Skip Header

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

Amyloid-beta A4 protein

Gene

APP

Organism
Pan troglodytes (Chimpanzee)
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). 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 ‘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 bindingi681Copper or zinc 2By similarity1
Metal bindingi684Copper or zinc 2By similarity1
Metal bindingi685Copper or zinc 2By similarity1
Sitei704Implicated in free radical propagationBy 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_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
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>OrganismiPan troglodytes (Chimpanzee)
<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 identifieri9598 [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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaePan
<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
  • UP000002277 <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: Unplaced

<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

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 – 699ExtracellularSequence analysisAdd BLAST682
<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>Transmembranei700 – 723HelicalSequence analysisAdd BLAST24
Topological domaini724 – 770CytoplasmicSequence analysisAdd BLAST47

Keywords - Cellular componenti

Amyloid, Cell membrane, Cell projection, Coated pit, Cytoplasmic vesicle, Endosome, Membrane

<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_000000012718 – 770Amyloid-beta A4 proteinAdd BLAST753
ChainiPRO_000000012818 – 687Soluble APP-alphaSequence analysisAdd BLAST670
ChainiPRO_000000012918 – 671Soluble APP-betaSequence analysisAdd BLAST654
ChainiPRO_000038196918 – 286N-APPBy similarityAdd BLAST269
ChainiPRO_0000000130672 – 770C99Sequence analysisAdd BLAST99
ChainiPRO_0000000131672 – 713Amyloid-beta protein 42Sequence analysisAdd BLAST42
ChainiPRO_0000000132672 – 711Amyloid-beta protein 40Sequence analysisAdd BLAST40
ChainiPRO_0000000133688 – 770C83Sequence 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_0000000134688 – 713P3(42)Sequence analysisAdd BLAST26
PeptideiPRO_0000000135688 – 711P3(40)Sequence analysisAdd BLAST24
ChainiPRO_0000384577691 – 770C80Add BLAST80
ChainiPRO_0000000136712 – 770Gamma-secretase C-terminal fragment 59Sequence analysisAdd BLAST59
ChainiPRO_0000000137714 – 770Gamma-secretase C-terminal fragment 57Sequence analysisAdd BLAST57
ChainiPRO_0000000138721 – 770Gamma-secretase C-terminal fragment 50Sequence analysisAdd BLAST50
ChainiPRO_0000000139740 – 770C31Sequence 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 CK2By similarity1
Modified residuei206Phosphoserine; by CK1By similarity1
Disulfide bondi291 ↔ 341PROSITE-ProRule annotation
Disulfide bondi300 ↔ 324PROSITE-ProRule annotation
Disulfide bondi316 ↔ 337PROSITE-ProRule annotation
Modified residuei441PhosphoserineBy similarity1
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
Modified residuei729PhosphothreonineBy similarity1
Modified residuei730Phosphoserine; by APP-kinase IBy similarity1
Modified residuei743Phosphothreonine; by CDK5 and MAPK10By similarity1
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)By similarity

<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) (By similarity).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- 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 (By similarity).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
Sitei671 – 672Cleavage; by beta-secretaseBy similarity2
Sitei672 – 673Cleavage; by caspase-6By similarity2
Sitei687 – 688Cleavage; by alpha-secretaseBy similarity2
Sitei690 – 691Cleavage; by theta-secretaseBy similarity2
Sitei711 – 712Cleavage; by gamma-secretase; site 1By similarity2
Sitei713 – 714Cleavage; by gamma-secretase; site 2By similarity2
Sitei720 – 721Cleavage; by gamma-secretase; site 3By similarity2
Sitei739 – 740Cleavage; by caspase-6, caspase-8 or caspase-9By similarity2

Keywords - PTMi

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

Proteomic databases

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

More...
PaxDbi
Q5IS80

PRoteomics IDEntifications database

More...
PRIDEi
Q5IS80

<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

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...
Bgeei
ENSPTRG00000013811 Expressed in 6 organ(s), highest expression level in prefrontal cortex

<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, FPRL1, 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).By similarity

Protein-protein interaction databases

STRING: functional protein association networks

More...
STRINGi
9598.ENSPTRP00000023795

<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

Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase

More...
ProteinModelPortali
Q5IS80

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

More...
SMRi
Q5IS80

Database of comparative protein structure models

More...
ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

More...
MobiDBi
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_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
Regioni181 – 188Zinc-bindingBy similarity8
Regioni391 – 423Heparin-bindingBy similarityAdd BLAST33
Regioni491 – 522Heparin-bindingBy similarityAdd BLAST32
Regioni523 – 540Collagen-bindingBy similarityAdd BLAST18
Regioni732 – 751Interaction with G(o)-alphaBy similarityAdd 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 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

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...
HOGENOMi
HOG000232190

The HOVERGEN Database of Homologous Vertebrate Genes

More...
HOVERGENi
HBG000051

InParanoid: Eukaryotic Ortholog Groups

More...
InParanoidi
Q5IS80

KEGG Orthology (KO)

More...
KOi
K04520

Database of Orthologous Groups

More...
OrthoDBi
EOG091G0UW4

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
IPR019744 Amyloid_glyco_extracell_CS
IPR015849 Amyloid_glyco_heparin-bd
IPR036454 Amyloid_glyco_heparin-bd_sf
IPR019745 Amyloid_glyco_intracell_CS
IPR028866 APP
IPR019543 APP_amyloid_C
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>Sequencei

<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.

Q5IS80-1 [UniParc]FASTAAdd to basket
« 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
GRKQCKTHPH FVIPYRCLVG EFVSDALLVP DKCKFLHQER MDVCETHLHW
160 170 180 190 200
HTVAKETCSE KSTNLHDYGM LLPCGIDKFR GVEFVCCPLA EESDNVDSAD
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 CGSVMSQSLL
360 370 380 390 400
KTTQEPLARD PVKLPTTAAS TPDAVDKYLE TPGDENEHAH FQKAKERLEA
410 420 430 440 450
KHRERMSQVM REWEEAERQA KNLPKADKKA VIQHFQEKVE SLEQEAANER
460 470 480 490 500
QQLVETHMAR VEAMLNDRRR LALENYITAL QAVPPRPRHV 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 WHSFGADSVP ANTENEVEPV DARPAADRGL
660 670 680 690 700
TTRPGSGLTN IKTEEISEVK MDAEFRHDSG YEVHHQKLVF FAEDVGSNKG
710 720 730 740 750
AIIGLMVGGV VIATVIVITL VMLKKKQYTS IHHGVVEVDA AVTPEERHLS
760 770
KMQQNGYENP TYKFFEQMQN
Length:770
Mass (Da):86,971
Last modified:February 15, 2005 - 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:i08EBAAFE7E4930A9
GO

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
AY665248 mRNA Translation: AAV74286.1

NCBI Reference Sequences

More...
RefSeqi
NP_001013036.1, NM_001013018.1

UniGene gene-oriented nucleotide sequence clusters

More...
UniGenei
Ptr.762

Genome annotation databases

Database of genes from NCBI RefSeq genomes

More...
GeneIDi
473931

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
ptr:473931

<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
AY665248 mRNA Translation: AAV74286.1
RefSeqiNP_001013036.1, NM_001013018.1
UniGeneiPtr.762

3D structure databases

ProteinModelPortaliQ5IS80
SMRiQ5IS80
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9598.ENSPTRP00000023795

Protein family/group databases

MEROPSiI02.015

Proteomic databases

PaxDbiQ5IS80
PRIDEiQ5IS80

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi473931
KEGGiptr:473931

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
351

Phylogenomic databases

eggNOGiKOG3540 Eukaryota
ENOG410ZTKC LUCA
HOGENOMiHOG000232190
HOVERGENiHBG000051
InParanoidiQ5IS80
KOiK04520
OrthoDBiEOG091G0UW4
TreeFamiTF317274

Gene expression databases

BgeeiENSPTRG00000013811 Expressed in 6 organ(s), highest expression level in prefrontal cortex

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
IPR019744 Amyloid_glyco_extracell_CS
IPR015849 Amyloid_glyco_heparin-bd
IPR036454 Amyloid_glyco_heparin-bd_sf
IPR019745 Amyloid_glyco_intracell_CS
IPR028866 APP
IPR019543 APP_amyloid_C
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_PANTR
<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: Q5IS80
<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: March 15, 2005
Last sequence update: February 15, 2005
Last modified: December 5, 2018
This is version 124 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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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