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Appears in Networks 32

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

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

Tau Modifications v1.9.5

Tau Modifications Sections of NESTOR

In-Edges 106

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

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

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

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

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

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

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

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

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

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

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

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

Annotations
Confidence
High

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

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

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

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

Annotations
Confidence
High
MeSH
Neurons

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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

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

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

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

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

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

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

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

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

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

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

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

Annotations
MeSH
Neurons

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Annotations
Confidence
Medium

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

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

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

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

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

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

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

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

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

Annotations
Confidence
High
MeSH
Neurons

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

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

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

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

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

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

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

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

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

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

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) 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

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

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

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

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

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

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

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

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

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

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.