alzheimer’s disease by Jiang et al, 2014

Role of the nicotinic acetylcholine receptor in Alzheimer's disease pathology and treatment v1.0.1

Nuclear receptors as therapeutic targets for Alzheimer's disease. v1.0.0

Cholinergic system during the progression of Alzheimer’s disease: therapeutic implications v1.0.0

Nicotinic Receptor Abnormalities of Alzheimer’s Disease: Therapeutic Implications v1.0.0

The Ubiquitin Proteasome System in Neurodegenerative Diseases: Sometimes the Chicken, Sometimes the Egg v1.0.0

Promoting the clearance of neurotoxic proteins in neurodegenerative disorders of ageing v1.0.0

Neuropathogenic role of adenylate kinase-1 in Aβ-mediated tau phosphorylation via AMPK and GSK3β. v1.0.0

Clearance systems in the brain-implications for Alzheimer disease. v1.0.1

Tau Modifications v1.9.5

Tau Modifications Sections of NESTOR

Inflammasome Involvement in Alzheimer’s Disease v1.0.0

Amyloid-Binding Alcohol Dehydrogenase (ABAD) Inhibitors for the Treatment of Alzheimer’s Disease v1.0.0

Protein phosphatase 2A dysfunction in Alzheimer’s disease v1.0.0

Axonal Transport, Tau Protein, and Neurodegeneration in Alzheimer’s Disease v1.0.0

Alzheimer’s disease and the autophagic-lysosomal system v1.0.0

The Ubiquitin–Proteasome System and the Autophagic–Lysosomal System in Alzheimer Disease v1.0.0

Autophagy and the ubiquitin-proteasome system: collaborators in neuroprotection v1.0.0

The Spleen Tyrosine Kinase (Syk) Regulates Alzheimer Amyloid-β Production and Tau Hyperphosphorylation* v1.0.0

Tau in physiology and pathology v1.0.0

New insights into the role of microRNAs and long noncoding RNAs in most common neurodegenerative diseases v1.0.0

Increased NF-κB signalling up-regulates BACE1 expression and its therapeutic potential in Alzheimer's disease. v1.0.0

Nuclear Factor Kappa-light-chain-enhancer of Activated B Cells (NF-κB) - a Friend, a Foe, or a Bystander - in the Neurodegenerative Cascade and Pathogenesis of Alzheimer's Disease v1.0.0

Upstream regulators and downstream effectors of NF-κBinAlzheimer's disease v1.0.0

Significance of NF-κB as a pivotal therapeutic target in the neurodegenerative pathologies of Alzheimer's disease and multiple sclerosis v1.0.0

In-Edges 106

complex(p(HGNC:APP), p(HGNC:LRP6)) hasComponent p(HGNC:APP) View Subject | View Object

Appears in Networks:

complex(p(HGNC:APP), p(HGNC:VANGL2)) hasComponent p(HGNC:APP) View Subject | View Object

Appears in Networks:

composite(p(HGNC:APP), p(HGNC:DKK1)) hasComponent p(HGNC:APP) View Subject | View Object

Appears in Networks:

composite(p(HGNC:APP), p(HGNC:LRP6)) hasComponent p(HGNC:APP) View Subject | View Object

Appears in Networks:

composite(p(HGNC:APP), p(HGNC:VANGL2)) hasComponent p(HGNC:APP) View Subject | View Object

Appears in Networks:

p(HGNC:BACE1) causesNoChange p(HGNC:APP) View Subject | View Object

However, expression of either of the Asp 2 mutants does not produce the increase in the secretion of sAPPb (Fig. 2b) seen for wild-type Asp 2. In contrast to this clear effect on sAPPb, Asp 2 has no effect on the secretion of soluble APPa or on full-length APP in the cell (data not shown). PubMed:10656250

Appears in Networks:

p(HGNC:BACE1, loc(GO:"endoplasmic reticulum")) association p(HGNC:APP, loc(GO:"endoplasmic reticulum")) View Subject | View Object

APP clearly localizes to the Golgi/endoplasmic reticulum region as revealed by distinctive juxtanuclear staining and a more generalized reticular staining throughout the cell (Figs. 6b and 6g). Asp 2 shows essentially the same subcellular distribution as revealed by simultaneous detection of myc-tagged Asp 2 and APP in COS-7 APP-751 cells (compare Figs. 6f and 6g), and merging of the confocal images for APP and Asp 2 indicates colocalization (Fig. 6h). PubMed:10656250

Appears in Networks:

composite(p(HGNC:APP), p(HGNC:CNTN2)) hasComponent p(HGNC:APP) View Subject | View Object

Appears in Networks:

p(FPLX:PKC) increases sec(p(HGNC:APP)) View Subject | View Object

Activation of protein kinase C increases APPs α-secretion by mechanisms involving the formation and release of secretory vesicles from the TGN, thus enhancing APP (and possiblyα-secretase) trafficking to the cell surface. PubMed:18650430

Appears in Networks:
Annotations
Confidence
High

rxn(reactants(p(HGNC:APP)), products(p(HGNC:APP, frag("11_*")), p(HGNC:APP, frag("1_10")))) hasReactant p(HGNC:APP) View Subject | View Object

Appears in Networks:

rxn(reactants(p(HGNC:APP)), products(p(HGNC:APP, frag("17_*")), p(HGNC:APP, frag("1_16")))) hasReactant p(HGNC:APP) View Subject | View Object

Appears in Networks:

act(a(HBP:HBP00071), ma(tscript)) regulates p(HGNC:APP) View Subject | View Object

In a similar fashion, released AICD has been shown to possess transactivation activity and can regulate transcription of multiple genes including APP, GSK- 3b, KAI1, neprilysin, BACE1, p53, EGFR, and LRP1 [127-132] PubMed:21214928

Appears in Networks:
Annotations
MeSH
Endosomes
Confidence
Medium
MeSH
Neurons

bp(GO:"anterograde axonal protein transport") association p(HGNC:APP) View Subject | View Object

APP undergoes rapid anterograde transport in neurons PubMed:21214928

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

bp(GO:"calcium ion homeostasis") association p(HGNC:APP) View Subject | View Object

A role for APP has been suggested in neurite outgrowth and synaptogenesis, neuronal protein trafficking along the axon, transmembrane signal transduction, cell adhesion, calcium metabolism, etc, all requiring additional in vivo evidence (reviewed in [19]) PubMed:21214928

Appears in Networks:
Annotations
Confidence
High

bp(GO:"cell adhesion") association p(HGNC:APP) View Subject | View Object

A role for APP has been suggested in neurite outgrowth and synaptogenesis, neuronal protein trafficking along the axon, transmembrane signal transduction, cell adhesion, calcium metabolism, etc, all requiring additional in vivo evidence (reviewed in [19]) PubMed:21214928

Appears in Networks:
Annotations
Confidence
High

bp(GO:"clathrin-dependent endocytosis") increases deg(p(HGNC:APP)) View Subject | View Object

Moreover, internalization of APP from the cell surface for endosomal/lysosomal degradation can be mediated by clathrin PubMed:21214928

Appears in Networks:
Annotations
MeSH
Endosomes
Confidence
High
MeSH
Hippocampus
MeSH
Down Syndrome

bp(GO:"protein transport") association p(HGNC:APP) View Subject | View Object

A role for APP has been suggested in neurite outgrowth and synaptogenesis, neuronal protein trafficking along the axon, transmembrane signal transduction, cell adhesion, calcium metabolism, etc, all requiring additional in vivo evidence (reviewed in [19]) PubMed:21214928

Appears in Networks:
Annotations
Confidence
High
MeSH
Axons
MeSH
Neurons

bp(GO:"signal transduction") association p(HGNC:APP) View Subject | View Object

A role for APP has been suggested in neurite outgrowth and synaptogenesis, neuronal protein trafficking along the axon, transmembrane signal transduction, cell adhesion, calcium metabolism, etc, all requiring additional in vivo evidence (reviewed in [19]) PubMed:21214928

Appears in Networks:
Annotations
Confidence
High

bp(GO:"synapse assembly") association p(HGNC:APP) View Subject | View Object

A role for APP has been suggested in neurite outgrowth and synaptogenesis, neuronal protein trafficking along the axon, transmembrane signal transduction, cell adhesion, calcium metabolism, etc, all requiring additional in vivo evidence (reviewed in [19]) PubMed:21214928

Appears in Networks:
Annotations
Confidence
High

bp(MESH:"Neuronal Outgrowth") association p(HGNC:APP) View Subject | View Object

A role for APP has been suggested in neurite outgrowth and synaptogenesis, neuronal protein trafficking along the axon, transmembrane signal transduction, cell adhesion, calcium metabolism, etc, all requiring additional in vivo evidence (reviewed in [19]) PubMed:21214928

Appears in Networks:
Annotations
Confidence
High

complex(a(CHEBI:"amyloid-beta"), p(HGNC:APP)) hasComponent p(HGNC:APP) View Subject | View Object

Appears in Networks:

complex(a(HBP:HBP00069), p(HGNC:APP)) hasComponent p(HGNC:APP) View Subject | View Object

Appears in Networks:

complex(complex(FPLX:"Gamma_secretase"), p(HGNC:APP)) hasComponent p(HGNC:APP) View Subject | View Object

Appears in Networks:

complex(p(HGNC:APBA1), p(HGNC:APP)) hasComponent p(HGNC:APP) View Subject | View Object

Appears in Networks:

complex(p(HGNC:APBA2), p(HGNC:APP)) hasComponent p(HGNC:APP) View Subject | View Object

Appears in Networks:

complex(p(HGNC:APBA3), p(HGNC:APP)) hasComponent p(HGNC:APP) View Subject | View Object

Appears in Networks:

complex(p(HGNC:APBB1), p(HGNC:APP), p(HGNC:LRP1)) hasComponent p(HGNC:APP) View Subject | View Object

Appears in Networks:

complex(p(HGNC:APP), p(HGNC:KIF5B)) hasComponent p(HGNC:APP) View Subject | View Object

Appears in Networks:

complex(p(HGNC:APP), p(HGNC:LRP1)) hasComponent p(HGNC:APP) View Subject | View Object

Appears in Networks:

complex(p(HGNC:APP), p(HGNC:LRP1)) decreases p(HGNC:APP) View Subject | View Object

Antagonizing the extracellular interaction between cell-surface APP and LRP increased the level of cell surface APP while decreasing Abeta generation [187] PubMed:21214928

Appears in Networks:
Annotations
MeSH
Endosomes
Confidence
Medium
MeSH
Hippocampus
MeSH
Down Syndrome

complex(p(HGNC:APP), p(HGNC:LRP1B)) hasComponent p(HGNC:APP) View Subject | View Object

Appears in Networks:

complex(p(HGNC:APP), p(HGNC:NCSTN), p(HGNC:NOTCH1)) hasComponent p(HGNC:APP) View Subject | View Object

Appears in Networks:

complex(p(HGNC:APP), p(HGNC:NTN1)) hasComponent p(HGNC:APP) View Subject | View Object

Appears in Networks:

complex(p(HGNC:APP), p(HGNC:SLC5A7)) hasComponent p(HGNC:APP) View Subject | View Object

Appears in Networks:

complex(p(HGNC:APP), p(HGNC:SPON1)) hasComponent p(HGNC:APP) View Subject | View Object

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complex(p(HGNC:PLD1), p(HGNC:PSEN1)) increases p(HGNC:APP) View Subject | View Object

This PS1-PLD1 interaction recruits PLD1 to the Golgi/TGN and thus potentially alters APP trafficking as PLD1 overexpression promotes budding of vesicles from the TGN containing APP and increases cell surface levels of APP [176,177] PubMed:21214928

Appears in Networks:
Annotations
MeSH
Endosomes
Confidence
High
MeSH
Hippocampus
MeSH
Down Syndrome

p(HGNC:PSEN1) regulates p(HGNC:APP) View Subject | View Object

We and others have shown that PS1 can also regulate the intracellular trafficking of APP PubMed:21214928

Appears in Networks:
Annotations
MeSH
Endosomes
Confidence
High
MeSH
Hippocampus
MeSH
Down Syndrome

composite(a(CHEBI:"phorbol ester"), p(HGNC:ADAM9), p(HGNC:APP)) hasComponent p(HGNC:APP) View Subject | View Object

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p(HGNC:ITGB1) association p(HGNC:APP) View Subject | View Object

APP was found to colocalize with beta1 intergrins in neural cells [23] PubMed:21214928

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

rxn(reactants(p(HGNC:APP)), products(a(CHEBI:"amyloid-beta"))) hasReactant p(HGNC:APP) View Subject | View Object

Appears in Networks:

rxn(reactants(p(HGNC:APP)), products(a(HBP:HBP00067))) hasReactant p(HGNC:APP) View Subject | View Object

Appears in Networks:

rxn(reactants(p(HGNC:APP)), products(a(HBP:HBP00069))) hasReactant p(HGNC:APP) View Subject | View Object

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rxn(reactants(p(HGNC:APP)), products(a(HBP:HBP00070))) hasReactant p(HGNC:APP) View Subject | View Object

Appears in Networks:

complex(p(HGNC:APLP2), p(HGNC:APP)) hasComponent p(HGNC:APP) View Subject | View Object

Appears in Networks:

complex(p(HGNC:APP), p(HGNC:APP)) hasComponent p(HGNC:APP) View Subject | View Object

Appears in Networks:

complex(p(HGNC:APP), p(HGNC:ITM2B)) hasComponent p(HGNC:APP) View Subject | View Object

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a(HBP:HBP00078) association p(HGNC:APP) View Subject | View Object

The extracellular portion of APP contains E1 and E2 domains and a Kunitz protease inhibitor (KPI) domain that is missing in APP695 (Kang and Muller-Hill 1990; Rohan de Silva et al. 1997) PubMed:22122372

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

a(HBP:HBP00079) association p(HGNC:APP) View Subject | View Object

The extracellular portion of APP contains E1 and E2 domains and a Kunitz protease inhibitor (KPI) domain that is missing in APP695 (Kang and Muller-Hill 1990; Rohan de Silva et al. 1997) PubMed:22122372

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

a(MESH:"Receptors, Cell Surface") association p(HGNC:APP) View Subject | View Object

Because of its highly similar structure to Notch, APP has been proposed to function as a cell surface receptor (reviewed in Zheng and Koo 2011) PubMed:22122372

Appears in Networks:
Annotations
Confidence
Low
MeSH
Neurons

complex(p(HGNC:APLP1), p(HGNC:APP)) hasComponent p(HGNC:APP) View Subject | View Object

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complex(p(HGNC:APP), p(HGNC:RTN4R)) hasComponent p(HGNC:APP) View Subject | View Object

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p(HGNC:ADAM10) increases sec(p(HGNC:APP)) View Subject | View Object

APP can also be cleaved by alpha-secretase to form a soluble or secreted APP ectodomain (sAPP-alpha) that has been shown to be mostly neuro-protective PubMed:22122372

Appears in Networks:
Annotations
Confidence
High

rxn(reactants(p(HGNC:APP)), products(a(HBP:HBP00042), a(HBP:HBP00081))) hasReactant p(HGNC:APP) View Subject | View Object

Appears in Networks:

rxn(reactants(p(HGNC:APP)), products(a(HBP:HBP00067), a(HBP:HBP00072))) hasReactant p(HGNC:APP) View Subject | View Object

Appears in Networks:

rxn(reactants(p(HGNC:APP)), products(a(HBP:HBP00069), a(HBP:HBP00070))) hasReactant p(HGNC:APP) View Subject | View Object

Appears in Networks:

composite(p(HBP:"gamma-secretase"), p(HGNC:APP), p(HGNC:BACE1)) hasComponent p(HGNC:APP) View Subject | View Object

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complex(p(HGNC:APP), p(HGNC:SLC5A7)) increases tloc(p(HGNC:APP), fromLoc(GO:"cell surface"), toLoc(GO:intracellular)) View Subject | View Object

In fact, it has been shown that APP interacts with CHT1 proteins increasing their endocytosis from the cell surface [258] and that mice that display disruption of CHT1 gene expression exhibit symptoms related to ACh deficit PubMed:26813123

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

p(HGNC:BACE1) increases deg(p(HGNC:APP)) View Subject | View Object

Abeta, an important player in AD, is derived from beta-amyloid precursor protein (APP) through sequential cleavages by beta- and gamma-secretases: APP is cleaved by beta-secretase (BACE1) to generate the large secreted derivative sAPPbeta and the membrane-bound APP C-terminal fragment-beta; the latter can be further cleaved by gamma-secretase to generate Abeta and APP intracellular domain. Alternatively, APP can be cleaved by alpha-secretase within the Abeta domain, which precludes Abeta production and instead generates secreted sAPPalpha that has been shown to be neuroprotective PubMed:24590577

Appears in Networks:

act(p(FPLX:PKC)) increases tloc(p(HGNC:APP), fromLoc(GO:"Golgi apparatus"), toLoc(GO:"cell surface")) View Subject | View Object

Interestingly, stimulation of M1 mAChR by agonists has been found to enhance sAPPalpha generation and reduce Abeta production[61-70]. Protein kinase C (PKC) is well-known to be activated upon stimulation of M1 mAChR. PKC may promote the activity of alpha-secretase[71] and the traffi cking of APP from the Golgi/ trans-Golgi network to the cell surface PubMed:24590577

Appears in Networks:

p(HGNC:ADAM10) increases deg(p(HGNC:APP)) View Subject | View Object

Abeta, an important player in AD, is derived from beta-amyloid precursor protein (APP) through sequential cleavages by beta- and gamma-secretases: APP is cleaved by beta-secretase (BACE1) to generate the large secreted derivative sAPPbeta and the membrane-bound APP C-terminal fragment-beta; the latter can be further cleaved by gamma-secretase to generate Abeta and APP intracellular domain. Alternatively, APP can be cleaved by alpha-secretase within the Abeta domain, which precludes Abeta production and instead generates secreted sAPPalpha that has been shown to be neuroprotective PubMed:24590577

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p(HGNC:APH1A) decreases p(HGNC:APP) View Subject | View Object

The Ab peptide is generated by the sequential cleavage of the amyloid precursor protein (APP) by the b and g secretases, resulting in the generation of peptides 40 or 42 amino acids in length [2]. PubMed:21718217

Appears in Networks:
Annotations
Confidence
Medium

p(HGNC:BACE1) decreases p(HGNC:APP) View Subject | View Object

The Ab peptide is generated by the sequential cleavage of the amyloid precursor protein (APP) by the b and g secretases, resulting in the generation of peptides 40 or 42 amino acids in length [2]. PubMed:21718217

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Annotations
Confidence
Medium

complex(p(HGNC:APP), p(HGNC:CHRNA7)) hasComponent p(HGNC:APP) View Subject | View Object

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p(HGNC:APP, var("p.Lys670Asn"), var("p.Met671Leu")) association act(p(HGNC:APP)) View Subject | View Object

This mutation at codon 670/671 on the APP gene on chromosome 21 was discovered in a Swedish family, and the mutation is unique in the sense that it is the only AD mutation that has been shown to alter the APP metabolism, resulting in an overexpression of the amyloid leading to plaque formation (Mullan et al 1992) PubMed:11230871

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rxn(reactants(p(HGNC:APP)), products(a(CHEBI:"amyloid-beta polypeptide 40"), a(CHEBI:"amyloid-beta polypeptide 42"))) hasReactant p(HGNC:APP) View Subject | View Object

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rxn(reactants(p(HGNC:APP)), products(a(MESH:"Amyloid beta-Peptides"))) hasReactant p(HGNC:APP) View Subject | View Object

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bp(GO:"chaperone-mediated autophagy") increases deg(p(HGNC:APP)) View Subject | View Object

Tau, α-synuclein and TDP43 are substrates for CMA degradation, as are amyloid precursor protein (APP) but not amyloid-β fragment 42 (Aβ42) itself 3,45–47,48 . PubMed:30116051

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p(HGNC:AK1) positiveCorrelation p(HGNC:APP) View Subject | View Object

AK1 also increased in the hippocampus of APP-J20, an AD model mouse expressing familial AD-mutant APP (Supple- mentary Material, Fig. S1A and B). PubMed:22419736

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act(complex(a(MESH:Endosomes), a(MESH:Lysosomes))) decreases p(HGNC:APP) View Subject | View Object

Intracellular degradation of proteins occurs via the ubiquitin– proteasome pathway, the autophagy–lysosome pathway, and the endosome–lysosome pathway.56 PubMed:26195256

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act(a(MESH:Astrocytes)) decreases p(HGNC:APP) View Subject | View Object

Extracellular degradation of ISF proteins mainly consists of degradation by proteases expressed and secreted by cells such as astrocytes PubMed:26195256

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bp(GO:autophagy) decreases p(HGNC:APP) View Subject | View Object

Intracellular degradation of proteins occurs via the ubiquitin– proteasome pathway, the autophagy–lysosome pathway, and the endosome–lysosome pathway.56 PubMed:26195256

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p(CHEBI:"amyloid-beta polypeptide 42", loc(MESH:"Cerebrospinal Fluid")) negativeCorrelation p(HGNC:APP, loc(GO:"extracellular region")) View Subject | View Object

ecifically, Aβ accumulation into extracellular plaques is marked by decreased CSF levels of Aβ1–42, and tau accumulation into NFTs is marked by increased CSF levels of total tau and hyperphosphory- lated tau. PubMed:26195256

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act(p(MESH:Ubiquitin)) decreases p(HGNC:APP) View Subject | View Object

Intracellular degradation of proteins occurs via the ubiquitin– proteasome pathway, the autophagy–lysosome pathway, and the endosome–lysosome pathway.56 PubMed:26195256

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path(MESH:"Alzheimer Disease") increases p(HGNC:APP) View Subject | View Object

Emerging evidence suggests that Aβ clearance is impaired in both early-onset and late-onset forms of AD. PubMed:26195256

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p(HGNC:DAPK1, frag("1271_1423")) association p(HGNC:APP) View Subject | View Object

In contrast, the DAPK1 fragments from 1 to 1423, from 637 to 1423 and from 848 to 1423 efficiently bound to APP, suggesting that the death domain (1271–1423, DD) is likely bound to APP (Fig. 4F). PubMed:27094130

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p(HGNC:DAPK1, frag("637_1423")) association p(HGNC:APP) View Subject | View Object

In contrast, the DAPK1 fragments from 1 to 1423, from 637 to 1423 and from 848 to 1423 efficiently bound to APP, suggesting that the death domain (1271–1423, DD) is likely bound to APP (Fig. 4F). PubMed:27094130

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p(HGNC:DAPK1, frag("848_1423")) association p(HGNC:APP) View Subject | View Object

In contrast, the DAPK1 fragments from 1 to 1423, from 637 to 1423 and from 848 to 1423 efficiently bound to APP, suggesting that the death domain (1271–1423, DD) is likely bound to APP (Fig. 4F). PubMed:27094130

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sec(p(HGNC:IL1B)) increases p(HGNC:APP) View Subject | View Object

NO can also bring about apoptosis of hippocampal neurons via caspase- 3 activity [50] whereas astrocyte-secreted IL-1 beta can increase the production of APP and A beta from neu- rons [51–53] (Fig. 1). PubMed:27314526

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons
MeSH
Alzheimer Disease
NeuroMMSigDB
Amyloidogenic subgraph
NeuroMMSigDB
Caspase subgraph
NeuroMMSigDB
Interleukin signaling subgraph
NeuroMMSigDB
Nitric oxide subgraph

complex(p(HGNC:APP), p(HGNC:HSD17B10)) hasComponent p(HGNC:APP) View Subject | View Object

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g(HBP:"APOE e4") decreases deg(p(HGNC:APP)) View Subject | View Object

Genetics have a role to play within AD; patients with a mutation in Amyloid Precursor Protein (APP), which results in overproduction of Aβ, will experience early onset AD. 36 Patients with a mutation in Apolipoprotein E4 (APOE4), which affects the clearance of Aβ, will experience late onset AD. PubMed:30444369

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rxn(reactants(p(HGNC:APP)), products(a(CHEBI:"amyloid-beta polypeptide 42"), p(HBP:"APP C-terminally truncated carboxyl-terminal fragments"))) hasReactant p(HGNC:APP) View Subject | View Object

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complex(p(HGNC:APP), p(HGNC:KLC1)) hasComponent p(HGNC:APP) View Subject | View Object

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bp(GO:"axonal transport") association p(HGNC:APP) View Subject | View Object

Tau protein is a typical microtubule-associated protein (MAP) and thus is directly implicated in maintaining the integrity and stability of the micro- tubules and involved in axonal transport. On the other hand, recent findings propose a direct role for APP in axonal transport, as APP can link to kinesins moving along the microtubules (Kamal et al., 2001). PubMed:12428809

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bp(GO:"negative regulation of neuron apoptotic process") association sec(p(HGNC:APP)) View Subject | View Object

However, it is believed that the secreted form of APP plays important roles in neuronal plasticity and survival (Mattson, 1997). PubMed:12428809

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bp(GO:"regulation of neuronal synaptic plasticity") association sec(p(HGNC:APP)) View Subject | View Object

However, it is believed that the secreted form of APP plays important roles in neuronal plasticity and survival (Mattson, 1997). PubMed:12428809

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a(GO:autophagosome) association p(HGNC:APP) View Subject | View Object

AVs are also enriched in APP substrates and secretases and, during autophagy, Ab peptide is generated from APP (Yu et al. 2005), although it is subsequently degraded in lysosomes under normal circumstances (Heinrich et al. 1999; Bahr et al. 2002; Florez-McClure et al. 2007). PubMed:22908190

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bp(GO:endocytosis) positiveCorrelation p(HGNC:APP) View Subject | View Object

In this regard, elevated bCTF levels induced by APP overexpression, elevated dietary cholesterol, or overexpression of its receptor ApoE (particularly ApoE 14) can upregulate endocytosis and enlarge endosomes (Laifenfeld et al. 2007; Chen et al. 2010; Cossec et al. 2010), leading to impaired endosome retrograde transport (S Kim and RA Nixon, unpubl.). PubMed:22908190

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p(HBP:"APP C-terminally truncated carboxyl-terminal fragments") positiveCorrelation p(HGNC:APP) View Subject | View Object

In this regard, elevated bCTF levels induced by APP overexpression, elevated dietary cholesterol, or overexpression of its receptor ApoE (particularly ApoE 14) can upregulate endocytosis and enlarge endosomes (Laifenfeld et al. 2007; Chen et al. 2010; Cossec et al. 2010), leading to impaired endosome retrograde transport (S Kim and RA Nixon, unpubl.). PubMed:22908190

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a(CHEBI:"amyloid-beta") association deg(p(HGNC:APP)) View Subject | View Object

Recent evidence suggests that the autophagic turnover of amyloid beta precursor protein (APP) may underlie the generation of toxic amyloid-β species [61]. PubMed:18930136

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bp(GO:autophagy) increases deg(p(HGNC:APP)) View Subject | View Object

Recent evidence suggests that the autophagic turnover of amyloid beta precursor protein (APP) may underlie the generation of toxic amyloid-β species [61]. PubMed:18930136

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a(CHEBI:Nilvadipine) decreases act(p(HGNC:APP)) View Subject | View Object

We have previously shown that racemic nilvadipine affects the β-cleavage of APP and reduces sAPPβ secretion PubMed:25331948

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p(HGNC:MAPT) increases tloc(p(HGNC:APP), fromLoc(GO:cytoplasm), toLoc(GO:"cell surface")) View Subject | View Object

This study revealed that tau deficiency can cause iron accumulation inside neurons by preventing the trafficking of APP to the cell surface, where APP usually interacts with ferroportin (FPN) to facilitate the export of iron PubMed:26631930

Appears in Networks:
Annotations
MeSH
Neurons

complex(p(HGNC:APP), p(HGNC:SLC40A1)) hasComponent p(HGNC:APP) View Subject | View Object

Appears in Networks:

complex(g(HGNC:"MIR153-1"), r(HGNC:BACE1)) decreases p(HGNC:APP) View Subject | View Object

By attaching to the 3′‐UTR sequence, the miR‐153 reduces the expression of the APP PubMed:30663117

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

g(HGNC:"MIR153-1") decreases p(HGNC:APP) View Subject | View Object

Downregulation of miR‐153 increases the expression of APP and eventually, the production of β‐ameloid is promoted, increasing the risk of AD PubMed:30663117

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

complex(g(HGNC:MIR384), r(HGNC:APP)) decreases p(HGNC:APP) View Subject | View Object

It was found that miR‐384, by binding to the 3′‐UTR sequence on BACE1 mRNA, could not only reduce expression in SH‐SY5Y cells but also attach to the 3′‐UTR sequence of the mRNA APP and reduce its expression, and this highlights the importance of miR‐384 in AD PubMed:30663117

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
SH-SY5Y
MeSH
Alzheimer Disease

g(HGNC:"MIR101-1") decreases p(HGNC:APP) View Subject | View Object

On the other hand, miR‐101, by downregulating RanBP9, can indirectly reduce the production of APP PubMed:30663117

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

g(HGNC:"MIR101-1") decreases act(p(HGNC:APP)) View Subject | View Object

Besides, by directly affecting APP, miR‐101 can cause its downregulation, which ultimately provides the basis for AD PubMed:30663117

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

p(HGNC:RANBP9) increases p(HGNC:APP) View Subject | View Object

One of these factors is Ran‐binding protein 9 (RanBP9) that can increase the amount of APP in the cell by its effects PubMed:30663117

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

p(HGNC:RELA) causesNoChange p(HGNC:APP) View Subject | View Object

There was no significant difference in APP level between p65 transfected cells and controls (p>0.05). PubMed:21329555

Appears in Networks:

a(CHEBI:"amyloid-beta") increases p(HGNC:APP) View Subject | View Object

Indeed, Checler and colleagues have shown in a recent study that, NF-κB mediates the Amyloid-β – induced increase in expression of AβPP in HEK293 cells PubMed:28745240

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
HEK293
MeSH
Alzheimer Disease

complex(GO:"NF-kappaB complex") regulates p(HGNC:APP) View Subject | View Object

Furthermore, two κB-binding sites have been identified in the proximal promoter region of AβPP, suggesting the potential regulation of AβPP expression by NF-κB PubMed:28745240

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

complex(GO:"NF-kappaB complex") regulates p(HGNC:APP) View Subject | View Object

Indeed, Checler and colleagues have shown in a recent study that, NF-κB mediates the Amyloid-β – induced increase in expression of AβPP in HEK293 cells PubMed:28745240

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
HEK293
MeSH
Alzheimer Disease

a(PUBCHEM:6440944) decreases p(HGNC:APP) View Subject | View Object

What's more, DLPC complete- ly abolishes TNF-α and H 2 O 2 induced neuronal tau phosphorylation, re- duces cellular APP levels and Aβ expression and secretion in SH-SY5Y cells [91,92] (Table 1). PubMed:27288790

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
SH-SY5Y
MeSH
Cerebral Cortex
MeSH
Hippocampus

a(CHEBI:"amyloid-beta polypeptide 42") regulates p(HGNC:APP) View Subject | View Object

In neuronal cells Aβ1-42 peptide has been shown to regulate APP and BACE1 proteins in NF-κB dependent manner PubMed:25652642

Appears in Networks:
Annotations
MeSH
Neurons
MeSH
Alzheimer Disease

act(complex(GO:"NF-kappaB complex")) regulates p(HGNC:APP) View Subject | View Object

In neuronal cells Aβ1-42 peptide has been shown to regulate APP and BACE1 proteins in NF-κB dependent manner PubMed:25652642

Appears in Networks:
Annotations
MeSH
Neurons
MeSH
Alzheimer Disease

Out-Edges 69

p(HGNC:APP) regulates act(p(HGNC:SLC5A7)) View Subject | View Object

Furthermore, APP also regulates the presynaptic expression and activity of the high affinity choline transporter. PubMed:18650430

Appears in Networks:
Annotations
Confidence
Medium

p(HGNC:APP) increases act(p(HGNC:WNT5A)) View Subject | View Object

APP did though potentiate both Wnt3a-driven Wnt-β-catenin signalling and Wnt5a-driven Wnt-PCP signalling. PubMed:30232325

Appears in Networks:
Annotations
Confidence
High

p(HGNC:APP) hasVariant p(HGNC:APP, var("p.Lys670Asn"), var("p.Met671Leu")) View Subject | View Object

Appears in Networks:

p(HGNC:APP) increases act(p(HGNC:WNT3A)) View Subject | View Object

APP did though potentiate both Wnt3a-driven Wnt-β-catenin signalling and Wnt5a-driven Wnt-PCP signalling. PubMed:30232325

Appears in Networks:
Annotations
Confidence
High

p(HGNC:APP) increases bp(GO:"canonical Wnt signaling pathway") View Subject | View Object

In contrast with wild-type APP which, as before, potentiated both canonical and non-canonical Wnt signalling, the Swedish mutant form of APP antagonised canonical Wnt signalling (Fig. 2a), and potentiated non-canonical Wnt signalling to a greater degree than wild-type APP (APPWT) (Fig. 2b). PubMed:30232325

Appears in Networks:
Annotations
Confidence
High

p(HGNC:APP) increases bp(GO:"non-canonical Wnt signaling pathway") View Subject | View Object

In contrast with wild-type APP which, as before, potentiated both canonical and non-canonical Wnt signalling, the Swedish mutant form of APP antagonised canonical Wnt signalling (Fig. 2a), and potentiated non-canonical Wnt signalling to a greater degree than wild-type APP (APPWT) (Fig. 2b). PubMed:30232325

Appears in Networks:
Annotations
Confidence
High

p(HGNC:APP) increases act(p(HGNC:DKK1)) View Subject | View Object

Overexpression of APP enhanced the inhibitory effects of Dkk1 on Wnt3a induced Wnt-β-catenin signalling, counteracting the enhanced activity resulting from APP overexpression and reducing the IC50 of Dkk1 to 122ng/mL from 173ng/mL in the absence of APP (Fig. 2f) . PubMed:30232325

Appears in Networks:
Annotations
Confidence
Medium

p(HGNC:APP) increases act(p(HGNC:DKK1)) View Subject | View Object

In contrast, the stimulatory effects of Dkk1 on WntPCP signalling induced by Wnt5a were enhanced by APP overexpression, decreasing the EC50 of Dkk1 to 599ng/ mL from 1405ng/mL (Fig. 2g). PubMed:30232325

Appears in Networks:
Annotations
Confidence
High

p(HGNC:APP) increases bp(HBP:HBP00061) View Subject | View Object

Aβ synaptoxicity is Dkk1-dependent12,24 and also appears to be APP-dependent25. PubMed:30232325

Appears in Networks:
Annotations
Confidence
High

p(HGNC:APP) hasVariant p(HGNC:APP, frag("672_770")) View Subject | View Object

Appears in Networks:

p(HGNC:APP, loc(GO:"endoplasmic reticulum")) association p(HGNC:BACE1, loc(GO:"endoplasmic reticulum")) View Subject | View Object

APP clearly localizes to the Golgi/endoplasmic reticulum region as revealed by distinctive juxtanuclear staining and a more generalized reticular staining throughout the cell (Figs. 6b and 6g). Asp 2 shows essentially the same subcellular distribution as revealed by simultaneous detection of myc-tagged Asp 2 and APP in COS-7 APP-751 cells (compare Figs. 6f and 6g), and merging of the confocal images for APP and Asp 2 indicates colocalization (Fig. 6h). PubMed:10656250

Appears in Networks:

p(HGNC:APP) hasVariant p(HGNC:APP, pmod(Ph)) View Subject | View Object

Appears in Networks:

p(HGNC:APP) hasVariant p(HGNC:APP, frag("11_*")) View Subject | View Object

Appears in Networks:

p(HGNC:APP) hasVariant p(HGNC:APP, frag("17_*")) View Subject | View Object

Appears in Networks:

p(HGNC:APP) hasVariant p(HGNC:APP, frag("1_10")) View Subject | View Object

Appears in Networks:

p(HGNC:APP) hasVariant p(HGNC:APP, frag("1_16")) View Subject | View Object

Appears in Networks:

p(HGNC:APP) hasVariant p(HGNC:APP, var("?")) View Subject | View Object

Appears in Networks:

p(HGNC:APP) increases bp(GO:"regulation of cell growth") View Subject | View Object

Because, as mentioned above, APPs is constitutively released from cells following α-secretase cleavage, these find- ings indicated that APP has autocrine and paracrine functions in growth regulation. PubMed:18650430

Appears in Networks:
Annotations
Confidence
High

p(HGNC:APP) increases bp(GO:"synapse assembly") View Subject | View Object

The N-terminal heparin-binding domain of APP (res- idues 28–123) upstream from the RERMS sequence also stim- ulates neurite outgrowth and promotes synaptogenesis. PubMed:18650430

Appears in Networks:
Annotations
Confidence
Medium

p(HGNC:APP) increases bp(MESH:"Neuronal Outgrowth") View Subject | View Object

The N-terminal heparin-binding domain of APP (res- idues 28–123) upstream from the RERMS sequence also stim- ulates neurite outgrowth and promotes synaptogenesis. PubMed:18650430

Appears in Networks:
Annotations
Confidence
Medium

p(HGNC:APP) increases bp(GO:"cell adhesion") View Subject | View Object

An RHDS motif near the extralumenal por- tion of APP or at the C terminus of APPs lying within the Aβ region appears to promote cell adhesion. PubMed:18650430

Appears in Networks:
Annotations
Confidence
High

p(HGNC:APP) hasVariant p(HGNC:APP, pmod(Ph, Ser, 655)) View Subject | View Object

Appears in Networks:

p(HGNC:APP) increases a(CHEBI:"amyloid-beta") View Subject | View Object

Abeta is generated from b-amyloid precursor protein (APP) through sequential cleavages first by beta-secretase and then by gamma-secretase complex PubMed:21214928

Appears in Networks:
Annotations
Confidence
Medium

p(HGNC:APP) hasVariant p(HGNC:APP, frag("672_711")) View Subject | View Object

Appears in Networks:

p(HGNC:APP) hasVariant p(HGNC:APP, frag("672_713")) View Subject | View Object

Appears in Networks:

p(HGNC:APP) association bp(MESH:"Neuronal Outgrowth") View Subject | View Object

A role for APP has been suggested in neurite outgrowth and synaptogenesis, neuronal protein trafficking along the axon, transmembrane signal transduction, cell adhesion, calcium metabolism, etc, all requiring additional in vivo evidence (reviewed in [19]) PubMed:21214928

Appears in Networks:
Annotations
Confidence
High

p(HGNC:APP) association bp(GO:"synapse assembly") View Subject | View Object

A role for APP has been suggested in neurite outgrowth and synaptogenesis, neuronal protein trafficking along the axon, transmembrane signal transduction, cell adhesion, calcium metabolism, etc, all requiring additional in vivo evidence (reviewed in [19]) PubMed:21214928

Appears in Networks:
Annotations
Confidence
High

p(HGNC:APP) association bp(GO:"signal transduction") View Subject | View Object

A role for APP has been suggested in neurite outgrowth and synaptogenesis, neuronal protein trafficking along the axon, transmembrane signal transduction, cell adhesion, calcium metabolism, etc, all requiring additional in vivo evidence (reviewed in [19]) PubMed:21214928

Appears in Networks:
Annotations
Confidence
High

p(HGNC:APP) association bp(GO:"cell adhesion") View Subject | View Object

A role for APP has been suggested in neurite outgrowth and synaptogenesis, neuronal protein trafficking along the axon, transmembrane signal transduction, cell adhesion, calcium metabolism, etc, all requiring additional in vivo evidence (reviewed in [19]) PubMed:21214928

Appears in Networks:
Annotations
Confidence
High

p(HGNC:APP) association bp(GO:"calcium ion homeostasis") View Subject | View Object

A role for APP has been suggested in neurite outgrowth and synaptogenesis, neuronal protein trafficking along the axon, transmembrane signal transduction, cell adhesion, calcium metabolism, etc, all requiring additional in vivo evidence (reviewed in [19]) PubMed:21214928

Appears in Networks:
Annotations
Confidence
High

p(HGNC:APP) association bp(GO:"protein transport") View Subject | View Object

A role for APP has been suggested in neurite outgrowth and synaptogenesis, neuronal protein trafficking along the axon, transmembrane signal transduction, cell adhesion, calcium metabolism, etc, all requiring additional in vivo evidence (reviewed in [19]) PubMed:21214928

Appears in Networks:
Annotations
Confidence
High
MeSH
Axons
MeSH
Neurons

p(HGNC:APP) regulates bp(GO:"protein transport") View Subject | View Object

Overall, most studies suggest that APP plays some role in regulating protein trafficking PubMed:21214928

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

p(HGNC:APP) association p(HGNC:ITGB1) View Subject | View Object

APP was found to colocalize with beta1 intergrins in neural cells [23] PubMed:21214928

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

p(HGNC:APP) association bp(GO:"anterograde axonal protein transport") View Subject | View Object

APP undergoes rapid anterograde transport in neurons PubMed:21214928

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

p(HGNC:APP) hasVariant p(HGNC:APP, frag("1_38")) View Subject | View Object

Appears in Networks:

p(HGNC:APP) hasVariant p(HGNC:APP, frag("1_43")) View Subject | View Object

Appears in Networks:

p(HGNC:APP) hasVariant p(HGNC:APP, pmod(Ph, Thr, 668)) View Subject | View Object

Appears in Networks:

p(HGNC:APP) increases a(MESH:"Amyloid beta-Peptides") View Subject | View Object

APP undergoes post-translational proteolysis/processing to generate the hydrophobic beta-amyloid (Abeta) peptides PubMed:22122372

Appears in Networks:
Annotations
Confidence
High

p(HGNC:APP) increases a(CHEBI:"amyloid-beta") View Subject | View Object

Cloning of the complementary DNA (cDNA) of Abeta revealed that Abeta is derived from a larger precursor protein (Tanzi et al. 1987) PubMed:22122372

Appears in Networks:
Annotations
Confidence
High
MeSH
Cerebral Cortex
MeSH
Hippocampus

p(HGNC:APP) association a(HBP:HBP00078) View Subject | View Object

The extracellular portion of APP contains E1 and E2 domains and a Kunitz protease inhibitor (KPI) domain that is missing in APP695 (Kang and Muller-Hill 1990; Rohan de Silva et al. 1997) PubMed:22122372

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

p(HGNC:APP) association a(HBP:HBP00079) View Subject | View Object

The extracellular portion of APP contains E1 and E2 domains and a Kunitz protease inhibitor (KPI) domain that is missing in APP695 (Kang and Muller-Hill 1990; Rohan de Silva et al. 1997) PubMed:22122372

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

p(HGNC:APP) association a(MESH:"Receptors, Cell Surface") View Subject | View Object

Because of its highly similar structure to Notch, APP has been proposed to function as a cell surface receptor (reviewed in Zheng and Koo 2011) PubMed:22122372

Appears in Networks:
Annotations
Confidence
Low
MeSH
Neurons

p(HGNC:APP) increases bp(GO:"cell adhesion") View Subject | View Object

Nevertheless, APP is more widely accepted as a protein contributing to cell adhesion via its extracellular domain PubMed:22122372

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

p(HGNC:APP) hasVariant p(HGNC:APP, frag("25_35")) View Subject | View Object

Appears in Networks:

p(HGNC:APP) hasVariant p(HGNC:APP, pmod(Sumo, Lys, 595)) View Subject | View Object

Appears in Networks:

p(HGNC:APP) hasVariant p(HGNC:APP, frag("12_28")) View Subject | View Object

Appears in Networks:

act(p(HGNC:APP)) association p(HGNC:APP, var("p.Lys670Asn"), var("p.Met671Leu")) View Subject | View Object

This mutation at codon 670/671 on the APP gene on chromosome 21 was discovered in a Swedish family, and the mutation is unique in the sense that it is the only AD mutation that has been shown to alter the APP metabolism, resulting in an overexpression of the amyloid leading to plaque formation (Mullan et al 1992) PubMed:11230871

Appears in Networks:

p(HGNC:APP) increases a(MESH:"Amyloid beta-Peptides") View Subject | View Object

The plaques in AD are rich in amyloid beta peptides (Abeta) that are produced by proteolytic cleavage of the amyloid precursor peptide (APP), a glycolipid located in the outer cell membrane PubMed:14556719

Appears in Networks:

p(HGNC:APP) hasVariant p(HGNC:APP, frag("23_35")) View Subject | View Object

Appears in Networks:

p(HGNC:APP) hasVariant p(HGNC:APP, var("c.27269938A>C"), var("c.27269939G>T")) View Subject | View Object

Appears in Networks:

p(HGNC:APP) positiveCorrelation p(HGNC:AK1) View Subject | View Object

AK1 also increased in the hippocampus of APP-J20, an AD model mouse expressing familial AD-mutant APP (Supple- mentary Material, Fig. S1A and B). PubMed:22419736

Appears in Networks:

p(HGNC:APP, loc(GO:"extracellular region")) negativeCorrelation p(CHEBI:"amyloid-beta polypeptide 42", loc(MESH:"Cerebrospinal Fluid")) View Subject | View Object

ecifically, Aβ accumulation into extracellular plaques is marked by decreased CSF levels of Aβ1–42, and tau accumulation into NFTs is marked by increased CSF levels of total tau and hyperphosphory- lated tau. PubMed:26195256

Appears in Networks:

p(HGNC:APP) association p(HGNC:DAPK1, frag("637_1423")) View Subject | View Object

In contrast, the DAPK1 fragments from 1 to 1423, from 637 to 1423 and from 848 to 1423 efficiently bound to APP, suggesting that the death domain (1271–1423, DD) is likely bound to APP (Fig. 4F). PubMed:27094130

Appears in Networks:

p(HGNC:APP) association p(HGNC:DAPK1, frag("848_1423")) View Subject | View Object

In contrast, the DAPK1 fragments from 1 to 1423, from 637 to 1423 and from 848 to 1423 efficiently bound to APP, suggesting that the death domain (1271–1423, DD) is likely bound to APP (Fig. 4F). PubMed:27094130

Appears in Networks:

p(HGNC:APP) association p(HGNC:DAPK1, frag("1271_1423")) View Subject | View Object

In contrast, the DAPK1 fragments from 1 to 1423, from 637 to 1423 and from 848 to 1423 efficiently bound to APP, suggesting that the death domain (1271–1423, DD) is likely bound to APP (Fig. 4F). PubMed:27094130

Appears in Networks:

p(HGNC:APP) hasVariant p(HGNC:APP, pmod(HBP:polysumoylation)) View Subject | View Object

Appears in Networks:

p(HGNC:APP) hasVariant p(HGNC:APP, pmod(Sumo)) View Subject | View Object

Appears in Networks:

p(HGNC:APP) hasVariant p(HGNC:APP, pmod(Sumo, Lys, 587)) View Subject | View Object

Appears in Networks:

p(HGNC:APP) association bp(GO:"axonal transport") View Subject | View Object

Tau protein is a typical microtubule-associated protein (MAP) and thus is directly implicated in maintaining the integrity and stability of the micro- tubules and involved in axonal transport. On the other hand, recent findings propose a direct role for APP in axonal transport, as APP can link to kinesins moving along the microtubules (Kamal et al., 2001). PubMed:12428809

Appears in Networks:

sec(p(HGNC:APP)) association bp(GO:"regulation of neuronal synaptic plasticity") View Subject | View Object

However, it is believed that the secreted form of APP plays important roles in neuronal plasticity and survival (Mattson, 1997). PubMed:12428809

Appears in Networks:

sec(p(HGNC:APP)) association bp(GO:"negative regulation of neuron apoptotic process") View Subject | View Object

However, it is believed that the secreted form of APP plays important roles in neuronal plasticity and survival (Mattson, 1997). PubMed:12428809

Appears in Networks:

p(HGNC:APP) hasVariant p(HGNC:APP, frag("?")) View Subject | View Object

Appears in Networks:

p(HGNC:APP) increases a(MESH:"Amyloid beta-Peptides") View Subject | View Object

Aβ peptides originate from the transmembrane protein amyloid precursor protein (APP) which undergoes sequential cleavage via two distinct pathways by the enzyme complexes β- and γ-secretase [31] PubMed:29758300

Appears in Networks:

p(HGNC:APP) positiveCorrelation p(HBP:"APP C-terminally truncated carboxyl-terminal fragments") View Subject | View Object

In this regard, elevated bCTF levels induced by APP overexpression, elevated dietary cholesterol, or overexpression of its receptor ApoE (particularly ApoE 14) can upregulate endocytosis and enlarge endosomes (Laifenfeld et al. 2007; Chen et al. 2010; Cossec et al. 2010), leading to impaired endosome retrograde transport (S Kim and RA Nixon, unpubl.). PubMed:22908190

Appears in Networks:

p(HGNC:APP) positiveCorrelation bp(GO:endocytosis) View Subject | View Object

In this regard, elevated bCTF levels induced by APP overexpression, elevated dietary cholesterol, or overexpression of its receptor ApoE (particularly ApoE 14) can upregulate endocytosis and enlarge endosomes (Laifenfeld et al. 2007; Chen et al. 2010; Cossec et al. 2010), leading to impaired endosome retrograde transport (S Kim and RA Nixon, unpubl.). PubMed:22908190

Appears in Networks:

p(HGNC:APP) increases a(GO:endosome) View Subject | View Object

In this regard, elevated bCTF levels induced by APP overexpression, elevated dietary cholesterol, or overexpression of its receptor ApoE (particularly ApoE 14) can upregulate endocytosis and enlarge endosomes (Laifenfeld et al. 2007; Chen et al. 2010; Cossec et al. 2010), leading to impaired endosome retrograde transport (S Kim and RA Nixon, unpubl.). PubMed:22908190

Appears in Networks:

p(HGNC:APP) association a(GO:autophagosome) View Subject | View Object

AVs are also enriched in APP substrates and secretases and, during autophagy, Ab peptide is generated from APP (Yu et al. 2005), although it is subsequently degraded in lysosomes under normal circumstances (Heinrich et al. 1999; Bahr et al. 2002; Florez-McClure et al. 2007). PubMed:22908190

Appears in Networks:

deg(p(HGNC:APP)) association a(CHEBI:"amyloid-beta") View Subject | View Object

Recent evidence suggests that the autophagic turnover of amyloid beta precursor protein (APP) may underlie the generation of toxic amyloid-β species [61]. PubMed:18930136

Appears in Networks:

surf(p(HGNC:APP)) increases complex(p(HGNC:APP), p(HGNC:SLC40A1)) View Subject | View Object

This study revealed that tau deficiency can cause iron accumulation inside neurons by preventing the trafficking of APP to the cell surface, where APP usually interacts with ferroportin (FPN) to facilitate the export of iron PubMed:26631930

Appears in Networks:
Annotations
MeSH
Neurons

About

BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.

If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.