UniProtKB - P05067 (A4_HUMAN)
Protein
Amyloid-beta precursor protein
Gene
APP
Organism
Homo sapiens (Human)
Status
Functioni
Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on neighboring cells promotes synaptogenesis (PubMed:25122912). Involved in cell mobility and transcription regulation through protein-protein interactions. Can promote transcription activation through binding to APBB1-KAT5 and inhibits Notch signaling through interaction with Numb. Couples to apoptosis-inducing pathways such as those mediated by G(O) and JIP. Inhibits G(o) alpha ATPase activity (By similarity). Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1 (By similarity). By acting as a kinesin I membrane receptor, plays a role in axonal anterograde transport of cargo towards synapes in axons (PubMed:17062754, PubMed:23011729). Involved in copper homeostasis/oxidative stress through copper ion reduction. In vitro, copper-metallated APP induces neuronal death directly or is potentiated through Cu2+-mediated low-density lipoprotein oxidation. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV. The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons. Provides Cu2+ ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1.By similarity3 Publications
Amyloid-beta peptides are lipophilic metal chelators with metal-reducing activity. Bind transient metals such as copper, zinc and iron. In vitro, can reduce Cu2+ and Fe3+ to Cu+ and Fe2+, respectively. Amyloid-beta protein 42 is a more effective reductant than amyloid-beta protein 40. Amyloid-beta peptides bind to lipoproteins and apolipoproteins E and J in the CSF and to HDL particles in plasma, inhibiting metal-catalyzed oxidation of lipoproteins. APP42-beta may activate mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Interaction with overexpressed HADH2 leads to oxidative stress and neurotoxicity. Also binds GPC1 in lipid rafts.
Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain.By similarity
The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.
N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6).
Miscellaneous
Chelation of metal ions, notably copper, iron and zinc, can induce histidine-bridging between amyloid-beta molecules resulting in amyloid-beta-metal aggregates. The affinity for copper is much higher than for other transient metals and is increased under acidic conditions. Extracellular zinc-binding increases binding of heparin to APP and inhibits collagen-binding.2 Publications
Sites
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Metal bindingi | 147 | Copper 1PROSITE-ProRule annotationCombined sources2 Publications | 1 | |
| Metal bindingi | 151 | Copper 1PROSITE-ProRule annotationCombined sources2 Publications | 1 | |
| Metal bindingi | 168 | Copper 1PROSITE-ProRule annotationCombined sources1 Publication | 1 | |
| Sitei | 170 | Required for Cu(2+) reductionPROSITE-ProRule annotation | 1 | |
| Sitei | 301 – 302 | Reactive bond | 2 | |
| Metal bindingi | 677 | Copper or zinc 22 Publications | 1 | |
| Metal bindingi | 681 | Copper or zinc 22 Publications | 1 | |
| Metal bindingi | 684 | Copper or zinc 23 Publications | 1 | |
| Metal bindingi | 685 | Copper or zinc 22 Publications | 1 | |
| Sitei | 704 | Implicated in free radical propagationBy similarity | 1 | |
| Sitei | 706 | Susceptible to oxidation1 Publication | 1 |
GO - Molecular functioni
- acetylcholine receptor activator activity Source: ARUK-UCL
- acetylcholine receptor binding Source: UniProtKB
- amylin binding Source: ARUK-UCL
- apolipoprotein binding Source: ARUK-UCL
- chaperone binding Source: ARUK-UCL
- chemoattractant activity Source: ARUK-UCL
- DNA binding Source: UniProtKB
- enzyme binding Source: ParkinsonsUK-UCL
- ephrin receptor binding Source: ARUK-UCL
- frizzled binding Source: ARUK-UCL
- G protein-coupled receptor binding Source: ARUK-UCL
- growth factor receptor binding Source: Ensembl
- heparan sulfate binding Source: ARUK-UCL
- heparan sulfate proteoglycan binding Source: ARUK-UCL
- heparin binding Source: UniProtKB-KW
- identical protein binding Source: IntAct
- insulin receptor binding Source: ARUK-UCL
- integrin binding Source: ARUK-UCL
- low-density lipoprotein particle receptor binding Source: ARUK-UCL
- peptidase activator activity Source: Ensembl
- protein dimerization activity Source: ARUK-UCL
- protein heterodimerization activity Source: ARUK-UCL
- protein homodimerization activity Source: ARUK-UCL
- PTB domain binding Source: BHF-UCL
- RAGE receptor binding Source: ARUK-UCL
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: Ensembl
- RNA polymerase II core promoter sequence-specific DNA binding Source: ARUK-UCL
- serine-type endopeptidase inhibitor activity Source: UniProtKB
- signaling receptor activator activity Source: ARUK-UCL
- signaling receptor binding Source: ARUK-UCL
- transition metal ion binding Source: InterPro
GO - Biological processi
- activation of MAPK activity Source: ARUK-UCL
- activation of MAPKKK activity Source: ARUK-UCL
- adenylate cyclase-activating G protein-coupled receptor signaling pathway Source: ARUK-UCL
- adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway Source: ARUK-UCL
- adult locomotory behavior Source: UniProtKB
- amyloid fibril formation Source: ParkinsonsUK-UCL
- antibacterial humoral response Source: UniProtKB
- antifungal humoral response Source: UniProtKB
- antimicrobial humoral immune response mediated by antimicrobial peptide Source: UniProtKB
- associative learning Source: ARUK-UCL
- astrocyte activation Source: ARUK-UCL
- astrocyte activation involved in immune response Source: ARUK-UCL
- axo-dendritic transport Source: UniProtKB
- axon midline choice point recognition Source: UniProtKB
- axonogenesis Source: UniProtKB
- calcium-mediated signaling Source: ARUK-UCL
- cell adhesion Source: UniProtKB-KW
- cellular copper ion homeostasis Source: UniProtKB
- cellular process Source: ParkinsonsUK-UCL
- cellular protein metabolic process Source: Reactome
- cellular response to amyloid-beta Source: ARUK-UCL
- cellular response to cAMP Source: Ensembl
- cellular response to copper ion Source: Ensembl
- cellular response to manganese ion Source: Ensembl
- cellular response to nerve growth factor stimulus Source: Ensembl
- cellular response to norepinephrine stimulus Source: Ensembl
- cholesterol metabolic process Source: Ensembl
- cognition Source: UniProtKB
- collateral sprouting in absence of injury Source: UniProtKB
- defense response to Gram-negative bacterium Source: UniProtKB
- defense response to Gram-positive bacterium Source: UniProtKB
- dendrite development Source: UniProtKB
- endocytosis Source: UniProtKB
- extracellular matrix organization Source: UniProtKB
- forebrain development Source: Ensembl
- G protein-coupled receptor signaling pathway Source: ARUK-UCL
- innate immune response Source: UniProtKB
- ionotropic glutamate receptor signaling pathway Source: UniProtKB
- learning Source: ARUK-UCL
- learning or memory Source: ARUK-UCL
- lipoprotein metabolic process Source: ARUK-UCL
- locomotory behavior Source: UniProtKB
- mating behavior Source: UniProtKB
- memory Source: ARUK-UCL
- microglia development Source: ARUK-UCL
- microglial cell activation Source: ARUK-UCL
- modulation of age-related behavioral decline Source: ARUK-UCL
- modulation of excitatory postsynaptic potential Source: ARUK-UCL
- mRNA polyadenylation Source: UniProtKB
- negative regulation of blood circulation Source: ARUK-UCL
- negative regulation of canonical Wnt signaling pathway Source: ARUK-UCL
- negative regulation of cell population proliferation Source: UniProtKB
- negative regulation of gene expression Source: ARUK-UCL
- negative regulation of long-term synaptic potentiation Source: ARUK-UCL
- negative regulation of mitochondrion organization Source: ARUK-UCL
- negative regulation of neuron death Source: ARUK-UCL
- negative regulation of neuron differentiation Source: Ensembl
- negative regulation of pri-miRNA transcription by RNA polymerase II Source: ARUK-UCL
- negative regulation of protein localization to nucleus Source: ARUK-UCL
- negative regulation of transcription by RNA polymerase II Source: ARUK-UCL
- neuromuscular process controlling balance Source: Ensembl
- neuron apoptotic process Source: UniProtKB
- neuron projection development Source: UniProtKB
- neuron projection maintenance Source: ARUK-UCL
- neuron remodeling Source: UniProtKB
- Notch signaling pathway Source: UniProtKB-KW
- platelet degranulation Source: Reactome
- positive regulation of 1-phosphatidylinositol-3-kinase activity Source: ARUK-UCL
- positive regulation of amyloid-beta formation Source: ARUK-UCL
- positive regulation of amyloid fibril formation Source: ARUK-UCL
- positive regulation of apoptotic process Source: ARUK-UCL
- positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process Source: ARUK-UCL
- positive regulation of cell activation Source: ARUK-UCL
- positive regulation of cellular response to thapsigargin Source: ARUK-UCL
- positive regulation of cellular response to tunicamycin Source: ARUK-UCL
- positive regulation of chemokine biosynthetic process Source: ARUK-UCL
- positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: ARUK-UCL
- positive regulation of cytosolic calcium ion concentration Source: ARUK-UCL
- positive regulation of DNA-binding transcription factor activity Source: ARUK-UCL
- positive regulation of endothelin production Source: ARUK-UCL
- positive regulation of ERK1 and ERK2 cascade Source: ARUK-UCL
- positive regulation of excitatory postsynaptic potential Source: ARUK-UCL
- positive regulation of G2/M transition of mitotic cell cycle Source: Ensembl
- positive regulation of gene expression Source: ARUK-UCL
- positive regulation of glycolytic process Source: ARUK-UCL
- positive regulation of G protein-coupled receptor internalization Source: ARUK-UCL
- positive regulation of G protein-coupled receptor signaling pathway Source: ARUK-UCL
- positive regulation of histone acetylation Source: ARUK-UCL
- positive regulation of inflammatory response Source: ARUK-UCL
- positive regulation of interferon-gamma production Source: ARUK-UCL
- positive regulation of interleukin-1 beta production Source: ARUK-UCL
- positive regulation of interleukin-6 production Source: ARUK-UCL
- positive regulation of JNK cascade Source: ARUK-UCL
- positive regulation of long-term synaptic potentiation Source: ARUK-UCL
- positive regulation of MAPK cascade Source: ARUK-UCL
- positive regulation of membrane protein ectodomain proteolysis Source: ARUK-UCL
- positive regulation of mitotic cell cycle Source: UniProtKB
- positive regulation of monocyte chemotaxis Source: ARUK-UCL
- positive regulation of neuron apoptotic process Source: ARUK-UCL
- positive regulation of neuron death Source: ARUK-UCL
- positive regulation of neuron differentiation Source: ARUK-UCL
- positive regulation of NF-kappaB transcription factor activity Source: ARUK-UCL
- positive regulation of NIK/NF-kappaB signaling Source: ARUK-UCL
- positive regulation of nitric oxide biosynthetic process Source: ARUK-UCL
- positive regulation of oxidative stress-induced neuron death Source: ARUK-UCL
- positive regulation of peptidyl-serine phosphorylation Source: ARUK-UCL
- positive regulation of peptidyl-threonine phosphorylation Source: ARUK-UCL
- positive regulation of phosphorylation Source: ARUK-UCL
- positive regulation of protein binding Source: ARUK-UCL
- positive regulation of protein import Source: ARUK-UCL
- positive regulation of protein kinase A signaling Source: ARUK-UCL
- positive regulation of protein kinase B signaling Source: ARUK-UCL
- positive regulation of protein metabolic process Source: ARUK-UCL
- positive regulation of protein phosphorylation Source: ARUK-UCL
- positive regulation of protein tyrosine kinase activity Source: ARUK-UCL
- positive regulation of receptor binding Source: ARUK-UCL
- positive regulation of response to endoplasmic reticulum stress Source: ARUK-UCL
- positive regulation of superoxide anion generation Source: ARUK-UCL
- positive regulation of tau-protein kinase activity Source: ARUK-UCL
- positive regulation of T cell migration Source: ARUK-UCL
- positive regulation of transcription by RNA polymerase II Source: ARUK-UCL
- positive regulation of tumor necrosis factor biosynthetic process Source: ARUK-UCL
- post-translational protein modification Source: Reactome
- protein homooligomerization Source: ARUK-UCL
- protein phosphorylation Source: UniProtKB
- protein tetramerization Source: ARUK-UCL
- protein trimerization Source: ARUK-UCL
- regulation of acetylcholine-gated cation channel activity Source: ARUK-UCL
- regulation of amyloid-beta clearance Source: ARUK-UCL
- regulation of amyloid fibril formation Source: ARUK-UCL
- regulation of dendritic spine maintenance Source: ARUK-UCL
- regulation of epidermal growth factor-activated receptor activity Source: UniProtKB
- regulation of gene expression Source: ARUK-UCL
- regulation of long-term neuronal synaptic plasticity Source: ARUK-UCL
- regulation of multicellular organism growth Source: UniProtKB
- regulation of NMDA receptor activity Source: ARUK-UCL
- regulation of peptidyl-tyrosine phosphorylation Source: ARUK-UCL
- regulation of presynapse assembly Source: SynGO
- regulation of response to calcium ion Source: ARUK-UCL
- regulation of spontaneous synaptic transmission Source: ARUK-UCL
- regulation of synapse structure or activity Source: UniProtKB
- regulation of toll-like receptor signaling pathway Source: ARUK-UCL
- regulation of transcription by RNA polymerase II Source: ARUK-UCL
- regulation of translation Source: UniProtKB
- regulation of Wnt signaling pathway Source: ARUK-UCL
- response to interleukin-1 Source: ARUK-UCL
- response to lead ion Source: Ensembl
- response to oxidative stress Source: Ensembl
- response to yeast Source: UniProtKB
- smooth endoplasmic reticulum calcium ion homeostasis Source: Ensembl
- suckling behavior Source: Ensembl
- synapse organization Source: ARUK-UCL
- synaptic growth at neuromuscular junction Source: Ensembl
- tumor necrosis factor production Source: ARUK-UCL
- visual learning Source: UniProtKB
Keywordsi
| Molecular function | Heparin-binding, Protease inhibitor, Serine protease inhibitor |
| Biological process | Apoptosis, Cell adhesion, Endocytosis, Notch signaling pathway |
| Ligand | Copper, Iron, Metal-binding, Zinc |
Enzyme and pathway databases
| BioCyci | MetaCyc:ENSG00000142192-MONOMER |
| PathwayCommonsi | P05067 |
| Reactomei | R-HSA-114608, Platelet degranulation R-HSA-3000178, ECM proteoglycans R-HSA-381426, Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) R-HSA-416476, G alpha (q) signalling events R-HSA-418594, G alpha (i) signalling events R-HSA-432720, Lysosome Vesicle Biogenesis R-HSA-444473, Formyl peptide receptors bind formyl peptides and many other ligands R-HSA-445989, TAK1 activates NFkB by phosphorylation and activation of IKKs complex R-HSA-844456, The NLRP3 inflammasome R-HSA-879415, Advanced glycosylation endproduct receptor signaling R-HSA-8862803, Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models R-HSA-8957275, Post-translational protein phosphorylation R-HSA-933542, TRAF6 mediated NF-kB activation R-HSA-9609523, Insertion of tail-anchored proteins into the endoplasmic reticulum membrane R-HSA-9660826, Purinergic signaling in leishmaniasis infection R-HSA-977225, Amyloid fiber formation |
| SABIO-RKi | P05067 |
| SIGNORi | P05067 |
Protein family/group databases
| MEROPSi | I02.015 |
| TCDBi | 1.C.50.1.2, the amyloid Beta-protein peptide (aBetapp) family |
Names & Taxonomyi
| Protein namesi | Recommended name: Amyloid-beta precursor proteinCuratedShort name: APPCurated Alternative name(s): ABPP APPI Alzheimer disease amyloid protein Amyloid precursor proteinCurated Amyloid-beta A4 protein Cerebral vascular amyloid peptide Short name: CVAP PreA4 Protease nexin-II Short name: PN-II Cleaved into the following 14 chains: Alternative name(s): Beta-secretase C-terminal fragment1 Publication Short name: Beta-CTF1 Publication Alternative name(s): Beta-APP42 Alternative name(s): Beta-APP40 Alternative name(s): Alpha-secretase C-terminal fragment1 Publication Short name: Alpha-CTF1 Publication Alternative name(s): Amyloid intracellular domain 59 Short name: AICD-59 Short name: AID(59) Gamma-CTF(59) Alternative name(s): Amyloid intracellular domain 57 Short name: AICD-57 Short name: AID(57) Gamma-CTF(57) Alternative name(s): Amyloid intracellular domain 50 Short name: AICD-50 Short name: AID(50) Gamma-CTF(50) |
| Gene namesi | |
| Organismi | Homo sapiens (Human) |
| Taxonomic identifieri | 9606 [NCBI] |
| Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
| Proteomesi |
|
Organism-specific databases
| EuPathDBi | HostDB:ENSG00000142192.20 |
| HGNCi | HGNC:620, APP |
| MIMi | 104760, gene |
| neXtProti | NX_P05067 |
Subcellular locationi
Plasma membrane
- Cell membrane 1 Publication3 Publications; Single-pass type I membrane protein 2 Publications1 Publication
Endosome
- Early endosome 1 Publication
Other locations
- Membrane 1 Publication1 Publication; Single-pass type I membrane protein 1 Publication2 Publications
- Perikaryon 1 Publication
- growth cone 1 Publication
- clathrin-coated pit 1 Publication
- Cytoplasmic vesicle 2 Publications
Note: Cell surface protein that rapidly becomes internalized via clathrin-coated pits. Only a minor proportion is present at the cell membrane; most of the protein is present in intracellular vesicles (PubMed:20580937). During maturation, the immature APP (N-glycosylated in the endoplasmic reticulum) moves to the Golgi complex where complete maturation occurs (O-glycosylated and sulfated). After alpha-secretase cleavage, soluble APP is released into the extracellular space and the C-terminal is internalized to endosomes and lysosomes. Some APP accumulates in secretory transport vesicles leaving the late Golgi compartment and returns to the cell surface. APP sorts to the basolateral surface in epithelial cells. During neuronal differentiation, the Thr-743 phosphorylated form is located mainly in growth cones, moderately in neurites and sparingly in the cell body (PubMed:10341243). Casein kinase phosphorylation can occur either at the cell surface or within a post-Golgi compartment. Associates with GPC1 in perinuclear compartments. Colocalizes with SORL1 in a vesicular pattern in cytoplasm and perinuclear regions.2 Publications
Extracellular region or secreted
- Secreted 2 Publications
Other locations
Note: Associates with FPR2 at the cell surface and the complex is then rapidly internalized.1 Publication
Nucleus
- Nucleus 1 Publication
Other locations
- Cytoplasm 1 Publication
Note: Located to both the cytoplasm and nuclei of neurons. It can be translocated to the nucleus through association with APBB1 (Fe65) (PubMed:11544248). In dopaminergic neurons, the phosphorylated Thr-743 form is localized to the nucleus (By similarity).By similarity1 Publication
Cytoskeleton
- ciliary rootlet Source: Ensembl
- spindle midzone Source: Ensembl
Cytosol
- cytosol Source: Reactome
Endoplasmic reticulum
- endoplasmic reticulum lumen Source: Reactome
- rough endoplasmic reticulum Source: Ensembl
- smooth endoplasmic reticulum Source: GOC
Endosome
- early endosome Source: ARUK-UCL
- endosome Source: UniProtKB
- endosome lumen Source: ARUK-UCL
- recycling endosome Source: UniProtKB
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
- extracellular region Source: Reactome
- extracellular space Source: ARUK-UCL
- high-density lipoprotein particle Source: ARUK-UCL
- intermediate-density lipoprotein particle Source: ARUK-UCL
Golgi apparatus
- Golgi apparatus Source: UniProtKB
- Golgi lumen Source: Reactome
- trans-Golgi network membrane Source: Reactome
Mitochondrion
- mitochondrion Source: ARUK-UCL
Nucleus
- nuclear envelope lumen Source: Alzheimers_University_of_Toronto
- nucleus Source: ARUK-UCL
Plasma Membrane
- clathrin-coated pit Source: UniProtKB-SubCell
- integral component of plasma membrane Source: ProtInc
- plasma membrane Source: ARUK-UCL
Other locations
- amyloid-beta complex Source: ARUK-UCL
- apical part of cell Source: Ensembl
- astrocyte projection Source: Ensembl
- axon Source: UniProtKB
- cell surface Source: UniProtKB
- cell-cell junction Source: Ensembl
- COPII-coated ER to Golgi transport vesicle Source: Ensembl
- cytoplasm Source: ARUK-UCL
- dendritic shaft Source: MGI
- dendritic spine Source: MGI
- endosome to plasma membrane transport vesicle Source: ARUK-UCL
- Golgi-associated vesicle Source: UniProtKB
- growth cone filopodium Source: Ensembl
- growth cone lamellipodium Source: Ensembl
- integral component of membrane Source: UniProtKB
- lipoprotein particle Source: ARUK-UCL
- main axon Source: Ensembl
- membrane Source: ARUK-UCL
- membrane raft Source: ParkinsonsUK-UCL
- neuromuscular junction Source: Ensembl
- perikaryon Source: UniProtKB-SubCell
- perinuclear region of cytoplasm Source: UniProtKB
- platelet alpha granule lumen Source: Reactome
- protein-containing complex Source: ARUK-UCL
- receptor complex Source: MGI
- synapse Source: MGI
- synaptic vesicle Source: Ensembl
Topology
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Topological domaini | 18 – 701 | ExtracellularCuratedAdd BLAST | 684 | |
| Transmembranei | 702 – 722 | Helical3 PublicationsAdd BLAST | 21 | |
| Topological domaini | 723 – 770 | CytoplasmicCuratedAdd BLAST | 48 |
Keywords - Cellular componenti
Amyloid, Cell membrane, Cell projection, Coated pit, Cytoplasm, Cytoplasmic vesicle, Endosome, Membrane, Nucleus, SecretedPathology & Biotechi
Involvement in diseasei
Alzheimer disease 1 (AD1)30 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA familial early-onset form of Alzheimer disease. It can be associated with cerebral amyloid angiopathy. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituents of these plaques are neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42, that are produced by the proteolysis of the transmembrane APP protein. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products, such as C31, are also implicated in neuronal death.
Related information in OMIM| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_000015 | 670 – 671 | KM → NL in AD1; Swedish mutation; highly increases hydrolysis by BACE1 and amyloid-beta proteins production. 4 PublicationsCorresponds to variant dbSNP:rs281865161Ensembl. | 2 | |
| Natural variantiVAR_044424 | 678 | D → N in AD1. 1 PublicationCorresponds to variant dbSNP:rs63750064EnsemblClinVar. | 1 | |
| Natural variantiVAR_000016 | 692 | A → G in AD1; Flemish mutation; increases the solubility of processed amyloid-beta peptides and increases the stability of peptide oligomers. 3 PublicationsCorresponds to variant dbSNP:rs63750671EnsemblClinVar. | 1 | |
| Natural variantiVAR_014215 | 693 | E → G in AD1. 2 PublicationsCorresponds to variant dbSNP:rs63751039EnsemblClinVar. | 1 | |
| Natural variantiVAR_000019 | 713 | A → T in AD1. 2 PublicationsCorresponds to variant dbSNP:rs63750066EnsemblClinVar. | 1 | |
| Natural variantiVAR_032277 | 714 | T → A in AD1. 1 PublicationCorresponds to variant dbSNP:rs63750643EnsemblClinVar. | 1 | |
| Natural variantiVAR_014218 | 714 | T → I in AD1; increased amyloid-beta protein 42/40 ratio. 2 PublicationsCorresponds to variant dbSNP:rs63750973EnsemblClinVar. | 1 | |
| Natural variantiVAR_010108 | 715 | V → M in AD1; decreased amyloid-beta protein 40/total amyloid-beta. 1 PublicationCorresponds to variant dbSNP:rs63750734EnsemblClinVar. | 1 | |
| Natural variantiVAR_000020 | 716 | I → V in AD1. 1 PublicationCorresponds to variant dbSNP:rs63750399EnsemblClinVar. | 1 | |
| Natural variantiVAR_000023 | 717 | V → F in AD1; increased amyloid-beta protein 42/40 ratio. 5 PublicationsCorresponds to variant dbSNP:rs63750264EnsemblClinVar. | 1 | |
| Natural variantiVAR_000022 | 717 | V → G in AD1; increased amyloid-beta protein 42/40 ratio. 3 PublicationsCorresponds to variant dbSNP:rs63749964EnsemblClinVar. | 1 | |
| Natural variantiVAR_000021 | 717 | V → I in AD1; increased amyloid-beta protein 42/40 ratio. 9 PublicationsCorresponds to variant dbSNP:rs63750264EnsemblClinVar. | 1 | |
| Natural variantiVAR_014219 | 717 | V → L in AD1. 1 PublicationCorresponds to variant dbSNP:rs63750264EnsemblClinVar. | 1 | |
| Natural variantiVAR_010109 | 723 | L → P in AD1. 1 PublicationCorresponds to variant dbSNP:rs63751122EnsemblClinVar. | 1 |
Cerebral amyloid angiopathy, APP-related (CAA-APP)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA hereditary localized amyloidosis due to amyloid-beta A4 peptide(s) deposition in the cerebral vessels. The principal clinical characteristics are recurrent cerebral and cerebellar hemorrhages, recurrent strokes, cerebral ischemia, cerebral infarction, and progressive mental deterioration. Patients develop cerebral hemorrhage because of the severe cerebral amyloid angiopathy. Parenchymal amyloid deposits are rare and largely in the form of pre-amyloid lesions or diffuse plaque-like structures. They are Congo red negative and lack the dense amyloid cores commonly present in Alzheimer disease. Some affected individuals manifest progressive aphasic dementia, leukoencephalopathy, and occipital calcifications.
Related information in OMIM| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_014216 | 693 | E → K in CAA-APP; Italian type. 1 PublicationCorresponds to variant dbSNP:rs63750579EnsemblClinVar. | 1 | |
| Natural variantiVAR_000017 | 693 | E → Q in CAA-APP; Dutch type. 1 PublicationCorresponds to variant dbSNP:rs63750579EnsemblClinVar. | 1 | |
| Natural variantiVAR_014217 | 694 | D → N in CAA-APP; Iowa type. 2 PublicationsCorresponds to variant dbSNP:rs63749810EnsemblClinVar. | 1 | |
| Natural variantiVAR_032276 | 705 | L → V in CAA-APP; Italian type. 1 PublicationCorresponds to variant dbSNP:rs63750921EnsemblClinVar. | 1 |
Mutagenesis
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Mutagenesisi | 99 – 102 | KRGR → NQGG: Reduced heparin-binding. 1 Publication | 4 | |
| Mutagenesisi | 108 | H → A: Loss of the copper binding site in the GFLD subdomain; when associated with A-110. 1 Publication | 1 | |
| Mutagenesisi | 110 | H → A: Loss of the copper binding site in the GFLD subdomain; when associated with A-108. 1 Publication | 1 | |
| Mutagenesisi | 137 | H → N: Binds copper. Forms dimer. 1 Publication | 1 | |
| Mutagenesisi | 141 | M → T: Binds copper. Forms dimer. 1 Publication | 1 | |
| Mutagenesisi | 144 | C → S: Binds copper. No dimer formation. No copper reducing activity. 2 Publications | 1 | |
| Mutagenesisi | 147 – 149 | HLH → ALA: 50% decrease in copper reducing activity. 1 Publication | 3 | |
| Mutagenesisi | 147 | H → A: Loss of a copper binding site; when associated with A-151. 1 Publication | 1 | |
| Mutagenesisi | 147 | H → A: Some decrease in copper reducing activity. 2 Publications | 1 | |
| Mutagenesisi | 147 | H → N: Binds copper. Forms dimer. 2 Publications | 1 | |
| Mutagenesisi | 147 | H → Y: Greatly reduced copper-mediated low-density lipoprotein oxidation. 2 Publications | 1 | |
| Mutagenesisi | 151 | H → A: Loss of a copper binding site; when associated with A-147. 1 Publication | 1 | |
| Mutagenesisi | 151 | H → K: Greatly reduced copper-mediated low-density lipoprotein oxidation. 2 Publications | 1 | |
| Mutagenesisi | 151 | H → N: Binds copper. Forms dimer. 2 Publications | 1 | |
| Mutagenesisi | 198 | S → A: Greatly reduced casein kinase phosphorylation. 2 Publications | 1 | |
| Mutagenesisi | 206 | S → A: Reduced casein kinase phosphorylation. 2 Publications | 1 | |
| Mutagenesisi | 499 | R → A: Reduced affinity for heparin; when associated with A-503. 1 Publication | 1 | |
| Mutagenesisi | 503 | K → A: Reduced affinity for heparin; when associated with A-499. 1 Publication | 1 | |
| Mutagenesisi | 656 | S → A: Abolishes chondroitin sulfate binding in L-APP733 isoform. 1 Publication | 1 | |
| Mutagenesisi | 676 | R → G: 60-70% zinc-induced amyloid-beta protein 28 aggregation. 1 Publication | 1 | |
| Mutagenesisi | 681 | Y → F: 60-70% zinc-induced amyloid-beta protein 28 aggregation. 1 Publication | 1 | |
| Mutagenesisi | 684 | H → R: Only 23% zinc-induced amyloid-beta protein 28 aggregation. 1 Publication | 1 | |
| Mutagenesisi | 695 | V → C: Causes formation of an artifactual disulfide bond with PSEN1. 1 Publication | 1 | |
| Mutagenesisi | 704 | G → V: Reduced protein oxidation. No hippocampal neuron toxicity. | 1 | |
| Mutagenesisi | 706 | M → L: Reduced lipid peroxidation inhibition. 2 Publications | 1 | |
| Mutagenesisi | 706 | M → V: No free radical production. No hippocampal neuron toxicity. 2 Publications | 1 | |
| Mutagenesisi | 717 | V → C or S: Unchanged amyloid-beta protein 42/total amyloid-beta ratio. 2 Publications | 1 | |
| Mutagenesisi | 717 | V → K: Decreased amyloid-beta protein 42/total amyloid-beta ratio. 2 Publications |