Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

Amyloid-beta precursor protein



Homo sapiens (Human)
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>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. 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 similarity1 Publication
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).


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


Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Function’ section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the ‘Description’ field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi147Copper 1PROSITE-ProRule annotationCombined sources2 Publications1
Metal bindingi151Copper 1PROSITE-ProRule annotationCombined sources2 Publications1
Metal bindingi168Copper 1PROSITE-ProRule annotationCombined sources1 Publication1
<p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections (‘Function’, ‘PTM / Processing’, ‘Pathology and Biotech’) according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei170Required for Cu(2+) reductionPROSITE-ProRule annotation1
Sitei301 – 302Reactive bond2
Metal bindingi677Copper or zinc 22 Publications1
Metal bindingi681Copper or zinc 22 Publications1
Metal bindingi684Copper or zinc 23 Publications1
Metal bindingi685Copper or zinc 22 Publications1
Sitei704Implicated in free radical propagationBy similarity1
Sitei706Susceptible to oxidation1 Publication1

<p>The <a href="">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionHeparin-binding, Protease inhibitor, Serine protease inhibitor
Biological processApoptosis, Cell adhesion, Endocytosis, Notch signaling pathway
LigandCopper, Iron, Metal-binding, Zinc

Enzyme and pathway databases

BioCyc Collection of Pathway/Genome Databases


Reactome - a knowledgebase of biological pathways and processes

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-977225 Amyloid fiber formation

SABIO-RK: Biochemical Reaction Kinetics Database


SIGNOR Signaling Network Open Resource


Protein family/group databases

MEROPS protease database


Transport Classification Database

1.C.50.1.2 the amyloid Beta-protein peptide (aBetapp) family

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Amyloid-beta precursor proteinCurated
Short name:
Alternative name(s):
Alzheimer disease amyloid protein
Amyloid precursor proteinCurated
Amyloid-beta A4 protein
Cerebral vascular amyloid peptide
Short name:
Protease nexin-II
Short name:
Cleaved into the following 14 chains:
Soluble APP-alpha1 Publication
Short name:
S-APP-alpha1 Publication
Soluble APP-beta1 Publication
Short name:
S-APP-beta1 Publication
Alternative name(s):
Beta-secretase C-terminal fragment1 Publication
Short name:
Beta-CTF1 Publication
Amyloid-beta protein 421 Publication
Short name:
Alternative name(s):
Amyloid-beta protein 401 Publication
Short name:
Alternative name(s):
Alternative name(s):
Alpha-secretase C-terminal fragment1 Publication
Short name:
Alpha-CTF1 Publication
Alternative name(s):
Amyloid intracellular domain 59
Short name:
Short name:
Alternative name(s):
Amyloid intracellular domain 57
Short name:
Short name:
Alternative name(s):
Amyloid intracellular domain 50
Short name:
Short name:
<p>This subsection of the <a href="">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Synonyms:A4, AD1
<p>This subsection of the <a href="">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="">Names and taxonomy</a> section is present for entries that are part of a <a href="">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 21

Organism-specific databases

Eukaryotic Pathogen Database Resources


Human Gene Nomenclature Database


Online Mendelian Inheritance in Man (OMIM)

104760 gene

neXtProt; the human protein knowledge platform


<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS


Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini18 – 701ExtracellularCuratedAdd BLAST684
<p>This subsection of the <a href="">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei702 – 722Helical2 PublicationsAdd BLAST21
Topological domaini723 – 770CytoplasmicCuratedAdd BLAST48

Keywords - Cellular componenti

Amyloid, Cell membrane, Cell projection, Coated pit, Cytoplasm, Cytoplasmic vesicle, Endosome, Membrane, Nucleus, Secreted

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="">OMIM</a> database are represented with a <a href="">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>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.
See also OMIM:104300
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_000015670 – 671KM → NL in AD1; Swedish mutation; highly increases hydrolysis by BACE1 and amyloid-beta proteins production. 4 PublicationsCorresponds to variant dbSNP:rs281865161Ensembl.2
Natural variantiVAR_044424678D → N in AD1. 1 PublicationCorresponds to variant dbSNP:rs63750064EnsemblClinVar.1
Natural variantiVAR_000016692A → 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_014215693E → G in AD1. 2 PublicationsCorresponds to variant dbSNP:rs63751039EnsemblClinVar.1
Natural variantiVAR_000019713A → T in AD1. 2 PublicationsCorresponds to variant dbSNP:rs63750066EnsemblClinVar.1
Natural variantiVAR_032277714T → A in AD1. 1 PublicationCorresponds to variant dbSNP:rs63750643EnsemblClinVar.1
Natural variantiVAR_014218714T → I in AD1; increased amyloid-beta protein 42/40 ratio. 2 PublicationsCorresponds to variant dbSNP:rs63750973EnsemblClinVar.1
Natural variantiVAR_010108715V → M in AD1; decreased amyloid-beta protein 40/total amyloid-beta. 1 PublicationCorresponds to variant dbSNP:rs63750734EnsemblClinVar.1
Natural variantiVAR_000020716I → V in AD1. 1 PublicationCorresponds to variant dbSNP:rs63750399EnsemblClinVar.1
Natural variantiVAR_000023717V → F in AD1; increased amyloid-beta protein 42/40 ratio. 5 PublicationsCorresponds to variant dbSNP:rs63750264EnsemblClinVar.1
Natural variantiVAR_000022717V → G in AD1; increased amyloid-beta protein 42/40 ratio. 3 PublicationsCorresponds to variant dbSNP:rs63749964EnsemblClinVar.1
Natural variantiVAR_000021717V → I in AD1; increased amyloid-beta protein 42/40 ratio. 9 PublicationsCorresponds to variant dbSNP:rs63750264EnsemblClinVar.1
Natural variantiVAR_014219717V → L in AD1. 1 PublicationCorresponds to variant dbSNP:rs63750264EnsemblClinVar.1
Natural variantiVAR_010109723L → 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.
See also OMIM:605714
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_014216693E → K in CAA-APP; Italian type. 1 PublicationCorresponds to variant dbSNP:rs63750579EnsemblClinVar.1
Natural variantiVAR_000017693E → Q in CAA-APP; Dutch type. 1 PublicationCorresponds to variant dbSNP:rs63750579EnsemblClinVar.1
Natural variantiVAR_014217694D → N in CAA-APP; Iowa type. 2 PublicationsCorresponds to variant dbSNP:rs63749810EnsemblClinVar.1
Natural variantiVAR_032276705L → V in CAA-APP; Italian type. 1 PublicationCorresponds to variant dbSNP:rs63750921EnsemblClinVar.1


Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi99 – 102KRGR → NQGG: Reduced heparin-binding. 1 Publication4
Mutagenesisi108H → A: Loss of the copper binding site in the GFLD subdomain; when associated with A-110. 1 Publication1
Mutagenesisi110H → A: Loss of the copper binding site in the GFLD subdomain; when associated with A-108. 1 Publication1
Mutagenesisi137H → N: Binds copper. Forms dimer. 1 Publication1
Mutagenesisi141M → T: Binds copper. Forms dimer. 1 Publication1
Mutagenesisi144C → S: Binds copper. No dimer formation. No copper reducing activity. 2 Publications1
Mutagenesisi147 – 149HLH → ALA: 50% decrease in copper reducing activity. 1 Publication3
Mutagenesisi147H → A: Loss of a copper binding site; when associated with A-151. 1 Publication1
Mutagenesisi147H → A: Some decrease in copper reducing activity. 2 Publications1
Mutagenesisi147H → N: Binds copper. Forms dimer. 2 Publications1
Mutagenesisi147H → Y: Greatly reduced copper-mediated low-density lipoprotein oxidation. 2 Publications1
Mutagenesisi151H → A: Loss of a copper binding site; when associated with A-147. 1 Publication1
Mutagenesisi151H → K: Greatly reduced copper-mediated low-density lipoprotein oxidation. 2 Publications1
Mutagenesisi151H → N: Binds copper. Forms dimer. 2 Publications1
Mutagenesisi198S → A: Greatly reduced casein kinase phosphorylation. 2 Publications1
Mutagenesisi206S → A: Reduced casein kinase phosphorylation. 2 Publications1
Mutagenesisi499R → A: Reduced affinity for heparin; when associated with A-503. 1 Publication1
Mutagenesisi503K → A: Reduced affinity for heparin; when associated with A-499. 1 Publication1
Mutagenesisi656S → A: Abolishes chondroitin sulfate binding in L-APP733 isoform. 1 Publication1
Mutagenesisi676R → G: 60-70% zinc-induced amyloid-beta protein 28 aggregation. 1 Publication1
Mutagenesisi681Y → F: 60-70% zinc-induced amyloid-beta protein 28 aggregation. 1 Publication1
Mutagenesisi684H → R: Only 23% zinc-induced amyloid-beta protein 28 aggregation. 1 Publication1
Mutagenesisi704G → V: Reduced protein oxidation. No hippocampal neuron toxicity. 1
Mutagenesisi706M → L: Reduced lipid peroxidation inhibition. 2 Publications1
Mutagenesisi706M → V: No free radical production. No hippocampal neuron toxicity. 2 Publications1
Mutagenesisi717V → C or S: Unchanged amyloid-beta protein 42/total amyloid-beta ratio. 2 Publications1
Mutagenesisi717V → K: Decreased amyloid-beta protein 42/total amyloid-beta ratio. 2 Publications1
Mutagenesisi717V → M: Increased amyloid-beta protein 42/40 ratio. No change in apoptosis after caspase cleavage. 2 Publications1
Mutagenesisi728Y → A: No effect on APBA1 nor APBB1 binding. Greatly reduces the binding to APPBP2. APP internalization unchanged. No change in amyloid-beta protein 42 secretion. 3 Publications1
Mutagenesisi739D → A: No cleavage by caspases during apoptosis. 3 Publications1
Mutagenesisi739D → N: No effect on FADD-induced apoptosis. 3 Publications1
Mutagenesisi743T → A: Greatly reduces the binding to SHC1 and APBB family members; no effect on NGF-stimulated neurite extension. 4 Publications1
Mutagenesisi743T → E: Reduced NGF-stimulated neurite extension. No effect on APP maturation. 4 Publications1
Mutagenesisi756G → A: APP internalization unchanged. No change in amyloid-beta protein 42 secretion. 1 Publication1
Mutagenesisi757Y → A: Little APP internalization. Reduced amyloid-beta protein 42 secretion. 4 Publications1
Mutagenesisi757Y → G: Loss of binding to MAPK8IP1, APBA1, APBB1, APPBP2 and SHC1. 4 Publications1
Mutagenesisi759N → A: No binding to APBA1, no effect on APBB1 binding. Little APP internalization. Reduced amyloid-beta protein 42 secretion. 2 Publications1
Mutagenesisi760P → A: Little APP internalization. Reduced amyloid-beta protein 42 secretion. 1 Publication1
Mutagenesisi762Y → A: Loss of binding to APBA1 and APBB1. APP internalization unchanged. No change in amyloid-beta protein 42 secretion. 2 Publications1

Keywords - Diseasei

Alzheimer disease, Amyloidosis, Disease mutation, Neurodegeneration

Organism-specific databases



MalaCards human disease database

MIMi104300 phenotype
605714 phenotype

Open Targets


Orphanet; a database dedicated to information on rare diseases and orphan drugs

324723 ABeta amyloidosis, Arctic type
100006 ABeta amyloidosis, Dutch type
324708 ABeta amyloidosis, Iowa type
324713 ABeta amyloidosis, Italian type
324718 ABetaA21G amyloidosis
324703 ABetaL34V amyloidosis
1020 Early-onset autosomal dominant Alzheimer disease

The Pharmacogenetics and Pharmacogenomics Knowledge Base


Chemistry databases

ChEMBL database of bioactive drug-like small molecules


Drug and drug target database

DB05150 CAD106
DB09148 Florbetaben (18F)
DB09149 Florbetapir (18F)
DB09151 Flutemetamol (18F)
DB02235 L-methionine (R)-S-oxide
DB05846 Mito-4509

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database


Domain mapping of disease mutations (DMDM)


<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section denotes the presence of an N-terminal signal peptide.<p><a href='/help/signal' target='_top'>More...</a></p>Signal peptidei1 – 173 PublicationsAdd BLAST17
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_000000008818 – 770Amyloid-beta precursor proteinAdd BLAST753
ChainiPRO_000000008918 – 687Soluble APP-alphaAdd BLAST670
ChainiPRO_000000009018 – 671Soluble APP-betaAdd BLAST654
ChainiPRO_000038196618 – 286N-APPAdd BLAST269
ChainiPRO_0000000091672 – 770C99Add BLAST99
ChainiPRO_0000000092672 – 713Amyloid-beta protein 42Add BLAST42
ChainiPRO_0000000093672 – 711Amyloid-beta protein 40Add BLAST40
ChainiPRO_0000000094688 – 770C83Add BLAST83
<p>This subsection of the ‘PTM / Processing’ section describes the position and length of an active peptide in the mature protein.<p><a href='/help/peptide' target='_top'>More...</a></p>PeptideiPRO_0000000095688 – 713P3(42)Add BLAST26
PeptideiPRO_0000000096688 – 711P3(40)Add BLAST24
ChainiPRO_0000384574691 – 770C80Add BLAST80
ChainiPRO_0000000097712 – 770Gamma-secretase C-terminal fragment 59Add BLAST59
ChainiPRO_0000000098714 – 770Gamma-secretase C-terminal fragment 57Add BLAST57
ChainiPRO_0000000099721 – 770Gamma-secretase C-terminal fragment 50By similarityAdd BLAST50
ChainiPRO_0000000100740 – 770C31Add BLAST31

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi38 ↔ 62PROSITE-ProRule annotationCombined sources
Disulfide bondi73 ↔ 117PROSITE-ProRule annotationCombined sources
Disulfide bondi98 ↔ 105PROSITE-ProRule annotationCombined sources
Disulfide bondi133 ↔ 187PROSITE-ProRule annotationCombined sources3 Publications
Disulfide bondi144 ↔ 174PROSITE-ProRule annotationCombined sources3 Publications
Disulfide bondi158 ↔ 186PROSITE-ProRule annotationCombined sources3 Publications
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="">lipids</a>, <a href="">glycans</a> and <a href="">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei198Phosphoserine; by CK21 Publication1
Modified residuei206Phosphoserine; by CK11 Publication1
Disulfide bondi291 ↔ 341Combined sources
Disulfide bondi300 ↔ 324Combined sources
Disulfide bondi316 ↔ 337Combined sources
Modified residuei441Phosphoserine; by FAM20C1 Publication1
Modified residuei497Phosphotyrosine1 Publication1
<p>This subsection of the <a href="">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi542N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi571N-linked (GlcNAc...) asparagineCurated1
Glycosylationi633O-linked (GalNAc...) threonine; partial2 Publications1
Glycosylationi651O-linked (GalNAc...) threonine; partial2 Publications1
Glycosylationi652O-linked (GalNAc...) threonine; partial2 Publications1
Glycosylationi656O-linked (Xyl...) (chondroitin sulfate) serine; in L-APP isoforms1 Publication1
Glycosylationi659O-linked (HexNAc...) threonine; partial1 Publication1
Glycosylationi663O-linked (GalNAc...) threonine; partial1 Publication1 Publication1
Glycosylationi667O-linked (GalNAc...) serine; partial1 Publication1 Publication1
Glycosylationi681O-linked (HexNAc...) tyrosine; partial1 Publication1
Modified residuei729PhosphothreonineBy similarity1
Modified residuei730Phosphoserine; by APP-kinase IBy similarity1
Modified residuei743Phosphothreonine; by CDK5 and MAPK10Combined sources1 Publication1
Modified residuei757Phosphotyrosine1 Publication1
<p>This subsection of the <a href="">PTM / Processing</a> section describes <strong>covalent linkages</strong> of various types formed <strong>between two proteins (interchain cross-links)</strong> or <strong>between two parts of the same protein (intrachain cross-links)</strong>, except the disulfide bonds that are annotated in the <a href="">'Disulfide bond'</a> subsection.<p><a href='/help/crosslnk' target='_top'>More...</a></p>Cross-linki763Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity

<p>This subsection of the <a href="">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Proteolytically processed under normal cellular conditions. Cleavage either by alpha-secretase, beta-secretase or theta-secretase leads to generation and extracellular release of soluble APP peptides, S-APP-alpha and S-APP-beta, and the retention of corresponding membrane-anchored C-terminal fragments, C80, C83 and C99. Subsequent processing of C80 and C83 by gamma-secretase yields P3 peptides. This is the major secretory pathway and is non-amyloidogenic. Alternatively, presenilin/nicastrin-mediated gamma-secretase processing of C99 releases the amyloid-beta proteins, amyloid-beta protein 40 and amyloid-beta protein 42, major components of amyloid plaques, and the cytotoxic C-terminal fragments, gamma-CTF(50), gamma-CTF(57) and gamma-CTF(59). Many other minor amyloid-beta peptides, amyloid-beta 1-X peptides, are found in cerebral spinal fluid (CSF) including the amyloid-beta X-15 peptides, produced from the cleavage by alpha-secretase and all terminating at Gln-686.1 Publication
Proteolytically cleaved by caspases during neuronal apoptosis. Cleavage at Asp-739 by either caspase-6, -8 or -9 results in the production of the neurotoxic C31 peptide and the increased production of amyloid-beta peptides.
N-glycosylated (PubMed:2900137). N- and O-glycosylated. O-glycosylation on Ser and Thr residues with core 1 or possibly core 8 glycans. Partial tyrosine glycosylation (Tyr-681) is found on some minor, short amyloid-beta peptides (amyloid-beta 1-15, 1-16, 1-17, 1-18, 1-19 and 1-20) but not found on amyloid-beta protein 38, amyloid-beta protein 40 nor on amyloid-beta protein 42. Modification on a tyrosine is unusual and is more prevelant in AD patients. Glycans had Neu5AcHex(Neu5Ac)HexNAc-O-Tyr, Neu5AcNeu5AcHex(Neu5Ac)HexNAc-O-Tyr and O-AcNeu5AcNeu5AcHex(Neu5Ac)HexNAc-O-Tyr structures, where O-Ac is O-acetylation of Neu5Ac. Neu5AcNeu5Ac is most likely Neu5Ac 2,8Neu5Ac linked. O-glycosylations in the vicinity of the cleavage sites may influence the proteolytic processing. Appicans are L-APP isoforms with O-linked chondroitin sulfate.4 Publications
Phosphorylation in the C-terminal on tyrosine, threonine and serine residues is neuron-specific. Phosphorylation can affect APP processing, neuronal differentiation and interaction with other proteins. Phosphorylated on Thr-743 in neuronal cells by Cdc5 kinase and Mapk10, in dividing cells by Cdc2 kinase in a cell-cycle dependent manner with maximal levels at the G2/M phase and, in vitro, by GSK-3-beta. The Thr-743 phosphorylated form causes a conformational change which reduces binding of Fe65 family members. Phosphorylation on Tyr-757 is required for SHC binding. Phosphorylated in the extracellular domain by casein kinases on both soluble and membrane-bound APP. This phosphorylation is inhibited by heparin.6 Publications
Extracellular binding and reduction of copper, results in a corresponding oxidation of Cys-144 and Cys-158, and the formation of a disulfide bond. In vitro, the APP-Cu+ complex in the presence of hydrogen peroxide results in an increased production of amyloid-beta-containing peptides.
Trophic-factor deprivation triggers the cleavage of surface APP by beta-secretase to release sAPP-beta which is further cleaved to release an N-terminal fragment of APP (N-APP).
Amyloid-beta peptides are degraded by IDE.


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei197 – 198Cleavage; by caspases1 Publication2
Sitei219 – 220Cleavage; by caspases1 Publication2
Sitei671 – 672Cleavage; by beta-secretase1 Publication2
Sitei672 – 673Cleavage; by caspase-6; when associated with variant 670-N-L-6712
Sitei687 – 688Cleavage; by alpha-secretase1 Publication2
Sitei690 – 691Cleavage; by theta-secretase1 Publication2
Sitei711 – 712Cleavage; by gamma-secretase; site 11 Publication2
Sitei713 – 714Cleavage; by gamma-secretase; site 21 Publication2
Sitei720 – 721Cleavage; by gamma-secretase; site 31 Publication2
Sitei739 – 740Cleavage; by caspase-6, caspase-8 or caspase-91 Publication2

Keywords - PTMi

Disulfide bond, Glycoprotein, Isopeptide bond, Oxidation, Phosphoprotein, Proteoglycan, Ubl conjugation

Proteomic databases

Encyclopedia of Proteome Dynamics


jPOST - Japan Proteome Standard Repository/Database


MaxQB - The MaxQuant DataBase


PaxDb, a database of protein abundance averages across all three domains of life




PRoteomics IDEntifications database


ProteomicsDB human proteome resource

51775 [P05067-10]
51776 [P05067-2]
51777 [P05067-3]
51778 [P05067-4]
51779 [P05067-5]
51780 [P05067-6]
51781 [P05067-7]
51782 [P05067-8]
51783 [P05067-9]

2D gel databases

Two-dimensional polyacrylamide gel electrophoresis database from the Geneva University Hospital


PTM databases

GlyConnect protein glycosylation platform


iPTMnet integrated resource for PTMs in systems biology context


Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.


SwissPalm database of S-palmitoylation events


UniCarbKB; an annotated and curated database of glycan structures


Miscellaneous databases

CutDB - Proteolytic event database


<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="">P92958</a>, <a href="">Q8TDN4</a>, <a href="">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Expressed in all fetal tissues examined with highest levels in brain, kidney, heart and spleen. Weak expression in liver. In adult brain, highest expression found in the frontal lobe of the cortex and in the anterior perisylvian cortex-opercular gyri. Moderate expression in the cerebellar cortex, the posterior perisylvian cortex-opercular gyri and the temporal associated cortex. Weak expression found in the striate, extra-striate and motor cortices. Expressed in cerebrospinal fluid, and plasma. Isoform APP695 is the predominant form in neuronal tissue, isoform APP751 and isoform APP770 are widely expressed in non-neuronal cells. Isoform APP751 is the most abundant form in T-lymphocytes. Appican is expressed in astrocytes.2 Publications

<p>This subsection of the ‘Expression’ section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductioni

Increased levels during neuronal differentiation.

Gene expression databases

Bgee dataBase for Gene Expression Evolution

ENSG00000142192 Expressed in 242 organ(s), highest expression level in frontal cortex

ExpressionAtlas, Differential and Baseline Expression

P05067 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

P05067 HS

Organism-specific databases

Human Protein Atlas


<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Binds, via its C-terminus, to the PID domain of several cytoplasmic proteins, including APBB family members, the APBA family, MAPK8IP1, SHC1 and, NUMB and DAB1 (By similarity). Binding to DAB1 inhibits its serine phosphorylation (By similarity). Interacts (via NPXY motif) with DAB2 (via PID domain); the interaction is impaired by tyrosine phosphorylation of the NPXY motif. Also interacts with GPCR-like protein BPP, APPBP1, IB1, KNS2 (via its TPR domains), APPBP2 (via BaSS) and DDB1. In vitro, it binds MAPT via the MT-binding domains (By similarity). Associates with microtubules in the presence of ATP and in a kinesin-dependent manner (By similarity). Interacts, through a C-terminal domain, with GNAO1. Amyloid-beta protein 42 binds CHRNA7 in hippocampal neurons. Amyloid-beta associates with HADH2. Soluble APP binds, via its N-terminal head, to FBLN1. Interacts with CPEB1 and AGER (By similarity). Interacts with ANKS1B and TNFRSF21. Interacts with ITM2B. Interacts with ITM2C. Interacts with IDE. Can form homodimers; dimerization is enhanced in the presence of Cu2+ ions (PubMed:25122912). Can form homodimers; this is promoted by heparin binding. Amyloid-beta protein 40 interacts with S100A9. CTF-alpha product of APP interacts with GSAP. Interacts with SORL1. Interacts with PLD3. Interacts with VDAC1 (PubMed:25168729). Interacts with NSG1; could regulate APP processing (By similarity). Amyloid-beta protein 42 interacts with FPR2 (PubMed:11689470).By similarity33 Publications

<p>This subsection of the '<a href="">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Q306T33EBI-77613,EBI-8294101From Streptomyces sp. KK565.
AGRNP316963EBI-2431589,EBI-457650From Gallus gallus.
CALRP152533EBI-77613,EBI-9005200From Oryctolagus cuniculus.
CALRQ8K3H72EBI-3894543,EBI-9005068From Cricetulus griseus.
Lilrb3P974848EBI-821758,EBI-15728641From Mus musculus.
NgfrP071742EBI-2431589,EBI-1038810From Rattus norvegicus.
Slc5a7Q8BGY92EBI-77613,EBI-2010752From Mus musculus.

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

106848, 2117 interactors

ComplexPortal: manually curated resource of macromolecular complexes

CPX-1062 Amyloid-beta protein 40/42 complex
CPX-1069 Amyloid-beta protein 40 complex
CPX-1070 Amyloid-beta protein 42 complex
CPX-1120 Amyloid-beta protein 40/42 oligomeric complex
CPX-1134 Amyloid-beta protein 42 oligomeric complex
CPX-1180 Amyloid-beta protein 40 oligomeric complex

CORUM comprehensive resource of mammalian protein complexes


Database of interacting proteins


The Eukaryotic Linear Motif resource for Functional Sites in Proteins


Protein interaction database and analysis system

P05067, 175 interactors

Molecular INTeraction database


STRING: functional protein association networks


Chemistry databases

BindingDB database of measured binding affinities


<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details