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Entry version 163 (07 Oct 2020)
Sequence version 1 (01 Feb 1997)
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Protein

Amyloid-beta A4 protein

Gene

APP

Organism
Saimiri sciureus (Common squirrel monkey)
Status
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 transcript 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. Involved in cell mobility and transcription regulation through protein-protein interactions (By similarity). Can promote transcription activation through binding to APBB1-KAT5 and inhibit Notch signaling through interaction with Numb (By similarity). Couples to apoptosis-inducing pathways such as those mediated by G(O) and JIP (By similarity). 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 (By similarity). May be involved in copper homeostasis/oxidative stress through copper ion reduction (By similarity). In vitro, copper-metallated APP induces neuronal death directly or is potentiated through Cu2+-mediated low-density lipoprotein oxidation (By similarity). Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and 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 similarity).By similarity
Amyloid-beta peptides are lipophilic metal chelators with metal-reducing activity. Binds transient metals such as copper, zinc and iron (By similarity).By similarity
The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.By similarity
N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6).By similarity

Miscellaneous

Chelation of metal ions, notably copper, iron and zinc, can induce histidine-bridging between amyloid-beta molecules resulting in amyloid-beta-metal aggregates. Extracellular zinc-binding increases binding of heparin to APP and inhibits collagen-binding.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> 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 annotation1
Metal bindingi151Copper 1PROSITE-ProRule annotation1
Metal bindingi168Copper 1PROSITE-ProRule annotation1
<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 bindingi658Copper or zinc 2By similarity1
Metal bindingi662Copper or zinc 2By similarity1
Metal bindingi665Copper or zinc 2By similarity1
Metal bindingi666Copper or zinc 2By similarity1
Sitei685Implicated in free radical propagationBy similarity1
Sitei687Susceptible to oxidationBy similarity1

<p>The <a href="http://www.geneontology.org/">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="http://www.uniprot.org/keywords">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

Protein family/group databases

MEROPS protease database

More...
MEROPSi
I02.015

<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="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">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 A4 protein
Alternative name(s):
ABPP
Short name:
APP
Alzheimer disease amyloid A4 protein homolog
Amyloid precursor proteinCurated
Amyloid-beta precursor proteinCurated
Cleaved into the following 14 chains:
Soluble APP-alpha
Short name:
S-APP-alpha
Soluble APP-beta
Short name:
S-APP-beta
Alternative name(s):
Beta-secretase C-terminal fragment
Short name:
Beta-CTF
Amyloid-beta protein 42
Short name:
Abeta42
Alternative name(s):
Beta-APP42
Amyloid-beta protein 40
Short name:
Abeta40
Alternative name(s):
Beta-APP40
Alternative name(s):
Alpha-secretase C-terminal fragment
Short name:
Alpha-CTF
Alternative name(s):
Gamma-CTF(59)
Alternative name(s):
Gamma-CTF(57)
Alternative name(s):
Gamma-CTF(50)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">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
Name:APP
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">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>OrganismiSaimiri sciureus (Common squirrel monkey)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">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 identifieri9521 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniPlatyrrhiniCebidaeSaimiriinaeSaimiri

<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 & Seán O’Donoghue; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'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 – 682ExtracellularCuratedAdd BLAST665
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'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>Transmembranei683 – 703HelicalBy similarityAdd BLAST21
Topological domaini704 – 751CytoplasmicCuratedAdd BLAST48

Keywords - Cellular componenti

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

<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 – 17By similarityAdd BLAST17
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_000000017218 – 751Amyloid-beta A4 proteinAdd BLAST734
ChainiPRO_000000017318 – 668Soluble APP-alphaSequence analysisAdd BLAST651
ChainiPRO_000000017418 – 652Soluble APP-betaSequence analysisAdd BLAST635
ChainiPRO_000038197218 – 286N-APPBy similarityAdd BLAST269
ChainiPRO_0000000175653 – 751C99Sequence analysisAdd BLAST99
ChainiPRO_0000000176653 – 694Amyloid-beta protein 42Sequence analysisAdd BLAST42
ChainiPRO_0000000177653 – 692Amyloid-beta protein 40Sequence analysisAdd BLAST40
ChainiPRO_0000000178669 – 751C83Sequence analysisAdd 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_0000000179669 – 694P3(42)Sequence analysisAdd BLAST26
PeptideiPRO_0000000180669 – 692P3(40)Sequence analysisAdd BLAST24
ChainiPRO_0000384580672 – 751C80Add BLAST80
ChainiPRO_0000000181693 – 751Gamma-secretase C-terminal fragment 59Sequence analysisAdd BLAST59
ChainiPRO_0000000182695 – 751Gamma-secretase C-terminal fragment 57Sequence analysisAdd BLAST57
ChainiPRO_0000000183702 – 751Gamma-secretase C-terminal fragment 50Sequence analysisAdd BLAST50
ChainiPRO_0000000184721 – 751C31Sequence analysisAdd 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 annotation
Disulfide bondi73 ↔ 117PROSITE-ProRule annotation
Disulfide bondi98 ↔ 105PROSITE-ProRule annotation
Disulfide bondi133 ↔ 187PROSITE-ProRule annotation
Disulfide bondi144 ↔ 174PROSITE-ProRule annotation
Disulfide bondi158 ↔ 186PROSITE-ProRule annotation
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei198Phosphoserine; by CK1 and CK2By similarity1
Modified residuei206Phosphoserine; by CK1 and CK2By similarity1
Modified residuei217SulfotyrosineSequence analysis1
Modified residuei262SulfotyrosineSequence analysis1
Disulfide bondi291 ↔ 341PROSITE-ProRule annotation
Disulfide bondi300 ↔ 324PROSITE-ProRule annotation
Disulfide bondi316 ↔ 337PROSITE-ProRule annotation
Modified residuei336SulfotyrosineSequence analysis1
Modified residuei422PhosphoserineBy similarity1
Modified residuei478PhosphotyrosineBy similarity1
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">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>Glycosylationi523N-linked (GlcNAc...) asparagineCurated1
Glycosylationi552N-linked (GlcNAc...) asparagineCurated1
Modified residuei710PhosphothreonineBy similarity1
Modified residuei711Phosphoserine; by APP-kinase IBy similarity1
Modified residuei724Phosphothreonine; by CDK5 and MAPK10By similarity1
Modified residuei738Phosphotyrosine; by ABL1By similarity1
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">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="http://www.uniprot.org/manual/disulfid">'Disulfide bond'</a> subsection.<p><a href='/help/crosslnk' target='_top'>More...</a></p>Cross-linki744Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">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). PSEN1 cleavage is more efficient with C83 than with C99 as substrate (in vitro).By similarity
Proteolytically cleaved by caspases during neuronal apoptosis. Cleavage at Asp-720 by either caspase-3, -8 or -9 results in the production of the neurotoxic C31 peptide and the increased production of amyloid-beta peptides.By similarity
N- and O-glycosylated.By similarity
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-724 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-724 phosphorylated form causes a conformational change which reduces binding of Fe65 family members. In dopaminergic (DA) neurons, phosphorylation on Thr-724 by LRKK2 promotes the production and the nuclear translocation of the APP intracellular domain (AICD) which induces DA neuron apoptosis. Phosphorylation on Tyr-738 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.By similarity
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).By similarity
Amyloid-beta peptides are degraded by IDE.By similarity
Sulfated on tyrosine residues.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei197 – 198Cleavage; by caspasesBy similarity2
Sitei219 – 220Cleavage; by caspasesBy similarity2
Sitei652 – 653Cleavage; by beta-secretaseBy similarity2
Sitei668 – 669Cleavage; by alpha-secretaseBy similarity2
Sitei671 – 672Cleavage; by theta-secretaseBy similarity2
Sitei692 – 693Cleavage; by gamma-secretase; site 1By similarity2
Sitei694 – 695Cleavage; by gamma-secretase; site 2By similarity2
Sitei701 – 702Cleavage; by gamma-secretase; site 3By similarity2
Sitei720 – 721Cleavage; by a caspaseBy similarity2

Keywords - PTMi

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

<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="http://www.uniprot.org/help/interaction%5Fsection">'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="http://www.uniprot.org/help/function%5Fsection">'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 (By similarity). Amyloid-beta associates with HADH2 (By similarity).

Interacts with CPEB1, ANKS1B, TNFRSF21 and AGER (By similarity).

Interacts with ITM2B.

Interacts with ITM2C.

Interacts with IDE. Can form homodimers; dimerization is enhanced in the presence of Cu2+ ions. Can form homodimers; this is promoted by heparin binding (By similarity). Amyloid-beta protein 40 interacts with S100A9 (By similarity). CTF-alpha product of APP interacts with GSAP (By similarity). Isoform APP695 interacts with SORL1 (via N-terminal ectodomain); this interaction retains APP in the trans-Golgi network and reduces processing into soluble APP-alpha and amyloid-beta peptides (By similarity). Isoform APP770 interacts with SORL1 (By similarity). The C99 fragment also interacts with SORL1 (By similarity).

Interacts with PLD3 (By similarity).

Interacts with VDAC1 (By similarity).

Interacts with NSG1; could regulate APP processing (By similarity). Amyloid-beta protein 42 interacts with FPR2 (By similarity).

Interacts (via transmembrane region) with PSEN1; the interaction is direct (By similarity).

Interacts with LRRK2 (By similarity).

Interacts (via cytoplasmic domain) with KIF5B (By similarity).

By similarity

Protein-protein interaction databases

Molecular INTeraction database

More...
MINTi
Q95241

<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

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...
SMRi
Q95241

Database of comparative protein structure models

More...
ModBasei
Search...

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family%5Fand%5Fdomains%5Fsection">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini28 – 189E1PROSITE-ProRule annotationAdd BLAST162
Domaini291 – 341BPTI/Kunitz inhibitorPROSITE-ProRule annotationAdd BLAST51
Domaini355 – 546E2PROSITE-ProRule annotationAdd BLAST192

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni28 – 123GFLD subdomainPROSITE-ProRule annotationAdd BLAST96
Regioni96 – 110Heparin-bindingBy similarityAdd BLAST15
Regioni131 – 189CuBD subdomainPROSITE-ProRule annotationAdd BLAST59
Regioni181 – 188Zinc-bindingBy similarity8
Regioni316 – 344Heparin-bindingBy similarityAdd BLAST29
Regioni363 – 428Heparin-bindingBy similarityAdd BLAST66
Regioni504 – 521Collagen-bindingBy similarityAdd BLAST18
Regioni676 – 703Interaction with PSEN1By similarityAdd BLAST28
Regioni713 – 732Interaction with G(o)-alphaBy similarityAdd BLAST20
Regioni737 – 751Required for the interaction with KIF5B and for anterograde transport in axonsBy similarityAdd BLAST15

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi344 – 346OX-2By similarity3
Motifi705 – 715Basolateral sorting signalBy similarityAdd BLAST11
Motifi738 – 743YENPXY motif; contains endocytosis signalBy similarity6

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes the position of regions of compositional bias within the protein and the particular amino acids that are over-represented within those regions.<p><a href='/help/compbias' target='_top'>More...</a></p>Compositional biasi230 – 260Asp/Glu-rich (acidic)Add BLAST31
Compositional biasi274 – 280Poly-Thr7

<p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

The transmembrane helix undergoes a conformation change and unravels partially when bound to PSEN1, facilitating cleavage by PSEN1.By similarity
The basolateral sorting signal (BaSS) is required for sorting of membrane proteins to the basolateral surface of epithelial cells.By similarity
The GFLD subdomain binds Cu2+ ions; this promotes homodimerization.By similarity
The NPXY sequence motif found in many tyrosine-phosphorylated proteins is required for the specific binding of the PID domain. However, additional amino acids either N- or C-terminal to the NPXY motif are often required for complete interaction. The PID domain-containing proteins which bind APP require the YENPTY motif for full interaction. These interactions are independent of phosphorylation on the terminal tyrosine residue. The YENPXY site is also involved in clathrin-mediated endocytosis.By similarity
The C-terminal region can bind zinc ions; this favors dimerization and formation of higher oligomers.By similarity
The OX-2 motif shows some similarity to a region in the N-terminus of CD200/MOX2.By similarity

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the APP family.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Family and domain databases

Conserved Domains Database

More...
CDDi
cd00109, KU, 1 hit

Gene3D Structural and Functional Annotation of Protein Families

More...
Gene3Di
1.20.120.770, 1 hit
2.30.29.30, 1 hit
3.30.1490.140, 1 hit
3.90.570.10, 1 hit
4.10.230.10, 1 hit
4.10.410.10, 1 hit

Integrated resource of protein families, domains and functional sites

More...
InterProi
View protein in InterPro
IPR036669, Amyloid_Cu-bd_sf
IPR008155, Amyloid_glyco
IPR013803, Amyloid_glyco_Abeta
IPR037071, Amyloid_glyco_Abeta_sf
IPR011178, Amyloid_glyco_Cu-bd
IPR024329, Amyloid_glyco_E2_domain
IPR008154, Amyloid_glyco_extra
IPR015849, Amyloid_glyco_heparin-bd
IPR036454, Amyloid_glyco_heparin-bd_sf
IPR019745, Amyloid_glyco_intracell_CS
IPR028866, APP
IPR019543, APP_amyloid_C
IPR019744, APP_CUBD_CS
IPR036176, E2_sf
IPR002223, Kunitz_BPTI
IPR036880, Kunitz_BPTI_sf
IPR011993, PH-like_dom_sf
IPR020901, Prtase_inh_Kunz-CS

The PANTHER Classification System

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PANTHERi
PTHR23103, PTHR23103, 1 hit
PTHR23103:SF7, PTHR23103:SF7, 1 hit

Pfam protein domain database

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Pfami
View protein in Pfam
PF10515, APP_amyloid, 1 hit
PF12924, APP_Cu_bd, 1 hit
PF12925, APP_E2, 1 hit
PF02177, APP_N, 1 hit
PF03494, Beta-APP, 1 hit
PF00014, Kunitz_BPTI, 1 hit

Protein Motif fingerprint database; a protein domain database

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PRINTSi
PR00203, AMYLOIDA4
PR00759, BASICPTASE
PR00204, BETAAMYLOID

Simple Modular Architecture Research Tool; a protein domain database

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SMARTi
View protein in SMART
SM00006, A4_EXTRA, 1 hit
SM00131, KU, 1 hit

Superfamily database of structural and functional annotation

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SUPFAMi
SSF109843, SSF109843, 1 hit
SSF56491, SSF56491, 1 hit
SSF57362, SSF57362, 1 hit
SSF89811, SSF89811, 1 hit

PROSITE; a protein domain and family database

More...
PROSITEi
View protein in PROSITE
PS00319, APP_CUBD, 1 hit
PS51869, APP_E1, 1 hit
PS51870, APP_E2, 1 hit
PS00320, APP_INTRA, 1 hit
PS00280, BPTI_KUNITZ_1, 1 hit
PS50279, BPTI_KUNITZ_2, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 <p>This subsection of the 'Sequence' section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform. This section is only present in reviewed entries, i.e. in UniProtKB/Swiss-Prot.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket
Note: Additional isoforms seem to exist.
Isoform APP770 (identifier: Q95241-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MLPGLALLLL AAWTARALEV PTDGNAGLLA EPQIAMFCGR LNMHMNVQNG
60 70 80 90 100
KWDSDPSGTK TCIDTKEGIL QYCQEVYPEL QITNVVEANQ PVTIQNWCKR
110 120 130 140 150
DRKQCKTHPH IVIPYRCLVG EFVSDALLVP DKCKFLHQER MDVCETHLHW
160 170 180 190 200
HTVAKETCSE KSTNLHDYGM LLPCGIDKFR GVEFVCCPLA EESDHVDSAD
210 220 230 240 250
AEEDDSDVWW GGADTDYADG SEDKVVEVAE EEEVAEVEEE EADDDEDDED
260 270 280 290 300
GDEVEEEAEE PYEEATERTT SIATTTTTTT ESVEEVVREV CSEQAETGPC
310 320 330 340 350
RAMISRWYFD VTEGKCAPFF YGGCGGNRNN FDTEEYCMAV CGSVIPTTAA
360 370 380 390 400
STPDAVDKYL ETPGDENEHA HFQKAKERLE AKHRERMSQV MREWEEAERQ
410 420 430 440 450
AKNLPKADKK AVIQHFQEKV ESLEQEAANE RQQLVETHMA RVEAMLNDRR
460 470 480 490 500
RLALENYITA LQAVPPRPRH VFNMLKKYVR AEQKDRQHTL KHFEHVRMVD
510 520 530 540 550
PKKAAQIRSQ VMTHLRVIYE RMNQSLSLLY NVPAVAEEIQ DEVDELLQKE
560 570 580 590 600
QNYSDDVLAN MISEPRISYG NDALMPSLTE TKTTVELLPV NGEFSLDDLQ
610 620 630 640 650
PWHSFGADSV PANTENEVEP VDARPAADRG LTTRPGSGLT NIKTEEISEV
660 670 680 690 700
KMDAEFRHDS GYEVHHQKLV FFAEDVGSNK GAIIGLMVGG VVIATVIVIT
710 720 730 740 750
LVMLKKKQYT SIHHGVVEVD AAVTPEERHL SKMQQNGYEN PTYKFFEQMQ

N
Length:751
Mass (Da):84,894
Last modified:February 1, 1997 - v1
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i6C3E431089569049
GO
Isoform APP695 (identifier: Q95241-2)
Sequence is not available
Length:
Mass (Da):

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...
EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
S81024 mRNA Translation: AAD14347.1

Keywords - Coding sequence diversityi

Alternative splicing

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S81024 mRNA Translation: AAD14347.1

3D structure databases

SMRiQ95241
ModBaseiSearch...

Protein-protein interaction databases

MINTiQ95241

Protein family/group databases

MEROPSiI02.015

Family and domain databases

CDDicd00109, KU, 1 hit
Gene3Di1.20.120.770, 1 hit
2.30.29.30, 1 hit
3.30.1490.140, 1 hit
3.90.570.10, 1 hit
4.10.230.10, 1 hit
4.10.410.10, 1 hit
InterProiView protein in InterPro
IPR036669, Amyloid_Cu-bd_sf
IPR008155, Amyloid_glyco
IPR013803, Amyloid_glyco_Abeta
IPR037071, Amyloid_glyco_Abeta_sf
IPR011178, Amyloid_glyco_Cu-bd
IPR024329, Amyloid_glyco_E2_domain
IPR008154, Amyloid_glyco_extra
IPR015849, Amyloid_glyco_heparin-bd
IPR036454, Amyloid_glyco_heparin-bd_sf
IPR019745, Amyloid_glyco_intracell_CS
IPR028866, APP
IPR019543, APP_amyloid_C
IPR019744, APP_CUBD_CS
IPR036176, E2_sf
IPR002223, Kunitz_BPTI
IPR036880, Kunitz_BPTI_sf
IPR011993, PH-like_dom_sf
IPR020901, Prtase_inh_Kunz-CS
PANTHERiPTHR23103, PTHR23103, 1 hit
PTHR23103:SF7, PTHR23103:SF7, 1 hit
PfamiView protein in Pfam
PF10515, APP_amyloid, 1 hit
PF12924, APP_Cu_bd, 1 hit
PF12925, APP_E2, 1 hit
PF02177, APP_N, 1 hit
PF03494, Beta-APP, 1 hit
PF00014, Kunitz_BPTI, 1 hit
PRINTSiPR00203, AMYLOIDA4
PR00759, BASICPTASE
PR00204, BETAAMYLOID
SMARTiView protein in SMART
SM00006, A4_EXTRA, 1 hit
SM00131, KU, 1 hit
SUPFAMiSSF109843, SSF109843, 1 hit
SSF56491, SSF56491, 1 hit
SSF57362, SSF57362, 1 hit
SSF89811, SSF89811, 1 hit
PROSITEiView protein in PROSITE
PS00319, APP_CUBD, 1 hit
PS51869, APP_E1, 1 hit
PS51870, APP_E2, 1 hit
PS00320, APP_INTRA, 1 hit
PS00280, BPTI_KUNITZ_1, 1 hit
PS50279, BPTI_KUNITZ_2, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

MobiDB: a database of protein disorder and mobility annotations

More...
MobiDBi
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiA4_SAISC
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: Q95241
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: February 1, 1997
Last modified: October 7, 2020
This is version 163 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Documents

  1. SIMILARITY comments
    Index of protein domains and families
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