Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Entry version 223 (08 May 2019)
Sequence version 2 (01 Dec 1992)
Previous versions | rss
Other tutorials and videosHelp videoFeedback
Protein

Amyloid-beta A4 protein

Gene

App

Organism
Rattus norvegicus (Rat)
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 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. 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. Inhibits G(o) alpha ATPase activity. Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1 (By similarity). May be involved in copper homeostasis/oxidative stress through copper ion reduction. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV (By similarity). 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 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. Rat and mouse amyloid-beta peptides bind only weakly transient metals and have little reducing activity due to substitutions of transient metal chelating residues. Amyloid-beta protein 42 may activate mononuclear phagocytes in the brain and elicits inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Also binds GPC1 in lipid rafts (By similarity).By similarity
Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain.
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. Rat and mouse amyloid-beta peptides have an arginine residue substituted for the bridging histidine residue and are thus less capable of forming amyloid aggregates. Extracellular zinc-binding increases binding of heparin to APP and inhibits collagen-binding (By similarity).By similarityCurated

Sites

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 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 bondBy similarity2
Metal bindingi677Copper or zinc 2By similarity1
Metal bindingi685Copper or zinc 2By similarity1
Sitei706Susceptible 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

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-RNO-114608 Platelet degranulation
R-RNO-3000178 ECM proteoglycans
R-RNO-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-RNO-416476 G alpha (q) signalling events
R-RNO-418594 G alpha (i) signalling events
R-RNO-432720 Lysosome Vesicle Biogenesis
R-RNO-444473 Formyl peptide receptors bind formyl peptides and many other ligands
R-RNO-445989 TAK1 activates NFkB by phosphorylation and activation of IKKs complex
R-RNO-879415 Advanced glycosylation endproduct receptor signaling
R-RNO-8957275 Post-translational protein phosphorylation
R-RNO-933542 TRAF6 mediated NF-kB activation
R-RNO-9609523 Insertion of tail-anchored proteins into the endoplasmic reticulum membrane

Protein family/group databases

MEROPS protease database

More...
MEROPSi
I02.015

Transport Classification Database

More...
TCDBi
1.C.50.1.1 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="http://www.uniprot.org/help/names_and_taxonomy_section">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
Amyloidogenic glycoprotein
Short name:
AG
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_and_taxonomy_section">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_and_taxonomy_section">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>OrganismiRattus norvegicus (Rat)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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 identifieri10116 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">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
  • UP000002494 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">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 11

Organism-specific databases

Rat genome database

More...
RGDi
2139 App

<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_location_section">'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="http://www.uniprot.org/help/subcellular_location_section">'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 – 722HelicalBy similarityAdd 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

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'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>Mutagenesisi656S → A: No chondroitin sulfate linkage to isoform L-APP733. 1 Publication1
Mutagenesisi704G → V: Little oxidized neuronal proteins. Scarce amyloid-beta protein 42 aggregation. No neurotoxicity. 1 Publication1
Mutagenesisi732 – 733HH → GL or GP: Almost complete loss of binding to GNAO1. No inhibition of GTPase activity. 1 Publication2
Mutagenesisi743T → A: No effect on neurite growth and maturation. 1 Publication1
Mutagenesisi743T → E: Inhibits neurite growth and maturation. 1 Publication1
Mutagenesisi757Y → G: No DBB1 binding. 1 Publication1
Mutagenesisi759N → A: Some DBB1 binding. 1 Publication1
Mutagenesisi762Y → A: Some DBB1 binding. 1 Publication1
Mutagenesisi763K → R: Loss of ubiquitination. 1 Publication1

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...
ChEMBLi
CHEMBL3638365

<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.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_000000015918 – 770Amyloid-beta A4 proteinAdd BLAST753
ChainiPRO_000000016018 – 687Soluble APP-alphaBy similarityAdd BLAST670
ChainiPRO_000000016118 – 671Soluble APP-betaSequence analysisAdd BLAST654
ChainiPRO_000038197118 – 286N-APPBy similarityAdd BLAST269
ChainiPRO_0000000162672 – 770C99Sequence analysisAdd BLAST99
ChainiPRO_0000000163672 – 713Amyloid-beta protein 42By similarityAdd BLAST42
ChainiPRO_0000000164672 – 711Amyloid-beta protein 40By similarityAdd BLAST40
ChainiPRO_0000000165688 – 770C83By similarityAdd 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_0000000166688 – 713P3(42)By similarityAdd BLAST26
PeptideiPRO_0000000167688 – 711P3(40)By similarityAdd BLAST24
ChainiPRO_0000384579691 – 770C80Add BLAST80
ChainiPRO_0000000168712 – 770Gamma-secretase C-terminal fragment 59Add BLAST59
ChainiPRO_0000000169714 – 770Gamma-secretase C-terminal fragment 57Add BLAST57
ChainiPRO_0000000170721 – 770Gamma-secretase C-terminal fragment 50Add BLAST50
ChainiPRO_0000000171740 – 770C31By similarityAdd 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 CK2By similarity1
Modified residuei206Phosphoserine; by CK1By similarity1
Disulfide bondi291 ↔ 341PROSITE-ProRule annotation
Disulfide bondi300 ↔ 324PROSITE-ProRule annotation
Disulfide bondi316 ↔ 337PROSITE-ProRule annotation
Modified residuei441PhosphoserineCombined sources1
Modified residuei497PhosphotyrosineBy similarity1
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">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...) asparagineSequence analysis1
Glycosylationi571N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi656O-linked (Xyl...) (chondroitin sulfate) serine; in L-APP isoforms1
Modified residuei729Phosphothreonine1 Publication1
Modified residuei730Phosphoserine; by APP-kinase I2 Publications1
Modified residuei743Phosphothreonine; by CDK5 and MAPK102 Publications1
Modified residuei757Phosphotyrosine; by ABL1By similarity1
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">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-linki763Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">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-739 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-glycosylated.By similarity
O-glycosylated. O-linkage of chondroitin sulfate to the L-APP isoforms produces the APP proteoglycan core proteins, the appicans. The chondroitin sulfate chain of appicans contains 4-O-sulfated galactose in the linkage region and chondroitin sulfate E in the repeated disaccharide region.1 Publication
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. 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.4 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.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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei197 – 198Cleavage; by caspasesBy similarity2
Sitei219 – 220Cleavage; by caspasesBy similarity2
Sitei671 – 672Cleavage; by beta-secretaseBy similarity2
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 2By similarity2
Sitei720 – 721Cleavage; by gamma-secretase; site 3By similarity2
Sitei739 – 740Cleavage; by a caspaseBy similarity2

Keywords - PTMi

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

Proteomic databases

jPOST - Japan Proteome Standard Repository/Database

More...
jPOSTi
P08592

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

More...
PaxDbi
P08592

PRoteomics IDEntifications database

More...
PRIDEi
P08592

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...
iPTMneti
P08592

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

More...
PhosphoSitePlusi
P08592

<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="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

In the brain, non-L-APP isoforms are expressed in neurons, isoform APP695 being the predominant form. In astrocytes and microglial cells, almost 50% is L-isoform (appican).2 Publications

<p>This subsection of the ‘Expression’ section provides information on the expression of the gene product at various stages of a cell, tissue or organism development. By default, the information is derived from experiments at the mRNA level, unless specified ‘at the protein level’.<p><a href='/help/developmental_stage' target='_top'>More...</a></p>Developmental stagei

From 6 days to 7 months, levels of KPI-containing isoforms increase in the brain cortex and hippocampus. Levels of L-APP increase in all brain regions during the same period, but levels are low compared to non-L-APP isoforms.

<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

Phosphorylation of mature, glycosylated APP occurs 48-72 hours after treatment of neuronal cells with nerve growth factor which correlates with the timing of neurite outgrowth.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...
Bgeei
ENSRNOG00000006997 Expressed in 10 organ(s), highest expression level in brain

ExpressionAtlas, Differential and Baseline Expression

More...
ExpressionAtlasi
P08592 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...
Genevisiblei
P08592 RN

<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_section">'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_section">'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). 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 with SYT7 (By similarity). Interacts (via transmembrane region) with PSEN1; the interaction is direct (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

More...
BioGridi
248450, 3 interactors

ComplexPortal: manually curated resource of macromolecular complexes

More...
ComplexPortali
CPX-1108 Amyloid-beta protein 40/42 complex
CPX-1109 Amyloid-beta protein 40 complex
CPX-1110 Amyloid-beta protein 42 complex
CPX-1182 Amyloid-beta protein 40 oligomeric complex
CPX-1183 Amyloid-beta protein 42 oligomeric complex
CPX-1184 Amyloid-beta protein 40/42 oligomeric complex

Database of interacting proteins

More...
DIPi
DIP-618N

The Eukaryotic Linear Motif resource for Functional Sites in Proteins

More...
ELMi
P08592

Protein interaction database and analysis system

More...
IntActi
P08592, 9 interactors

STRING: functional protein association networks

More...
STRINGi
10116.ENSRNOP00000041613

Chemistry databases

BindingDB database of measured binding affinities

More...
BindingDBi
P08592

<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

1770
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...
PDBei

Protein Data Bank RCSB

More...
RCSB PDBi

Protein Data Bank Japan

More...
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1M7EX-ray2.45D/E/F755-763[»]
1NMJNMR-A672-699[»]
1OQNX-ray2.30C/D755-763[»]
2LI9NMR-A/B672-687[»]

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

More...
SMRi
P08592

Database of comparative protein structure models

More...
ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

More...
MobiDBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

More...
EvolutionaryTracei
P08592

<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_and_domains_section">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
Domaini374 – 565E2PROSITE-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
Regioni135 – 155Copper-bindingBy similarityAdd BLAST21
Regioni181 – 188Zinc-bindingBy similarity8
Regioni391 – 423Heparin-bindingBy similarityAdd BLAST33
Regioni491 – 522Heparin-bindingBy similarityAdd BLAST32
Regioni523 – 540Collagen-bindingBy similarityAdd BLAST18
Regioni695 – 722Interaction with PSEN1By similarityAdd BLAST28
Regioni732 – 751Interaction with G(o)-alphaAdd BLAST20

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>Motifi724 – 734Basolateral sorting signalBy similarityAdd BLAST11
Motifi757 – 762YENPXY 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

<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

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...
eggNOGi
KOG3540 Eukaryota
ENOG410ZTKC LUCA

Ensembl GeneTree

More...
GeneTreei
ENSGT00530000063252

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...
HOGENOMi
HOG000232190

InParanoid: Eukaryotic Ortholog Groups

More...
InParanoidi
P08592

KEGG Orthology (KO)

More...
KOi
K04520

Identification of Orthologs from Complete Genome Data

More...
OMAi
KQCKTHA

Database of Orthologous Groups

More...
OrthoDBi
953529at2759

Database for complete collections of gene phylogenies

More...
PhylomeDBi
P08592

TreeFam database of animal gene trees

More...
TreeFami
TF317274

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

More...
PANTHERi
PTHR23103 PTHR23103, 1 hit
PTHR23103:SF7 PTHR23103:SF7, 1 hit

Pfam protein domain database

More...
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

More...
PRINTSi
PR00203 AMYLOIDA4
PR00759 BASICPTASE
PR00204 BETAAMYLOID

Simple Modular Architecture Research Tool; a protein domain database

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

Superfamily database of structural and functional annotation

More...
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_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (8+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">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_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">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 8 <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.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 8 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform APP770 (identifier: P08592-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' 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
MLPSLALLLL AAWTVRALEV PTDGNAGLLA EPQIAMFCGK LNMHMNVQNG
60 70 80 90 100
KWESDPSGTK TCIGTKEGIL QYCQEVYPEL QITNVVEANQ PVTIQNWCKR
110 120 130 140 150
GRKQCKTHTH IVIPYRCLVG EFVSDALLVP DKCKFLHQER MDVCETHLHW
160 170 180 190 200
HTVAKETCSE KSTNLHDYGM LLPCGIDKFR GVEFVCCPLA EESDSIDSAD
210 220 230 240 250
AEEDDSDVWW GGADTDYADG GEDKVVEVAE EEEVADVEEE EAEDDEDVED
260 270 280 290 300
GDEVEEEAEE PYEEATERTT SIATTTTTTT ESVEEVVREV CSEQAETGPC
310 320 330 340 350
RAMISRWYFD VTEGKCAPFF YGGCGGNRNN FDTEEYCMAV CGSVSSQSLL
360 370 380 390 400
KTTSEPLPQD PVKLPTTAAS TPDAVDKYLE TPGDENEHAH FQKAKERLEA
410 420 430 440 450
KHRERMSQVM REWEEAERQA KNLPKADKKA VIQHFQEKVE SLEQEAANER
460 470 480 490 500
QQLVETHMAR VEAMLNDRRR LALENYITAL QAVPPRPHHV FNMLKKYVRA
510 520 530 540 550
EQKDRQHTLK HFEHVRMVDP KKAAQIRSQV MTHLRVIYER MNQSLSLLYN
560 570 580 590 600
VPAVAEEIQD EVDELLQKEQ NYSDDVLANM ISEPRISYGN DALMPSLTET
610 620 630 640 650
KTTVELLPVN GEFSLDDLQP WHPFGVDSVP ANTENEVEPV DARPAADRGL
660 670 680 690 700
TTRPGSGLTN IKTEEISEVK MDAEFGHDSG FEVRHQKLVF FAEDVGSNKG
710 720 730 740 750
AIIGLMVGGV VIATVIVITL VMLKKKQYTS IHHGVVEVDA AVTPEERHLS
760 770
KMQQNGYENP TYKFFEQMQN
Length:770
Mass (Da):86,704
Last modified:December 1, 1992 - v2
<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:iC26C9D6BB2D929A7
GO
Isoform APP695 (identifier: P08592-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     289-289: E → V
     290-364: Missing.

Show »
Length:695
Mass (Da):78,483
Checksum:i61D21E1E941972DC
GO
Isoform L-APP677 (identifier: P08592-3)
Sequence is not available
Note: L-isoforms are referred to as appicans.
Length:
Mass (Da):
Isoform L-APP696 (identifier: P08592-4)
Sequence is not available
Note: L-isoforms are referred to as appicans.
Length:
Mass (Da):
Isoform APP714 (identifier: P08592-5)
Sequence is not available
Length:
Mass (Da):
Isoform L-APP733 (identifier: P08592-6)
Sequence is not available
Note: L-isoforms are referred to as appicans.
Length:
Mass (Da):
Isoform APP751 (identifier: P08592-7)
Sequence is not available
Length:
Mass (Da):
Isoform L-APP752 (identifier: P08592-8)
Sequence is not available
Note: L-isoforms are referred to as appicans.
Length:
Mass (Da):

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q6P6Q5Q6P6Q5_RAT
Amyloid-beta A4 protein
App
733Annotation score:

Annotation score:2 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>

<p>This subsection of the ‘Sequence’ section reports information derived from mass spectrometry experiments done on the entire protein or on biologically active derived peptide(s).<p><a href='/help/mass_spectrometry' target='_top'>More...</a></p>Mass spectrometryi

Molecular mass is 5911.3 Da from positions 721 - 770. Determined by MALDI. 1 Publication
Molecular mass is 6024.4 Da from positions 720 - 770. Determined by MALDI. 1 Publication

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_000015289E → V in isoform APP695. 1 Publication1
Alternative sequenceiVSP_000016290 – 364Missing in isoform APP695. 1 PublicationAdd BLAST75

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...
EMBLi

GenBank nucleotide sequence database

More...
GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
X07648 mRNA Translation: CAA30488.1
AF513015 mRNA Translation: AAM90259.1
X14066 mRNA Translation: CAA32229.1

Protein sequence database of the Protein Information Resource

More...
PIRi
S00550
S03607
S23094

NCBI Reference Sequences

More...
RefSeqi
NP_062161.1, NM_019288.2 [P08592-1]
XP_006248073.1, XM_006248011.3 [P08592-2]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENSRNOT00000048854; ENSRNOP00000041613; ENSRNOG00000006997 [P08592-1]

Database of genes from NCBI RefSeq genomes

More...
GeneIDi
54226

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
rno:54226

UCSC genome browser

More...
UCSCi
RGD:2139 rat [P08592-1]

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
X07648 mRNA Translation: CAA30488.1
AF513015 mRNA Translation: AAM90259.1
X14066 mRNA Translation: CAA32229.1
PIRiS00550
S03607
S23094
RefSeqiNP_062161.1, NM_019288.2 [P08592-1]
XP_006248073.1, XM_006248011.3 [P08592-2]

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1M7EX-ray2.45D/E/F755-763[»]
1NMJNMR-A672-699[»]
1OQNX-ray2.30C/D755-763[»]
2LI9NMR-A/B672-687[»]
SMRiP08592
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi248450, 3 interactors
ComplexPortaliCPX-1108 Amyloid-beta protein 40/42 complex
CPX-1109 Amyloid-beta protein 40 complex
CPX-1110 Amyloid-beta protein 42 complex
CPX-1182 Amyloid-beta protein 40 oligomeric complex
CPX-1183 Amyloid-beta protein 42 oligomeric complex
CPX-1184 Amyloid-beta protein 40/42 oligomeric complex
DIPiDIP-618N
ELMiP08592
IntActiP08592, 9 interactors
STRINGi10116.ENSRNOP00000041613

Chemistry databases

BindingDBiP08592
ChEMBLiCHEMBL3638365

Protein family/group databases

MEROPSiI02.015
TCDBi1.C.50.1.1 the amyloid Beta-protein peptide (aBetapp) family

PTM databases

iPTMnetiP08592
PhosphoSitePlusiP08592

Proteomic databases

jPOSTiP08592
PaxDbiP08592
PRIDEiP08592

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000048854; ENSRNOP00000041613; ENSRNOG00000006997 [P08592-1]
GeneIDi54226
KEGGirno:54226
UCSCiRGD:2139 rat [P08592-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
351
RGDi2139 App

Phylogenomic databases

eggNOGiKOG3540 Eukaryota
ENOG410ZTKC LUCA
GeneTreeiENSGT00530000063252
HOGENOMiHOG000232190
InParanoidiP08592
KOiK04520
OMAiKQCKTHA
OrthoDBi953529at2759
PhylomeDBiP08592
TreeFamiTF317274

Enzyme and pathway databases

ReactomeiR-RNO-114608 Platelet degranulation
R-RNO-3000178 ECM proteoglycans
R-RNO-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-RNO-416476 G alpha (q) signalling events
R-RNO-418594 G alpha (i) signalling events
R-RNO-432720 Lysosome Vesicle Biogenesis
R-RNO-444473 Formyl peptide receptors bind formyl peptides and many other ligands
R-RNO-445989 TAK1 activates NFkB by phosphorylation and activation of IKKs complex
R-RNO-879415 Advanced glycosylation endproduct receptor signaling
R-RNO-8957275 Post-translational protein phosphorylation
R-RNO-933542 TRAF6 mediated NF-kB activation
R-RNO-9609523 Insertion of tail-anchored proteins into the endoplasmic reticulum membrane

Miscellaneous databases

EvolutionaryTraceiP08592

Protein Ontology

More...
PROi
PR:P08592

Gene expression databases

BgeeiENSRNOG00000006997 Expressed in 10 organ(s), highest expression level in brain
ExpressionAtlasiP08592 baseline and differential
GenevisibleiP08592 RN

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...

<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_RAT
<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: P08592
Secondary accession number(s): Q547B7
<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_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: December 1, 1992
Last modified: May 8, 2019
This is version 223 of the entry and version 2 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

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again