1. Catalog
  2. Citations
  3. PubMed:18650430

PubMed: 18650430

Title
Amyloid precursor protein trafficking, processing, and function.
Journal
The Journal of biological chemistry
Volume
283
Issue
None
Pages
29615-9
Date
2008-10-31
Authors
Koo EH | Thinakaran G

Evidence 024124b5cc
JSON

Interestingly, because the RHDS sequence is contained within the N terminus of Aβ, similar cell adhesion-promoting properties have also been attributed to the Aβ peptide itself.

a(CHEBI:"amyloid-beta") increases bp(GO:"cell adhesion") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium

a(MESH:"Amyloid beta-Peptides") increases bp(GO:"cell adhesion") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium

Evidence dab0434a87
JSON

γ-Secretase cleaves at multiple sites within the transmembrane domain of APP, generating Aβ peptides ranging in length from 38 to 43 residues (4).

complex(FPLX:"Gamma_secretase") increases a(MESH:"Amyloid beta-Peptides") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium

Evidence e3ac974310
JSON

As mentioned above, γ-secretase processing of APP also releases AICD (Fig. 1).

complex(FPLX:"Gamma_secretase") increases a(HBP:HBP00071) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High

Evidence 5f2c293aa5
JSON

Finally, a recent study reported a surprising twist, viz. that APP in conjunction with TAG1, a molecule found in the outer plasma membrane, and presenilins act to suppress neurogenesis.

composite(p(HGNC:APP), p(HGNC:CNTN2)) decreases bp(GO:neurogenesis) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High

Evidence af2c509914
JSON

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.

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

Appears in Networks:
Annotations
Confidence
High

Evidence 25004bd0e1
JSON

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.

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

Appears in Networks:
Annotations
Confidence
Medium

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

Appears in Networks:
Annotations
Confidence
Medium

Evidence 922d2952fd
JSON

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.

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

Appears in Networks:
Annotations
Confidence
High

Evidence 3865be1750
JSON

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

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

Appears in Networks:
Annotations
Confidence
Medium

Evidence b0ae9c3833
JSON

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.

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

Appears in Networks:
Annotations
Confidence
High

Evidence b24b1c5e3b
JSON

Several zinc metallo proteinases such asTACE/ADAM17, ADAM9, ADAM10 and MDC-9 and the aspartyl protease BACE2 can cleave APP at the α-secretase site, located within the Aβ domain between Lys 16 and Leu 17 , essentially precluding the generation of intact Aβ(1).

act(p(HGNC:ADAM10), ma(pep)) increases rxn(reactants(p(HGNC:APP)), products(p(HGNC:APP, frag("17_*")), p(HGNC:APP, frag("1_16")))) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High

act(p(HGNC:ADAM17), ma(pep)) increases rxn(reactants(p(HGNC:APP)), products(p(HGNC:APP, frag("17_*")), p(HGNC:APP, frag("1_16")))) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High

act(p(HGNC:ADAM9), ma(pep)) increases rxn(reactants(p(HGNC:APP)), products(p(HGNC:APP, frag("17_*")), p(HGNC:APP, frag("1_16")))) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High

act(p(HGNC:BACE2), ma(pep)) increases rxn(reactants(p(HGNC:APP)), products(p(HGNC:APP, frag("17_*")), p(HGNC:APP, frag("1_16")))) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High

Evidence fecf8c04b1
JSON

Overexpression of Mint1, Mint2, or Fe65 causes reduction in Aβ generation and deposition in the brains of transgenic mice, strongly suggesting a physiological role for these adaptors in regulating APP processing in the nervous tis- sue (17).

p(HGNC:APBA1) decreases a(CHEBI:"amyloid-beta") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium

p(HGNC:APBA1) decreases a(HBP:HBP00018) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium

p(HGNC:APBA1) regulates bp(HBP:HBP00073) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium

p(HGNC:APBA2) decreases a(CHEBI:"amyloid-beta") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium

p(HGNC:APBA2) decreases a(HBP:HBP00018) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium

p(HGNC:APBA2) regulates bp(HBP:HBP00073) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium

p(HGNC:APBB1) decreases a(CHEBI:"amyloid-beta") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium

p(HGNC:APBB1) decreases a(HBP:HBP00018) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium

p(HGNC:APBB1) regulates bp(HBP:HBP00073) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium

Evidence e716be40da
JSON

Moreover, Fe65 stabilizes the highly labile AICD, which may serve as a regulatory step in modulating the physiological func- tion of AICD (see below).

p(HGNC:APBB1) increases a(HBP:HBP00071) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High

Evidence 0b9e96b1fe
JSON

More than 25 mutations in APP have been identified that are causative of the hereditary form of familial AD and a related condition of hereditary cerebral amyloid angiopathy.

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

Appears in Networks:
Annotations
Confidence
Medium

p(HGNC:APP, var("?")) increases path(MESH:"Cerebral Amyloid Angiopathy, Familial") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium

Evidence c9351c047e
JSON

BACE1 generates the N terminus of Aβ.In addition,BACE1 can also cleave within the Aβ domain between Tyr 10 and Glu 11.

act(p(HGNC:BACE1), ma(pep)) increases rxn(reactants(p(HGNC:APP)), products(p(HGNC:APP, frag("11_*")), p(HGNC:APP, frag("1_10")))) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High

Evidence 135cece2ad
JSON

Finally, the type I transmembrane protein SorLA/LR11 (a member of the VPS10p domain receptor fam- ily), which functionally interacts with cytosolic adaptors GGA and PACS-1, attenuates Aβ production by acting as a Golgi/ TGN retention factor (22).

p(HGNC:SORL1) decreases a(CHEBI:"amyloid-beta") View Subject | View Object

Appears in Networks:
Annotations
Confidence
High

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.