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This gene encodes a cell surface receptor and transmembrane precursor protein that is cleaved by secretases to form a number of peptides. Some of these peptides are secreted and can bind to the acetyltransferase complex APBB1/TIP60 to promote transcriptional activation, while others form the protein basis of the amyloid plaques found in the brains of patients with Alzheimer disease. In addition, two of the peptides are antimicrobial peptides, having been shown to have bacteriocidal and antifungal activities. Mutations in this gene have been implicated in autosomal dominant Alzheimer disease and cerebroarterial amyloidosis (cerebral amyloid angiopathy). Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Aug 2014]
APP (Amyloid Beta Precursor Protein) is a Protein Coding gene. Diseases associated with APP include Cerebral Amyloid Angiopathy, App-Related and Alzheimer Disease. Among its related pathways are Neuroscience and Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways. Gene Ontology (GO) annotations related to this gene include identical protein binding and enzyme binding. An important paralog of this gene is APLP2.
Amyloid beta (Abeta) peptides are the major component of amyloid plaques found in the brains of Alzheimer's patients. Abeta is formed from the progressive cleavage of amyloid precursor protein (APP) by beta- and gamma-secretase. Two Abeta peptides are formed from APP degradation.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000978 | RNA polymerase II proximal promoter sequence-specific DNA binding | IEA | -- |
GO:0003677 | DNA binding | ISS | -- |
GO:0004867 | serine-type endopeptidase inhibitor activity | IEA,IDA | 10652580 |
GO:0005102 | signaling receptor binding | IPI | 19849849 |
GO:0005515 | protein binding | IPI | 2119582 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005576 | extracellular region | TAS | -- |
GO:0005615 | extracellular space | IDA | 23921129 |
GO:0005623 | cell | IEA | -- |
GO:0005634 | nucleus | IEA | -- |
GO:0005641 | nuclear envelope lumen | IDA | 21989385 |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Activated TLR4 signalling | ||
2 | Cytosolic sensors of pathogen-associated DNA | ||
3 | Peptide ligand-binding receptors | ||
4 | Response to elevated platelet cytosolic Ca2+ |
.44
|
|
5 | Clathrin derived vesicle budding |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0001774 | microglial cell activation | IGI | 15457210 |
GO:0001934 | positive regulation of protein phosphorylation | IGI | 15457210 |
GO:0001967 | suckling behavior | IEA | -- |
GO:0002265 | astrocyte activation involved in immune response | IGI | 23152628 |
GO:0002576 | platelet degranulation | TAS | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Copper | Approved, Investigational | Pharma | Target, aggregation inhibitor | 249 | ||
Dimercaprol | Approved | Pharma | Target | 0 | ||
Aluminium | Approved, Investigational | Pharma | Target | 0 | ||
Aluminium phosphate | Approved, Investigational | Pharma | Target | 0 | ||
Aluminum acetate | Approved, Investigational | Pharma | Target | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
EGCG |
|
989-51-5 |
|
|||
Dimebon dihydrochloride |
|
97657-92-6 |
|
|
||
NQTrp |
|
185351-19-3 |
|
|
||
SEN 1269 |
|
956128-01-1 |
|
|
Compound | Action | Cas Number |
---|---|---|
Dimebon dihydrochloride | Neuroprotectant; protects against beta-amyloid neurotoxicity | 97657-92-6 |
EGCG | Inhibits formation of amyloid fibrils | 989-51-5 |
NQTrp | Potent inhibitor of Abeta oligomer and fibril formation | 185351-19-3 |
Ro 90-7501 | Inhibitor of Abeta42 fibril formation | 293762-45-5 |
SEN 1269 | Amyloid-beta aggregation inhibitor | 956128-01-1 |
Compound | Action | Cas Number |
---|---|---|
amyloid A protein fragment [Homo sapiens] | Apolipoproteins related to HDL in plasma | |
Amyloid Beta-Peptide (12-28) (human) | 107015-83-8 | |
Amyloid Beta-Peptide (1-40) (human) | Amyloid precursor protein | 131438-79-4 |
Amyloid Beta-peptide (25-35) (human) | Functional domain of Aβ | 131602-53-4 |
Amyloid Precursor C-Terminal Peptide | For beta amyloid generation | |
Amyloid β-Peptide (10-20) (human) | Initiates neurodegeneration in Alzheimer disease | 152286-31-2 |
Amyloid β-Protein (1-15) | Principal component of amyloid | 183745-81-5 |
ARN2966 | APP expression modulator | 102212-26-0 |
Begacestat | γ-secretase inhibitor | 769169-27-9 |
Beta-Amyloid (1-11) | Amyloidogenic peptide | 190436-05-6 |
Colivelin | 867021-83-8 | |
CRANAD 2 | 1193447-34-5 | |
DAPT (GSI-IX) | γ-secretase inhibitor,potent and specific | 208255-80-5 |
EHT 1864 | Rac family small GTPases inhibitor | 754240-09-0 |
EUK 134 | Salen-manganese complexes;SOD mimetic | 81065-76-1 |
Flurizan | NSAID,inhibits γ-secretase activity | 51543-40-9 |
J 147 | 1146963-51-0 | |
JLK 6 | γ-secretase inhibitor | 62252-26-0 |
L-685,458 | γ-secretase inhibitor | 292632-98-5 |
LPYFD-NH2 | 700361-48-4 | |
Methoxy-X04 | 863918-78-9 | |
MRK 560 | γ-secretase inhibitor | 677772-84-8 |
Ro 90-7501 | 293762-45-5 | |
Semagacestat (LY450139) | γ-secretase inhibitor | 425386-60-3 |
TC-E 5006 | 1257395-14-4 | |
Tramiprosate | 3687-18-1 |
This gene was present in the common ancestor of animals.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | APP 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | APP 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | APP 30 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | APP 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | App 30 17 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | App 30 |
|
||
Platypus (Ornithorhynchus anatinus) |
Mammalia | APP 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | APP 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | APP 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | app 30 |
|
||
Str.11113 30 |
|
||||
African clawed frog (Xenopus laevis) |
Amphibia | MGC52816 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | appb 30 31 |
|
OneToMany | |
appa 31 |
|
OneToMany | |||
APP (1 of 3) 31 |
|
OneToMany | |||
-- 30 |
|
||||
Fruit Fly (Drosophila melanogaster) |
Insecta | Appl 31 |
|
OneToMany | |
Worm (Caenorhabditis elegans) |
Secernentea | apl-1 30 31 32 |
|
OneToMany |
SNP ID | Clinical significance and condition | Chr 21 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
638317 | Likely Pathogenic: Hereditary cerebral hemorrhage with amyloidosis; Cerebral amyloid angiopathy, APP-related | 25,891,808(-) | C/T | MISSENSE_VARIANT | |
640843 | Uncertain Significance: Alzheimer disease | 25,997,356(-) | G/A | INTRON_VARIANT | |
644611 | Uncertain Significance: Alzheimer disease | 26,021,902(-) | C/T | MISSENSE_VARIANT | |
645976 | Uncertain Significance: Early-onset Alzheimer's disease; Alzheimer disease | 25,997,360(-) | G/A | MISSENSE_VARIANT,INTRON_VARIANT | |
649787 | Uncertain Significance: Alzheimer disease | 25,975,973(-) | T/A | MISSENSE_VARIANT |